Reviewed, UniProtKB/Swiss-Prot Q16620 (NTRK2_HUMAN)

Names and origin

Protein names

Recommended name:
    BDNF/NT-3 growth factors receptor
    EC=2.7.10.1
Alternative name(s):
    Neurotrophic tyrosine kinase receptor type 2
    TrkB tyrosine kinase
    GP145-TrkB
      Short name=Trk-B

Gene names

Name:	NTRK2
Synonyms:	TRKB

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	822 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 brain-derived neurotrophic factor (BDNF), neurotrophin-3 and neurotrophin-4/5 but not nerve growth factor (NGF). Involved in the development and/or maintenance of the nervous system. This is a tyrosine-protein kinase receptor. Known substrates for the TRK receptors are SHC1, PI-3 kinase, and PLC-gamma-1.
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	Isoform TrkB is widely expressed, mainly in the nervous tissue. In the CNS, expression is observed in the cerebral cortex, hippocampus, thalamus, choroid plexus, granular layer of the cerebellum, brain stem, and spinal cord. In the peripheral nervous system, it is expressed in many cranial ganglia, the ophtalmic nerve, the vestibular system, multiple facial structures, the submaxillary glands, and dorsal root ganglia. Isoform TrkB-T1 is expressed in multiple tissues, mainly in brain, pancreas, kidney and heart. Isoform TrkB-T-Shc is predominantly expressed in 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
Gene Ontology (GO)
Biological process	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 Traceable author statement. Source: ProtInc
Cellular component	integral to plasma membrane Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro neurotrophin binding 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 3 isoforms produced by alternative splicing. [Align] [Select]

Notes: Additional isoforms seem to exist.

Isoform TrkB (identifier: Q16620-1)

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 TrkB-T1 (identifier: Q16620-2)

The sequence of this isoform differs from the canonical sequence as follows:
     467-477: PASVISNDDDS → FVLFHKIPLDG
     478-822: Missing.

Isoform TrkB-T-Shc (identifier: Q16620-3)

The sequence of this isoform differs from the canonical sequence as follows:
     529-537: FVQHIKRHN → WPRGSPKTA
     538-822: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 31

31

Chain

32 – 822

791

BDNF/NT-3 growth factors receptor

PRO_0000016727

Regions

Topological domain

32 – 430

399

Extracellular Potential

Transmembrane

431 – 454

24

Potential

Topological domain

455 – 822

368

Cytoplasmic Potential

Repeat

72 – 93

22

LRR 1

Repeat

96 – 117

22

LRR 2

Domain

197 – 282

86

Ig-like C2-type 1

Domain

295 – 365

71

Ig-like C2-type 2

Domain

538 – 807

270

Protein kinase

Nucleotide binding

544 – 552

9

ATP By similarity

Sites

Active site

676

1

Proton acceptor By similarity

Binding site

572

1

ATP By similarity

Site

516

1

Interaction with SHC1 By similarity

Site

817

1

Interaction with PLC-gamma-1 By similarity

Amino acid modifications

Modified residue

516

1

Phosphotyrosine; by autocatalysis By similarity

Modified residue

702

1

Phosphotyrosine; by autocatalysis By similarity

Modified residue

706

1

Phosphotyrosine; by autocatalysis By similarity

Modified residue

707

1

Phosphotyrosine; by autocatalysis By similarity

Modified residue

817

1

Phosphotyrosine; by autocatalysis By similarity

Glycosylation

67

1

N-linked (GlcNAc...)

Glycosylation

95

1

N-linked (GlcNAc...) Potential

Glycosylation

121

1

N-linked (GlcNAc...)

Glycosylation

178

1

N-linked (GlcNAc...) Potential

Glycosylation

205

1

N-linked (GlcNAc...) Potential

Glycosylation

241

1

N-linked (GlcNAc...) Potential

Glycosylation

254

1

N-linked (GlcNAc...)

Glycosylation

280

1

N-linked (GlcNAc...) Potential

Glycosylation

325

1

N-linked (GlcNAc...) Potential

Glycosylation

338

1

N-linked (GlcNAc...) Potential

Glycosylation

412

1

N-linked (GlcNAc...) Potential

Disulfide bond

32 ↔ 38

Disulfide bond

36 ↔ 45

Disulfide bond

152 ↔ 176

Disulfide bond

154 ↔ 194

Disulfide bond

218 ↔ 266

Disulfide bond

302 ↔ 345

Natural variations

Alternative sequence

467 – 477

11

PASVISNDDDS → FVLFHKIPLDG in isoform TrkB-T1.

VSP_002901

Alternative sequence

478 – 822

345

Missing in isoform TrkB-T1.

