Reviewed, UniProtKB/Swiss-Prot P04629 (NTRK1_HUMAN)

Names and origin

Protein names

Recommended name:
    High affinity nerve growth factor receptor
    EC=2.7.10.1
Alternative name(s):
    Neurotrophic tyrosine kinase receptor type 1
    TRK1-transforming tyrosine kinase protein
    p140-TrkA
      Short name=Trk-A

Gene names

Name:	NTRK1
Synonyms:	TRK

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	796 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	Required for high-affinity binding to nerve growth factor (NGF), neurotrophin-3 and neurotrophin-4/5 but not brain-derived neurotrophic factor (BDNF). Known substrates for the Trk receptors are SHC1, PI 3-kinase, and PLC-gamma-1. Has a crucial role in the development and function of the nociceptive reception system as well as establishment of thermal regulation via sweating. Activates ERK1 by either SHC1- or PLC-gamma-1-dependent signaling pathway. Ref.12 Ref.13
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 which bridges NTRK1 to NGFR. Interacts with KIDINS220 and NGFR. Can form a ternary complex with NGFR and KIDINS220 and this complex is affected by the expression levels of KIDINS220. An increase in KIDINS220 expression leads to a decreased association of NGFR and NTRK1 By similarity.
Subcellular location	Cell membrane; Single-pass type I membrane protein By similarity. Note: Endocytosed to the endosomes upon treatment of cells with NGF By similarity.
Tissue specificity	Isoform TrkA-II is primarily expressed in neuronal cells; isoform TrkA-I is found in non-neuronal tissues.
Domain	The transmembrane domain mediates interaction with KIDINS220 By similarity. The extracellular domain mediates interaction with NGFR By similarity.
Post-translational modification	Ligand-mediated auto-phosphorylation. Interaction with SQSTM1 is phosphotyrosine-dependent.
Involvement in disease	Defects in NTRK1 are a cause of congenital insensitivity to pain with anhidrosis (CIPA) [MIM:256800]. CIPA is characterized by a congenital insensitivity to pain, anhidrosis (absence of sweating), absence of reaction to noxious stimuli, self-mutilating behavior, and mental retardation. This rare autosomal recessive disorder is also known as congenital sensory neuropathy with anhidrosis or hereditary sensory and autonomic neuropathy type IV or familial dysautonomia type II. Ref.22 Ref.23 Ref.24 Ref.26 Ref.29 Ref.30 Ref.31 Chromosomal aberrations involving NTRK1 are a cause of thyroid papillary carcinoma (PACT) [MIM:188550]. Translocation t(1;3)(q21;q11) with TFG generates the TRKT3 (TRK-T3) transcript by fusing TFG to the 3'-end of NTRK1; a rearrangement with TPM3 generates the TRK transcript by fusing TPM3 to the 3'-end of NTRK1. Chromosomal aberrations involving NTRK1 are a cause of thyroid papillary carcinoma (PACT) [MIM:188550]. Intrachromosomal rearrangement that links the protein kinase domain of NTRK1 to the 5'-end of the TPR gene forms the fusion protein TRK-T1. TRK-T1 is a 55 kDa protein reacting with antibodies against the C-terminus of the NTRK1 protein.
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 3 LRR (leucine-rich) repeats. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Differentiation Neurogenesis
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Chromosomal rearrangement Polymorphism
Disease	Disease mutation Proto-oncogene
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	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	Ras protein signal transduction Inferred from Experiment. Source: Reactome activation of adenylate cyclase activity Inferred from Experiment. Source: Reactome 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.3 Inferred from Experiment. Source: Reactome
Cellular component	endosome Inferred from Experiment. Source: Reactome integral to plasma membrane Ref.3 Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW neurotrophin binding Ref.3 Traceable author statement. Source: ProtInc transmembrane receptor protein tyrosine kinase activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PTPN12	Q05209	1	EBI-1028226,EBI-2266035
PTPN22	Q9Y2R2	1	EBI-1028226,EBI-1211241
PTPRB	P23467	1	EBI-1028226,EBI-1265766
PTPRC	P08575	1	EBI-1028226,EBI-1341
PTPRG	P23470	1	EBI-1028226,EBI-2258115
PTPRJ	Q12913	1	EBI-1028226,EBI-2264500
PTPRO	Q16827	1	EBI-1028226,EBI-723739

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: Both isoforms have similar biological properties.

