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Q03351 (NTRK3_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified May 14, 2014. Version 148. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
NT-3 growth factor receptor

EC=2.7.10.1
Alternative name(s):
GP145-TrkC
Short name=Trk-C
Neurotrophic tyrosine kinase receptor type 3
TrkC tyrosine kinase
Gene names
Name:Ntrk3
Synonyms:Trkc
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length864 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 (NTF3). This is a tyrosine-protein kinase receptor. Known substrates for the TRK receptors are SHC1, PI-3 kinase, and PLCG1. TrkC isoforms containing insertions within the kinase domain can autophosphorylate in response to NT-3, but cannot mediate downstream phenotypic responses.

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. Ref.4 Ref.5 Ref.6

Subcellular location

Membrane; Single-pass type I membrane protein.

Tissue specificity

Widely expressed, mainly in the nervous tissue.

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 LRRCT domain.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processDifferentiation
Neurogenesis
   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
   DomainImmunoglobulin domain
Leucine-rich repeat
Repeat
Signal
Transmembrane
Transmembrane helix
   LigandATP-binding
Nucleotide-binding
   Molecular functionDevelopmental protein
Kinase
Receptor
Transferase
Tyrosine-protein kinase
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of MAPK activity

Inferred from electronic annotation. Source: Ensembl

activation of Ras GTPase activity

Inferred from electronic annotation. Source: Ensembl

activation of protein kinase B activity

Inferred from electronic annotation. Source: Ensembl

cellular response to retinoic acid

Inferred from expression pattern PubMed 10027563. Source: RGD

cochlea development

Inferred from expression pattern PubMed 10494076. Source: RGD

mechanoreceptor differentiation

Inferred from electronic annotation. Source: Ensembl

modulation by virus of host transcription

Inferred from expression pattern PubMed 11175319. Source: RGD

negative regulation of astrocyte differentiation

Inferred from mutant phenotype PubMed 12075995. Source: RGD

negative regulation of cell death

Inferred from mutant phenotype PubMed 12075995. Source: RGD

negative regulation of protein phosphorylation

Inferred from electronic annotation. Source: Ensembl

neuron fate specification

Inferred from mutant phenotype PubMed 15247919. Source: RGD

neuron migration

Inferred from mutant phenotype PubMed 12075995. Source: RGD

positive regulation of actin cytoskeleton reorganization

Inferred from electronic annotation. Source: Ensembl

positive regulation of axon extension involved in regeneration

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell migration

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of gene expression

Inferred from electronic annotation. Source: Ensembl

positive regulation of peptidyl-serine phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of positive chemotaxis

Inferred from electronic annotation. Source: Ensembl

protein autophosphorylation

Inferred from mutant phenotype Ref.2. Source: RGD

response to axon injury

Inferred from expression pattern PubMed 17532148. Source: RGD

response to corticosterone

Inferred from expression pattern PubMed 14557907. Source: RGD

response to ethanol

Inferred from expression pattern PubMed 11743997. Source: RGD

transmembrane receptor protein tyrosine kinase signaling pathway

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentGolgi membrane

Traceable author statement. Source: Reactome

integral component of plasma membrane

Inferred from electronic annotation. Source: InterPro

membrane

Inferred from direct assay PubMed 12882781. Source: RGD

plasma membrane

Inferred from direct assay PubMed 17532148. Source: RGD

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

ephrin receptor binding

Inferred from physical interaction PubMed 19036963. Source: BHF-UCL

neurotrophin receptor activity

Inferred from mutant phenotype Ref.2. Source: RGD

transmembrane receptor protein tyrosine kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Alternative products

This entry describes 8 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform KI39 (identifier: Q03351-1)

Also known as: TRKC(KI39); TRKC-39;

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 TRKC (identifier: Q03351-2)

The sequence of this isoform differs from the canonical sequence as follows:
     712-736: Missing.
     737-750: Missing.
Isoform KI14 (identifier: Q03351-3)

Also known as: TRKC(KI14); TRKC-14;

