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Protein

NT-3 growth factor receptor

Gene

Ntrk3

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Receptor tyrosine kinase involved in nervous system and probably heart development. Upon binding of its ligand NTF3/neurotrophin-3, NTRK3 autophosphorylates and activates different signaling pathways, including the phosphatidylinositol 3-kinase/AKT and the MAPK pathways, that control cell survival and differentiation (By similarity). NTRK3 isoforms containing insertions within the kinase domain can autophosphorylate in response to NTF3/neurotrophin-3, but cannot mediate downstream phenotypic responses (PubMed:8494647, PubMed:8494648).By similarity2 Publications

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei572ATPPROSITE-ProRule annotation1
Active sitei679Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi544 – 552ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • GPI-linked ephrin receptor activity Source: BHF-UCL
  • neurotrophin receptor activity Source: RGD
  • p53 binding Source: Ensembl
  • transmembrane receptor protein serine/threonine kinase activity Source: Reactome

GO - Biological processi

  • activation of GTPase activity Source: Ensembl
  • activation of MAPK activity Source: Ensembl
  • activation of protein kinase B activity Source: Ensembl
  • cellular response to retinoic acid Source: RGD
  • circadian rhythm Source: Ensembl
  • cochlea development Source: RGD
  • heart development Source: UniProtKB
  • lens fiber cell differentiation Source: Ensembl
  • mechanoreceptor differentiation Source: Ensembl
  • modulation by virus of host transcription Source: RGD
  • negative regulation of astrocyte differentiation Source: RGD
  • negative regulation of cell death Source: RGD
  • negative regulation of protein phosphorylation Source: Ensembl
  • neuron fate specification Source: RGD
  • neuron migration Source: RGD
  • positive regulation of actin cytoskeleton reorganization Source: Ensembl
  • positive regulation of apoptotic process Source: Ensembl
  • positive regulation of axon extension involved in regeneration Source: Ensembl
  • positive regulation of cell migration Source: Ensembl
  • positive regulation of cell proliferation Source: Ensembl
  • positive regulation of gene expression Source: Ensembl
  • positive regulation of peptidyl-serine phosphorylation Source: Ensembl
  • positive regulation of positive chemotaxis Source: Ensembl
  • positive regulation of synapse assembly Source: Ensembl
  • protein autophosphorylation Source: RGD
  • response to axon injury Source: RGD
  • response to corticosterone Source: RGD
  • response to ethanol Source: RGD

Keywordsi

Molecular functionDevelopmental protein, Kinase, Receptor, Transferase, Tyrosine-protein kinase
Biological processDifferentiation, Neurogenesis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1 5301
ReactomeiR-RNO-388844 Receptor-type tyrosine-protein phosphatases

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Ntrk3
Synonyms:Trkc
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi3214 Ntrk3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini32 – 429ExtracellularSequence analysisAdd BLAST398
Transmembranei430 – 453HelicalSequence analysisAdd BLAST24
Topological domaini454 – 864CytoplasmicSequence analysisAdd BLAST411

Keywords - Cellular componenti

Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 31By similarityAdd BLAST31
ChainiPRO_000001673532 – 864NT-3 growth factor receptorAdd BLAST833

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi32 ↔ 38By similarity
Disulfide bondi36 ↔ 45By similarity
Glycosylationi68N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi72N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi79N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi133N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi163N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi164 ↔ 189By similarity
Disulfide bondi166 ↔ 207By similarity
Glycosylationi203N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi218N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi231 ↔ 284By similarity
Glycosylationi232N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi259N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi267N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi272N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi294N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi320 ↔ 362PROSITE-ProRule annotation
Glycosylationi375N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi388N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei493PhosphoserineBy similarity1
Modified residuei516Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei705Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei709Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei710Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei859Phosphotyrosine; by autocatalysisBy similarity1

Post-translational modificationi

Ligand-mediated auto-phosphorylation.

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ03351
PRIDEiQ03351

PTM databases

iPTMnetiQ03351
PhosphoSitePlusiQ03351

Expressioni

Tissue specificityi

Widely expressed, mainly in the nervous tissue.

