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P07949 (RET_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 193. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Proto-oncogene tyrosine-protein kinase receptor Ret

EC=2.7.10.1
Alternative name(s):
Cadherin family member 12
Proto-oncogene c-Ret
Gene names
Name:RET
Synonyms:CDHF12, CDHR16, PTC, RET51
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1114 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell derived neurotrophic factor family ligands. Phosphorylates PTK2/FAK1. Regulates both cell death/survival balance and positional information. Required for the molecular mechanisms orchestration during intestine organogenesis; involved in the development of enteric nervous system and renal organogenesis during embryonic life, and promotes the formation of Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue. Modulates cell adhesion via its cleavage by caspase in sympathetic neurons and mediates cell migration in an integrin (e.g. ITGB1 and ITGB3)-dependent manner. Involved in the development of the neural crest. Active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage. Acts as a dependence receptor; in the presence of the ligand GDNF in somatotrophs (within pituitary), promotes survival and down regulates growth hormone (GH) production, but triggers apoptosis in absence of GDNF. Regulates nociceptor survival and size. Triggers the differentiation of rapidly adapting (RA) mechanoreceptors. Mediator of several diseases such as neuroendocrine cancers; these diseases are characterized by aberrant integrins-regulated cell migration. Ref.23 Ref.26 Ref.27 Ref.30 Ref.31

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Enzyme regulation

Repressed by 4-(3-hydroxyanilino)-quinolines derivatives, indolin-2-one-derivatives, 2-(alkylsulfanyl)-4-(3-thienyl) nicotinonitrile analogs, 3- and 4-substituted beta-carbolin-1-ones, vandetanib, motesanib, sorafenib (BAY 43-9006), cabozantinib (XL184), sunitinib, and withaferin A (WA). Inactivation by sorafenib both reduces kinase activity and promotes lysosomal degradation. Ref.16 Ref.17 Ref.18 Ref.24 Ref.25 Ref.29 Ref.33

Subunit structure

Phosphorylated form interacts with the PBT domain of DOK2, DOK4 and DOK5. The phosphorylated form interacts with PLCG1 and GRB7. Interacts (not phosphorylated) with CC PTK2/FAK1 (via FERM domain). Extracellular cell-membrane anchored RET cadherin fragments form complex in neurons with reduced trophic status, preferentially at the contact sites between somas. Interacts with AIP in the pituitary gland; this interaction prevents the formation of the AIP-survivin complex. Binds to ARTN. Interacts (inactive) with CBLC and CD2AP; dissociates upon activation by GDNF which increases CBLC:CD2AP interaction. Ref.19 Ref.20 Ref.30 Ref.31

Subcellular location

Cell membrane; Single-pass type I membrane protein. Endosome membrane; Single-pass type I membrane protein Ref.28.

Induction

Positively regulated by NKX2-1, PHOX2B, SOX10 and PAX3. Ref.16 Ref.17 Ref.18 Ref.21 Ref.24 Ref.25 Ref.29 Ref.33

Post-translational modification

Autophosphorylated on C-terminal tyrosine residues upon ligand stimulation. Dephosphorylated by PTPRJ on Tyr-905, Tyr-1015 and Tyr-1062. Ref.12 Ref.13 Ref.15 Ref.32 Ref.33

Proteolytically cleaved by caspase-3. The soluble RET kinase fragment is able to induce cell death. The extracellular cell-membrane anchored RET cadherin fragment accelerates cell adhesion in sympathetic neurons. Ref.30

Polymorphism

The Cys-982 polymorphism may be associated with an increased risk for developing Hirschsprung disease.

Involvement in disease

Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history.
Note: The disease may be caused by mutations affecting the gene represented in this entry.

Hirschsprung disease 1 (HSCR1) [MIM:142623]: A disorder of neural crest development characterized by absence of enteric ganglia along a variable length of the intestine. It is the most common cause of congenital intestinal obstruction. Early symptoms range from complete acute neonatal obstruction, characterized by vomiting, abdominal distention and failure to pass stool, to chronic constipation in the older child.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.39 Ref.44 Ref.46 Ref.47 Ref.51 Ref.52 Ref.56 Ref.57 Ref.62 Ref.63 Ref.66 Ref.72 Ref.77 Ref.78 Ref.83 Ref.91

Medullary thyroid carcinoma (MTC) [MIM:155240]: Rare tumor derived from the C cells of the thyroid. Three hereditary forms are known, that are transmitted in an autosomal dominant fashion: (a) multiple neoplasia type 2A (MEN2A), (b) multiple neoplasia type IIB (MEN2B) and (c) familial MTC (FMTC), which occurs in 25-30% of MTC cases and where MTC is the only clinical manifestation.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.42 Ref.43 Ref.44 Ref.49 Ref.54 Ref.55 Ref.58 Ref.59 Ref.63 Ref.65 Ref.67 Ref.70 Ref.74 Ref.75 Ref.76 Ref.79 Ref.81 Ref.84

Multiple neoplasia 2B (MEN2B) [MIM:162300]: Uncommon inherited cancer syndrome characterized by predisposition to MTC and phaeochromocytoma which is associated with marfanoid habitus, mucosal neuromas, skeletal and ophthalmic abnormalities, and ganglioneuromas of the intestine tract. Then the disease progresses rapidly with the development of metastatic MTC and a pheochromocytome in 50% of cases.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.40 Ref.45 Ref.48 Ref.49 Ref.53 Ref.59 Ref.64 Ref.67 Ref.68

Pheochromocytoma (PCC) [MIM:171300]: A catecholamine-producing tumor of chromaffin tissue of the adrenal medulla or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of epinephrine and norepinephrine, is hypertension, which may be persistent or intermittent.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.

Multiple neoplasia 2A (MEN2A) [MIM:171400]: The most frequent form of medullary thyroid cancer (MTC). It is an inherited cancer syndrome characterized by MTC, phaeochromocytoma and/or hyperparathyroidism.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.37 Ref.38 Ref.41 Ref.43 Ref.44 Ref.49 Ref.50 Ref.59 Ref.60 Ref.61 Ref.67 Ref.72 Ref.73 Ref.76 Ref.80

Thyroid papillary carcinoma (TPC) [MIM:188550]: A common tumor of the thyroid that typically arises as an irregular, solid or cystic mass from otherwise normal thyroid tissue. Papillary carcinomas are malignant neoplasm characterized by the formation of numerous, irregular, finger-like projections of fibrous stroma that is covered with a surface layer of neoplastic epithelial cells.
Note: The gene represented in this entry is involved in disease pathogenesis. Chromosomal aberrations involving RET have been found in thyroid papillary carcinomas. Inversion inv10(q11.2;q21) generates the RET/CCDC6 (PTC1) oncogene; inversion inv10(q11.2;q11.2) generates the RET/NCOA4 (PTC3) oncogene; translocation t(10;14)(q11;q32) with GOLGA5 generates the RET/GOLGA5 (PTC5) oncogene; translocation t(8;10)(p21.3;q11.2) with PCM1 generates the PCM1/RET fusion; translocation t(6;10)(p21.3;q11.2) with RFP generates the Delta RFP/RET oncogene; translocation t(1;10)(p13;q11) with TRIM33 generates the TRIM33/RET (PTC7) oncogene; translocation t(7;10)(q32;q11) with TRIM24/TIF1 generates the TRIM24/RET (PTC6) oncogene. The PTC5 oncogene has been found in 2 cases of PACT in children exposed to radioactive fallout after Chernobyl. A chromosomal aberration involving TRIM27/RFP is found in thyroid papillary carcinomas. Translocation t(6;10)(p21.3;q11.2) with RET. The translocation generates TRIM27/RET and delta TRIM27/RET oncogenes.

Renal adysplasia (RADYS) [MIM:191830]: Renal agenesis refers to the absence of one (unilateral) or both (bilateral) kidneys at birth. Bilateral renal agenesis belongs to a group of perinatally lethal renal diseases, including severe bilateral renal dysplasia, unilateral renal agenesis with contralateral dysplasia and severe obstructive uropathy.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.90

Congenital central hypoventilation syndrome (CCHS) [MIM:209880]: Rare disorder characterized by abnormal control of respiration in the absence of neuromuscular or lung disease, or an identifiable brain stem lesion. A deficiency in autonomic control of respiration results in inadequate or negligible ventilatory and arousal responses to hypercapnia and hypoxemia.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.69 Ref.86 Ref.87

Miscellaneous

Treatment with withaferin A (WA) leads tumor regression in medullary thyroid carcinomas (MTC).

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family.

Contains 1 cadherin domain.

Contains 1 protein kinase domain.

