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Reviewed, UniProtKB/Swiss-Prot Q16288 (NTRK3_HUMAN)

Last modified November 3, 2009. Version 115. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    NT-3 growth factor receptor
    EC=2.7.10.1
Alternative name(s):
    Neurotrophic tyrosine kinase receptor type 3
    TrkC tyrosine kinase
    GP145-TrkC
      Short name=Trk-C
Gene names
Name: NTRK3
Synonyms: TRKC
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length839 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Receptor for neurotrophin-3 (NT-3). This is a tyrosine-protein kinase receptor. Known substrates for the trk receptors are SHC1, PI-3 kinase, and PLCG1. The different isoforms do not have identical signaling properties.

Catalytic activity

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

Subunit structure

Exists in a dynamic equilibrium between monomeric (low affinity) and dimeric (high affinity) structures. Binds SH2B2. Interacts with SQSTM1 and KIDINS220 By similarity.

Subcellular location

Membrane; Single-pass type I membrane protein.

Tissue specificity

Widely expressed but mainly in nervous tissue. Isoform B is expressed at higher levels in adult brain than in fetal brain.

Post-translational modification

Ligand-mediated auto-phosphorylation.

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.

Contains 2 Ig-like C2-type (immunoglobulin-like) domains.

Contains 2 LRR (leucine-rich) repeats.

Contains 1 protein kinase domain.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform A (identifier: Q16288-1)

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.
Isoform B (identifier: Q16288-2)

The sequence of this isoform differs from the canonical sequence as follows:
     529-612: YVQHIKRRDI...FYGVCGDGDP → WVFSNIDNHG...VYFSKGRHGF
     613-839: Missing.
Isoform C (identifier: Q16288-3)

The sequence of this isoform differs from the canonical sequence as follows:
     712-725: Missing.
Isoform D (identifier: Q16288-4)

The sequence of this isoform differs from the canonical sequence as follows:
     402-410: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3131
Chain32 – 839808NT-3 growth factor receptor
PRO_0000016731

Regions

Topological domain32 – 429398Extracellular Potential
Transmembrane430 – 45324 Potential
Topological domain454 – 839386Cytoplasmic Potential
Repeat102 – 12524LRR 1
Repeat126 – 14924LRR 2
Domain210 – 30091Ig-like C2-type 1
Domain309 – 38274Ig-like C2-type 2
Domain538 – 839302Protein kinase
Nucleotide binding544 – 5529ATP By similarity

Sites

Active site6791Proton acceptor By similarity
Binding site5721ATP By similarity
Site5161Interaction with SHC1 By similarity
Site8341Interaction with PLC-gamma-1 By similarity

Amino acid modifications

Modified residue5161Phosphotyrosine; by autocatalysis By similarity
Modified residue7051Phosphotyrosine; by autocatalysis By similarity
Modified residue7091Phosphotyrosine; by autocatalysis By similarity
Modified residue7101Phosphotyrosine; by autocatalysis By similarity
Modified residue8341Phosphotyrosine By similarity
Glycosylation721N-linked (GlcNAc...) Potential
Glycosylation791N-linked (GlcNAc...) Potential
Glycosylation1331N-linked (GlcNAc...) Potential
Glycosylation1631N-linked (GlcNAc...) Potential
Glycosylation2031N-linked (GlcNAc...) Potential
Glycosylation2181N-linked (GlcNAc...) Potential
Glycosylation2321N-linked (GlcNAc...) Potential
Glycosylation2591N-linked (GlcNAc...) Potential
Glycosylation2671N-linked (GlcNAc...) Potential
Glycosylation2721N-linked (GlcNAc...) Potential
Glycosylation2941N-linked (GlcNAc...) Potential
Glycosylation3751N-linked (GlcNAc...) Potential
Glycosylation3881N-linked (GlcNAc...) Potential
Disulfide bond320 ↔ 362 Ref.4

Natural variations

Alternative sequence402 – 4109Missing in isoform D.
VSP_002924
Alternative sequence529 – 61284YVQHI…GDGDP → WVFSNIDNHGILNLKDNRDH LVPSTHYIYEEPEVQSGEVS YPRSHGFREIMLNPISLPGH SKPLNHGIYVEDVNVYFSKG RHGF in isoform B.
VSP_002925
Alternative sequence613 – 839227Missing in isoform B.
VSP_002926
Alternative sequence712 – 72514Missing in isoform C.
VSP_002927
Natural variant1491T → R in a gastric adenocarcinoma sample; somatic mutation. Ref.5
VAR_041471
Natural variant3061R → C: dbSNP rs56386352. Ref.5
VAR_041472
Natural variant3071V → L in a lung adenocarcinoma sample; somatic mutation. Ref.5
VAR_041473
Natural variant3361L → Q in a lung adenocarcinoma sample; somatic mutation. Ref.5
VAR_041474
Natural variant6641A → S in a lung carcinoma sample; somatic mutation. Ref.6
VAR_046521
Natural variant6771H → Y in a lung adenocarcinoma sample; somatic mutation. Ref.5 Ref.6
VAR_041475
Natural variant6781R → Q
VAR_041476
Natural variant7351R → F in a lung large cell carcinoma sample; somatic mutation; requires 2 nucleotide substitutions.
VAR_046770
Natural variant7361W → C in a lung carcinoma sample; somatic mutation. Ref.6
VAR_046522
Natural variant7451R → P in a lung carcinoma sample; somatic mutation. Ref.6
VAR_046523
Natural variant7661Y → F in a lung carcinoma sample; somatic mutation. Ref.6
VAR_046524
Natural variant7681K → R
VAR_046771
Natural variant7811E → K
VAR_046772