Isoform TrkA-II (identifier: P04629-1)

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 TrkA-I (identifier: P04629-2)

The sequence of this isoform differs from the canonical sequence as follows:
     393-398: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 32

32

Potential

Chain

33 – 796

764

High affinity nerve growth factor receptor

PRO_0000016724

Regions

Topological domain

33 – 423

391

Extracellular Potential

Transmembrane

424 – 439

16

Potential

Topological domain

440 – 796

357

Cytoplasmic Potential

Repeat

90 – 113

24

LRR 1

Repeat

115 – 137

23

LRR 2

Repeat

139 – 161

23

LRR 3

Domain

194 – 283

90

Ig-like C2-type 1

Domain

299 – 365

67

Ig-like C2-type 2

Domain

510 – 781

272

Protein kinase

Nucleotide binding

516 – 524

9

ATP By similarity

Region

469 – 490

22

Interaction with SQSTM1 By similarity

Sites

Active site

650

1

Proton acceptor By similarity

Binding site

544

1

ATP By similarity

Site

398 – 399

2

Breakpoint for translocation to form TRK and TRK-T3

Site

486

1

Breakpoint for translocation to form TRK-T1

Site

496

1

Interaction with SHC1

Site

791

1

Interaction with PLC-gamma-1

Amino acid modifications

Modified residue

496

1

Phosphotyrosine; by autocatalysis Ref.16

Modified residue

676

1

Phosphotyrosine; by autocatalysis

Modified residue

680

1

Phosphotyrosine; by autocatalysis

Modified residue

681

1

Phosphotyrosine; by autocatalysis

Modified residue

791

1

Phosphotyrosine; by autocatalysis Ref.16

Glycosylation

67

1

N-linked (GlcNAc...) Potential

Glycosylation

95

1

N-linked (GlcNAc...) Ref.21

Glycosylation

121

1

N-linked (GlcNAc...) Ref.21

Glycosylation

188

1

N-linked (GlcNAc...) Ref.21

Glycosylation

202

1

N-linked (GlcNAc...) Potential

Glycosylation

253

1

N-linked (GlcNAc...) Potential

Glycosylation

262

1

N-linked (GlcNAc...) Ref.21

Glycosylation

281

1

N-linked (GlcNAc...) Ref.21

Glycosylation

318

1

N-linked (GlcNAc...) Potential

Glycosylation

323

1

N-linked (GlcNAc...) Potential

Glycosylation

338

1

N-linked (GlcNAc...) Potential

Glycosylation

358

1

N-linked (GlcNAc...) Ref.21

Glycosylation

401

1

N-linked (GlcNAc...) Potential

Disulfide bond

154 ↔ 191

Ref.21

Disulfide bond

215 ↔ 265

Ref.21

Natural variations

Alternative sequence

393 – 398

6

Missing in isoform TrkA-I.

VSP_002899

Natural variant

18

1

G → E: dbSNP rs1007211.