Sequence caution

The sequence AAA36524.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

The sequence AAA36786.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

The sequence CAA33787.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

The sequence CAC14882.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
   Biological processCell adhesion
   Cellular componentCell membrane
Endosome
Membrane
   Coding sequence diversityAlternative splicing
Chromosomal rearrangement
Polymorphism
   DiseaseDisease mutation
Hirschsprung disease
Proto-oncogene
   DomainSignal
Transmembrane
Transmembrane helix
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
Tyrosine-protein kinase
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processMAPK cascade

Inferred from electronic annotation. Source: Ensembl

Peyer's patch morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

activation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from mutant phenotype PubMed 10921886. Source: UniProtKB

cellular response to retinoic acid

Inferred from mutant phenotype PubMed 17910947. Source: BHF-UCL

embryonic epithelial tube formation

Inferred from electronic annotation. Source: Ensembl

enteric nervous system development

Inferred from electronic annotation. Source: Ensembl

homophilic cell adhesion

Inferred from electronic annotation. Source: InterPro

innervation

Inferred from electronic annotation. Source: Ensembl

lymphocyte migration into lymphoid organs

Inferred from sequence or structural similarity. Source: UniProtKB

membrane protein proteolysis

Inferred from direct assay Ref.30. Source: UniProtKB

neural crest cell migration

Inferred from electronic annotation. Source: Ensembl

neuron cell-cell adhesion

Inferred from mutant phenotype Ref.30. Source: UniProtKB

neuron maturation

Inferred from electronic annotation. Source: Ensembl

peptidyl-tyrosine phosphorylation

Traceable author statement PubMed 7824936. Source: GOC

positive regulation of cell adhesion mediated by integrin

Inferred from direct assay Ref.27. Source: UniProtKB

positive regulation of cell migration

Inferred from direct assay Ref.27. Source: UniProtKB

positive regulation of cell size

Inferred from electronic annotation. Source: Ensembl

positive regulation of extrinsic apoptotic signaling pathway in absence of ligand

Inferred from mutant phenotype PubMed 10921886. Source: UniProtKB

positive regulation of metanephric glomerulus development

Inferred from sequence or structural similarity PubMed 17047028. Source: UniProtKB

positive regulation of neuron maturation

Inferred from electronic annotation. Source: Ensembl

positive regulation of neuron projection development

Inferred from mutant phenotype PubMed 17910947. Source: BHF-UCL

positive regulation of transcription, DNA-templated

Inferred from sequence or structural similarity PubMed 17047028. Source: UniProtKB

posterior midgut development

Traceable author statement Ref.47. Source: ProtInc

protein phosphorylation

Traceable author statement PubMed 7824936. Source: ProtInc

regulation of axonogenesis

Inferred from electronic annotation. Source: Ensembl

regulation of cell adhesion

Inferred from direct assay Ref.30. Source: UniProtKB

response to drug

Inferred from electronic annotation. Source: Ensembl

response to pain

Inferred from sequence or structural similarity. Source: UniProtKB

retina development in camera-type eye

Inferred from electronic annotation. Source: Ensembl

signal transduction

Traceable author statement PubMed 7824936. Source: ProtInc

transmembrane receptor protein tyrosine kinase signaling pathway

Inferred from electronic annotation. Source: Ensembl

ureter maturation

Inferred from electronic annotation. Source: Ensembl

ureteric bud development

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentendosome membrane

Inferred from direct assay Ref.28. Source: UniProtKB

integral component of plasma membrane

Inferred from direct assay Ref.28. Source: UniProtKB

membrane raft

Inferred from electronic annotation. Source: Ensembl

receptor complex

Inferred from direct assay PubMed 23382219. Source: MGI

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

calcium ion binding

Inferred from direct assay PubMed 11445581. Source: FlyBase

protein tyrosine kinase activity

Traceable author statement PubMed 7824936. Source: ProtInc

receptor activity

Traceable author statement PubMed 7824936. Source: ProtInc

transmembrane receptor protein tyrosine kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sh2b1Q629853EBI-2480756,EBI-7395583From a different organism.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P07949-1)

Also known as: RET51;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Note: No experimental confirmation available.
Isoform 2 (identifier: P07949-2)

Also known as: RET9;

The sequence of this isoform differs from the canonical sequence as follows:
     1064-1114: MSDPNWPGESPVPLTRADGTNTGFPRYPNDSVYANWMLSPSAAKLMDTFDS → RISHAFTRF

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2828 Potential
Chain29 – 11141086Proto-oncogene tyrosine-protein kinase receptor Ret
PRO_0000024450
Chain29 – 707679Extracellular cell-membrane anchored RET cadherin 120 kDa fragment
PRO_0000415292
Chain708 – 1017310Soluble RET kinase fragment
PRO_0000415293

Regions

Topological domain29 – 635607Extracellular Potential
Transmembrane636 – 65722Helical; Potential
Topological domain658 – 1114457Cytoplasmic Potential
Domain168 – 272105Cadherin
Domain724 – 1016293Protein kinase
Nucleotide binding730 – 7389ATP By similarity
Region805 – 8073Inhibitors binding

Sites

Active site8741Proton acceptor By similarity
Binding site7581ATP By similarity
Binding site8921Inhibitor
Site587 – 5882Breakpoint for translocation to form the TRIM27/RET oncogene
Site707 – 7082Cleavage; by caspase-3
Site712 – 7132Breakpoint for translocation to form PCM1-RET; RET-CCDC6; RET-GOLGA5; RET-TRIM24 and RET-TRIM33 oncogenes
Site1017 – 10182Cleavage; by caspase-3

Amino acid modifications

Modified residue6961Phosphoserine Ref.22
Modified residue8061Phosphotyrosine; by autocatalysis Ref.13
Modified residue8091Phosphotyrosine; by autocatalysis Ref.13
Modified residue9001Phosphotyrosine; by autocatalysis Ref.13 Ref.32
Modified residue9051Phosphotyrosine; by autocatalysis Ref.13 Ref.15 Ref.32 Ref.33
Modified residue9811Phosphotyrosine; by autocatalysis Ref.13
Modified residue10151Phosphotyrosine; by autocatalysis Ref.12 Ref.13 Ref.15
Modified residue10621Phosphotyrosine; by autocatalysis Ref.12 Ref.13 Ref.15
Modified residue10901Phosphotyrosine; by autocatalysis Ref.13
Modified residue10961Phosphotyrosine; by autocatalysis Ref.13
Glycosylation981N-linked (GlcNAc...) Potential
Glycosylation1511N-linked (GlcNAc...) Ref.34
Glycosylation1991N-linked (GlcNAc...) Potential
Glycosylation3361N-linked (GlcNAc...) Potential
Glycosylation3431N-linked (GlcNAc...) Potential
Glycosylation3611N-linked (GlcNAc...) Potential
Glycosylation3671N-linked (GlcNAc...) Potential
Glycosylation3771N-linked (GlcNAc...) Potential
Glycosylation3941N-linked (GlcNAc...) Potential
Glycosylation4481N-linked (GlcNAc...) Potential
Glycosylation4681N-linked (GlcNAc...) Potential
Glycosylation5541N-linked (GlcNAc...) Potential
Disulfide bond137 ↔ 142 Ref.34

