P07949 (RET_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Proto-oncogene tyrosine-protein kinase receptor Ret
EC=2.7.10.1

Alternative name(s):
Cadherin family member 12
Proto-oncogene c-Ret

Cleaved into the following 2 chains:

1. Soluble RET kinase fragment
2. Extracellular cell-membrane anchored RET cadherin 120 kDa fragment

Gene names

Name:	RET
Synonyms:	CDHF12, CDHR16, PTC, RET51

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1114 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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. Act 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.22 Ref.25 Ref.26 Ref.29 Ref.30
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.23 Ref.24 Ref.28 Ref.32
Subunit structure	Phosphorylated form interacts with the PBT domain of DOK2, DOK4 and DOK5. The phosphorylated form interacts with PLCG1 and GRB7 By similarity. 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. Ref.19 Ref.29 Ref.30
Subcellular location	Cell membrane; Single-pass type I membrane protein. Endosome membrane; Single-pass type I membrane protein Ref.27.
Induction	Positively regulated by NKX2-1, PHOX2B, SOX10 and PAX3. Ref.16 Ref.17 Ref.18 Ref.20 Ref.23 Ref.24 Ref.28 Ref.32
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.21 Ref.30 Ref.31 Ref.32 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.29
Polymorphism	The Cys-982 polymorphism may be associated with an increased risk for developing Hirschsprung disease.
Involvement in disease	Defects in RET may be a cause of colorectal cancer (CRC) [MIM:114500]. Defects in RET are a cause of Hirschsprung disease type 1 (HSCR1) [MIM:142623]. HSCR1 is a disorder of neural crest development characterized by the absence of intramural ganglion cells in the myenteric and submucosal plexuses of the gastrointestinal tract, often resulting in intestinal obstruction. Total colonic aganglionosis and total intestinal Hirschsprung disease also occur. Occasionally, MEN2A or FMTC occur in association with HSCR1. Ref.38 Ref.43 Ref.45 Ref.46 Ref.50 Ref.51 Ref.55 Ref.56 Ref.61 Ref.62 Ref.65 Ref.71 Ref.76 Ref.77 Ref.82 Defects in RET are the cause of medullary thyroid carcinoma (MTC) [MIM:155240]. MTC is a 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. Ref.41 Ref.42 Ref.43 Ref.48 Ref.53 Ref.54 Ref.57 Ref.58 Ref.62 Ref.64 Ref.66 Ref.69 Ref.73 Ref.74 Ref.75 Ref.78 Ref.80 Ref.83 Defects in RET are the cause of multiple neoplasia type 2B (MEN2B) [MIM:162300]. MEN2B is an uncommon inherited cancer syndrome characterized by predisposition to MTC and phaeochromocytoma which is associated with marfanoid habitus, mucosal neuromas, skeletal and ophtalmic 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. Ref.39 Ref.44 Ref.47 Ref.48 Ref.52 Ref.58 Ref.63 Ref.66 Ref.67 Defects in RET are a cause of susceptibility to 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. Defects in RET are the cause of multiple neoplasia type 2A (MEN2A) [MIM:171400]; also known as multiple neoplasia type 2 (MEN2). MEN2A is the most frequent form of medullary thyroid cancer (MTC). It is an inherited cancer syndrome characterized by MTC, phaeochromocytoma and/or hyperparathyroidism. Defects in RET are a cause of thyroid papillary carcinoma (TPC) [MIM:188550]. TPC is 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=Chromosomal aberrations involving RET are found in thyroid papillary carcinomas. Inversion inv(10)(q11.2;q21) generates the RET/CCDC6 (PTC1) oncogene; inversion inv(10)(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. Defects in RET are a cause of renal adysplasia (RADYS) [MIM:191830]; also known as renal agenesis or renal aplasia. 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. Ref.89 Defects in RET are a cause of congenital central hypoventilation syndrome (CCHS) [MIM:209880]; also known as congenital failure of autonomic control or Ondine curse. CCHS is a 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. Ref.68 Ref.85 Ref.86
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. The sequence AAA36786.1 differs from that shown. Reason: Erroneous initiation. The sequence CAA33787.1 differs from that shown. Reason: Erroneous initiation. The sequence CAC14882.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Cell membrane Endosome Membrane
Coding sequence diversity	Alternative splicing Chromosomal rearrangement Polymorphism
Disease	Disease mutation Hirschsprung disease Proto-oncogene
Domain	Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cellular response to retinoic acid Inferred from mutant phenotype. Source: BHF-UCL homophilic cell adhesion Inferred from electronic annotation. Source: InterPro positive regulation of metanephric glomerulus development Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of neuron projection development Inferred from mutant phenotype. Source: BHF-UCL positive regulation of transcription, DNA-dependent Inferred from sequence or structural similarity. Source: UniProtKB posterior midgut development Traceable author statement. Source: ProtInc
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW calcium ion binding Inferred from electronic annotation. Source: InterPro protein binding Inferred from physical interaction. Source: UniProtKB transmembrane receptor protein tyrosine kinase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P07949-1)