Experimental info

Sequence conflict701S → N in AAB33111. Ref.2
Sequence conflict701S → N in AAB33112. Ref.2
Sequence conflict6351D → N in AAA75374. Ref.1

Secondary structure

................. 839
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform A [UniParc].

Last modified March 6, 2007. Version 2.
Checksum: 7FE8846830083C08

FASTA83994,428
        10         20         30         40         50         60 
MDVSLCPAKC SFWRIFLLGS VWLDYVGSVL ACPANCVCSK TEINCRRPDD GNLFPLLEGQ 

        70         80         90        100        110        120 
DSGNSNGNAS INITDISRNI TSIHIENWRS LHTLNAVDME LYTGLQKLTI KNSGLRSIQP 

       130        140        150        160        170        180 
RAFAKNPHLR YINLSSNRLT TLSWQLFQTL SLRELQLEQN FFNCSCDIRW MQLWQEQGEA 

       190        200        210        220        230        240 
KLNSQNLYCI NADGSQLPLF RMNISQCDLP EISVSHVNLT VREGDNAVIT CNGSGSPLPD 

       250        260        270        280        290        300 
VDWIVTGLQS INTHQTNLNW TNVHAINLTL VNVTSEDNGF TLTCIAENVV GMSNASVALT 

       310        320        330        340        350        360 
VYYPPRVVSL EEPELRLEHC IEFVVRGNPP PTLHWLHNGQ PLRESKIIHV EYYQEGEISE 

       370        380        390        400        410        420 
GCLLFNKPTH YNNGNYTLIA KNPLGTANQT INGHFLKEPF PESTDNFILF DEVSPTPPIT 

       430        440        450        460        470        480 
VTHKPEEDTF GVSIAVGLAA FACVLLVVLF VMINKYGRRS KFGMKGPVAV ISGEEDSASP 

       490        500        510        520        530        540 
LHHINHGITT PSSLDAGPDT VVIGMTRIPV IENPQYFRQG HNCHKPDTYV QHIKRRDIVL 

       550        560        570        580        590        600 
KRELGEGAFG KVFLAECYNL SPTKDKMLVA VKALKDPTLA ARKDFQREAE LLTNLQHEHI 

       610        620        630        640        650        660 
VKFYGVCGDG DPLIMVFEYM KHGDLNKFLR AHGPDAMILV DGQPRQAKGE LGLSQMLHIA 

       670        680        690        700        710        720 
SQIASGMVYL ASQHFVHRDL ATRNCLVGAN LLVKIGDFGM SRDVYSTDYY RLFNPSGNDF 

       730        740        750        760        770        780 
CIWCEVGGHT MLPIRWMPPE SIMYRKFTTE SDVWSFGVIL WEIFTYGKQP WFQLSNTEVI 

       790        800        810        820        830 
ECITQGRVLE RPRVCPKEVY DVMLGCWQRE PQQRLNIKEI YKILHALGKA TPIYLDILG 

« Hide

Isoform B.

Checksum: F2E84DC71B8E4DB3
Show »

FASTA61268,452
Isoform C.

Checksum: 7ADBE1AF6DB280BF
Show »

FASTA82592,801
Isoform D.

Checksum: 4409D52CA249C0FE
Show »

FASTA83093,361

References

« Hide 'large scale' references
[1]"Molecular cloning of the cDNA for human TrkC (NTRK3), chromosomal assignment, and evidence for a splice variant."
McGregor L.M., Baylin S.B., Griffin C.A., Hawkins A.L., Nelkin B.D.
Genomics 22:267-272(1994) [PubMed: 7806211] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND C).
Tissue: Fetal brain.
[2]"Human trks: molecular cloning, tissue distribution, and expression of extracellular domain immunoadhesins."
Shelton D.L., Sutherland J., Gripp J., Camerato T., Armanini M.P., Phillips H.S., Carroll K., Spencer S.D., Levinson A.D.
J. Neurosci. 15:477-491(1995) [PubMed: 7823156] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B; C AND D), PARTIAL PROTEIN SEQUENCE.
Tissue: Brain.
[3]"Genomic characterization of the human trkC gene."
Ichaso N., Rodriguez R.E., Martin-Zanca D., Gonzalez-Sarmiento R.
Oncogene 17:1871-1875(1998) [PubMed: 9778053] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Crystal structures of the neurotrophin-binding domain of TrkA, TrkB and TrkC."
Ultsch M.H., Wiesmann C., Simmons L.C., Henrich J., Yang M., Reilly D., Bass S.H., de Vos A.M.
J. Mol. Biol. 290:149-159(1999) [PubMed: 10388563] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 297-401, DISULFIDE BOND.
[5]"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: 17344846] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] ARG-149; CYS-306; LEU-307; GLN-336; TYR-677; GLN-678; ARG-768 AND LYS-781.
[6]"Frequent mutations in the neurotrophic tyrosine receptor kinase gene family in large cell neuroendocrine carcinoma of the lung."
Marchetti A., Felicioni L., Pelosi G., Del Grammastro M., Fumagalli C., Sciarrotta M., Malatesta S., Chella A., Barassi F., Mucilli F., Camplese P., D'Antuono T., Sacco R., Buttitta F.
Hum. Mutat. 29:609-616(2008) [PubMed: 18293376] [Abstract]
Cited for: VARIANTS SER-664; TYR-677; CYS-736; PRO-745 AND PHE-766.
+Additional computationally mapped references.