Natural variations

Alternative sequence1064 – 111451MSDPN…DTFDS → RISHAFTRF in isoform 2.
VSP_040735
Natural variant201P → L in HSCR1; sporadic form. Ref.51
VAR_009459
Natural variant321S → L in HSCR1; familial form. Ref.47 Ref.83
Corresponds to variant rs76764689 [ dbSNP | Ensembl ].
VAR_006295
Natural variant401L → P in HSCR1. Ref.39 Ref.57
VAR_009492
Natural variant641P → L in HSCR1; familial form. Ref.47
Corresponds to variant rs77596424 [ dbSNP | Ensembl ].
VAR_006296
Natural variant671R → H in CCHS. Ref.87
Corresponds to variant rs192489011 [ dbSNP | Ensembl ].
VAR_018153
Natural variant771R → C in HSCR1. Ref.83
VAR_009460
Natural variant931G → S in HSCR1; unknown pathological significance. Ref.51
VAR_006297
Natural variant1141R → C in HSCR1. Ref.91
VAR_067101
Natural variant1141R → H in CCHS and HSCR1. Ref.86 Ref.87 Ref.91
VAR_018154
Natural variant1421C → S in HSCR1; sporadic form.
VAR_006298
Natural variant1451V → G in HSCR1; also in a colorectal cancer sample; somatic mutation. Ref.88 Ref.91
VAR_035711
Natural variant1551P → L in HSCR1. Ref.91
VAR_067102
Natural variant1571C → Y in HSCR1; unknown pathological significance. Ref.56
VAR_009461
Natural variant1631R → Q in a colorectal adenocarcinoma sample; somatic mutation. Ref.89
Corresponds to variant rs149403911 [ dbSNP | Ensembl ].
VAR_041762
Natural variant1741F → S in HSCR1; sporadic form. Ref.66
VAR_009462
Natural variant1751R → P in HSCR1. Ref.91
VAR_067103
Natural variant1801R → P in HSCR1; sporadic form. Ref.62
VAR_009463
Natural variant1971C → Y in HSCR1; sporadic form. Ref.66
VAR_009464
Natural variant1981P → T in RADYS; prevents phosphorylation in response to GDNF. Ref.90
Corresponds to variant rs76736111 [ dbSNP | Ensembl ].
VAR_044392
Natural variant2311R → H in HSCR1; familial form.
Corresponds to variant rs79661516 [ dbSNP | Ensembl ].
VAR_006299
Natural variant2511E → K in HSCR1; familial form.
VAR_006300
Natural variant2781T → A in HSCR1. Ref.91
VAR_067104
Natural variant2781T → N Found in two patients with Hirschsprung disease. Ref.89 Ref.91
Corresponds to variant rs35118262 [ dbSNP | Ensembl ].
VAR_041763
Natural variant2781T → P in HSCR1. Ref.91
VAR_067105
Natural variant2871R → Q in HSCR1; sporadic form.
VAR_006301
Natural variant2921V → M Found in patients with Hirschsprung disease; unknown pathological significance. Ref.89 Ref.91
Corresponds to variant rs34682185 [ dbSNP | Ensembl ].
VAR_041764
Natural variant3001D → N in HSCR1. Ref.91
VAR_067106
Natural variant3131R → Q in HSCR1. Ref.62 Ref.91
Corresponds to variant rs77702891 [ dbSNP | Ensembl ].
VAR_009465
Natural variant3161S → I in HSCR1. Ref.91
VAR_067107
Natural variant3301R → Q in HSCR1. Ref.47 Ref.51
Corresponds to variant rs80236571 [ dbSNP | Ensembl ].
VAR_006302
Natural variant3391S → L in HSCR1. Ref.91
VAR_067108
Natural variant3531D → Y in HSCR1. Ref.91
VAR_067109
Natural variant3591N → K in HSCR1; unknown pathological significance. Ref.56
VAR_009466
Natural variant3601R → Q in HSCR1. Ref.91
VAR_067110
Natural variant3601R → W in HSCR1. Ref.83 Ref.88
VAR_009467
Natural variant3761V → A in RADYS; constitutively phosphorylated; expressed only the immature intracellular form. Ref.90
VAR_044393
Natural variant3931F → L in HSCR1; familial form. Ref.47
Corresponds to variant rs78098482 [ dbSNP | Ensembl ].
VAR_006303
Natural variant3941N → H in RADYS; prevents phosphorylation in response to GDNF. Ref.90
VAR_044394
Natural variant3941N → K in HSCR1. Ref.83
VAR_009468
Natural variant3971V → M in HSCR1. Ref.91
Corresponds to variant rs183729115 [ dbSNP | Ensembl ].
VAR_067111
Natural variant3991P → L in HSCR1; sporadic form. Ref.39
VAR_006304
Natural variant4121V → M in HSCR1. Ref.91
VAR_067112
Natural variant4231G → R in HSCR1. Ref.91
VAR_067113
Natural variant4321A → E in CCHS. Ref.87
VAR_018155
Natural variant4751R → Q in HSCR1; sporadic form.
Corresponds to variant rs138624658 [ dbSNP | Ensembl ].
VAR_006305
Natural variant4801E → K in HSCR1. Ref.91
VAR_067114
Natural variant4891D → N. Ref.87 Ref.89
Corresponds to variant rs9282834 [ dbSNP | Ensembl ].
VAR_018156
Natural variant5311C → CEEC in MTC; familial form.
VAR_009469
Natural variant549 – 5502Missing in HSCR1.
VAR_067115
Natural variant5931G → E in a colorectal cancer sample; somatic mutation. Ref.88
VAR_035712
Natural variant5951E → Q in HSCR1. Ref.91
VAR_067116
Natural variant6001R → Q. Ref.82
VAR_008966
Natural variant6091C → G in MEN2A.
VAR_009470
Natural variant6091C → R in MEN2A.
Corresponds to variant rs77558292 [ dbSNP | Ensembl ].
VAR_009471
Natural variant6091C → W in HSCR1; familial form. Ref.44
VAR_006307
Natural variant6091C → Y in MTC, MEN2A and HSCR1; familial and sporadic forms. Ref.42 Ref.51 Ref.56 Ref.72
Corresponds to variant rs77939446 [ dbSNP | Ensembl ].
VAR_006306
Natural variant6111C → G in MTC; familial form. Ref.70
VAR_009472
Natural variant6111C → R in MEN2A.
VAR_009473
Natural variant6111C → S in MEN2A.
VAR_009474
Natural variant6111C → W in MEN2A and MTC; familial form. Ref.37
Corresponds to variant rs80069458 [ dbSNP | Ensembl ].
VAR_006308
Natural variant6111C → Y in MEN2A.
VAR_006309
Natural variant6181C → F in MEN2A and MTC; familial form.
VAR_006312
Natural variant6181C → G in MEN2A. Ref.38
VAR_006310
Natural variant6181C → R in MEN2A, MTC and HSCR1. Ref.41 Ref.42 Ref.44 Ref.63
Corresponds to variant rs76262710 [ dbSNP | Ensembl ].
VAR_006311
Natural variant6181C → S in MEN2A, HSCR1 and MTC; familial and sporadic forms. Ref.37 Ref.41 Ref.42 Ref.50 Ref.72
Corresponds to variant rs79781594 [ dbSNP | Ensembl ].
VAR_006313
Natural variant6181C → Y in MEN2A and MTC; familial form.
VAR_006314
Natural variant6201C → F in MEN2A and MTC; familial form. Ref.41
Corresponds to variant rs77503355 [ dbSNP | Ensembl ].
VAR_006318
Natural variant6201C → G in MEN2A and MTC; familial and sporadic forms.
VAR_006315
Natural variant6201C → R in MEN2A, MTC and HSCR1; familial and sporadic forms. Ref.37 Ref.41 Ref.44 Ref.51 Ref.56 Ref.62 Ref.72
VAR_006316
Natural variant6201C → S in MEN2A and MTC; familial form. Ref.42 Ref.50
VAR_006317
Natural variant6201C → W in MEN2A and HSCR1. Ref.72
VAR_009475
Natural variant6201C → Y in MEN2A. Ref.37
VAR_006319
Natural variant6261Q → K in HSCR1; sporadic form. Ref.77
VAR_009476
Natural variant6301C → F in MEN2A and MTC; familial form.
VAR_006320
Natural variant6301C → S in MTC; sporadic form.
VAR_009477
Natural variant6301C → Y in MTC; familial and sporadic forms.
VAR_009478
Natural variant6311D → G in thyroid carcinoma; somatic mutation.
Corresponds to variant rs121913308 [ dbSNP | Ensembl ].
VAR_006321
Natural variant632 – 6343ELC → DVR in MEN2A.
VAR_006322
Natural variant634 – 6352CR → WG in MEN2A.
VAR_006329
Natural variant6341C → CHELC in MEN2A.
VAR_009479
Natural variant6341C → F in MEN2A and pheochromocytoma. Ref.38 Ref.41 Ref.85
VAR_006324
Natural variant6341C → G in MEN2A and pheochromocytoma. Ref.38 Ref.41 Ref.85
VAR_006323
Natural variant6341C → R in MEN2A, pheochromocytoma and MTC; familial form; also found as somatic mutation in a sporadic thyroid carcinoma. Ref.37 Ref.38 Ref.50 Ref.85
VAR_006326
Natural variant6341C → S in MEN2A, pheochromocytoma and MTC; familial form. Ref.38 Ref.85
VAR_006327
Natural variant6341C → W in MEN2A, pheochromocytoma and MTC; familial form. Ref.85
VAR_006328
Natural variant6341C → Y in MEN2A, pheochromocytoma and MTC; familial form. Ref.38 Ref.41 Ref.50 Ref.85
VAR_006325
Natural variant6361T → TCRT in MEN2A.
VAR_006330
Natural variant6391A → G in MTC; sporadic form. Ref.84
VAR_012743
Natural variant6401A → G in MEN2A. Ref.80
Corresponds to variant rs78935588 [ dbSNP | Ensembl ].
VAR_009480
Natural variant6411A → G in MTC; sporadic form. Ref.84
VAR_012744
Natural variant6791P → L in HSCR1. Ref.91
VAR_067117
Natural variant6901S → P in HSCR1; sporadic form.
VAR_006331
Natural variant6911G → S. Ref.67 Ref.69 Ref.87 Ref.89
Corresponds to variant rs1799939 [ dbSNP | Ensembl ].
VAR_006332
Natural variant6941R → Q in HSCR1. Ref.91
Corresponds to variant rs141185224 [ dbSNP | Ensembl ].
VAR_067118
Natural variant7491R → T. Ref.89
Corresponds to variant rs34288963 [ dbSNP | Ensembl ].
VAR_041765
Natural variant7621E → Q in HSCR1; sporadic form. Ref.39
VAR_009481
Natural variant7651S → P in HSCR1. Ref.39 Ref.46 Ref.57
Corresponds to variant rs75075748 [ dbSNP | Ensembl ].
VAR_009493
Natural variant7671S → R in HSCR1; sporadic form.
VAR_006334
Natural variant7681E → D in MTC; familial and sporadic forms. Ref.54 Ref.55 Ref.59
Corresponds to variant rs78014899 [ dbSNP | Ensembl ].
VAR_006335
Natural variant7781V → I in RADYS; constitutively phosphorylated. Ref.90
Corresponds to variant rs75686697 [ dbSNP | Ensembl ].
VAR_044395
Natural variant7831N → S in HSCR1. Ref.91
VAR_067119
Natural variant7901L → F in MEN2A and MTC; familial form. Ref.75
Corresponds to variant rs75030001 [ dbSNP | Ensembl ].
VAR_009482
Natural variant7911Y → F in HSCR1, pheochromocytoma, MTC and MEN2A; familial form. Ref.62 Ref.75 Ref.85
Corresponds to variant rs77724903 [ dbSNP | Ensembl ].
VAR_009483
Natural variant8041V → L in MTC; familial form. Ref.55
Corresponds to variant rs79658334 [ dbSNP | Ensembl ].
VAR_006336
Natural variant8041V → M in MTC; familial form. Ref.74 Ref.81
Corresponds to variant rs79658334 [ dbSNP | Ensembl ].
VAR_006337
Natural variant8131R → Q in HSCR1; sporadic form. Ref.77
VAR_009484
Natural variant8261Y → S. Ref.89
Corresponds to variant rs34617196 [ dbSNP | Ensembl ].
VAR_041766
Natural variant8301G → R in HSCR1. Ref.91
Corresponds to variant rs200127630 [ dbSNP | Ensembl ].
VAR_067120
Natural variant8441R → L in MTC; familial form. Ref.81 Ref.89
Corresponds to variant rs55947360 [ dbSNP | Ensembl ].
VAR_011582
Natural variant8731R → Q in HSCR1; sporadic form.
VAR_006338
Natural variant8831A → F in MEN2B; somatic mutation in sporadic medullary thyroid carcinoma; requires 2 nucleotide substitutions. Ref.64 Ref.68
VAR_009485
Natural variant8911S → A in MTC; familial form. Ref.65
Corresponds to variant rs75234356 [ dbSNP | Ensembl ].
VAR_009486
Natural variant8931F → L in HSCR1; sporadic form.
VAR_006339
Natural variant8941G → S in RADYS; constitutively phosphorylated; expressed only the immature intracellular form. Ref.90
VAR_044396
Natural variant8971R → Q in HSCR1; sporadic form. Ref.39 Ref.46
Corresponds to variant rs76087194 [ dbSNP | Ensembl ].
VAR_006340
Natural variant9071K → E in HSCR1; sporadic form.
VAR_006341
Natural variant9071K → T in HSCR1. Ref.91
VAR_067121
Natural variant9181M → T in RADYS, MEN2B and MTC; sporadic form; somatic mutation. Ref.40 Ref.45 Ref.48 Ref.53 Ref.59 Ref.90
Corresponds to variant rs74799832 [ dbSNP | Ensembl ].
VAR_006342
Natural variant9211E → K in HSCR1; sporadic form.
VAR_006343
Natural variant9221S → F in MTC; sporadic form. Ref.84
VAR_012745
Natural variant9221S → Y Rare polymorphism. Ref.53
VAR_009487
Natural variant9461T → M in MEN2B and MTC; familial form.
VAR_006345
Natural variant9611F → L in HSCR1. Ref.91
VAR_067122
Natural variant9721R → G in HSCR1; familial form. Ref.39 Ref.46
Corresponds to variant rs76534745 [ dbSNP | Ensembl ].
VAR_006346
Natural variant9731P → L in HSCR1; familial form. Ref.39
VAR_006347
Natural variant9801M → T in HSCR1; sporadic form.
VAR_006348
Natural variant9821R → C. Ref.3 Ref.51 Ref.71 Ref.87 Ref.89
Corresponds to variant rs17158558 [ dbSNP | Ensembl ].
VAR_006349
Natural variant10391P → L in CCHS; with colonic aganglionosis. Ref.69
Corresponds to variant rs79853121 [ dbSNP | Ensembl ].
VAR_018157
Natural variant10391P → Q.
VAR_009488
Natural variant10491P → L in RADYS; prevents phosphorylation in response to GDNF. Ref.90
VAR_044397
Natural variant10521L → V in HSCR1. Ref.91
VAR_067123
Natural variant10591Missing in HSCR1. Ref.56 Ref.78
VAR_009489
Natural variant10611L → P in HSCR1. Ref.56 Ref.78
VAR_009490
Natural variant10621Y → C in HSCR1. Ref.91
VAR_067124
Natural variant10641M → T in HSCR1; familial form. Ref.91
VAR_009491
Natural variant10671P → S in RADYS; prevents phosphorylation in response to GDNF. Ref.90
VAR_044398
Natural variant11121F → Y in a bladder transitional cell carcinoma sample; somatic mutation. Ref.89
VAR_041767