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)

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 28

28

Potential

Chain

29 – 1114

1086

Proto-oncogene tyrosine-protein kinase receptor Ret

PRO_0000024450

Chain

29 – 707

679

Extracellular cell-membrane anchored RET cadherin 120 kDa fragment

PRO_0000415292

Chain

708 – 1017

310

Soluble RET kinase fragment

PRO_0000415293

Regions

Topological domain

29 – 635

607

Extracellular Potential

Transmembrane

636 – 657

22

Helical; Potential

Topological domain

658 – 1114

457

Cytoplasmic Potential

Domain

168 – 272

105

Cadherin

Domain

724 – 1016

293

Protein kinase

Nucleotide binding

730 – 738

9

ATP By similarity

Region

805 – 807

3

Inhibitors binding

Sites

Active site

874

1

Proton acceptor By similarity

Binding site

758

1

ATP By similarity

Binding site

892

1

Inhibitors

Site

587 – 588

2

Breakpoint for translocation to form the TRIM27/RET oncogene

Site

707 – 708

2

Cleavage; by caspase-3

Site

712 – 713

2

Breakpoint for translocation to form PCM1-RET; RET-CCDC6; RET-GOLGA5; RET-TRIM24 and RET-TRIM33 oncogenes

Site

1017 – 1018

2

Cleavage; by caspase-3

Amino acid modifications

Modified residue

696

1

Phosphoserine Ref.21

Modified residue

806

1

Phosphotyrosine; by autocatalysis Ref.13

Modified residue

809

1

Phosphotyrosine; by autocatalysis Ref.13

Modified residue

900

1

Phosphotyrosine; by autocatalysis Ref.13 Ref.31

Modified residue

905

1

Phosphotyrosine; by autocatalysis Ref.13 Ref.15 Ref.31 Ref.32

Modified residue

981

1

Phosphotyrosine; by autocatalysis Ref.13

Modified residue

1015

1

Phosphotyrosine; by autocatalysis Ref.12 Ref.13 Ref.15

Modified residue

1062

1

Phosphotyrosine; by autocatalysis Ref.12 Ref.13 Ref.15

Modified residue

1090

1

Phosphotyrosine; by autocatalysis Ref.13

Modified residue

1096

1

Phosphotyrosine; by autocatalysis Ref.13

Glycosylation

98

1

N-linked (GlcNAc...) Potential

Glycosylation

151

1

N-linked (GlcNAc...) Ref.33

Glycosylation

199

1

N-linked (GlcNAc...) Potential

Glycosylation

336

1

N-linked (GlcNAc...) Potential

Glycosylation

343

1

N-linked (GlcNAc...) Potential

Glycosylation

361

1

N-linked (GlcNAc...) Potential

Glycosylation

367

1

N-linked (GlcNAc...) Potential

Glycosylation

377

1

N-linked (GlcNAc...) Potential

Glycosylation

394

1

N-linked (GlcNAc...) Potential

Glycosylation

448

1

N-linked (GlcNAc...) Potential

Glycosylation

468

1

N-linked (GlcNAc...) Potential

Glycosylation

554

1

N-linked (GlcNAc...) Potential

Disulfide bond

137 ↔ 142

Ref.33

Natural variations

Alternative sequence

1064 – 1114

51

MSDPN…DTFDS → RISHAFTRF in isoform 2.

VSP_040735

Natural variant

20

1

P → L in HSCR1; sporadic form. Ref.50

VAR_009459

Natural variant

32

1

S → L in HSCR1; familial form. Ref.46 Ref.82

VAR_006295

Natural variant

40

1

L → P in HSCR1. Ref.38 Ref.56

VAR_009492

Natural variant

64

1

P → L in HSCR1; familial form. Ref.46

VAR_006296

Natural variant

67

1

R → H in CCHS. Ref.86

VAR_018153

Natural variant

77

1

R → C in HSCR1. Ref.82

VAR_009460

Natural variant

93

1

G → S in HSCR1; could be a rare polymorphism. Ref.50

VAR_006297

Natural variant

114

1

R → H in CCHS. Ref.85 Ref.86

VAR_018154

Natural variant

142

1

C → S in HSCR1; sporadic form.