The sequence of this isoform differs from the canonical sequence as follows:
     712-736: Missing.
Isoform KI25 (identifier: Q03351-4)

Also known as: TRKC-25;

The sequence of this isoform differs from the canonical sequence as follows:
     737-750: Missing.
Isoform IC158 (identifier: Q03351-5)

Also known as: TRKC(IC158); TRKCTK-;

The sequence of this isoform differs from the canonical sequence as follows:
     529-612: YVQHIKRRDI...FYGVCGDGDP → WVFSNIDNHG...VYFSKGRHGF
     613-864: Missing.
Isoform IC143 (identifier: Q03351-6)

Also known as: TRKC(IC143);

The sequence of this isoform differs from the canonical sequence as follows:
     529-597: YVQHIKRRDI...EAELLTNLQH → WVFSNIDNHG...LPLPVLILKT
     598-864: Missing.
Isoform IC113 (identifier: Q03351-7)

Also known as: TRKC(IC113);

The sequence of this isoform differs from the canonical sequence as follows:
     529-567: YVQHIKRRDI...YNLSPTKDKM → CFREIMLNPI...VYFSKGRHGF
     568-864: Missing.
Isoform IC108 (identifier: Q03351-8)

Also known as: TRKC(IC108);

The sequence of this isoform differs from the canonical sequence as follows:
     529-562: YVQHIKRRDIVLKRELGEGAFGKVFLAECYNLSP → FGRIEGFAYGKRYVVMTSVHCHPCWFRFGGLEWL
     563-864: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3131 By similarity
Chain32 – 864833NT-3 growth factor receptor
PRO_0000016735

Regions

Topological domain32 – 429398Extracellular Potential
Transmembrane430 – 45324Helical; Potential
Topological domain454 – 864411Cytoplasmic Potential
Repeat104 – 12522LRR 1
Repeat128 – 14922LRR 2
Domain160 – 20950LRRCT
Domain210 – 30091Ig-like C2-type 1
Domain309 – 38274Ig-like C2-type 2
Domain538 – 853316Protein kinase
Nucleotide binding544 – 5529ATP By similarity

Sites

Active site6791Proton acceptor By similarity
Binding site5721ATP By similarity
Site5161Interaction with SHC1 By similarity
Site8591Interaction 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 residue8591Phosphotyrosine; by autocatalysis By similarity
Glycosylation681N-linked (GlcNAc...) Potential
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 By similarity

Natural variations

Alternative sequence529 – 61284YVQHI…GDGDP → WVFSNIDNHGILNLKDNRDH LVPSTHYIYEEPEVQSGDVS YPRSHGFREIMLNPISLSGH SKPLNHGIYVEDVNVYFSKG RHGF in isoform IC158.
VSP_002934
Alternative sequence529 – 59769YVQHI…TNLQH → WVFSNIDNHGILNLKDNRDH LVPSTHYIYEEPEVQSGDVS YPRSHGELLPLTSLYEVKPL PLPVLILKT in isoform IC143.
VSP_002932
Alternative sequence529 – 56739YVQHI…TKDKM → CFREIMLNPISLSGHSKPLN HGIYVEDVNVYFSKGRHGF in isoform IC113.
VSP_002930
Alternative sequence529 – 56234YVQHI…YNLSP → FGRIEGFAYGKRYVVMTSVH CHPCWFRFGGLEWL in isoform IC108.
VSP_002928
Alternative sequence563 – 864302Missing in isoform IC108.
VSP_002929
Alternative sequence568 – 864297Missing in isoform IC113.
VSP_002931
Alternative sequence598 – 864267Missing in isoform IC143.
VSP_002933
Alternative sequence613 – 864252Missing in isoform IC158.
VSP_002935
Alternative sequence712 – 73625Missing in isoform KI14 and isoform TRKC.
VSP_002936
Alternative sequence737 – 75014Missing in isoform KI25 and isoform TRKC.
VSP_002937

Sequences

Sequence LengthMass (Da)Tools
Isoform KI39 (TRKC(KI39)) (TRKC-39) [UniParc].