Experimental info

Mutagenesis7071D → N: Impaired cleavage by caspase-3 and loss of induced cell death. Ref.30
Mutagenesis708 – 1114407Missing: Loss of induced cell death, but increased cell aggregation. Ref.30
Mutagenesis7581K → R: Loss of kinase activity. No effect on interaction with and dissociation from CBLC and CD2AP. Ref.19 Ref.30
Sequence conflict6471I → V in AAA36786. Ref.6
Sequence conflict6641A → S in BAF84496. Ref.1
Sequence conflict7501A → G in AAA36524. Ref.9
Sequence conflict9041S → P in AAA36786. Ref.6

Secondary structure

.................................................................................................. 1114
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (RET51) [UniParc].

Last modified June 1, 1994. Version 3.
Checksum: A3DA0CE01A19A441

FASTA1,114124,319
        10         20         30         40         50         60 
MAKATSGAAG LRLLLLLLLP LLGKVALGLY FSRDAYWEKL YVDQAAGTPL LYVHALRDAP 

        70         80         90        100        110        120 
EEVPSFRLGQ HLYGTYRTRL HENNWICIQE DTGLLYLNRS LDHSSWEKLS VRNRGFPLLT 

       130        140        150        160        170        180 
VYLKVFLSPT SLREGECQWP GCARVYFSFF NTSFPACSSL KPRELCFPET RPSFRIRENR 

       190        200        210        220        230        240 
PPGTFHQFRL LPVQFLCPNI SVAYRLLEGE GLPFRCAPDS LEVSTRWALD REQREKYELV 

       250        260        270        280        290        300 
AVCTVHAGAR EEVVMVPFPV TVYDEDDSAP TFPAGVDTAS AVVEFKRKED TVVATLRVFD 

       310        320        330        340        350        360 
ADVVPASGEL VRRYTSTLLP GDTWAQQTFR VEHWPNETSV QANGSFVRAT VHDYRLVLNR 

       370        380        390        400        410        420 
NLSISENRTM QLAVLVNDSD FQGPGAGVLL LHFNVSVLPV SLHLPSTYSL SVSRRARRFA 

       430        440        450        460        470        480 
QIGKVCVENC QAFSGINVQY KLHSSGANCS TLGVVTSAED TSGILFVNDT KALRRPKCAE 

       490        500        510        520        530        540 
LHYMVVATDQ QTSRQAQAQL LVTVEGSYVA EEAGCPLSCA VSKRRLECEE CGGLGSPTGR 

       550        560        570        580        590        600 
CEWRQGDGKG ITRNFSTCSP STKTCPDGHC DVVETQDINI CPQDCLRGSI VGGHEPGEPR 

       610        620        630        640        650        660 
GIKAGYGTCN CFPEEEKCFC EPEDIQDPLC DELCRTVIAA AVLFSFIVSV LLSAFCIHCY 

       670        680        690        700        710        720 
HKFAHKPPIS SAEMTFRRPA QAFPVSYSSS GARRPSLDSM ENQVSVDAFK ILEDPKWEFP 

       730        740        750        760        770        780 
RKNLVLGKTL GEGEFGKVVK ATAFHLKGRA GYTTVAVKML KENASPSELR DLLSEFNVLK 

       790        800        810        820        830        840 
QVNHPHVIKL YGACSQDGPL LLIVEYAKYG SLRGFLRESR KVGPGYLGSG GSRNSSSLDH 

       850        860        870        880        890        900 
PDERALTMGD LISFAWQISQ GMQYLAEMKL VHRDLAARNI LVAEGRKMKI SDFGLSRDVY 

       910        920        930        940        950        960 
EEDSYVKRSQ GRIPVKWMAI ESLFDHIYTT QSDVWSFGVL LWEIVTLGGN PYPGIPPERL 

       970        980        990       1000       1010       1020 
FNLLKTGHRM ERPDNCSEEM YRLMLQCWKQ EPDKRPVFAD ISKDLEKMMV KRRDYLDLAA 

      1030       1040       1050       1060       1070       1080 
STPSDSLIYD DGLSEEETPL VDCNNAPLPR ALPSTWIENK LYGMSDPNWP GESPVPLTRA 

      1090       1100       1110 
DGTNTGFPRY PNDSVYANWM LSPSAAKLMD TFDS 

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Isoform 2 (RET9) [UniParc].