VAR_049714

Natural variant

80

1

Q → R Ref.32

VAR_041461

Natural variant

85

1

R → S Ref.24

VAR_009623

Natural variant

93

1

L → P in CIPA. Ref.30

VAR_009624

Natural variant

107

1

A → V in an ovarian serous carcinoma sample; somatic mutation. Ref.32

VAR_041462

Natural variant

213

1

L → P in CIPA. Ref.24

VAR_009625

Natural variant

237

1

T → M Ref.32

VAR_041463

Natural variant

238

1

V → G Ref.32

VAR_041464

Natural variant

260

1

R → G Ref.32

VAR_041465

Natural variant

444

1

R → Q Ref.32

VAR_041466

Natural variant

452

1

R → C: dbSNP rs34900547. Ref.32

VAR_041467

Natural variant

522

1

G → R in CIPA. Ref.30

VAR_009626

Natural variant

566

1

M → T Ref.32

VAR_041468

Natural variant

577

1

G → R in CIPA; loss of function. Ref.22 Ref.30 Ref.31

VAR_004103

Natural variant

587

1

M → V in CIPA. Ref.26

VAR_009627

Natural variant

604

1

H → Y: dbSNP rs6336. Ref.24 Ref.32 Ref.25 Ref.27

VAR_009628

Natural variant

613

1

G → V: dbSNP rs6339. Ref.24 Ref.29 Ref.32 Ref.25 Ref.27

VAR_009629

Natural variant

649

1

R → W in CIPA. Ref.24

VAR_009630

Natural variant

654

1

R → C in CIPA. Ref.30

VAR_009631

Natural variant

674

1

D → Y in CIPA. Ref.30

VAR_009632

Natural variant

695

1

P → L in CIPA. Ref.29

VAR_009633

Natural variant

714

1

G → S in CIPA. Ref.24

VAR_009634

Natural variant

780

1

R → P in CIPA; loss of function. Ref.23

VAR_009635

Natural variant

780

1

R → Q Ref.23 Ref.32 Ref.25

VAR_009636

Natural variant

790

1

V → I Ref.32

VAR_041469

Experimental info

Mutagenesis

496

1

Y → F: No phosphorylation of SHC1. Ref.16

Mutagenesis

544

1

K → N: Inactive.

Mutagenesis

791

1

Y → F: No phosphorylation of PLC-gamma-1. Lack of NGF-promoted increase of the peripherin protein. Ref.16 Ref.15

Sequence conflict

263

1

V → L Ref.1

Sequence conflict

263

1

V → L Ref.2

Sequence conflict

300

1

C → S in AAA36770. Ref.1

Sequence conflict

529

1

C → S in CAA59936. Ref.10

Sequence conflict

765 – 766

2

QR → HG in CAA29888. Ref.9

Sequence conflict

769 – 796

28

QQRHS…LDVLG → SNATASRMCTPGCKPWPRHL LSTWMSWARGPAQGLGVVSR NTGACPQHPP in CAA27243. Ref.9

Secondary structure

1

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796

Helix Strand Turn

Details...

Beta strand

38 – 40

3

Beta strand

43 – 46

4

Turn

57 – 61

5

Beta strand

69 – 72

4

Helix

84 – 86

3

Beta strand

94 – 97

4

Helix

110 – 112

3

Beta strand

119 – 121

3

Turn

133 – 135

3

Beta strand

142 – 144

3

Helix

154 – 156

3

Helix

157 – 164

8

Helix

171 – 173

3

Beta strand

178 – 181

4

Beta strand

195 – 199

5

Beta strand

211 – 218

8

Beta strand

227 – 230

4

Beta strand

234 – 238

5

Beta strand

244 – 253

10

Turn

257 – 260

4

Beta strand

263 – 265

3

Beta strand

285 – 290

6

Beta strand

298 – 309

12

Beta strand

312 – 317

6

Beta strand

326 – 333

8

Beta strand

342 – 350

9

Helix

353 – 355

3

Beta strand

357 – 365

9

Beta strand

368 – 376

9

Turn

494 – 496

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform TrkA-II [UniParc]. Last modified May 2, 2006. Version 4. Checksum: 6C15C721E336B601	FASTA	796	87,497
	10 20 30 40 50 60 MLRGGRRGQL GWHSWAAGPG SLLAWLILAS AGAAPCPDAC CPHGSSGLRC TRDGALDSLH 70 80 90 100 110 120 HLPGAENLTE LYIENQQHLQ HLELRDLRGL GELRNLTIVK SGLRFVAPDA FHFTPRLSRL 130 140 150 160 170 180 NLSFNALESL SWKTVQGLSL QELVLSGNPL HCSCALRWLQ RWEEEGLGGV PEQKLQCHGQ 190 200 210 220 230 240 GPLAHMPNAS CGVPTLKVQV PNASVDVGDD VLLRCQVEGR GLEQAGWILT ELEQSATVMK 250 260 270 280 290 300 SGGLPSLGLT LANVTSDLNR KNVTCWAEND VGRAEVSVQV NVSFPASVQL HTAVEMHHWC 310 320 330 340 350 360 IPFSVDGQPA PSLRWLFNGS VLNETSFIFT EFLEPAANET VRHGCLRLNQ PTHVNNGNYT 370 380 390 400 410 420 LLAANPFGQA SASIMAAFMD NPFEFNPEDP IPVSFSPVDT NSTSGDPVEK KDETPFGVSV 430 440 450 460 470 480 AVGLAVFACL FLSTLLLVLN KCGRRNKFGI NRPAVLAPED GLAMSLHFMT LGGSSLSPTE 490 500 510 520 530 540 GKGSGLQGHI IENPQYFSDA CVHHIKRRDI VLKWELGEGA FGKVFLAECH NLLPEQDKML 550 560 570 580 590 600 VAVKALKEAS ESARQDFQRE AELLTMLQHQ HIVRFFGVCT EGRPLLMVFE YMRHGDLNRF 610 620 630 640 650 660 LRSHGPDAKL LAGGEDVAPG PLGLGQLLAV ASQVAAGMVY LAGLHFVHRD LATRNCLVGQ 670 680 690 700 710 720 GLVVKIGDFG MSRDIYSTDY YRVGGRTMLP IRWMPPESIL YRKFTTESDV WSFGVVLWEI 730 740 750 760 770 780 FTYGKQPWYQ LSNTEAIDCI TQGRELERPR ACPPEVYAIM RGCWQREPQQ RHSIKDVHAR 790 LQALAQAPPV YLDVLG
	Isoform TrkA-I. Checksum: 25F05BADA8A2A50C	FASTA	790	86,880
	10 20 30 40 50 60 MLRGGRRGQL GWHSWAAGPG SLLAWLILAS AGAAPCPDAC CPHGSSGLRC TRDGALDSLH 70 80 90 100 110 120 HLPGAENLTE LYIENQQHLQ HLELRDLRGL GELRNLTIVK SGLRFVAPDA FHFTPRLSRL 130 140 150 160 170 180 NLSFNALESL SWKTVQGLSL QELVLSGNPL HCSCALRWLQ RWEEEGLGGV PEQKLQCHGQ 190 200 210 220 230 240 GPLAHMPNAS CGVPTLKVQV PNASVDVGDD VLLRCQVEGR GLEQAGWILT ELEQSATVMK 250 260 270 280 290 300 SGGLPSLGLT LANVTSDLNR KNVTCWAEND VGRAEVSVQV NVSFPASVQL HTAVEMHHWC 310 320 330 340 350 360 IPFSVDGQPA PSLRWLFNGS VLNETSFIFT EFLEPAANET VRHGCLRLNQ PTHVNNGNYT 370 380 390 400 410 420 LLAANPFGQA SASIMAAFMD NPFEFNPEDP IPDTNSTSGD PVEKKDETPF GVSVAVGLAV 430 440 450 460 470 480 FACLFLSTLL LVLNKCGRRN KFGINRPAVL APEDGLAMSL HFMTLGGSSL SPTEGKGSGL 490 500 510 520 530 540 QGHIIENPQY FSDACVHHIK RRDIVLKWEL GEGAFGKVFL AECHNLLPEQ DKMLVAVKAL 550 560 570 580 590 600 KEASESARQD FQREAELLTM LQHQHIVRFF GVCTEGRPLL MVFEYMRHGD LNRFLRSHGP 610 620 630 640 650 660 DAKLLAGGED VAPGPLGLGQ LLAVASQVAA GMVYLAGLHF VHRDLATRNC LVGQGLVVKI 670 680 690 700 710 720 GDFGMSRDIY STDYYRVGGR TMLPIRWMPP ESILYRKFTT ESDVWSFGVV LWEIFTYGKQ 730 740 750 760 770 780 PWYQLSNTEA IDCITQGREL ERPRACPPEV YAIMRGCWQR EPQQRHSIKD VHARLQALAQ 790 APPVYLDVLG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular and biochemical characterization of the human trk proto-oncogene." Martin-Zanca D., Oskam R., Mitra G., Copeland T.D., Barbacid M. Mol. Cell. Biol. 9:24-33(1989) [PubMed: 2927393] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TRKA-I). Tissue: Colon.
[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]. Tissue: Brain.
[3]	"Structure and organization of the human TRKA gene encoding a high affinity receptor for nerve growth factor." Indo Y., Mardy S., Tsuruta M., Karim M.A., Matsuda I. Jpn. J. Hum. Genet. 42:343-351(1997) [PubMed: 9290260] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM TRKA-II).
[5]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[7]	"Methylation adjacent to negatively regulating AP-1 site reactivates TrkA gene expression during cancer progression." Fujimoto M., Kitazawa R., Maeda S., Kitazawa S. Oncogene 24:5108-5118(2005) [PubMed: 15870692] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-71.
[8]	"A human oncogene formed by the fusion of truncated tropomyosin and protein tyrosine kinase sequences." Martin-Zanca D., Hughes S.H., Barbacid M. Nature 319:743-748(1986) [PubMed: 2869410] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 399-796, CHROMOSOMAL TRANSLOCATION WITH TPM3.
[9]	"Activation of the receptor kinase domain of the trk oncogene by recombination with two different cellular sequences." Kozma S.C., Redmond S.M.S., Saurer S.M., Groner B., Hynes N.E. EMBO J. 7:147-154(1988) [PubMed: 2966065] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 399-796.
[10]	"The DNA rearrangement that generates the TRK-T3 oncogene involves a novel gene on chromosome 3 whose product has a potential coiled-coil domain." Greco A., Mariani C., Miranda C., Lupas A., Pagliardini S., Pomati M., Pierotti M.A. Mol. Cell. Biol. 15:6118-6127(1995) [PubMed: 7565764] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 399-796, CHROMOSOMAL TRANSLOCATION WITH TFG.
[11]	"TRK-T1 is a novel oncogene formed by the fusion of TPR and TRK genes in human papillary thyroid carcinomas." Greco A., Pierotti M.A., Bongarzone I., Pagliardini S., Lanzi C., Della Porta G. Oncogene 7:237-242(1992) [PubMed: 1532241] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 486-796, CHROMOSOMAL REARRANGEMENT WITH TPR.
[12]	"High-affinity NGF binding requires coexpression of the trk proto-oncogene and the low-affinity NGF receptor." Hempstead B.L., Martin-Zanca D., Kaplan D.R., Parada L.F., Chao M.V. Nature 350:678-683(1991) [PubMed: 1850821] [Abstract] Cited for: FUNCTION.
[13]	"The trk proto-oncogene encodes a receptor for nerve growth factor." Klein R., Jing S., Nanduri V., O'Rourke E., Barbacid M. Cell 65:189-197(1991) [PubMed: 1849459] [Abstract] Cited for: FUNCTION.
[14]	"Tissue-specific alternative splicing generates two isoforms of the trkA receptor." Barker P.A., Lomen-Hoerth C., Gensch E.M., Meakin S.O., Glass D.J., Shooter E.M. J. Biol. Chem. 268:15150-15157(1993) [PubMed: 8325889] [Abstract] Cited for: ALTERNATIVE SPLICING.
[15]	"A Trk nerve growth factor (NGF) receptor point mutation affecting interaction with phospholipase C-gamma 1 abolishes NGF-promoted peripherin induction but not neurite outgrowth." Loeb D.M., Stephens R.M., Copeland T.D., Kaplan D.R., Greene L.A. J. Biol. Chem. 269:8901-8910(1994) [PubMed: 7510697] [Abstract] Cited for: MUTAGENESIS OF TYR-791.
[16]	"Trk receptors use redundant signal transduction pathways involving SHC and PLC-gamma 1 to mediate NGF responses." Stephens R.M., Loeb D.M., Copeland T.D., Pawson T., Greene L.A., Kaplan D.R. Neuron 12:691-705(1994) [PubMed: 8155326] [Abstract] Cited for: MUTAGENESIS OF TYR-496 AND TYR-791, PHOSPHORYLATION AT TYR-496 AND TYR-791.
[17]	"The atypical protein kinase C-interacting protein p62 is a scaffold for NF-kappaB activation by nerve growth factor." Wooten M.W., Seibenhener M.L., Mamidipudi V., Diaz-Meco M.T., Barker P.A., Moscat J. J. Biol. Chem. 276:7709-7712(2001) [PubMed: 11244088] [Abstract] Cited for: INTERACTION WITH SQSTM1.
[18]	"Structure and ligand recognition of the phosphotyrosine binding domain of Shc." Zhou M.-M., Ravichandran K.S., Olejniczak E.F., Petros A.M., Meadows R.P., Sattler M., Harlan J.E., Wade W.S., Burakoff S.J., Fesik S.W. Nature 378:584-592(1995) [PubMed: 8524391] [Abstract] Cited for: STRUCTURE BY NMR OF 489-500.
[19]	"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 (2.5 ANGSTROMS) OF 278-386.
[20]	"Crystal structure of nerve growth factor in complex with the ligand-binding domain of the TrkA receptor." Wiesmann C., Ultsch M.H., Bass S.H., de Vos A.M. Nature 401:184-188(1999) [PubMed: 10490030] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 282-382.
[21]	"Structural and mechanistic insights into nerve growth factor interactions with the TrkA and p75 receptors." Wehrman T., He X., Raab B., Dukipatti A., Blau H., Garcia K.C. Neuron 53:25-38(2007) [PubMed: 17196528] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS) OF 36-382 IN COMPLEX WITH NGF, DISULFIDE BONDS, GLYCOSYLATION AT ASN-95; ASN-121; ASN-188; ASN-262; ASN-281 AND ASN-358.
[22]	"Mutations in the TRKA/NGF receptor gene in patients with congenital insensitivity to pain with anhidrosis." Indo Y., Tsuruta M., Hayashida Y., Karim M.A., Ohta K., Kawano T., Mitsubuchi H., Tonoki H., Awaya Y., Matsuda I. Nat. Genet. 13:485-488(1996) [PubMed: 8696348] [Abstract] Cited for: VARIANT CIPA ARG-577.
[23]	"A novel NTRK1 mutation associated with congenital insensitivity to pain with anhidrosis." Greco A., Villa R., Tubino B., Romano L., Penso D., Pierotti M.A. Am. J. Hum. Genet. 64:1207-1210(1999) [PubMed: 10090906] [Abstract] Cited for: VARIANT CIPA PRO-780.
[24]	"Congenital insensitivity to pain with anhidrosis: novel mutations in the TRKA (NTRK1) gene encoding a high-affinity receptor for nerve growth factor." Mardy S., Miura Y., Endo F., Matsuda I., Sztriha L., Frossard P., Moosa A., Ismail E.A.R., Macaya A., Andria G., Toscano E., Gibson W., Graham G.E., Indo Y. Am. J. Hum. Genet. 64:1570-1579(1999) [PubMed: 10330344] [Abstract] Cited for: VARIANTS CIPA PRO-213; TRP-649 AND SER-714, VARIANTS SER-85; TYR-604 AND VAL-613.
[25]	"Mutation analysis reveals novel sequence variants in NTRK1 in sporadic human medullary thyroid carcinoma." Gimm O., Greco A., Hoang-Vu C., Dralle H., Pierotti M.A., Eng C. J. Clin. Endocrinol. Metab. 84:2784-2787(1999) [PubMed: 10443680] [Abstract] Cited for: VARIANTS TYR-604; VAL-613 AND GLN-780.
[26]	"A novel point mutation affecting the tyrosine kinase domain of the TRKA gene in a family with congenital insensitivity to pain with anhidrosis." Yotsumoto S., Setoyama M., Hozumi H., Mizoguchi S., Fukumaru S., Kobayashi K., Saheki T., Kanzaki T. J. Invest. Dermatol. 112:810-814(1999) [PubMed: 10233776] [Abstract] Cited for: VARIANT CIPA VAL-587.
[27]	"Characterization of single-nucleotide polymorphisms in coding regions of human genes." Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S. Nat. Genet. 22:231-238(1999) [PubMed: 10391209] [Abstract] Cited for: VARIANTS TYR-604 AND VAL-613.
[28]	Erratum Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S. Nat. Genet. 23:373-373(1999)
[29]	"Congenital insensitivity to pain with anhidrosis (CIPA) in Israeli-Bedouins: genetic heterogeneity, novel mutations in the TRKA/NGF receptor gene, clinical findings, and results of nerve conduction studies." Shatzky S., Moses S., Levy J., Pinsk V., Hershkovitz E., Herzog L., Shorer Z., Luder A., Parvari R. Am. J. Med. Genet. 92:353-360(2000) [PubMed: 10861667] [Abstract] Cited for: VARIANT CIPA LEU-695, VARIANT VAL-613. Tissue: Peripheral blood.
[30]	"Mutation and polymorphism analysis of the TRKA (NTRK1) gene encoding a high-affinity receptor for nerve growth factor in congenital insensitivity to pain with anhidrosis (CIPA) families." Miura Y., Mardy S., Awaya Y., Nihei K., Endo F., Matsuda I., Indo Y. Hum. Genet. 106:116-124(2000) [PubMed: 10982191] [Abstract] Cited for: VARIANTS CIPA PRO-93; ARG-522; ARG-577; CYS-654 AND TYR-674.
[31]	"The Gly571Arg mutation, associated with the autonomic and sensory disorder congenital insensitivity to pain with anhidrosis, causes the inactivation of the NTRK1/nerve growth factor receptor." Greco A., Villa R., Fusetti L., Orlandi R., Pierotti M.A. J. Cell. Physiol. 182:127-133(2000) [PubMed: 10567924] [Abstract] Cited for: VARIANT CIPA ARG-577.
[32]	"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. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] ARG-80; VAL-107; MET-237; GLY-238; GLY-260; GLN-444; CYS-452; THR-566; TYR-604; VAL-613; GLN-780 AND ILE-790.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBLGenBankDDBJ

M23102 mRNA. Translation: AAA36770.1.
AB019488 Genomic DNA. Translation: BAA34355.1.
AL158169 Genomic DNA. Translation: CAH70010.1.
AK312704 mRNA. Translation: BAG35582.1.
BC062580 mRNA. Translation: AAH62580.1. Different initiation.
AY321513 Genomic DNA. Translation: AAP88292.1.
X03541 mRNA. Translation: CAA27243.1. Different initiation.
X06704 mRNA. Translation: CAA29888.1. Different initiation.
X85960 mRNA. Translation: CAA59936.1. Different initiation.
X62947 mRNA. Translation: CAA44719.1. Different initiation.

IPI

IPI00025076.
IPI00514519.

PIR

TVHUTT. A30124.
S23741.

RefSeq

NP_001007793.1.
NP_001012331.1.
NP_002520.2.

UniGene

Hs.406293

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1HE7	X-ray	2.00	A	285-413	[»]
1SHC	NMR	-	B	489-500	[»]
1WWA	X-ray	2.50	X/Y	278-386	[»]
1WWW	X-ray	2.20	X/Y	282-382	[»]
2IFG	X-ray	3.40	A/B	36-382	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:5714N.

IntAct

P04629. 13 interactions.

PTM databases

PhosphoSite

P04629.

Proteomic databases

PRIDE

P04629.

Genome annotation databases

Ensembl

ENSG00000198400. Homo sapiens. [Contig view]

GeneID

4914.

KEGG

hsa:4914.

Organism-specific databases

GeneCards

GC01P155052.

HGNC

HGNC:8031. NTRK1.

HPA

CAB004606.

MIM

164970. gene.
188550. phenotype.
191315. gene.
256800. phenotype.

Orphanet

642. Hereditary sensory and autonomic neuropathy, type 4.

PharmGKB

PA31817.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P04629.

OMA

P04629. SCGVPTL.

Enzyme and pathway databases

BRENDA

2.7.10.1. 247.

Pathway_Interaction_DB

trkrpathway. Neurotrophic factor-mediated Trk receptor signaling.
p75ntrpathway. p75(NTR)-mediated signaling.
pi3kplctrkpathway. Trk receptor signaling mediated by PI3K and PLC-gamma.

Reactome

REACT_11061. Signalling by NGF.

Gene expression databases

ArrayExpress

P04629.

Bgee

P04629.

GermOnline

ENSG00000198400. Homo sapiens.

Family and domain databases

InterPro

IPR007110. Ig-like.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
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. 1 hit.

Pfam

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.
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

DrugBank

DB00619. Imatinib.

NextBio

18907.

SOURCE

Search...

Entry information

Entry name

NTRK1_HUMAN

Accession

Primary (citable) accession number: P04629
Secondary accession number(s): B2R6T5 , P08119, Q15655, Q15656, Q5D056, Q5VZS2, Q7Z5C3, Q9UIU7

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	May 2, 2006
Last modified:	June 16, 2009
This is version 137 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)