VAR_006298

Natural variant

145

1

V → G in a colorectal cancer sample; somatic mutation. Ref.87

VAR_035711

Natural variant

157

1

C → Y in HSCR1; could be a polymorphism. Ref.55

VAR_009461

Natural variant

163

1

R → Q in a colorectal adenocarcinoma sample; somatic mutation. Ref.88

VAR_041762

Natural variant

174

1

F → S in HSCR1; sporadic form. Ref.65

VAR_009462

Natural variant

180

1

R → P in HSCR1; sporadic form. Ref.61

VAR_009463

Natural variant

197

1

C → Y in HSCR1; sporadic form. Ref.65

VAR_009464

Natural variant

198

1

P → T in RADYS; prevents phosphorylation in response to GDNF. Ref.89

VAR_044392

Natural variant

231

1

R → H in HSCR1; familial form.

VAR_006299

Natural variant

251

1

E → K in HSCR1; familial form.

VAR_006300

Natural variant

278

1

T → N. Ref.88
Corresponds to variant rs35118262 [ dbSNP | Ensembl ].

VAR_041763

Natural variant

287

1

R → Q in HSCR1; sporadic form.

VAR_006301

Natural variant

292

1

V → M. Ref.88
Corresponds to variant rs34682185 [ dbSNP | Ensembl ].

VAR_041764

Natural variant

313

1

R → Q in HSCR1; sporadic form. Ref.61

VAR_009465

Natural variant

330

1

R → Q in HSCR1. Ref.46 Ref.50

VAR_006302

Natural variant

359

1

N → K in HSCR1; could be a polymorphism. Ref.55

VAR_009466

Natural variant

360

1

R → W in HSCR1. Ref.82 Ref.87

VAR_009467

Natural variant

376

1

V → A in RADYS; constitutively phosphorylated; expressed only the immature intracellular form. Ref.89

VAR_044393

Natural variant

393

1

F → L in HSCR1; familial form. Ref.46

VAR_006303

Natural variant

394

1

N → H in RADYS; prevents phosphorylation in response to GDNF. Ref.89

VAR_044394

Natural variant

394

1

N → K in HSCR1. Ref.82

VAR_009468

Natural variant

399

1

P → L in HSCR1; sporadic form. Ref.38

VAR_006304

Natural variant

432

1

A → E in CCHS. Ref.86

VAR_018155

Natural variant

475

1

R → Q in HSCR1; sporadic form.

VAR_006305

Natural variant

489

1

D → N. Ref.86 Ref.88
Corresponds to variant rs9282834 [ dbSNP | Ensembl ].

VAR_018156

Natural variant

531

1

C → CEEC in MTC; familial form.

VAR_009469

Natural variant

593

1

G → E in a colorectal cancer sample; somatic mutation. Ref.87

VAR_035712

Natural variant

600

1

R → Q. Ref.81

VAR_008966

Natural variant

609

1

C → G in MEN2A.

VAR_009470

Natural variant

609

1

C → R in MEN2A.

VAR_009471

Natural variant

609

1

C → W in HSCR1; familial form. Ref.43

VAR_006307

Natural variant

609

1

C → Y in MTC, MEN2A and HSCR1; familial and sporadic forms. Ref.41 Ref.50 Ref.55 Ref.71

VAR_006306

Natural variant

611

1

C → G in MTC; familial form. Ref.69

VAR_009472

Natural variant

611

1

C → R in MEN2A.

VAR_009473

Natural variant

611

1

C → S in MEN2A.

VAR_009474

Natural variant

611

1

C → W in MEN2A and MTC; familial form. Ref.36

VAR_006308

Natural variant

611

1

C → Y in MEN2A.

VAR_006309

Natural variant

618

1

C → F in MEN2A and MTC; familial form.

VAR_006312

Natural variant

618

1

C → G in MEN2A. Ref.37

VAR_006310

Natural variant

618

1

C → R in MEN2A, MTC and HSCR1. Ref.40 Ref.41 Ref.43 Ref.62

VAR_006311

Natural variant

618

1

C → S in MEN2A, HSCR1 and MTC; familial and sporadic forms. Ref.36 Ref.40 Ref.41 Ref.49 Ref.71

VAR_006313

Natural variant

618

1

C → Y in MEN2A and MTC; familial form.

VAR_006314

Natural variant

620

1

C → F in MEN2A and MTC; familial form. Ref.40

VAR_006318

Natural variant

620

1

C → G in MEN2A and MTC; familial and sporadic forms.