Checksum: 85868CBFCEA0D24C
Show »

FASTA1,072119,847

References

« Hide 'large scale' references
[1]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Prostate.
[2]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT CYS-982.
Tissue: Brain.
[4]"Isolation of ret proto-oncogene cDNA with an amino-terminal signal sequence."
Takahashi M.
Oncogene 4:805-806(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-280 (ISOFORMS 1/2).
[5]"Cloning and expression of the ret proto-oncogene encoding a tyrosine kinase with two potential transmembrane domains."
Takahashi M., Buma Y., Iwamoto T., Inaguma Y., Ikeda H., Hiai H.
Oncogene 3:571-578(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 255-1114 (ISOFORM 1).
[6]"ret transforming gene encodes a fusion protein homologous to tyrosine kinases."
Takahashi M., Cooper G.M.
Mol. Cell. Biol. 7:1378-1385(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 588-1063 (ISOFORM 2), CHROMOSOMAL TRANSLOCATION WITH TRIM27.
[7]"Activation of the ret-II oncogene without a sequence encoding a transmembrane domain and transforming activity of two ret-II oncogene products differing in carboxy-termini due to alternative splicing."
Ishizaka Y., Ochiai M., Tahira T., Suhimura T., Nahao M.
Oncogene 4:789-794(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 713-1114 (ISOFORM 1), CHROMOSOMAL TRANSLOCATION WITH GOLGA5.
Tissue: Fibroblast.
[8]Erratum
Ishizaka Y., Ochiai M., Tahira T., Suhimura T., Nahao M.
Oncogene 4:1415-1415(1989)
[9]"PTC is a novel rearranged form of the ret proto-oncogene and is frequently detected in vivo in human thyroid papillary carcinomas."
Grieco M., Santoro M., Berlingieri M.T., Melillo R.M., Donghi R., Bongarzone I., Pierotti M.A., Della Porta G., Fusco A., Vecchio G.
Cell 60:557-563(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 713-1114 (ISOFORM 1), CHROMOSOMAL TRANSLOCATION WITH CCDC6.
Tissue: Thyroid papillary carcinoma.
[10]"RET/PCM-1: a novel fusion gene in papillary thyroid carcinoma."
Corvi R., Berger N., Balczon R., Romeo G.
Oncogene 19:4236-4242(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 713-770 (ISOFORMS 1/2), CHROMOSOMAL TRANSLOCATION WITH PCM1.
[11]"The transcription coactivator HTIF1 and a related protein are fused to the RET receptor tyrosine kinase in childhood papillary thyroid carcinomas."
Klugbauer S., Rabes H.M.
Oncogene 18:4388-4393(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: CHROMOSOMAL TRANSLOCATION WITH TRIM33 AND TRIM24.
[12]"Tyrosines 1015 and 1062 are in vivo autophosphorylation sites in ret and ret-derived oncoproteins."
Salvatore D., Barone M.V., Salvatore G., Melillo R.M., Chiappetta G., Mineo A., Fenzi G., Vecchio G., Fusco A., Santoro M.
J. Clin. Endocrinol. Metab. 85:3898-3907(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-1015 AND TYR-1062.
[13]"Identification of RET autophosphorylation sites by mass spectrometry."
Kawamoto Y., Takeda K., Okuno Y., Yamakawa Y., Ito Y., Taguchi R., Kato M., Suzuki H., Takahashi M., Nakashima I.
J. Biol. Chem. 279:14213-14224(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-806; TYR-809; TYR-900; TYR-905; TYR-981; TYR-1015; TYR-1062; TYR-1090 AND TYR-1096.
[14]"Novel tumorigenic rearrangement, Delta rfp/ret, in a papillary thyroid carcinoma from externally irradiated patient."
Saenko V., Rogounovitch T., Shimizu-Yoshida Y., Abrosimov A., Lushnikov E., Roumiantsev P., Matsumoto N., Nakashima M., Meirmanov S., Ohtsuru A., Namba H., Tsyb A., Yamashita S.
Mutat. Res. 527:81-90(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: CHROMOSOMAL TRANSLOCATION WITH TRIM27.
[15]"The receptor-type protein tyrosine phosphatase J antagonizes the biochemical and biological effects of RET-derived oncoproteins."
Iervolino A., Iuliano R., Trapasso F., Viglietto G., Melillo R.M., Carlomagno F., Santoro M., Fusco A.
Cancer Res. 66:6280-6287(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: AUTOPHOSPHORYLATION AT TYR-905; TYR-1015 AND TYR-1062, DEPHOSPHORYLATION BY PTPRJ AT TYR-905; TYR-1015 AND TYR-1062.
[16]"The discovery of substituted 4-(3-hydroxyanilino)-quinolines as potent RET kinase inhibitors."
Graham Robinett R., Freemerman A.J., Skinner M.A., Shewchuk L., Lackey K.
Bioorg. Med. Chem. Lett. 17:5886-5893(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[17]"Sorafenib functions to potently suppress RET tyrosine kinase activity by direct enzymatic inhibition and promoting RET lysosomal degradation independent of proteasomal targeting."
Plaza-Menacho I., Mologni L., Sala E., Gambacorti-Passerini C., Magee A.I., Links T.P., Hofstra R.M.W., Barford D., Isacke C.M.
J. Biol. Chem. 282:29230-29240(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION BY SORAFENIB.
[18]"Synthesis, modeling, and RET protein kinase inhibitory activity of 3- and 4-substituted beta-carbolin-1-ones."
Cincinelli R., Cassinelli G., Dallavalle S., Lanzi C., Merlini L., Botta M., Tuccinardi T., Martinelli A., Penco S., Zunino F.
J. Med. Chem. 51:7777-7787(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION BY 3- AND 4-SUBSTITUTED BETA-CARBOLIN-1-ONES.
[19]"CD2AP and Cbl-3/Cbl-c constitute a critical checkpoint in the regulation of ret signal transduction."
Tsui C.C., Pierchala B.A.
J. Neurosci. 28:8789-8800(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CD2AP, MUTAGENESIS OF LYS-758.
[20]"The tyrosine kinase receptor RET interacts in vivo with aryl hydrocarbon receptor-interacting protein to alter survivin availability."
Vargiolu M., Fusco D., Kurelac I., Dirnberger D., Baumeister R., Morra I., Melcarne A., Rimondini R., Romeo G., Bonora E.
J. Clin. Endocrinol. Metab. 94:2571-2578(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH AIP.
[21]"Transcriptional regulation of RET by Nkx2-1, Phox2b, Sox10, and Pax3."
Leon T.Y.Y., Ngan E.S.W., Poon H.-C., So M.-T., Lui V.C.H., Tam P.K.H., Garcia-Barcelo M.M.
J. Pediatr. Surg. 44:1904-1912(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION BY NKX2-1; PHOX2B; SOX10 AND PAX3.
[22]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-696, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[23]"RETouching upon mechanoreceptors."
Ma Q.
Neuron 64:773-776(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEVELOPMENT OF MECHANORECEPTORS.
[24]"The evolving field of tyrosine kinase inhibitors in the treatment of endocrine tumors."
Ye L., Santarpia L., Gagel R.F.
Endocr. Rev. 31:578-599(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, REVIEW ON KINASE INHIBITORS.
[25]"Inhibitors of the RET tyrosine kinase based on a 2-(alkylsulfanyl)-4-(3-thienyl)nicotinonitrile scaffold."
Brandt W., Mologni L., Preu L., Lemcke T., Gambacorti-Passerini C., Kunick C.
Eur. J. Med. Chem. 45:2919-2927(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[26]"Functional role of the RET dependence receptor, GFRa co-receptors and ligands in the pituitary."
Garcia-Lavandeira M., Diaz-Rodriguez E., Garcia-Rendueles M.E., Rodrigues J.S., Perez-Romero S., Bravo S.B., Alvarez C.V.
Front. Horm. Res. 38:127-138(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PITUITARY.
[27]"RET-mediated cell adhesion and migration require multiple integrin subunits."
Cockburn J.G., Richardson D.S., Gujral T.S., Mulligan L.M.
J. Clin. Endocrinol. Metab. 95:E342-E346(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CELL ADHESION/MIGRATION.
[28]"Direct visualization of vesicle maturation and plasma membrane protein trafficking."
Richardson D.S., Mulligan L.M.
J. Fluoresc. 20:401-405(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[29]"A novel RET inhibitor with potent efficacy against medullary thyroid cancer in vivo."
Samadi A.K., Mukerji R., Shah A., Timmermann B.N., Cohen M.S.
Surgery 148:1228-1236(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[30]"RET modulates cell adhesion via its cleavage by caspase in sympathetic neurons."
Cabrera J.R., Bouzas-Rodriguez J., Tauszig-Delamasure S., Mehlen P.
J. Biol. Chem. 286:14628-14638(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CELL ADHESION, FUNCTION IN APOPTOSIS, PROTEOLYTIC PROCESSING BY CASPASE-3 AT ASP-707 AND ASP-1017, MUTAGENESIS OF ASP-707; LYS-758 AND 708-ALA--SER-1114, SUBUNIT.
[31]"Focal adhesion kinase (FAK) binds RET kinase via its FERM domain, priming a direct and reciprocal RET-FAK transactivation mechanism."
Plaza-Menacho I., Morandi A., Mologni L., Boender P., Gambacorti-Passerini C., Magee A.I., Hofstra R.M.W., Knowles P., McDonald N.Q., Isacke C.M.
J. Biol. Chem. 286:17292-17302(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PTK2/FAK1, FUNCTION IN PTK2/FAK1 PHOSPHORYLATION.
[32]"Structure and chemical inhibition of the RET tyrosine kinase domain."
Knowles P.P., Murray-Rust J., Kjaer S., Scott R.P., Hanrahan S., Santoro M., Ibanez C.F., McDonald N.Q.
J. Biol. Chem. 281:33577-33587(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 705-1013 ALONE AND IN COMPLEX WITH INHIBITORS, IDENTIFICATION BY MASS SPECTROMETRY, PHOSPHORYLATION AT TYR-900 AND TYR-905.
[33]"Synthesis, structure-activity relationship and crystallographic studies of 3-substituted indolin-2-one RET inhibitors."
Mologni L., Rostagno R., Brussolo S., Knowles P.P., Kjaer S., Murray-Rust J., Rosso E., Zambon A., Scapozza L., McDonald N.Q., Lucchini V., Gambacorti-Passerini C.
Bioorg. Med. Chem. 18:1482-1496(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 705-1013 IN COMPLEX WITH INHIBITORS, ENZYME REGULATION, PHOSPHORYLATION AT TYR-905.
[34]"Mammal-restricted elements predispose human RET to folding impairment by HSCR mutations."
Kjaer S., Hanrahan S., Totty N., McDonald N.Q.
Nat. Struct. Mol. Biol. 17:726-731(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 29-270, GLYCOSYLATION AT ASN-151, DISULFIDE BOND.
[35]"Mutations in Hirschsprung disease: when does a mutation contribute to the phenotype."
Hofstra R.M.W., Osinga J., Buys C.H.C.M.
Eur. J. Hum. Genet. 5:180-185(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON HSCR VARIANTS.
[36]"Mutations of the RET proto-oncogene in the multiple endocrine neoplasia type 2 syndromes, related sporadic tumours, and Hirschsprung disease."
Eng C., Mulligan L.M.
Hum. Mutat. 9:97-109(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON VARIANTS.
[37]"Mutations in the RET proto-oncogene are associated with MEN 2A and FMTC."
