Reviewed,
UniProtKB/Swiss-Prot Q16288 (NTRK3_HUMAN)
Last modified
June 16, 2009.
Version 109.
History...
Clusters with 100%,
90%,
50% identity |
Documents (7) |
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Names and origin
| Protein names | Recommended 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 |
| ||||
| 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 | 839 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 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 | |
| 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. |
Ontologies
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 key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||||||||||||||||
Molecule processing | |||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Signal peptide | 1 – 31 | 31 | |||||||||||||||||||||||
| Chain | 32 – 839 | 808 | NT-3 growth factor receptor | PRO_0000016731 | |||||||||||||||||||||
Regions | |||||||||||||||||||||||||
| Topological domain | 32 – 429 | 398 | Extracellular Potential | ||||||||||||||||||||||
| Transmembrane | 430 – 453 | 24 | Potential | ||||||||||||||||||||||
| Topological domain | 454 – 839 | 386 | Cytoplasmic Potential | ||||||||||||||||||||||
| Repeat | 102 – 125 | 24 | LRR 1 | ||||||||||||||||||||||
| Repeat | 126 – 149 | 24 | LRR 2 | ||||||||||||||||||||||
| Domain | 210 – 300 | 91 | Ig-like C2-type 1 | ||||||||||||||||||||||
| Domain | 309 – 382 | 74 | Ig-like C2-type 2 | ||||||||||||||||||||||
| Domain | 538 – 839 | 302 | Protein kinase | ||||||||||||||||||||||
| Nucleotide binding | 544 – 552 | 9 | ATP By similarity | ||||||||||||||||||||||
Sites | |||||||||||||||||||||||||
| Active site | 679 | 1 | Proton acceptor By similarity | ||||||||||||||||||||||
| Binding site | 572 | 1 | ATP By similarity | ||||||||||||||||||||||
| Site | 516 | 1 | Interaction with SHC1 By similarity | ||||||||||||||||||||||
| Site | 834 | 1 | Interaction with PLC-gamma-1 By similarity | ||||||||||||||||||||||
Amino acid modifications | |||||||||||||||||||||||||
| Modified residue | 516 | 1 | Phosphotyrosine; by autocatalysis By similarity | ||||||||||||||||||||||
| Modified residue | 705 | 1 | Phosphotyrosine; by autocatalysis By similarity | ||||||||||||||||||||||
| Modified residue | 709 | 1 | Phosphotyrosine; by autocatalysis By similarity | ||||||||||||||||||||||
| Modified residue | 710 | 1 | Phosphotyrosine; by autocatalysis By similarity | ||||||||||||||||||||||
| Modified residue | 834 | 1 | Phosphotyrosine By similarity | ||||||||||||||||||||||
| Glycosylation | 72 | 1 | N-linked (GlcNAc...) Potential | ||||||||||||||||||||||
| Glycosylation | 79 | 1 | N-linked (GlcNAc...) Potential | ||||||||||||||||||||||
| Glycosylation | 133 | 1 | N-linked (GlcNAc...) Potential | ||||||||||||||||||||||
| Glycosylation | 163 | 1 | N-linked (GlcNAc...) Potential | ||||||||||||||||||||||
| Glycosylation | 203 | 1 | N-linked (GlcNAc...) Potential | ||||||||||||||||||||||
| Glycosylation | 218 | 1 | N-linked (GlcNAc...) Potential | ||||||||||||||||||||||
| Glycosylation | 232 | 1 | N-linked (GlcNAc...) Potential | ||||||||||||||||||||||
| Glycosylation | 259 | 1 | N-linked (GlcNAc...) Potential | ||||||||||||||||||||||
| Glycosylation | 267 | 1 | N-linked (GlcNAc...) Potential | ||||||||||||||||||||||
| Glycosylation | 272 | 1 | N-linked (GlcNAc...) Potential | ||||||||||||||||||||||
| Glycosylation | 294 | 1 | N-linked (GlcNAc...) Potential | ||||||||||||||||||||||
| Glycosylation | 375 | 1 | N-linked (GlcNAc...) Potential | ||||||||||||||||||||||
| Glycosylation | 388 | 1 | N-linked (GlcNAc...) Potential | ||||||||||||||||||||||
| Disulfide bond | 320 ↔ 362 | Ref.4 | |||||||||||||||||||||||
Natural variations | |||||||||||||||||||||||||
| Alternative sequence | 402 – 410 | 9 | Missing in isoform D. | VSP_002924 | |||||||||||||||||||||
| Alternative sequence | 529 – 612 | 84 | YVQHI…GDGDP → WVFSNIDNHGILNLKDNRDH LVPSTHYIYEEPEVQSGEVS YPRSHGFREIMLNPISLPGH SKPLNHGIYVEDVNVYFSKG RHGF in isoform B. | VSP_002925 | |||||||||||||||||||||
| Alternative sequence | 613 – 839 | 227 | Missing in isoform B. | VSP_002926 | |||||||||||||||||||||
| Alternative sequence | 712 – 725 | 14 | Missing in isoform C. | VSP_002927 | |||||||||||||||||||||
| Natural variant | 149 | 1 | T → R in a gastric adenocarcinoma sample; somatic mutation. Ref.5 | VAR_041471 | |||||||||||||||||||||
| Natural variant | 306 | 1 | R → C: dbSNP rs56386352. Ref.5 | VAR_041472 | |||||||||||||||||||||
| Natural variant | 307 | 1 | V → L in a lung adenocarcinoma sample; somatic mutation. Ref.5 | VAR_041473 | |||||||||||||||||||||
| Natural variant | 336 | 1 | L → Q in a lung adenocarcinoma sample; somatic mutation. Ref.5 | VAR_041474 | |||||||||||||||||||||
| Natural variant | 664 | 1 | A → S in a lung carcinoma sample; somatic mutation. Ref.6 | VAR_046521 | |||||||||||||||||||||
| Natural variant | 677 | 1 | H → Y in a lung adenocarcinoma sample; somatic mutation. Ref.5 Ref.6 | VAR_041475 | |||||||||||||||||||||
| Natural variant | 678 | 1 | R → Q Ref.5 | VAR_041476 | |||||||||||||||||||||
| Natural variant | 735 | 1 | R → F in a lung large cell carcinoma sample; somatic mutation; requires 2 nucleotide substitutions. | VAR_046770 | |||||||||||||||||||||
| Natural variant | 736 | 1 | W → C in a lung carcinoma sample; somatic mutation. Ref.6 | VAR_046522 | |||||||||||||||||||||
| Natural variant | 745 | 1 | R → P in a lung carcinoma sample; somatic mutation. Ref.6 | VAR_046523 | |||||||||||||||||||||
| Natural variant | 766 | 1 | Y → F in a lung carcinoma sample; somatic mutation. Ref.6 | VAR_046524 | |||||||||||||||||||||
| Natural variant | 768 | 1 | K → R Ref.5 | VAR_046771 | |||||||||||||||||||||
| Natural variant | 781 | 1 | E → K Ref.5 | VAR_046772 | |||||||||||||||||||||
Experimental info | |||||||||||||||||||||||||
| Sequence conflict | 70 | 1 | S → N in AAB33111. Ref.2 | ||||||||||||||||||||||
| Sequence conflict | 70 | 1 | S → N in AAB33112. Ref.2 | ||||||||||||||||||||||
| Sequence conflict | 635 | 1 | D → N in AAA75374. Ref.1 | ||||||||||||||||||||||
Secondary structure | |||||||||||||||||||||||||
Helix Strand Turn | |||||||||||||||||||||||||
| Beta strand | 303 – 310 | 8 | |||||||||||||||||||||||
| Beta strand | 314 – 329 | 16 | |||||||||||||||||||||||
| Beta strand | 332 – 337 | 6 | |||||||||||||||||||||||
| Beta strand | 345 – 354 | 10 | |||||||||||||||||||||||
| Beta strand | 356 – 367 | 12 | |||||||||||||||||||||||
| Helix | 370 – 372 | 3 | |||||||||||||||||||||||
| Beta strand | 374 – 382 | 9 | |||||||||||||||||||||||
| Beta strand | 385 – 393 | 9 | |||||||||||||||||||||||