VAR_006315

Natural variant

620

1

C → R in MEN2A, MTC and HSCR1; familial and sporadic forms. Ref.36 Ref.40 Ref.43 Ref.50 Ref.55 Ref.61 Ref.71

VAR_006316

Natural variant

620

1

C → S in MEN2A and MTC; familial form. Ref.41 Ref.49

VAR_006317

Natural variant

620

1

C → W in MEN2A and HSCR1. Ref.71

VAR_009475

Natural variant

620

1

C → Y in MEN2A. Ref.36

VAR_006319

Natural variant

626

1

Q → K in HSCR1; sporadic form. Ref.76

VAR_009476

Natural variant

630

1

C → F in MEN2A and MTC; familial form.

VAR_006320

Natural variant

630

1

C → S in MTC; sporadic form.

VAR_009477

Natural variant

630

1

C → Y in MTC; familial and sporadic forms.

VAR_009478

Natural variant

631

1

D → G in thyroid carcinoma; somatic mutation.

VAR_006321

Natural variant

632 – 634

3

ELC → DVR in MEN2A.

VAR_006322

Natural variant

634 – 635

2

CR → WG in MEN2A.

VAR_006329

Natural variant

634

1

C → CHELC in MEN2A.

VAR_009479

Natural variant

634

1

C → F in MEN2A and pheochromocytoma. Ref.37 Ref.40 Ref.84

VAR_006324

Natural variant

634

1

C → G in MEN2A and pheochromocytoma. Ref.37 Ref.40 Ref.84

VAR_006323

Natural variant

634

1

C → R in MEN2A, pheochromocytoma and MTC; familial form; also found as somatic mutation in a sporadic thyroid carcinoma. Ref.36 Ref.37 Ref.49 Ref.84

VAR_006326

Natural variant

634

1

C → S in MEN2A, pheochromocytoma and MTC; familial form. Ref.37 Ref.84

VAR_006327

Natural variant

634

1

C → W in MEN2A, pheochromocytoma and MTC; familial form. Ref.84

VAR_006328

Natural variant

634

1

C → Y in MEN2A, pheochromocytoma and MTC; familial form. Ref.37 Ref.40 Ref.49 Ref.84

VAR_006325

Natural variant

636

1

T → TCRT in MEN2A.

VAR_006330

Natural variant

639

1

A → G in MTC; sporadic form. Ref.83

VAR_012743

Natural variant

640

1

A → G in MEN2A. Ref.79

VAR_009480

Natural variant

641

1

A → G in MTC; sporadic form. Ref.83

VAR_012744

Natural variant

690

1

S → P in HSCR1; sporadic form.

VAR_006331

Natural variant

691

1

G → S. Ref.66 Ref.68 Ref.86 Ref.88
Corresponds to variant rs1799939 [ dbSNP | Ensembl ].

VAR_006332

Natural variant

749

1

R → T. Ref.88
Corresponds to variant rs34288963 [ dbSNP | Ensembl ].

VAR_041765

Natural variant

762

1

E → Q in HSCR1; sporadic form. Ref.38

VAR_009481

Natural variant

765

1

S → P in HSCR1. Ref.38 Ref.45 Ref.56

VAR_009493

Natural variant

767

1

S → R in HSCR1; sporadic form.

VAR_006334

Natural variant

768

1

E → D in MTC; familial and sporadic forms. Ref.53 Ref.54 Ref.58

VAR_006335

Natural variant

778

1

V → I in RADYS; constitutively phosphorylated. Ref.89

VAR_044395

Natural variant

790

1

L → F in MEN2A and MTC; familial form. Ref.74

VAR_009482

Natural variant

791

1

Y → F in HSCR1, pheochromocytoma, MTC and MEN2A; familial form. Ref.61 Ref.74 Ref.84

VAR_009483

Natural variant

804

1

V → L in MTC; familial form. Ref.54

VAR_006336

Natural variant

804

1

V → M in MTC; familial form. Ref.73 Ref.80

VAR_006337

Natural variant

813

1

R → Q in HSCR1; sporadic form. Ref.76

VAR_009484

Natural variant

826

1

Y → S. Ref.88
Corresponds to variant rs34617196 [ dbSNP | Ensembl ].

VAR_041766

Natural variant

844

1

R → L in MTC; familial form. Ref.80 Ref.88
Corresponds to variant rs55947360 [ dbSNP | Ensembl ].

VAR_011582

Natural variant

873

1

R → Q in HSCR1; sporadic form.