Donis-Keller H., Dou S., Chi D., Carlson K.M., Toshima K., Lairmore T.C., Howe J.R., Moley J.F., Goodfellow P., Wells S.A. Jr.
Hum. Mol. Genet. 2:851-856(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MEN2A/MTC TRP-611; SER-618; ARG-620; TYR-620 AND ARG-634.
[38]"Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A."
Mulligan L.M., Kwok J.B.J., Healey C.S., Elsdon M.J., Eng C., Gardner E., Love D.R., Mole S.E., Moore J.K., Papi L., Ponder M.A., Telenius H., Tunnacliffe A., Ponder B.A.J.
Nature 363:458-460(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MEN2A GLY-618; 632-ASP--ARG-634; GLY-634; PHE-634; TYR-634 AND SER-634.
[39]"Heterogeneity and low detection rate of RET mutations in Hirschsprung disease."
Yin L., Barone V., Seri M., Bolino A., Bocciardi R., Ceccherini I., Pasini B., Tocco T., Lerone M., Cywes S., Moore S., Vanderwinden J.-M., Abramowicz M.J., Kristoffersson U., Larsson L.T., Hamel B.C.J., Silengo M., Martucciello G., Romeo G.
Eur. J. Hum. Genet. 2:272-280(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HSCR1 PRO-40; LEU-399; GLN-762; PRO-765; GLN-897; GLY-972 AND LEU-973.
[40]"Point mutation within the tyrosine kinase domain of the RET proto-oncogene in multiple endocrine neoplasia type 2B and related sporadic tumours."
Eng C., Smith D.P., Mulligan L.M., Nagai M.A., Healey C.S., Ponder M.A., Gardner E., Scheumann G.F., Jackson C.E., Tunnacliffe A., Ponder B.A.J.
Hum. Mol. Genet. 3:237-241(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MEN2B THR-918.
[41]"Germline RET mutations in MEN 2A and FMTC and their detection by simple DNA diagnostic tests."
Xue F., Yu H., Maurer L.H., Memoli V.A., Nutile-Mcmenemy N., Schuster M.K., Browden D.W., Mao J.-I., Noll W.W.
Hum. Mol. Genet. 3:635-638(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MEN2A/MTC ARG-618; SER-618; PHE-620; ARG-620; PHE-634; GLY-634 AND TYR-634.
[42]"RET proto-oncogene mutations in inherited and sporadic medullary thyroid cancer."
Blaugrund J.E., Johns M.M. Jr., Eby Y.J., Ball D.W., Baylin S.B., Hruban R.H., Sidransky D.
Hum. Mol. Genet. 3:1895-1897(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MTC/MEN2A TYR-609; ARG-618; SER-618 AND SER-620.
[43]"RET proto-oncogene mutations in French MEN 2A and FMTC families."
Schuffenecker I., Billaud M., Calender A., Chambe B., Ginet N., Calmettes C., Modigliani E., Lenoir G.M.
Hum. Mol. Genet. 3:1939-1943(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MTC, VARIANTS MEN2A.
[44]"Diverse phenotypes associated with exon 10 mutations of the RET proto-oncogene."
Mulligan L.M., Eng C., Attie T., Lyonnet S., Marsh D.J., Hyland V.J., Robinson B.G., Frilling A., Verellen-Dumoulin C., Safar A., Venter D.J., Munnich A., Ponder B.A.J.
Hum. Mol. Genet. 3:2163-2167(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HSCR1 TRP-609; ARG-618 AND ARG-620, VARIANT MEN2A ARG-618, VARIANT MTC ARG-620.
[45]"A mutation in the RET proto-oncogene associated with multiple endocrine neoplasia type 2B and sporadic medullary thyroid carcinoma."
Hofstra R.M.W., Landsvater R.M., Ceccherini I., Stulp R.P., Stelwagen T., Luo Y., Pasini B., Hoeppener J.W.M., Ploos van Amstel H.K., Romeo G., Lips C.J.M., Buys C.H.C.M.
Nature 367:375-376(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MEN2B THR-918.
[46]"Point mutations affecting the tyrosine kinase domain of the RET proto-oncogene in Hirschsprung's disease."
Romeo G., Ronchetto P., Luo Y., Barone V., Seri M., Ceccherini I., Pasini B., Bocciardi R., Lerone M., Kaarlainen H., Martucciello G.
Nature 367:377-378(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HSCR1 PRO-765; GLN-897 AND GLY-972.
[47]"Mutations of the RET proto-oncogene in Hirschsprung's disease."
Edery P., Lyonnet S., Mulligan L.M., Pelet A., Dow E., Abel L., Holder S., Nihoul-Fkete C., Ponder B.A.J., Munnich A.
Nature 367:378-380(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HSCR1 LEU-32; LEU-64; GLN-330 AND LEU-393.
[48]"Single missense mutation in the tyrosine kinase catalytic domain of the RET protooncogene is associated with multiple endocrine neoplasia type 2B."
Carlson K.M., Dou S., Chi D., Scavarda N., Toshima K., Jackson C.E., Wells S.A. Jr., Goodfellow P.J., Donis-Keller H.
Proc. Natl. Acad. Sci. U.S.A. 91:1579-1583(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MEN2B THR-918.
[49]"Analysis of RET protooncogene point mutations distinguishes heritable from nonheritable medullary thyroid carcinomas."
Komminoth P., Kunz E.K., Matias-Guiu X., Hiort O., Christiansen G., Colomer A., Roth J., Heitz P.U.
Cancer 76:479-489(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MTC; MEN2A AND MEN2B.
[50]"Germline mutations of the RET proto-oncogene in eight Japanese patients with multiple endocrine neoplasia type 2A (MEN2A)."
Takiguchi-Shirahama S., Koyama K., Miyauchi A., Wakasugi T., Oishi S., Takami H., Hikiji K., Nakamura Y.
Hum. Genet. 95:187-190(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MEN2A SER-618; SER-620; ARG-634 AND TYR-634.
[51]"Mutation analysis of the RET receptor tyrosine kinase in Hirschsprung disease."
Angrist M., Bolk S., Thiel B., Puffenberger E.G., Hofstra R.M.W., Buys C.H.C.M., Cass D.T., Chakravarti A.
Hum. Mol. Genet. 4:821-830(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HSCR1 LEU-20; SER-93; GLN-330; TYR-609 AND ARG-620, VARIANT CYS-982.
Tissue: Blood.
[52]"Diversity of RET proto-oncogene mutations in familial and sporadic Hirschsprung disease."
Attie T., Pelet A., Edery P., Eng C., Mulligan L.M., Amiel J., Boutrand L., Beldjord C., Nihoul-Fekete C., Munnich A., Ponder B.A.J., Lyonnet S.
Hum. Mol. Genet. 4:1381-1386(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HSCR1.
Tissue: Leukocyte.
[53]"Two maternally derived missense mutations in the tyrosine kinase domain of the RET protooncogene in a patient with de novo MEN 2B."
Kitamura Y., Scavarda N., Wells S.A. Jr., Jackson C.E., Goodfellow P.J.
Hum. Mol. Genet. 4:1987-1988(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MEN2B THR-918, VARIANT TYR-922.
[54]"A novel point mutation in the tyrosine kinase domain of the RET proto-oncogene in sporadic medullary thyroid carcinoma and in a family with FMTC."
Eng C., Smith D.P., Mulligan L.M., Healey C.S., Zvelebil M.J., Stonehouse T.J., Ponder M.A., Jackson C.E., Waterfield M.D., Ponder B.A.J.
Oncogene 10:509-513(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MTC ASP-768.
[55]"RET mutations in exons 13 and 14 of FMTC patients."
Bolino A., Schuffenecker I., Luo Y., Seri M., Silengo M., Tocco T., Chabrier G., Houdent C., Murat A., Schlumberger M., Tournaire J., Lenoir G.M., Romeo G.
Oncogene 10:2415-2419(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MTC ASP-768 AND LEU-804.
[56]"Mutations in three genes are found associated with the development of Hirschsprung disease: RET, EDNRB and EDN3."
Hofstra R.M.W., Osinga J., Stulp R.P., Scheffer H., Meijers C., Buys C.H.C.M.
Am. J. Hum. Genet. 59:A263-A263(1996)
Cited for: VARIANTS HSCR1 TYR-157; LYS-359; TYR-609; ARG-620; ASN-1059 DEL AND PRO-1061.
[57]"Prevalence and parental origin of de novo RET mutations in Hirschsprung's disease."
Yin L., Seri M., Barone V., Tocco T., Scaranari M., Romeo G.
Eur. J. Hum. Genet. 4:356-358(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HSCR1 PRO-40 AND PRO-765.
[58]"Mutation analysis of the RET proto-oncogene in Dutch families with MEN 2A, MEN 2B and FMTC: two novel mutations and one de novo mutation for MEN 2A."
Landsvater R.M., Jansen R.P.M., Hofstra R.M.W., Buys C.H.C.M., Lips C.J.M., van Amstel H.K.P.
Hum. Genet. 97:11-14(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MTC/MEN2A.
[59]"Diagnosis of multiple endocrine neoplasia [MEN] 2A, 2B and familial medullary thyroid cancer [FMTC] by multiplex PCR and heteroduplex analyses of RET proto-oncogene mutations."
Kambouris M., Jackson C.E., Feldman G.L.
Hum. Mutat. 8:64-70(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MEN2A, VARIANT MTC ASP-768, VARIANT MEN2B THR-918.
[60]"Mutations of the ret protooncogene in German multiple endocrine neoplasia families: relation between genotype and phenotype."
Frank-Raue K., Hoeppner W., Frilling A., Kotzerke J., Dralle H., Haase R., Mann K., Seif F., Kirchner R., Rendl J., Deckart H.F., Ritter M.M., Hampel R., Klempa J., Scholz G.H., Raue F., Bogner U., Brabant G. expand/collapse author list , Grussendorf M., Hartenstein C.H., Heidemann P., Hensen J., Doerr A.G., Hoehne T., Hoernig-Franz I., Huefner M., Kress J., Langer H.J., Lottermoser K., Schweikert H.U., Kusterer K., Menken U., Mercier J., Oelkers W., Sauer J., Simon D., Starrach G., Ziegler R.
J. Clin. Endocrinol. Metab. 81:1780-1783(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MEN2A.
[61]"A duplication of 12 bp in the critical cysteine rich domain of the RET proto-oncogene results in a distinct phenotype of multiple endocrine neoplasia type 2A."
Hoeppner W., Ritter M.M.
Hum. Mol. Genet. 6:587-590(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MEN2A HIS-GLU-LEU-CYS-634 INS.
[62]"Frequency of RET mutations in long- and short-segment Hirschsprung disease."
Seri M., Yin L., Barone V., Bolino A., Celli I., Bocciardi R., Pasini B., Ceccherini I., Lerone M., Kristoffersson U., Larsson L.T., Casasa J.M., Cass D.T., Abramowicz M.J., Vanderwinden J.-M., Kravcenkiene I., Baric I., Silengo M., Martucciello G., Romeo G.
Hum. Mutat. 9:243-249(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HSCR1 PRO-180; GLN-313; ARG-620 AND PHE-791.
[63]"Cys 618 Arg mutation in the RET proto-oncogene associated with familial medullary thyroid carcinoma and maternally transmitted Hirschsprung's disease suggesting a role for imprinting."
Peretz H., Luboshitsky R., Baron E., Biton A., Gershoni R., Usher S., Grynberg E., Yakobson E., Graff E., Lapidot M.
Hum. Mutat. 10:155-159(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MTC ARG-618, VARIANT HSCR1 ARG-618.
[64]"Germline dinucleotide mutation in codon 883 of the RET proto-oncogene in multiple endocrine neoplasia type 2B without codon 918 mutation."
Gimm O., Marsh D.J., Andrew S.D., Frilling A., Dahia P.L.M., Mulligan L.M., Zajac J.D., Robinson B.G., Eng C.
J. Clin. Endocrinol. Metab. 82:3902-3904(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MEN2B PHE-883.
Tissue: Peripheral blood leukocyte.