Last modified February 1, 1994. Version 2.
Checksum: A202E993E208F636

FASTA86497,064
        10         20         30         40         50         60 
MDVSLCPAKC SFWRIFLLGS VWLDYVGSVL ACPANCVCSK TEINCRRPDD GNLFPLLEGQ 

        70         80         90        100        110        120 
DSGNSNGNAS INITDISRNI TSIHIENWRG LHTLNAVDME LYTGLQKLTI KNSGLRNIQP 

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

       190        200        210        220        230        240 
RLDSQSLYCI SADGSQLPLF RMNISQCDLP EISVSHVNLT VREGDNAVIT CNGSGSPLPD 

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

       310        320        330        340        350        360 
VYYPPRVVSL VEPEVRLEHC IEFVVRGNPT PTLHWLYNGQ PLRESKIIHM DYYQEGEVSE 

       370        380        390        400        410        420 
GCLLFNKPTH YNNGNYTLIA KNALGTANQT INGHFLKEPF PESTDFFDFE SDASPTPPIT 

       430        440        450        460        470        480 
VTHKPEEDTF GVSIAVGLAA FACVLLVVLF IMINKYGRRS 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 REGPYQKGPF 

       730        740        750        760        770        780 
SVSWQQQRLA ASAASTLFNP SGNDFCIWCE VGGHTMLPIR WMPPESIMYR KFTTESDVWS 

       790        800        810        820        830        840 
FGVILWEIFT YGKQPWFQLS NTEVIECITQ GRVLERPRVC PKEVYDVMLG CWQREPQQRL 

       850        860 
NIKEIYKILH ALGKATPIYL DILG 

« Hide

Isoform TRKC [UniParc].

Checksum: 4DE08AB546CC5BD6
Show »

FASTA82592,760
Isoform KI14 (TRKC(KI14)) (TRKC-14) [UniParc].

Checksum: 78F3574FD80D983A
Show »

FASTA83994,387
Isoform KI25 (TRKC-25) [UniParc].

Checksum: C4CDDD82FF313324
Show »

FASTA85095,437
Isoform IC158 (TRKC(IC158)) (TRKCTK-) [UniParc].

Checksum: 376F0F449792CE46
Show »

FASTA61268,387
Isoform IC143 (TRKC(IC143)) [UniParc].

Checksum: 202BBA3831315D3D
Show »

FASTA59766,618
Isoform IC113 (TRKC(IC113)) [UniParc].

Checksum: 87C245CD9147639B
Show »

FASTA56763,172
Isoform IC108 (TRKC(IC108)) [UniParc].

Checksum: A93D87527814D99C
Show »

FASTA56262,759

References

[1]"Molecular cloning of rat trkC and distribution of cells expressing messenger RNAs for members of the trk family in the rat central nervous system."
Merlio J.P., Ernfors P., Jaber M., Persson H.
Neuroscience 51:513-532(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TRKC).
[2]"Alternative forms of rat TrkC with different functional capabilities."
Valenzuela D.M., Maisonpierre P.C., Glass D.J., Rojas E., Nunez L., Kong Y., Gies D.R., Stitt T.N., Ip N.Y., Yancopoulos G.D.
Neuron 10:963-974(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING.
Strain: Sprague-Dawley.
Tissue: Brain.
[3]"The rat trkC locus encodes multiple neurogenic receptors that exhibit differential response to neurotrophin-3 in PC12 cells."
Tsoulfas P., Soppet D., Escandon E., Tessarollo L., Mendoza-Ramirez J.-L., Rosenthal A., Nikolics K., Parada L.F.
Neuron 10:975-990(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING.
Tissue: Brain cortex and Hippocampus.
[4]"Identification and characterization of novel substrates of Trk receptors in developing neurons."
Qian X., Riccio A., Zhang Y., Ginty D.D.
Neuron 21:1017-1029(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SH2B2.
[5]"Association of the atypical protein kinase C-interacting protein p62/ZIP with nerve growth factor receptor TrkA regulates receptor trafficking and Erk5 signaling."
Geetha T., Wooten M.W.
J. Biol. Chem. 278:4730-4739(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SQSTM1.
[6]"A unique pathway for sustained neurotrophin signaling through an ankyrin-rich membrane-spanning protein."
Arevalo J.C., Yano H., Teng K.K., Chao M.V.
EMBO J. 23:2358-2368(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH KIDINS220.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L03813 mRNA. Translation: AAA42285.1.
L14445 mRNA. Translation: AAA42282.1.
L14446 mRNA. Translation: AAA42283.1.
L14447 mRNA. Translation: AAA42284.1.
S60953 mRNA. Translation: AAB26714.2.
S62924 mRNA. Translation: AAB26716.2.
S62933 mRNA. Translation: AAB26715.2.
RefSeqNP_001257584.1. NM_001270655.1. [Q03351-3]
NP_001257585.1. NM_001270656.1. [Q03351-1]
NP_062121.1. NM_019248.2. [Q03351-2]
UniGeneRn.9963.