VAR_006338

Natural variant

883

1

A → F in MEN2B; somatic mutation in sporadic medullary thyroid carcinoma; requires 2 nucleotide substitutions. Ref.63 Ref.67

VAR_009485

Natural variant

891

1

S → A in MTC; familial form. Ref.64

VAR_009486

Natural variant

893

1

F → L in HSCR1; sporadic form.

VAR_006339

Natural variant

894

1

G → S in RADYS; constitutively phosphorylated; expressed only the immature intracellular form. Ref.89

VAR_044396

Natural variant

897

1

R → Q in HSCR1; sporadic form. Ref.38 Ref.45

VAR_006340

Natural variant

907

1

K → E in HSCR1; sporadic form.

VAR_006341

Natural variant

918

1

M → T in RADYS, MEN2B and MTC; sporadic form; somatic mutation. Ref.39 Ref.44 Ref.47 Ref.52 Ref.58 Ref.89

VAR_006342

Natural variant

921

1

E → K in HSCR1; sporadic form.

VAR_006343

Natural variant

922

1

S → F in MTC; sporadic form. Ref.83

VAR_012745

Natural variant

922

1

S → Y Rare polymorphism. Ref.52

VAR_009487

Natural variant

946

1

T → M in MEN2B and MTC; familial form.

VAR_006345

Natural variant

972

1

R → G in HSCR1; familial form. Ref.38 Ref.45

VAR_006346

Natural variant

973

1

P → L in HSCR1; familial form. Ref.38

VAR_006347

Natural variant

980

1

M → T in HSCR1; sporadic form.

VAR_006348

Natural variant

982

1

R → C. Ref.3 Ref.50 Ref.70 Ref.86 Ref.88
Corresponds to variant rs17158558 [ dbSNP | Ensembl ].

VAR_006349

Natural variant

1039

1

P → L in CCHS; with colonic aganglionosis. Ref.68

VAR_018157

Natural variant

1039

1

P → Q.

VAR_009488

Natural variant

1049

1

P → L in RADYS; prevents phosphorylation in response to GDNF. Ref.89

VAR_044397

Natural variant

1059

1

Missing in HSCR1.

VAR_009489

Natural variant

1061

1

L → P in HSCR1. Ref.55 Ref.77

VAR_009490

Natural variant

1064

1

M → T in HSCR1; familial form.

VAR_009491

Natural variant

1067

1

P → S in RADYS; prevents phosphorylation in response to GDNF. Ref.89

VAR_044398

Natural variant

1112

1

F → Y in a bladder transitional cell carcinoma sample; somatic mutation. Ref.88

VAR_041767

Experimental info

Mutagenesis

707

1

D → N: Impaired cleavage by caspase-3 and loss of induced cell death. Ref.29

Mutagenesis

708 – 1114

407

Missing: Loss of induced cell death, but increased cell aggregation. Ref.29

Mutagenesis

758

1

K → R: Loss of kinase activity. Ref.29

Sequence conflict

647

1

I → V in AAA36786. Ref.6

Sequence conflict

664

1

A → S in BAF84496. Ref.1

Sequence conflict

750

1

A → G in AAA36524. Ref.9

Sequence conflict

904

1

S → P in AAA36786. Ref.6

Secondary structure

1

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1114

Helix Strand Turn

Details...

Helix

705 – 710

6

Turn

715 – 717

3

Helix

721 – 723

3

Beta strand

724 – 732

9

Beta strand

734 – 744

11

Helix

746 – 748

3

Beta strand

750 – 759

10

Helix

766 – 779

14

Beta strand

790 – 794

5

Beta strand

796 – 799

4

Beta strand

801 – 805

5

Helix

812 – 818

7

Turn

819 – 821

3

Helix

848 – 867

20

Helix

877 – 879

3

Beta strand

880 – 883

4

Turn

884 – 886

3

Beta strand

887 – 890

4

Turn

900 – 902

3

Helix

915 – 917

3

Helix

920 – 925

6

Helix

930 – 945

16

Helix

957 – 959

3

Helix

960 – 965

6

Helix

978 – 987

10

Helix

992 – 994

3

Helix

998 – 1010

13

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 1994. Version 3. Checksum: A3DA0CE01A19A441	FASTA	1,114	124,319
	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
	Isoform 2 [UniParc]. Checksum: 85868CBFCEA0D24C	FASTA	1,072	119,847
	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 STPSDSLIYD DGLSEEETPL VDCNNAPLPR ALPSTWIENK LYGRISHAFT RF

References

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[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. , 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: 14702039] [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. , 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: 15164054] [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: 15489334] [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: 2660074] [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: 3078962] [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: 3037315] [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: 2734021] [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: 2406025] [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: 10980597] [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: 10439047] [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: 11061555] [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: 14711813] [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: 12787916] [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: 16778204] [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: 17884497] [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: 17664273] [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: 19053769] [Abstract] Cited for: ENZYME REGULATION BY 3- AND 4-SUBSTITUTED BETA-CARBOLIN-1-ONES.
[19]	"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: 19366855] [Abstract] Cited for: INTERACTION WITH AIP.
[20]	"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: 19853745] [Abstract] Cited for: INDUCTION BY NKX2-1; PHOX2B; SOX10 AND PAX3.
[21]	"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: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-696, MASS SPECTROMETRY.
[22]	"RETouching upon mechanoreceptors." Ma Q. Neuron 64:773-776(2009) [PubMed: 20064382] [Abstract] Cited for: FUNCTION IN DEVELOPMENT OF MECHANORECEPTORS.
[23]	"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: 20605972] [Abstract] Cited for: ENZYME REGULATION, REVIEW ON KINASE INHIBITORS.
[24]	"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: 20409618] [Abstract] Cited for: ENZYME REGULATION.
[25]	"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: 20616503] [Abstract] Cited for: FUNCTION IN PITUITARY.
[26]	"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: 20702524] [Abstract] Cited for: FUNCTION IN CELL ADHESION/MIGRATION.
[27]	"Direct visualization of vesicle maturation and plasma membrane protein trafficking." Richardson D.S., Mulligan L.M. J. Fluoresc. 20:401-405(2010) [PubMed: 19823924] [Abstract] Cited for: SUBCELLULAR LOCATION.
[28]	"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: 21134556] [Abstract] Cited for: ENZYME REGULATION.
[29]	"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: 21357690] [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.
[30]	"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: 21454698] [Abstract] Cited for: INTERACTION WITH PTK2/FAK1, FUNCTION IN PTK2/FAK1 PHOSPHORYLATION.
[31]	"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: 16928683] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 705-1013 ALONE AND IN COMPLEX WITH INHIBITORS, MASS SPECTROMETRY, PHOSPHORYLATION AT TYR-900 AND TYR-905.
[32]	"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: 20117004] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 705-1013 IN COMPLEX WITH INHIBITORS, ENZYME REGULATION, PHOSPHORYLATION AT TYR-905.
[33]	"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: 20473317] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 29-270, GLYCOSYLATION AT ASN-151, DISULFIDE BOND.
[34]	"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: 9359036] [Abstract] Cited for: REVIEW ON HSCR VARIANTS.
[35]	"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: 9067749] [Abstract] Cited for: REVIEW ON VARIANTS.
[36]	"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: 8103403] [Abstract] Cited for: VARIANTS MEN2A/MTC TRP-611; SER-618; ARG-620; TYR-620 AND ARG-634.
[37]	"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: 8099202] [Abstract] Cited for: VARIANTS MEN2A GLY-618; 632-ASP--ARG-634; GLY-634; PHE-634; TYR-634 AND SER-634.
[38]	"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: 7704557] [Abstract] Cited for: VARIANTS HSCR1 PRO-40; LEU-399; GLN-762; PRO-765; GLN-897; GLY-972 AND LEU-973.
[39]	"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: 7911697] [Abstract] Cited for: VARIANT MEN2B THR-918.
[40]	"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: 7915165] [Abstract] Cited for: VARIANTS MEN2A/MTC ARG-618; SER-618; PHE-620; ARG-620; PHE-634; GLY-634 AND TYR-634.
[41]	"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: 7849720] [Abstract] Cited for: VARIANTS MTC/MEN2A TYR-609; ARG-618; SER-618 AND SER-620.
[42]	"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: 7874109] [Abstract] Cited for: VARIANTS MTC, VARIANTS MEN2A.
[43]	"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: 7881414] [Abstract] Cited for: VARIANTS HSCR1 TRP-609; ARG-618 AND ARG-620, VARIANT MEN2A ARG-618, VARIANT MTC ARG-620.
[44]	"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: 7906866] [Abstract] Cited for: VARIANT MEN2B THR-918.
[45]	"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: 8114938] [Abstract] Cited for: VARIANTS HSCR1 PRO-765; GLN-897 AND GLY-972.
[46]	"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: 8114939] [Abstract] Cited for: VARIANTS HSCR1 LEU-32; LEU-64; GLN-330 AND LEU-393.
[47]	"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: 7906417] [Abstract] Cited for: VARIANT MEN2B THR-918.
[48]	"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: 8625130] [Abstract] Cited for: VARIANTS MTC; MEN2A AND MEN2B.