[65]"A novel point mutation in the intracellular domain of the ret protooncogene in a family with medullary thyroid carcinoma."
Hofstra R.M.W., Fattoruso O., Quadro L., Wu Y., Libroia A., Verga U., Colantuoni V., Buys C.H.C.M.
J. Clin. Endocrinol. Metab. 82:4176-4178(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MTC ALA-891.
[66]"Mutation analysis of the RET, the endothelin-B receptor, and the endothelin-3 genes in sporadic cases of Hirschsprung's disease."
Kusafuka T., Wang Y., Puri P.
J. Pediatr. Surg. 32:501-504(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HSCR1 SER-174 AND TYR-197.
[67]"Novel germline RET proto-oncogene mutations associated with medullary thyroid carcinoma (MTC): mutation analysis in Japanese patients with MTC."
Kitamura Y., Goodfellow P.J., Shimizu K., Nagahama M., Ito K., Kitagawa W., Akasu H., Takami H., Tanaka S., Wells S.A. Jr.
Oncogene 14:3103-3106(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MTC; MEN2A AND MEN2B, VARIANT SER-691.
[68]"Germline mutation of RET codon 883 in two cases of de novo MEN 2B."
Smith D.P., Houghton C., Ponder B.A.J.
Oncogene 15:1213-1217(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MEN2B PHE-883.
[69]"Mutations of the RET-GDNF signaling pathway in Ondine's curse."
Amiel J., Salomon R., Attie T., Pelet A., Trang H., Mokhtari M., Gaultier C., Munnich A., Lyonnet S.
Am. J. Hum. Genet. 62:715-717(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CCHS LEU-1039, VARIANT SER-691.
[70]"Novel point mutation in exon 10 of the RET proto-oncogene in a family with medullary thyroid carcinoma."
Oriola J., Paramo C., Halperin I., Garcia-Mayor R.V., Rivera-Fillat F.
Am. J. Med. Genet. 78:271-273(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MTC GLY-611.
[71]"Phenotypic variation in a family with mutations in two Hirschsprung-related genes (RET and endothelin receptor B)."
Svensson P.J., Anvret M., Molander M.L., Nordenskjold A.
Hum. Genet. 103:145-148(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CYS-982.
[72]"Hirschsprung disease in MEN 2A: increased spectrum of RET exon 10 genotypes and strong genotype-phenotype correlation."
Decker R.A., Peacock M.L., Watson P.
Hum. Mol. Genet. 7:129-134(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MEN2A TYR-609; SER-618; ARG-620 AND TRP-620, VARIANTS HSCR1 TYR-609; SER-618; ARG-620 AND TRP-620.
[73]"Duplication of 9 base pairs in the critical cysteine-rich domain of the RET proto-oncogene causes multiple endocrine neoplasia type 2A."
Hoeppner W., Dralle H., Brabant G.
Hum. Mutat. Suppl. 1:S128-S130(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MEN2A CYS-ARG-THR-636 INS.
[74]"A GTG to ATG novel point mutation at codon 804 in exon 14 of the RET proto-oncogene in two families affected by familial medullary thyroid carcinoma."
Fattoruso O., Quadro L., Libroia A., Verga U., Lupoli G., Cascone E., Colantuoni V.
Hum. Mutat. Suppl. 1:S167-S171(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MTC MET-804.
[75]"A new hot spot for mutations in the ret protooncogene causing familial medullary thyroid carcinoma and multiple endocrine neoplasia type 2A."
Berndt I., Reuter M., Saller B., Frank-Raue K., Groth P., Grussendorf M., Raue F., Ritter M.M., Hoeppner W.
J. Clin. Endocrinol. Metab. 83:770-774(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MTC/MEN2A PHE-790 AND PHE-791.
[76]"Mutational analysis of the RET proto-oncogene in 71 Japanese patients with medullary thyroid carcinoma."
Shirahama S., Ogura K., Takami H., Ito K., Tohsen T., Miyauchi A., Nakamura Y.
J. Hum. Genet. 43:101-106(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MTC AND MEN2A.
[77]"Double heterozygosity for a RET substitution interfering with splicing and an EDNRB missense mutation in Hirschsprung disease."
Auricchio A., Griseri P., Carpentieri M.L., Betsos N., Staiano A., Tozzi A., Priolo M., Thompson H., Bocciardi R., Romeo G., Ballabio A., Ceccherini I.
Am. J. Hum. Genet. 64:1216-1221(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HSCR1 LYS-626 AND GLN-813.
[78]"Two distinct mutations of the RET receptor causing Hirschsprung's disease impair the binding of signalling effectors to a multifunctional docking site."
Geneste O., Bidaud C., De Vita G., Hofstra R.M.W., Tartare-Deckert S., Buys C.H.C.M., Lenoir G.M., Santoro M., Billaud M.
Hum. Mol. Genet. 8:1989-1999(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HSCR1 ASN-1059 DEL AND PRO-1061.
[79]"A novel 9-base pair duplication in RET exon 8 in familial medullary thyroid carcinoma."
Pigny P., Bauters C., Wemeau J.-L., Houcke M.L., Crepin M., Caron P., Giraud S., Calender A., Buisine M.-P., Kerckaert J.-P., Porchet N.
J. Clin. Endocrinol. Metab. 84:1700-1704(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MTC GLU-GLU-CYS-531 INS.
[80]"A novel case of multiple endocrine neoplasia type 2A associated with two de novo mutations of the RET protooncogene."
Tessitore A., Sinisi A.A., Pasquali D., Cardone M., Vitale D., Bellastella A., Colantuoni V.
J. Clin. Endocrinol. Metab. 84:3522-3527(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MEN2A GLY-640.
[81]"A RET double mutation in the germline of a kindred with FMTC."
Bartsch D.K., Hasse C., Schug C., Barth P., Rothmund M., Hoeppner W.
Exp. Clin. Endocrinol. Diabetes 108:128-132(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MTC MET-804 AND LEU-844.
[82]"A new germline mutation, R600Q, within the coding region of RET proto-oncogene: a rare polymorphism or a MEN 2 causing mutation?"
Saez M.E., Ruiz A., Cebrian A., Morales F., Robledo M., Antinolo G., Borrego S.
Hum. Mutat. 15:122-122(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GLN-600.
[83]"A human model for multigenic inheritance: phenotypic expression in Hirschsprung disease requires both the RET gene and a new 9q31 locus."
Bolk S., Pelet A., Hofstra R.M.W., Angrist M., Salomon R., Croaker D., Buys C.H.C.M., Lyonnet S., Chakravarti A.
Proc. Natl. Acad. Sci. U.S.A. 97:268-273(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HSCR1 LEU-32; CYS-77; TRP-360 AND LYS-394.
[84]"Three novel mutations in the RET proto-oncogene."
Kalinin V.N., Amosenko F.A., Shabanov M.A., Lubchenko L.N., Hosch S.B., Garkavtseva R.F., Izbicki J.R.
J. Mol. Med. 79:609-612(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MTC GLY-639; GLY-641 AND PHE-922.
[85]"Germ-line mutations in nonsyndromic pheochromocytoma."
The Freiburg-Warsaw-Columbus pheochromocytoma study group
Neumann H.P.H., Bausch B., McWhinney S.R., Bender B.U., Gimm O., Franke G., Schipper J., Klisch J., Altehoefer C., Zerres K., Januszewicz A., Smith W.M., Munk R., Manz T., Glaesker S., Apel T.W., Treier M., Reineke M. expand/collapse author list , Walz M.K., Hoang-Vu C., Brauckhoff M., Klein-Franke A., Klose P., Schmidt H., Maier-Woelfle M., Peczkowska M., Szmigielski C., Eng C.
N. Engl. J. Med. 346:1459-1466(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PHEOCHROMOCYTOMA ARG-634; GLY-634; TYR-634; SER-634; PHE-634; TRP-634 AND PHE-791.
[86]"Congenital central hypoventilation syndrome: a novel mutation of the RET gene in an isolated case."
Kanai M., Numakura C., Sasaki A., Shirahata E., Akaba K., Hashimoto M., Hasegawa H., Shirasawa S., Hayasaka K.
Tohoku J. Exp. Med. 196:241-246(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CCHS HIS-114.
[87]"Molecular analysis of congenital central hypoventilation syndrome."
Sasaki A., Kanai M., Kijima K., Akaba K., Hashimoto M., Hasegawa H., Otaki S., Koizumi T., Kusuda S., Ogawa Y., Tuchiya K., Yamamoto W., Nakamura T., Hayasaka K.
Hum. Genet. 114:22-26(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ASN-489; SER-691 AND CYS-982, VARIANTS CCHS HIS-67; HIS-114 AND GLU-432.
[88]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLY-145; TRP-360 AND GLU-593.
[89]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLN-163; ASN-278; MET-292; ASN-489; SER-691; THR-749; SER-826; LEU-844; CYS-982 AND TYR-1112.
[90]"Renal aplasia in humans is associated with RET mutations."
Skinner M.A., Safford S.D., Reeves J.G., Jackson M.E., Freemerman A.J.
Am. J. Hum. Genet. 82:344-351(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS RADYS THR-198; ALA-376; HIS-394; ILE-778; SER-894; THR-918; LEU-1049 AND SER-1067, CHARACTERIZATION OF VARIANTS RADYS THR-198; ALA-376; HIS-394; ILE-778; SER-894; LEU-1049 AND SER-1067.
[91]"RET mutational spectrum in Hirschsprung disease: evaluation of 601 Chinese patients."
So M.T., Leon T.Y., Cheng G., Tang C.S., Miao X.P., Cornes B.K., Diem N.N., Cui L., Ngan E.S., Lui V.C., Wu X.Z., Wang B., Wang H., Yuan Z.W., Huang L.M., Li L., Xia H., Zhu D. expand/collapse author list , Liu J., Nguyen T.L., Chan I.H., Chung P.H., Liu X.L., Zhang R., Wong K.K., Sham P.C., Cherny S.S., Tam P.K., Garcia-Barcelo M.M.
PLoS ONE 6:E28986-E28986(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HSCR1 549-LYS-GLY-550 DEL; CYS-114; HIS-114; GLY-145; LEU-155; PRO-175; ALA-278; PRO-278; ASN-300; GLN-313; ILE-316; LEU-339; TYR-353; GLN-360; MET-397; MET-412; ARG-423; LYS-480; GLN-595; LEU-679; GLN-694; SER-783; ARG-830; THR-907; LEU-961; VAL-1052; CYS-1062 AND THR-1064, VARIANTS ASN-278 AND MET-292.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK291807 mRNA. Translation: BAF84496.1.
AC010864 Genomic DNA. No translation available.
BC004257 mRNA. Translation: AAH04257.1.
X15262 mRNA. Translation: CAA33333.1.
X12949 mRNA. Translation: CAA31408.1.
M16029 mRNA. Translation: AAA36786.1. Different initiation.
X15786 mRNA. Translation: CAA33787.1. Different initiation.
M31213 mRNA. Translation: AAA36524.1. Different initiation.
AJ297349 mRNA. Translation: CAC14882.1. Different initiation.
PIRTVHURE. A27203.
A34630.
B34735.
S05582.
RefSeqNP_065681.1. NM_020630.4.
NP_066124.1. NM_020975.4.
UniGeneHs.350321.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1XPDmodel-A709-1013[»]
2IVSX-ray2.00A/B705-1013[»]
2IVTX-ray2.60A705-1013[»]
2IVUX-ray2.50A705-1013[»]
2IVVX-ray2.25A705-1013[»]
2X2KX-ray2.60A705-1013[»]
2X2LX-ray2.00A705-1013[»]
2X2MX-ray2.50A/B705-1013[»]
2X2UX-ray2.00A29-270[»]
4CKIX-ray2.12A705-1013[»]
4CKJX-ray1.65A705-1013[»]
ProteinModelPortalP07949.
SMRP07949. Positions 29-272, 713-1037.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111911. 26 interactions.
DIPDIP-41449N.
IntActP07949. 10 interactions.
MINTMINT-1217685.
STRING9606.ENSP00000347942.