3D structure databases

ProteinModelPortalQ03351.
SMRQ03351. Positions 300-401.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-5718N.
MINTMINT-1208236.
STRING10116.ENSRNOP00000046935.

Protein family/group databases

MEROPSI43.001.

PTM databases

PhosphoSiteQ03351.

Proteomic databases

PaxDbQ03351.
PRIDEQ03351.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000025536; ENSRNOP00000025536; ENSRNOG00000018674. [Q03351-5]
ENSRNOT00000041839; ENSRNOP00000046059; ENSRNOG00000018674. [Q03351-2]
ENSRNOT00000045165; ENSRNOP00000049463; ENSRNOG00000018674. [Q03351-3]
ENSRNOT00000046080; ENSRNOP00000044960; ENSRNOG00000018674. [Q03351-7]
ENSRNOT00000046849; ENSRNOP00000044402; ENSRNOG00000018674. [Q03351-4]
ENSRNOT00000047776; ENSRNOP00000050248; ENSRNOG00000018674. [Q03351-8]
GeneID29613.
KEGGrno:29613.
UCSCRGD:3214. rat. [Q03351-1]

Organism-specific databases

CTD4916.
RGD3214. Ntrk3.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00730000110657.
HOGENOMHOG000264255.
HOVERGENHBG056735.
InParanoidQ03351.
KOK05101.
OMANFVSIYE.
OrthoDBEOG7GTT32.
PhylomeDBQ03351.
TreeFamTF106465.

Enzyme and pathway databases

BRENDA2.7.10.1. 5301.
ReactomeREACT_212996. Signal Transduction.

Gene expression databases

GenevestigatorQ03351.

Family and domain databases

Gene3D2.60.40.10. 2 hits.
InterProIPR000483. Cys-rich_flank_reg_C.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR011009. Kinase-like_dom.
IPR001611. Leu-rich_rpt.
IPR000372. LRR-contain_N.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR020446. Tyr_kin_neurotrophic_rcpt_3.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR020777. Tyr_kinase_NGF_rcpt.
IPR002011. Tyr_kinase_rcpt_2_CS.
[Graphical view]
PfamPF07679. I-set. 2 hits.
PF13855. LRR_8. 1 hit.
PF01462. LRRNT. 1 hit.
PF07714. Pkinase_Tyr. 2 hits.
[Graphical view]
PRINTSPR01939. NTKRECEPTOR.
PR01942. NTKRECEPTOR3.
PR00109. TYRKINASE.
SMARTSM00409. IG. 1 hit.
SM00082. LRRCT. 1 hit.
SM00013. LRRNT. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 2 hits.
PROSITEPS50835. IG_LIKE. 1 hit.
PS51450. LRR. 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

NextBio609800.
PROQ03351.

Entry information

Entry nameNTRK3_RAT
AccessionPrimary (citable) accession number: Q03351
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: February 1, 1994
Last modified: May 14, 2014
This is version 148 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families