VSP_002902

Alternative sequence

529 – 537

9

FVQHIKRHN → WPRGSPKTA in isoform TrkB-T-Shc.

VSP_002903

Alternative sequence

538 – 822

285

Missing in isoform TrkB-T-Shc.

VSP_002904

Natural variant

138

1

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

VAR_041470

Natural variant

309

1

G → R

VAR_016320

Natural variant

338

1

N → Y: dbSNP rs1047856.

VAR_011973

Natural variant

697

1

M → I in a lung carcinoma sample; somatic mutation.

VAR_046518

Natural variant

699

1

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

VAR_046519

Natural variant

718

1

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

VAR_046520

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

822

Helix Strand Turn

Details...

Beta strand

285 – 292

8

Beta strand

296 – 311

16

Beta strand

314 – 319

6

Beta strand

322 – 324

3

Beta strand

328 – 337

10

Beta strand

339 – 350

12

Helix

353 – 355

3

Beta strand

357 – 364

8

Beta strand

369 – 376

8

Sequences

	Sequence		Length	Mass (Da)
	Isoform TrkB [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 2FEB9159948F0D13	FASTA	822	91,999
	10 20 30 40 50 60 MSSWIRWHGP AMARLWGFCW LVVGFWRAAF ACPTSCKCSA SRIWCSDPSP GIVAFPRLEP 70 80 90 100 110 120 NSVDPENITE IFIANQKRLE IINEDDVEAY VGLRNLTIVD SGLKFVAHKA FLKNSNLQHI 130 140 150 160 170 180 NFTRNKLTSL SRKHFRHLDL SELILVGNPF TCSCDIMWIK TLQEAKSSPD TQDLYCLNES 190 200 210 220 230 240 SKNIPLANLQ IPNCGLPSAN LAAPNLTVEE GKSITLSCSV AGDPVPNMYW DVGNLVSKHM 250 260 270 280 290 300 NETSHTQGSL RITNISSDDS GKQISCVAEN LVGEDQDSVN LTVHFAPTIT FLESPTSDHH 310 320 330 340 350 360 WCIPFTVKGN PKPALQWFYN GAILNESKYI CTKIHVTNHT EYHGCLQLDN PTHMNNGDYT 370 380 390 400 410 420 LIAKNEYGKD EKQISAHFMG WPGIDDGANP NYPDVIYEDY GTAANDIGDT TNRSNEIPST 430 440 450 460 470 480 DVTDKTGREH LSVYAVVVIA SVVGFCLLVM LFLLKLARHS KFGMKGPASV ISNDDDSASP 490 500 510 520 530 540 LHHISNGSNT PSSSEGGPDA VIIGMTKIPV IENPQYFGIT NSQLKPDTFV QHIKRHNIVL 550 560 570 580 590 600 KRELGEGAFG KVFLAECYNL CPEQDKILVA VKTLKDASDN ARKDFHREAE LLTNLQHEHI 610 620 630 640 650 660 VKFYGVCVEG DPLIMVFEYM KHGDLNKFLR AHGPDAVLMA EGNPPTELTQ SQMLHIAQQI 670 680 690 700 710 720 AAGMVYLASQ HFVHRDLATR NCLVGENLLV KIGDFGMSRD VYSTDYYRVG GHTMLPIRWM 730 740 750 760 770 780 PPESIMYRKF TTESDVWSLG VVLWEIFTYG KQPWYQLSNN EVIECITQGR VLQRPRTCPQ 790 800 810 820 EVYELMLGCW QREPHMRKNI KGIHTLLQNL AKASPVYLDI LG
	Isoform TrkB-T1 [UniParc]. Checksum: C4A7F565BC88372F		477	53,051
	10 20 30 40 50 60 MSSWIRWHGP AMARLWGFCW LVVGFWRAAF ACPTSCKCSA SRIWCSDPSP GIVAFPRLEP 70 80 90 100 110 120 NSVDPENITE IFIANQKRLE IINEDDVEAY VGLRNLTIVD SGLKFVAHKA FLKNSNLQHI 130 140 150 160 170 180 NFTRNKLTSL SRKHFRHLDL SELILVGNPF TCSCDIMWIK TLQEAKSSPD TQDLYCLNES 190 200 210 220 230 240 SKNIPLANLQ IPNCGLPSAN LAAPNLTVEE GKSITLSCSV AGDPVPNMYW DVGNLVSKHM 250 260 270 280 290 300 NETSHTQGSL RITNISSDDS GKQISCVAEN LVGEDQDSVN LTVHFAPTIT FLESPTSDHH 310 320 330 340 350 360 WCIPFTVKGN PKPALQWFYN GAILNESKYI CTKIHVTNHT EYHGCLQLDN PTHMNNGDYT 370 380 390 400 410 420 LIAKNEYGKD EKQISAHFMG WPGIDDGANP NYPDVIYEDY GTAANDIGDT TNRSNEIPST 430 440 450 460 470 DVTDKTGREH LSVYAVVVIA SVVGFCLLVM LFLLKLARHS KFGMKGFVLF HKIPLDG
	Isoform TrkB-T-Shc [UniParc]. Checksum: 5A8FA252A3871CC1		537	59,167
	10 20 30 40 50 60 MSSWIRWHGP AMARLWGFCW LVVGFWRAAF ACPTSCKCSA SRIWCSDPSP GIVAFPRLEP 70 80 90 100 110 120 NSVDPENITE IFIANQKRLE IINEDDVEAY VGLRNLTIVD SGLKFVAHKA FLKNSNLQHI 130 140 150 160 170 180 NFTRNKLTSL SRKHFRHLDL SELILVGNPF TCSCDIMWIK TLQEAKSSPD TQDLYCLNES 190 200 210 220 230 240 SKNIPLANLQ IPNCGLPSAN LAAPNLTVEE GKSITLSCSV AGDPVPNMYW DVGNLVSKHM 250 260 270 280 290 300 NETSHTQGSL RITNISSDDS GKQISCVAEN LVGEDQDSVN LTVHFAPTIT FLESPTSDHH 310 320 330 340 350 360 WCIPFTVKGN PKPALQWFYN GAILNESKYI CTKIHVTNHT EYHGCLQLDN PTHMNNGDYT 370 380 390 400 410 420 LIAKNEYGKD EKQISAHFMG WPGIDDGANP NYPDVIYEDY GTAANDIGDT TNRSNEIPST 430 440 450 460 470 480 DVTDKTGREH LSVYAVVVIA SVVGFCLLVM LFLLKLARHS KFGMKGPASV ISNDDDSASP 490 500 510 520 530 LHHISNGSNT PSSSEGGPDA VIIGMTKIPV IENPQYFGIT NSQLKPDTWP RGSPKTA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and chromosomal localization of the human TRK-B tyrosine kinase receptor gene (NTRK2)." Nakagawara A., Liu X.-G., Ikegaki N., White P.S., Yamashiro D.J., Nycum L.M., Biegel J.A., Brodeur G.M. Genomics 25:538-546(1995) [PubMed: 7789988] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TRKB). Tissue: Hippocampus.
[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 TRKB AND TRKB-T1). Tissue: Brain.
[3]	"Cloning of a non-catalytic form of human trkB and distribution of messenger RNA for trkB in human brain." Allen S.J., Dawbarn D., Eckford S.D., Wilcock G.K., Ashcroft M., Colebrook S.M., Feeney R., Macgowan S.H. Neuroscience 60:825-834(1994) [PubMed: 7936202] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TRKB-T1). Tissue: Hippocampus.
[4]	"Analysis of the human TrkB gene genomic organization reveals novel TrkB isoforms, unusual gene length, and splicing mechanism." Stoilov P., Castren E., Stamm S. Biochem. Biophys. Res. Commun. 290:1054-1065(2002) [PubMed: 11798182] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS TRKB; TRKB-T1 AND TRKB-T-SHC).
[5]	"Full length truncated TrkB sequence identified in a screen for genes regulated by ischemic preconditioning." Steinbeck J.A., Thomsen S., Wessig J., Leypoldt F., Lewerenz J., Methner A. Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TRKB-T1), VARIANT ARG-309.
[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] (ISOFORM TRKB-T1). Tissue: Brain.
[7]	"Extracellular domain of neurotrophin receptor trkB: disulfide structure, N-glycosylation sites, and ligand binding." Haniu M., Talvenheimo J., Le J., Katta V., Welcher A., Rohde M.F. Arch. Biochem. Biophys. 322:256-264(1995) [PubMed: 7574684] [Abstract] Cited for: DISULFIDE BONDS.
[8]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed: 16335952] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-67; ASN-121 AND ASN-254, MASS SPECTROMETRY. Tissue: Plasma.
[9]	"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 (2.1 ANGSTROMS) OF 283-385.
[10]	"Specificity in Trk receptor:neurotrophin interactions: the crystal structure of TrkB-d5 in complex with neurotrophin-4/5." Banfield M.J., Naylor R.L., Robertson A.G., Allen S.J., Dawbarn D., Brady R.L. Structure 9:1191-1199(2001) [PubMed: 11738045] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 284-383.
[11]	"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.,