[49]	"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: 7860065] [Abstract] Cited for: VARIANTS MEN2A SER-618; SER-620; ARG-634 AND TYR-634.
[50]	"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: 7633441] [Abstract] Cited for: VARIANTS HSCR1 LEU-20; SER-93; GLN-330; TYR-609 AND ARG-620, VARIANT CYS-982. Tissue: Blood.
[51]	"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: 7581377] [Abstract] Cited for: VARIANTS HSCR1. Tissue: Leukocyte.
[52]	"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: 8595427] [Abstract] Cited for: VARIANT MEN2B THR-918, VARIANT TYR-922.
[53]	"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: 7845675] [Abstract] Cited for: VARIANT MTC ASP-768.
[54]	"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: 7784092] [Abstract] Cited for: VARIANTS MTC ASP-768 AND LEU-804.
[55]	"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.
[56]	"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: 9043870] [Abstract] Cited for: VARIANTS HSCR1 PRO-40 AND PRO-765.
[57]	"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: 8557249] [Abstract] Cited for: VARIANTS MTC/MEN2A.
[58]	"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: 8807338] [Abstract] Cited for: VARIANTS MEN2A, VARIANT MTC ASP-768, VARIANT MEN2B THR-918.
[59]	"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. , 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: 8626834] [Abstract] Cited for: VARIANTS MEN2A.
[60]	"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: 9097963] [Abstract] Cited for: VARIANT MEN2A HIS-GLU-LEU-CYS-634 INS.
[61]	"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: 9090527] [Abstract] Cited for: VARIANTS HSCR1 PRO-180; GLN-313; ARG-620 AND PHE-791.
[62]	"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: 9259198] [Abstract] Cited for: VARIANT MTC ARG-618, VARIANT HSCR1 ARG-618.
[63]	"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: 9360560] [Abstract] Cited for: VARIANT MEN2B PHE-883. Tissue: Peripheral blood leukocyte.
[64]	"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: 9398735] [Abstract] Cited for: VARIANT MTC ALA-891.
[65]	"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: 9094028] [Abstract] Cited for: VARIANTS HSCR1 SER-174 AND TYR-197.
[66]	"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: 9223675] [Abstract] Cited for: VARIANTS MTC; MEN2A AND MEN2B, VARIANT SER-691.
[67]	"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: 9294615] [Abstract] Cited for: VARIANT MEN2B PHE-883.
[68]	"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: 9497256] [Abstract] Cited for: VARIANT CCHS LEU-1039, VARIANT SER-691.
[69]	"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: 9677065] [Abstract] Cited for: VARIANT MTC GLY-611.
[70]	"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: 9760196] [Abstract] Cited for: VARIANT CYS-982.
[71]	"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: 9384613] [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.
[72]	"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: 9452064] [Abstract] Cited for: VARIANT MEN2A CYS-ARG-THR-636 INS.
[73]	"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: 9452077] [Abstract] Cited for: VARIANT MTC MET-804.
[74]	"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: 9506724] [Abstract] Cited for: VARIANTS MTC/MEN2A PHE-790 AND PHE-791.
[75]	"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: 9621513] [Abstract] Cited for: VARIANTS MTC AND MEN2A.
[76]	"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: 10090908] [Abstract] Cited for: VARIANTS HSCR1 LYS-626 AND GLN-813.
[77]	"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: 10484767] [Abstract] Cited for: VARIANTS HSCR1 ASN-1059 DEL AND PRO-1061.
[78]	"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: 10323403] [Abstract] Cited for: VARIANT MTC GLU-GLU-CYS-531 INS.
[79]	"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: 10522989] [Abstract] Cited for: VARIANT MEN2A GLY-640.
[80]	"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: 10826520] [Abstract] Cited for: VARIANTS MTC MET-804 AND LEU-844.
[81]	"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: 10612852] [Abstract] Cited for: VARIANT GLN-600.
[82]	"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: 10618407] [Abstract] Cited for: VARIANTS HSCR1 LEU-32; CYS-77; TRP-360 AND LYS-394.
[83]	"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: 11692159] [Abstract] Cited for: VARIANTS MTC GLY-639; GLY-641 AND PHE-922.
[84]	"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. , 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: 12000816] [Abstract] Cited for: VARIANTS PHEOCHROMOCYTOMA ARG-634; GLY-634; TYR-634; SER-634; PHE-634; TRP-634 AND PHE-791.
[85]	"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: 12086152] [Abstract] Cited for: VARIANT CCHS HIS-114.
[86]	"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: 14566559] [Abstract] Cited for: VARIANTS ASN-489; SER-691 AND CYS-982, VARIANTS CCHS HIS-67; HIS-114 AND GLU-432.
[87]	"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. , 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: 16959974] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLY-145; TRP-360 AND GLU-593.
[88]	"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. , 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: 17344846] [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.
[89]	"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: 18252215] [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.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

MEN2 RET database

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.