Chemistry

BindingDBP07949.
ChEMBLCHEMBL2041.
DrugBankDB01268. Sunitinib.
GuidetoPHARMACOLOGY2185.

PTM databases

PhosphoSiteP07949.

Polymorphism databases

DMDM547807.

Proteomic databases

PaxDbP07949.
PRIDEP07949.

Protocols and materials databases

DNASU5979.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000340058; ENSP00000344798; ENSG00000165731. [P07949-2]
ENST00000355710; ENSP00000347942; ENSG00000165731. [P07949-1]
GeneID5979.
KEGGhsa:5979.
UCSCuc001jak.1. human. [P07949-2]
uc001jal.3. human. [P07949-1]

Organism-specific databases

CTD5979.
GeneCardsGC10P043572.
HGNCHGNC:9967. RET.
HPACAB002581.
CAB018342.
HPA008356.
MIM114500. phenotype.
142623. phenotype.
155240. phenotype.
162300. phenotype.
164761. gene.
171300. phenotype.
171400. phenotype.
188550. phenotype.
191830. phenotype.
209880. phenotype.
neXtProtNX_P07949.
Orphanet1848. Bilateral renal agenesis.
93173. Bilateral renal dysplasia.
99361. Familial medullary thyroid carcinoma.
99803. Haddad syndrome.
388. Hirschsprung disease.
247698. Multiple endocrine neoplasia type 2A.
247709. Multiple endocrine neoplasia type 2B.
146. Papillary or follicular thyroid carcinoma.
93172. Unilateral renal dysplasia.
PharmGKBPA34335.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000010301.
HOVERGENHBG002609.
InParanoidP07949.
KOK05126.
OMAWRQGDGK.
OrthoDBEOG7NGQ9N.
PhylomeDBP07949.
TreeFamTF317640.

Enzyme and pathway databases

BRENDA2.7.10.1. 2681.
SignaLinkP07949.

Gene expression databases

ArrayExpressP07949.
BgeeP07949.
CleanExHS_RET.
GenevestigatorP07949.

Family and domain databases

Gene3D2.60.40.60. 1 hit.
InterProIPR002126. Cadherin.
IPR015919. Cadherin-like.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016249. Tyr_kinase_Ret_rcpt.
[Graphical view]
PfamPF00028. Cadherin. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFPIRSF000631. TyrPK_receptor_Ret. 1 hit.
PRINTSPR00109. TYRKINASE.
SMARTSM00112. CA. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF49313. SSF49313. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS50268. CADHERIN_2. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSRET. human.
EvolutionaryTraceP07949.
GeneWikiRET_proto-oncogene.
GenomeRNAi5979.
NextBio23271.
PROP07949.
SOURCESearch...

Entry information

Entry nameRET_HUMAN
AccessionPrimary (citable) accession number: P07949
Secondary accession number(s): A8K6Z2 expand/collapse secondary AC list , Q15250, Q9BTB0, Q9H4A2
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: June 1, 1994
Last modified: April 16, 2014
This is version 193 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM