Q6VNS1 (NTRK3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	Ntrk3
Synonyms:	TrkC

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	825 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 PLC-gamma-1 By similarity.
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 By similarity.
Tissue specificity	Isoform 2 expression is restricted to specific areas in adult brain. Isoform 3 transcripts are readily detected early during embryogenesis and are expressed predominantly in adult brain and gonads. Ref.2
Post-translational modification	Ligand-mediated auto-phosphorylation By similarity.
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 process	Differentiation Neurogenesis
Cellular component	Membrane
Coding sequence diversity	Alternative splicing
Domain	Immunoglobulin domain Leucine-rich repeat Repeat Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Developmental protein Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to retinoic acid Inferred from electronic annotation. Source: Compara cochlea development Inferred from electronic annotation. Source: Compara mechanoreceptor differentiation Inferred from mutant phenotype PubMed 15376326. Source: MGI modulation by virus of host transcription Inferred from electronic annotation. Source: Compara negative regulation of astrocyte differentiation Inferred from electronic annotation. Source: Compara negative regulation of cell death Inferred from electronic annotation. Source: Compara neuron fate specification Inferred from electronic annotation. Source: Compara neuron migration Inferred from electronic annotation. Source: Compara positive regulation of axon extension involved in regeneration Inferred from genetic interaction PubMed 16142215. Source: MGI protein autophosphorylation Inferred from electronic annotation. Source: Compara response to axon injury Inferred from electronic annotation. Source: Compara response to corticosterone stimulus Inferred from electronic annotation. Source: Compara response to ethanol Inferred from electronic annotation. Source: Compara transmembrane receptor protein tyrosine kinase signaling pathway Inferred from electronic annotation. Source: InterPro
Cellular_component	cytoplasm Inferred from direct assay PubMed 10207144. Source: MGI integral to plasma membrane Inferred from electronic annotation. Source: InterPro
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW neurotrophin receptor activity Inferred from electronic annotation. Source: Compara transmembrane receptor protein tyrosine kinase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q6VNS1-1)

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 2 (identifier: Q6VNS1-2)

Also known as: TrkC NC1;

The sequence of this isoform differs from the canonical sequence as follows:
     467-502: PVAVISGEEDSASPLHHINHGITTPSSLDAGPDTVV → KVLFFQSQEFHGFHLLIKRYCTSICSLRKPLVTGPW
     503-825: Missing.

Note: Non-catalytic.

Isoform 3 (identifier: Q6VNS1-3)

Also known as: TrkC NC2;

The sequence of this isoform differs from the canonical sequence as follows:
     529-612: YVQHIKRRDI...FYGVCGDGDP → WVFSNIDNHG...VYFSKGRHGF
     613-825: Missing.