IPI

IPI00013983.
IPI00479572.

PIR

TVHURE. A27203.
A34630.
B34735.
S05582.

RefSeq

NP_065681.1. NM_020630.4.
NP_066124.1. NM_020975.4.

UniGene

Hs.350321.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1XPD	model	-	A	709-1013	[»]
2IVS	X-ray	2.00	A/B	705-1013	[»]
2IVT	X-ray	2.60	A	705-1013	[»]
2IVU	X-ray	2.50	A	705-1013	[»]
2IVV	X-ray	2.25	A	705-1013	[»]
2X2K	X-ray	2.60	A	705-1013	[»]
2X2L	X-ray	2.00	A	705-1013	[»]
2X2M	X-ray	2.50	A/B	705-1013	[»]
2X2U	X-ray	2.00	A	29-270	[»]

ProteinModelPortal

P07949.

SMR

P07949. Positions 29-360, 713-1012.

ModBase

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Protein-protein interaction databases

DIP

DIP-41449N.

IntAct

P07949. 3 interactions.

MINT

MINT-265342.

STRING

P07949.

PTM databases

PhosphoSite

P07949.

Polymorphism databases

DMDM

547807.

Proteomic databases

PRIDE

P07949.

Protocols and materials databases

StructuralBiologyKnowledgebase

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Genome annotation databases

Ensembl

ENST00000340058; ENSP00000344798; ENSG00000165731.
ENST00000355710; ENSP00000347942; ENSG00000165731.

GeneID

5979.

KEGG

hsa:5979.

UCSC

uc001jal.1. human.

Organism-specific databases

CTD

5979.

GeneCards

GC10P043572.

HGNC

HGNC:9967. RET.

HPA

CAB002581.
CAB018342.
HPA008356.

MIM

114500. phenotype.
142623. phenotype.
155240. phenotype.
162300. phenotype.
164761. gene.
171300. phenotype.
171400. phenotype.
188550. phenotype.
191830. phenotype.
209880. phenotype.

neXtProt

NX_P07949.

Orphanet

1848. Bilateral renal agenesis.
388. Hirschsprung disease.
1332. Medullary thyroid carcinoma.
247698. Multiple endocrine neoplasia type 2A.
661. Ondine syndrome.
146. Papillary or follicular thyroid carcinoma.
93172. Unilateral renal dysplasia.

PharmGKB

PA34335.

GenAtlas

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Phylogenomic databases

eggNOG

prNOG12621.

HOGENOM

HBG444015.

HOVERGEN

HBG002609.

InParanoid

P07949.

OMA

GCARVYF.

OrthoDB

EOG4P2Q1H.

PhylomeDB

P07949.

Enzyme and pathway databases

BRENDA

2.7.10.1. 2681.

Pathway_Interaction_DB

ret_pathway. Signaling events regulated by Ret tyrosine kinase.

Gene expression databases

ArrayExpress

P07949.

Bgee

P07949.

CleanEx

HS_RET.

Genevestigator

P07949.

GermOnline

ENSG00000165731. Homo sapiens.

Family and domain databases

InterPro

IPR002126. Cadherin.
IPR015919. Cadherin-like.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016249. Tyr_kinase_Ret_rcpt.
[Graphical view]

Gene3D

G3DSA:2.60.40.60. Cadherin. 1 hit.

KO

K05126.

Pfam

PF00028. Cadherin. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]

PIRSF

PIRSF000631. TyrPK_receptor_Ret. 1 hit.

PRINTS

PR00109. TYRKINASE.

SMART

SM00112. CA. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]

SUPFAM

SSF49313. Cadherin. 1 hit.
SSF56112. Kinase_like. 1 hit.

PROSITE

PS50268. CADHERIN_2. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]

ProtoNet

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Other

DrugBank

DB01268. Sunitinib.

NextBio

23271.

SOURCE

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Entry information

Entry name

RET_HUMAN

Accession

Primary (citable) accession number: P07949
Secondary accession number(s): A8K6Z2 , Q15250, Q9BTB0, Q9H4A2

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	June 1, 1994
Last modified:	January 25, 2012
This is version 169 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.