Gene expression databases

BgeeiENSRNOG00000018674
ExpressionAtlasiQ03351 baseline and differential
GenevisibleiQ03351 RN

Interactioni

Subunit structurei

Exists in a dynamic equilibrium between monomeric (low affinity) and dimeric (high affinity) structures (By similarity). Binds SH2B2 (PubMed:9856458). Interacts with SQSTM1 and KIDINS220 (PubMed:12471037, PubMed:15167895). Interacts with PTPRS (PubMed:17967490).By similarity4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei516Interaction with SHC1By similarity1
Sitei859Interaction with PLC-gamma-1By similarity1

Binary interactionsi

WithEntry#Exp.IntActNotes
Cdk5Q031142EBI-7365348,EBI-2008531

GO - Molecular functioni

Protein-protein interaction databases

BioGridi248241, 2 interactors
DIPiDIP-5718N
IntActiQ03351, 3 interactors
MINTiQ03351
STRINGi10116.ENSRNOP00000044402

Structurei

3D structure databases

ProteinModelPortaliQ03351
SMRiQ03351
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati104 – 125LRR 1Add BLAST22
Repeati128 – 149LRR 2Add BLAST22
Domaini160 – 209LRRCTAdd BLAST50
Domaini210 – 300Ig-like C2-type 1Add BLAST91
Domaini309 – 382Ig-like C2-type 2Add BLAST74
Domaini538 – 853Protein kinasePROSITE-ProRule annotationAdd BLAST316

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Immunoglobulin domain, Leucine-rich repeat, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1026 Eukaryota
ENOG410YGKQ LUCA
GeneTreeiENSGT00760000118818
HOGENOMiHOG000264255
HOVERGENiHBG056735
InParanoidiQ03351
KOiK05101
OMAiWCEVGGH
OrthoDBiEOG091G01JY
PhylomeDBiQ03351
TreeFamiTF106465

Family and domain databases

Gene3Di2.60.40.10, 2 hits
3.80.10.10, 1 hit
InterProiView protein in InterPro
IPR000483 Cys-rich_flank_reg_C
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR013098 Ig_I-set
IPR003599 Ig_sub
IPR013151 Immunoglobulin
IPR011009 Kinase-like_dom_sf
IPR001611 Leu-rich_rpt
IPR032675 LRR_dom_sf
IPR000372 LRRNT
IPR031635 NTRK_C2
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
PfamiView protein in Pfam
PF07679 I-set, 1 hit
PF00047 ig, 1 hit
PF13855 LRR_8, 1 hit
PF01462 LRRNT, 1 hit
PF07714 Pkinase_Tyr, 2 hits
PF16920 TPKR_C2, 1 hit
PRINTSiPR01939 NTKRECEPTOR
PR01942 NTKRECEPTOR3
PR00109 TYRKINASE
SMARTiView protein in SMART
SM00409 IG, 1 hit
SM00082 LRRCT, 1 hit
SM00013 LRRNT, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF48726 SSF48726, 2 hits
SSF56112 SSF56112, 2 hits
PROSITEiView protein in PROSITE
PS50835 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

Sequences (8)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 8 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform KI39 (identifier: Q03351-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MDVSLCPAKC SFWRIFLLGS VWLDYVGSVL ACPANCVCSK TEINCRRPDD
60 70 80 90 100
GNLFPLLEGQ DSGNSNGNAS INITDISRNI TSIHIENWRG LHTLNAVDME
110 120 130 140 150
LYTGLQKLTI KNSGLRNIQP RAFAKNPHLR YINLSSNRLT TLSWQLFQTL
160 170 180 190 200
SLRELRLEQN FFNCSCDIRW MQLWQEQGEA RLDSQSLYCI SADGSQLPLF
210 220 230 240 250
RMNISQCDLP EISVSHVNLT VREGDNAVIT CNGSGSPLPD VDWIVTGLQS
260 270 280 290 300
INTHQTNLNW TNVHAINLTL VNVTSEDNGF TLTCIAENVV GMSNASVALT
310 320 330 340 350
VYYPPRVVSL VEPEVRLEHC IEFVVRGNPT PTLHWLYNGQ PLRESKIIHM
360 370 380 390 400
DYYQEGEVSE GCLLFNKPTH YNNGNYTLIA KNALGTANQT INGHFLKEPF
410 420 430 440 450
PESTDFFDFE SDASPTPPIT VTHKPEEDTF GVSIAVGLAA FACVLLVVLF
460 470 480 490 500
IMINKYGRRS KFGMKGPVAV ISGEEDSASP LHHINHGITT PSSLDAGPDT
510 520 530 540 550
VVIGMTRIPV IENPQYFRQG HNCHKPDTYV QHIKRRDIVL KRELGEGAFG
560 570 580 590 600
KVFLAECYNL SPTKDKMLVA VKALKDPTLA ARKDFQREAE LLTNLQHEHI
610 620 630 640 650
VKFYGVCGDG DPLIMVFEYM KHGDLNKFLR AHGPDAMILV DGQPRQAKGE
660 670 680 690 700
LGLSQMLHIA SQIASGMVYL ASQHFVHRDL ATRNCLVGAN LLVKIGDFGM
710 720 730 740 750
SRDVYSTDYY REGPYQKGPF SVSWQQQRLA ASAASTLFNP SGNDFCIWCE
760 770 780 790 800
VGGHTMLPIR WMPPESIMYR KFTTESDVWS FGVILWEIFT YGKQPWFQLS
810 820 830 840 850
NTEVIECITQ GRVLERPRVC PKEVYDVMLG CWQREPQQRL NIKEIYKILH
860
ALGKATPIYL DILG
Length:864
Mass (Da):97,064
Last modified:February 1, 1994 - v2
Checksum:iA202E993E208F636
GO
Isoform TRKC (identifier: Q03351-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     712-736: Missing.
     737-750: Missing.

Show »
Length:825
Mass (Da):92,760
Checksum:i4DE08AB546CC5BD6
GO
Isoform KI14 (identifier: Q03351-3) [UniParc]FASTAAdd to basket
Also known as: TRKC(KI14), TRKC-14

The sequence of this isoform differs from the canonical sequence as follows:
     712-736: Missing.

Show »
Length:839
Mass (Da):94,387
Checksum:i78F3574FD80D983A
GO
Isoform KI25 (identifier: Q03351-4) [UniParc]FASTAAdd to basket
Also known as: TRKC-25

The sequence of this isoform differs from the canonical sequence as follows:
     737-750: Missing.

Show »
Length:850
Mass (Da):95,437
Checksum:iC4CDDD82FF313324
GO
Isoform IC158 (identifier: Q03351-5) [UniParc]FASTAAdd to basket
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.

Show »
Length:612
Mass (Da):68,387
Checksum:i376F0F449792CE46
GO
Isoform IC143 (identifier: Q03351-6) [UniParc]FASTAAdd to basket
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.

Show »
Length:597
Mass (Da):66,618
Checksum:i202BBA3831315D3D
GO
Isoform IC113 (identifier: Q03351-7) [UniParc]FASTAAdd to basket
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.

Show »
Length:567
Mass (Da):63,172
Checksum:i87C245CD9147639B
GO
Isoform IC108 (identifier: Q03351-8) [UniParc]FASTAAdd to basket
Also known as: TRKC(IC108)

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

Show »
Length:562
Mass (Da):62,759
Checksum:iA93D87527814D99C
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_002934529 – 612YVQHI…GDGDP → WVFSNIDNHGILNLKDNRDH LVPSTHYIYEEPEVQSGDVS YPRSHGFREIMLNPISLSGH SKPLNHGIYVEDVNVYFSKG RHGF in isoform IC158. CuratedAdd BLAST84
Alternative sequenceiVSP_002932529 – 597YVQHI…TNLQH → WVFSNIDNHGILNLKDNRDH LVPSTHYIYEEPEVQSGDVS YPRSHGELLPLTSLYEVKPL PLPVLILKT in isoform IC143. CuratedAdd BLAST69
Alternative sequenceiVSP_002930529 – 567YVQHI…TKDKM → CFREIMLNPISLSGHSKPLN HGIYVEDVNVYFSKGRHGF in isoform IC113. CuratedAdd BLAST39
Alternative sequenceiVSP_002928529 – 562YVQHI…YNLSP → FGRIEGFAYGKRYVVMTSVH CHPCWFRFGGLEWL in isoform IC108. CuratedAdd BLAST34
Alternative sequenceiVSP_002929563 – 864Missing in isoform IC108. CuratedAdd BLAST302
Alternative sequenceiVSP_002931568 – 864Missing in isoform IC113. CuratedAdd BLAST297
Alternative sequenceiVSP_002933598 – 864Missing in isoform IC143. CuratedAdd BLAST267
Alternative sequenceiVSP_002935613 – 864Missing in isoform IC158. CuratedAdd BLAST252
Alternative sequenceiVSP_002936712 – 736Missing in isoform KI14 and isoform TRKC. 1 PublicationAdd BLAST25
Alternative sequenceiVSP_002937737 – 750Missing in isoform KI25 and isoform TRKC. 1 PublicationAdd BLAST14

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
RefSeqiNP_001257584.1, NM_001270655.1 [Q03351-3]
NP_001257585.1, NM_001270656.1 [Q03351-1]
NP_062121.1, NM_019248.2 [Q03351-2]
XP_017444550.1, XM_017589061.1 [Q03351-4]
UniGeneiRn.9963

Genome annotation databases

EnsembliENSRNOT00000025536; ENSRNOP00000025536; ENSRNOG00000018674 [Q03351-5]
ENSRNOT00000041839; ENSRNOP00000046059; ENSRNOG00000018674 [Q03351-2]
ENSRNOT00000045165; ENSRNOP00000049463; ENSRNOG00000018674 [Q03351-3]
ENSRNOT00000046849; ENSRNOP00000044402; ENSRNOG00000018674 [Q03351-1]
GeneIDi29613
KEGGirno:29613
UCSCiRGD:3214 rat [Q03351-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiNTRK3_RAT
AccessioniPrimary (citable) accession number: Q03351
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: February 1, 1994
Last modified: May 23, 2018
This is version 182 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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