Sequences
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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. 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 AJ224535 Genomic DNA. Translation: CAA12029.1. | |||||||||||||
| IPI | IPI00000824. IPI00185466. IPI00289961. IPI00376986. | ||||||||||||
| PIR | A55178. I73632. I73633. | ||||||||||||
| RefSeq | NP_001012338.1. NP_002521.2. | ||||||||||||
| UniGene | Hs.410969 Hs.706364 | ||||||||||||
3D structure databases | |||||||||||||
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| ModBase | Search... | ||||||||||||
Protein-protein interaction databases | |||||||||||||
| DIP | DIP:5723N. | ||||||||||||
PTM databases | |||||||||||||
| PhosphoSite | Q16288. | ||||||||||||
Genome annotation databases | |||||||||||||
| Ensembl | ENSG00000140538. Homo sapiens. [Contig view] | ||||||||||||
| GeneID | 4916. | ||||||||||||
Organism-specific databases | |||||||||||||
| GeneCards | GC15M086221. | ||||||||||||
| H-InvDB | HIX0012549. | ||||||||||||
| HGNC | HGNC:8033. NTRK3. | ||||||||||||
| HPA | CAB009233. | ||||||||||||
| MIM | 191316. gene. | ||||||||||||
| PharmGKB | PA31819. | ||||||||||||
| GenAtlas | Search... | ||||||||||||
Phylogenomic databases | |||||||||||||
| HOGENOM | Q16288. | ||||||||||||
| HOVERGEN | Q16288. | ||||||||||||
| OMA | Q16288. ESTDNFV. | ||||||||||||
Enzyme and pathway databases | |||||||||||||
| BRENDA | 2.7.10.1. 247. | ||||||||||||
| Pathway_Interaction_DB | trkrpathway. Neurotrophic factor-mediated Trk receptor signaling. | ||||||||||||
Gene expression databases | |||||||||||||
| ArrayExpress | Q16288. | ||||||||||||
| Bgee | Q16288. | ||||||||||||
| CleanEx | HS_NTRK3. | ||||||||||||
| GermOnline | ENSG00000140538. Homo sapiens. | ||||||||||||
Family and domain databases | |||||||||||||
| InterPro | IPR013151. 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-reg_N. IPR000483. LRR_C. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR002011. Recept_tyr_kinase-II_CS. IPR001245. Tyr_pkinase. IPR008266. Tyr_pkinase_AS. [Graphical view] | ||||||||||||
| Gene3D | G3DSA:2.60.40.10. Ig-like_fold. 2 hits. | ||||||||||||
| Pfam | PF07679. I-set. 1 hit. PF00047. ig. 1 hit. PF00560. LRR_1. 1 hit. PF01462. LRRNT. 1 hit. PF07714. Pkinase_Tyr. 1 hit. [Graphical view] | ||||||||||||
| PRINTS | PR00109. TYRKINASE. | ||||||||||||
| ProDom | PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain] | ||||||||||||
| SMART | SM00409. IG. 1 hit. SM00082. LRRCT. 1 hit. SM00013. LRRNT. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view] | ||||||||||||
| PROSITE | PS50835. 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] | ||||||||||||
| ProtoNet | Search... | ||||||||||||
Other Resources | |||||||||||||
| NextBio | 18927. | ||||||||||||
| SOURCE | Search... | ||||||||||||
Entry information
| Entry name | NTRK3_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q16288 Secondary accession number(s): O75682, Q12827, Q16289 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 15 Human chromosome 15: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| Human and mouse protein kinases Human and mouse protein kinases: classification and index |
| SIMILARITY comments Index of protein domains and families |

Clusters with


