Reviewed, UniProtKB/Swiss-Prot Q16288 (NTRK3_HUMAN)

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

Name:	NTRK3
Synonyms:	TRKC

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 ARMS By similarity.
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Widely expressed, mainly in the nervous tissue. The isoform B is expressed in a relatively large amount in the adult brain comparatively to 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

Keywords
Biological process	Differentiation Neurogenesis
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Immunoglobulin domain Leucine-rich repeat Repeat Signal Transmembrane
Ligand	ATP-binding Nucleotide-binding
Molecular function	Developmental protein Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Glycoprotein Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW nervous system development Inferred from electronic annotation. Source: UniProtKB-KW protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro transmembrane receptor protein tyrosine kinase signaling pathway Ref.1 Traceable author statement. Source: ProtInc
Cellular component	integral to plasma membrane Ref.1 Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro neurotrophin binding Ref.1 Traceable author statement. Source: ProtInc transmembrane receptor protein tyrosine kinase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

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

Notes: 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

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.

VAR_041471

Natural variant

306

1

R → C: dbSNP rs56386352.

VAR_041472

Natural variant

307

1

V → L in a lung adenocarcinoma sample; somatic mutation.

VAR_041473

Natural variant

336

1

L → Q in a lung adenocarcinoma sample; somatic mutation.

VAR_041474

Natural variant

664

1

A → S in a lung carcinoma sample; somatic mutation.

VAR_046521

Natural variant

677

1

H → Y in a lung adenocarcinoma sample; somatic mutation.

VAR_041475

Natural variant

678

1

R → Q

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.

VAR_046522

Natural variant

745

1

R → P in a lung carcinoma sample; somatic mutation.

VAR_046523

Natural variant

766

1

Y → F in a lung carcinoma sample; somatic mutation.

VAR_046524

Natural variant

768

1

K → R

VAR_046771

Natural variant

781

1

E → K

VAR_046772

Experimental info

Sequence conflict

70

1

S → N in AAB33111 and AAB33112. Ref.2

Sequence conflict

635

1

D → N in AAA75374. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

839

Helix Strand Turn

Details...

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

	Sequence		Length	Mass (Da)
	Isoform A [UniParc]. Last modified March 6, 2007. Version 2. Checksum: 7FE8846830083C08	FASTA	839	94,428
	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
	Isoform B [UniParc]. Checksum: F2E84DC71B8E4DB3		612	68,452
	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 HNCHKPDTWV FSNIDNHGIL 550 560 570 580 590 600 NLKDNRDHLV PSTHYIYEEP EVQSGEVSYP RSHGFREIML NPISLPGHSK PLNHGIYVED 610 VNVYFSKGRH GF
	Isoform C [UniParc]. Checksum: 7ADBE1AF6DB280BF		825	92,801
	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 RVGGHTMLPI 730 740 750 760 770 780 RWMPPESIMY RKFTTESDVW SFGVILWEIF TYGKQPWFQL SNTEVIECIT QGRVLERPRV 790 800 810 820 CPKEVYDVML GCWQREPQQR LNIKEIYKIL HALGKATPIY LDILG
	Isoform D [UniParc]. Checksum: 4409D52CA249C0FE		830	93,361
	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 PDEVSPTPPI TVTHKPEEDT 430 440 450 460 470 480 FGVSIAVGLA AFACVLLVVL FVMINKYGRR SKFGMKGPVA VISGEEDSAS PLHHINHGIT 490 500 510 520 530 540 TPSSLDAGPD TVVIGMTRIP VIENPQYFRQ GHNCHKPDTY VQHIKRRDIV LKRELGEGAF 550 560 570 580 590 600 GKVFLAECYN LSPTKDKMLV AVKALKDPTL AARKDFQREA ELLTNLQHEH IVKFYGVCGD 610 620 630 640 650 660 GDPLIMVFEY MKHGDLNKFL RAHGPDAMIL VDGQPRQAKG ELGLSQMLHI ASQIASGMVY 670 680 690 700 710 720 LASQHFVHRD LATRNCLVGA NLLVKIGDFG MSRDVYSTDY YRLFNPSGND FCIWCEVGGH 730 740 750 760 770 780 TMLPIRWMPP ESIMYRKFTT ESDVWSFGVI LWEIFTYGKQ PWFQLSNTEV IECITQGRVL 790 800 810 820 830 ERPRVCPKEV YDVMLGCWQR EPQQRLNIKE IYKILHALGK ATPIYLDILG

References

	« Hide 'large scale' referencesShow '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.,