Note: Non-catalytic.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 31	31	By similarity
	Chain	32 – 825	794	NT-3 growth factor receptor		PRO_0000260434
Regions
	Topological domain	32 – 429	398	Extracellular Potential
	Transmembrane	430 – 453	24	Helical; Potential
	Topological domain	454 – 825	372	Cytoplasmic Potential
	Repeat	104 – 125	22	LRR 1
	Repeat	128 – 149	22	LRR 2
	Domain	160 – 209	50	LRRCT
	Domain	210 – 300	91	Ig-like C2-type 1
	Domain	309 – 382	74	Ig-like C2-type 2
	Domain	538 – 825	288	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	820	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
	Glycosylation	68	1	N-linked (GlcNAc...) Potential
	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		By similarity
Natural variations
	Alternative sequence	467 – 502	36	PVAVI…PDTVV → KVLFFQSQEFHGFHLLIKRY CTSICSLRKPLVTGPW in isoform 2.		VSP_021596
	Alternative sequence	503 – 825	323	Missing in isoform 2.		VSP_021597
	Alternative sequence	529 – 612	84	YVQHI…GDGDP → WVFSNIDNHGILNLKDNRDH LVPSTHYIYEEPEVQSGDVS YPRSHGFREIMLNPISLSGH SKPLNHGIYVEDVNVYFSKG RHGF in isoform 3.		VSP_021598
	Alternative sequence	613 – 825	213	Missing in isoform 3.		VSP_021599
Experimental info
	Sequence conflict	366	1	N → K in AAC72289. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 5, 2004. Version 1. Checksum: 4DE08AB546CC5BD6	FASTA	825	92,760
	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 RVGGHTMLPI 730 740 750 760 770 780 RWMPPESIMY RKFTTESDVW SFGVILWEIF TYGKQPWFQL SNTEVIECIT QGRVLERPRV 790 800 810 820 CPKEVYDVML GCWQREPQQR LNIKEIYKIL HALGKATPIY LDILG
	Isoform 2 (TrkC NC1) [UniParc]. Checksum: 535D9ED9D7AF50CC	FASTA	502	56,352
	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 KFGMKGKVLF FQSQEFHGFH 490 500 LLIKRYCTSI CSLRKPLVTG PW
	Isoform 3 (TrkC NC2) [UniParc]. Checksum: 376F0F449792CE46	FASTA	612	68,387
	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 HNCHKPDTWV FSNIDNHGIL 550 560 570 580 590 600 NLKDNRDHLV PSTHYIYEEP EVQSGDVSYP RSHGFREIML NPISLSGHSK PLNHGIYVED 610 VNVYFSKGRH GF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Neurotrophin 3 activation of TrkC induces Schwann cell migration through the c-Jun N-terminal kinase pathway." Yamauchi J., Chan J.R., Shooter E.M. Proc. Natl. Acad. Sci. U.S.A. 100:14421-14426(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Strain: BALB/c.
[2]	"Differential expression of TrkC catalytic and noncatalytic isoforms suggests that they act independently or in association." Menn B., Timsit S., Calothy G., Lamballe F. J. Comp. Neurol. 401:47-64(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), TISSUE SPECIFICITY. Strain: C57BL/6. Tissue: Brain.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
[4]	"Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain." Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P. J. Proteome Res. 7:311-318(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-516; TYR-705; TYR-709 AND TYR-710, MASS SPECTROMETRY. Tissue: Brain.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY336094 mRNA. Translation: AAP94280.1. AF035399 mRNA. Translation: AAC72289.1. AF035400 mRNA. Translation: AAC72290.1. BC139764 mRNA. Translation: AAI39765.1.
IPI	IPI00131278. IPI00380220. IPI00807839.
RefSeq	NP_032772.3. NM_008746.5. NP_877961.1. NM_182809.2.
UniGene	Mm.33496. Mm.421361.
3D structure databases
HSSP	HSSP built from PDB template 1WWC based on UniProtKB Q16288.
ProteinModelPortal	Q6VNS1.
SMR	Q6VNS1. Positions 28-428, 529-818.
ModBase	Search...
PTM databases
PhosphoSite	Q6VNS1.
Proteomic databases
PaxDb	Q6VNS1.
PRIDE	Q6VNS1.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000039431; ENSMUSP00000037909; ENSMUSG00000059146. ENSMUST00000039438; ENSMUSP00000038324; ENSMUSG00000059146.
GeneID	18213.
KEGG	mmu:18213.
UCSC	uc009hxf.2. mouse. uc009hxh.2. mouse. uc009hxi.2. mouse.
Organism-specific databases
CTD	4916.
MGI	MGI:97385. Ntrk3.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00700000104172.
HOGENOM	HOG000264255.
HOVERGEN	HBG056735.
InParanoid	Q6VNS1.
KO	K05101.
OMA	NFVSIYE.
OrthoDB	EOG4W3SM8.
Gene expression databases
ArrayExpress	Q6VNS1.
Bgee	Q6VNS1.
CleanEx	MM_NTRK3.
Genevestigator	Q6VNS1.
GermOnline	ENSMUSG00000059146. Mus musculus.
Family and domain databases
Gene3D	2.60.40.10. 2 hits.
InterPro	IPR000483. 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_cat_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]
Pfam	PF07679. I-set. 2 hits. PF01462. LRRNT. 1 hit. PF07714. Pkinase_Tyr. 1 hit. [Graphical view]
PRINTS	PR01939. NTKRECEPTOR. PR01942. NTKRECEPTOR3. PR00109. TYRKINASE.
SMART	SM00409. IG. 1 hit. SM00082. LRRCT. 1 hit. SM00013. LRRNT. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
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. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL2791.
NextBio	293614.
SOURCE	Search...

Entry information

Entry name

NTRK3_MOUSE

Accession

Primary (citable) accession number: Q6VNS1
Secondary accession number(s): A4QPD0, Q9Z2P9, Q9Z2Q0

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 28, 2006
Last sequence update:	July 5, 2004
Last modified:	May 1, 2013
This is version 90 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program