Cross-references

Sequence databases

U05012 mRNA. Translation: AAA75374.1.
S76475 mRNA. Translation: AAB33111.1.
S76476 mRNA. Translation: AAB33112.1.
AJ224521 expand/collapse EMBL AC list , AJ224522, AJ224523, AJ224524, AJ224525, AJ224526, AJ224527, AJ224528, AJ224529, AJ224530, AJ224531, AJ224532, AJ224533, AJ224534, AJ224535 Genomic DNA. Translation: CAA12029.1.
IPIIPI00000824.
IPI00185466.
IPI00289961.
IPI00376986.
PIRA55178.
I73632.
I73633.
RefSeqNP_001007157.1.
NP_001012338.1.
NP_002521.2.
UniGeneHs.410969
Hs.706364

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1WWCX-ray1.90A297-422[»]
ModBaseSearch...

Protein-protein interaction databases

DIPDIP:5723N.
STRINGQ16288.

PTM databases

PhosphoSiteQ16288.

Genome annotation databases

EnsemblENST00000317501; ENSP00000318328; ENSG00000140538; Homo sapiens. [Genome view]
ENST00000343782; ENSP00000342792; ENSG00000140538; Homo sapiens. [Genome view]
ENST00000355254; ENSP00000347397; ENSG00000140538; Homo sapiens. [Genome view]
ENST00000357724; ENSP00000350356; ENSG00000140538; Homo sapiens. [Genome view]
ENST00000360948; ENSP00000354207; ENSG00000140538; Homo sapiens. [Genome view]
ENST00000394480; ENSP00000377990; ENSG00000140538; Homo sapiens. [Genome view]
GeneID4916.
KEGGhsa:4916.
UCSCuc002bme.1. human.
uc002bmf.1. human.
uc010bnh.1. human.

Organism-specific databases

CTD4916.
GeneCardsGC15M086221.
H-InvDBHIX0012549.
HGNCHGNC:8033. NTRK3.
HPACAB009233.
MIM191316. gene.
PharmGKBPA31819.
GenAtlasSearch...

Phylogenomic databases

HOGENOMQ16288.
HOVERGENQ16288.
OMAESTDNFV.

Enzyme and pathway databases

BRENDA2.7.10.1. 247.
Pathway_Interaction_DBtrkrpathway. Neurotrophic factor-mediated Trk receptor signaling.

Gene expression databases

ArrayExpressQ16288.
BgeeQ16288.
CleanExHS_NTRK3.
GenevestigatorQ16288.
GermOnlineENSG00000140538. Homo sapiens.

Family and domain databases

InterProIPR013151. Ig.
IPR007110. Ig-like.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR001611. Leu-rich_rpt.
IPR000372. Leu-rich_rpt_Cys-rich-dom_N.
IPR000483. LRR_C.
IPR020426. Neuro_Tyr_kinase_rcpt_fam.
IPR020446. Neuro_Tyr_kinase_rcpt_fam_3.
IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_BS.
IPR002011. Recept_tyr_kinase-II_CS.
IPR001245. Tyr_pkinase.
IPR008266. Tyr_pkinase_AS.
[Graphical view]
Gene3DG3DSA:2.60.40.10. Ig-like_fold. 2 hits.
PfamPF07679. I-set. 1 hit.
PF00047. ig. 1 hit.
PF00560. LRR_1. 1 hit.
PF01462. LRRNT. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSPR01939. NTKRECEPTOR.
PR01942. NTKRECEPTOR3.
PR00109. TYRKINASE.
ProDomPD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00409. IG. 1 hit.
SM00082. LRRCT. 1 hit.
SM00013. LRRNT. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
PROSITEPS50835. IG_LIKE. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS00239. RECEPTOR_TYR_KIN_II. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio18927.
SOURCESearch...

Entry information

Entry nameNTRK3_HUMAN
AccessionPrimary (citable) accession number: Q16288
Secondary accession number(s): O75682, Q12827, Q16289
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: March 6, 2007
Last modified: November 3, 2009
This is version 115 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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.

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents