Q16620 (NTRK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
BDNF/NT-3 growth factors receptor
EC=2.7.10.1

Alternative name(s):
GP145-TrkB
Short name=Trk-B
Neurotrophic tyrosine kinase receptor type 2
TrkB tyrosine kinase
Tropomyosin-related kinase 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 tyrosine kinase involved in the development and the maturation of the central and the peripheral nervous systems through regulation of neuron survival, proliferation, migration, differentiation, and synapse formation and plasticity. Receptor for BDNF/brain-derived neurotrophic factor and NTF4/neurotrophin-4. Alternatively can also bind NTF3/neurotrophin-3 which is less efficient in activating the receptor but regulates neuron survival through NTRK2. Upon ligand-binding, undergoes homodimerization, autophosphorylation and activation. Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades. Through SHC1, FRS2, SH2B1, SH2B2 activates the GRB2-Ras-MAPK cascade that regulates for instance neuronal differentiation including neurite outgrowth. Through the same effectors controls the Ras-PI3 kinase-AKT1 signaling cascade that mainly regulates growth and survival. Through PLCG1 and the downstream protein kinase C-regulated pathways controls synaptic plasticity. Thereby, plays a role in learning and memory by regulating both short term synaptic function and long-term potentiation. PLCG1 also leads to NF-Kappa-B activation and the transcription of genes involved in cell survival. Hence, it is able to suppress anoikis, the apoptosis resulting from loss of cell-matrix interactions. May also play a role in neutrophin-dependent calcium signaling in glial cells and mediate communication between neurons and glia. Ref.17
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Enzyme regulation	The neuronal activity and the influx of calcium positively regulate the kinase activity and the internalization of the receptor which are both important for active signaling. Regulated by NGFR that may control the internalization of the receptor. NGFR may also stimulate the activation by BDNF compared to NTF3 and NTF4. SH2D1A inhibits the autophosphorylation of the receptor, and alters the recruitment and activation of downstream effectors and signaling cascades. The formation of active receptors dimers able to fully transduce the ligand-mediated signal, may be negatively regulated by the formation of inactive heterodimers with the non-catalytic isoforms By similarity.
Subunit structure	Exists in a dynamic equilibrium between monomeric (low affinity) and dimeric (high affinity) structures. Interacts (phosphorylated upon activation by BDNF) with SHC1; mediates SHC1 phosphorylation and activation. Interacts (phosphorylated upon activation by BDNF) with PLCG1 and/or PLCG2; mediates PLCG1 phosphorylation and activation. Interacts with SH2B1 and SH2B2. Interacts with NGFR; may regulate the ligand specificity of the receptor. Interacts (phosphorylated upon ligand-binding) with SH2D1A; regulates NTRK2. Interacts with SQSTM1 and KIDINS220 By similarity. Interacts (phosphorylated upon ligand-binding) with FRS2; activates the MAPK signaling pathway. Ref.12
Subcellular location	Cell membrane; Single-pass type I membrane protein. Endosome membrane; Single-pass type I membrane protein By similarity. Note: Internalized to endosomes upon ligand-binding By similarity. Ref.4 Ref.17
Tissue specificity	Isoform TrkB is expressed in the central and peripheral nervous system. In the central nervous system (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 mainly expressed in the brain but also detected in other tissues including pancreas, kidney and heart. Isoform TrkB-T-Shc is predominantly expressed in the brain. Ref.3 Ref.4
Developmental stage	Widely expressed in fetal brain. Ref.3
Post-translational modification	Phosphorylated. Undergoes ligand-mediated autophosphorylation that is required for interaction with SHC1 and PLCG1 and other downstream effectors. Isoform TrkB-T-Shc is not phosphorylated. Ref.17 Ubiquitinated. Undergoes polyubiquitination upon activation; regulated by NGFR. Ubiquitination regulates the internalization of the receptor By similarity.
Involvement in disease	Defects in NTRK2 are the cause of obesity hyperphagia and developmental delay (OHPDD) [MIM:613886]. OHPDD is a disorder characterized by early-onset obesity, hyperphagia, and severe developmental delay in motor function, speech, and language. Ref.17
Miscellaneous	Trk also stands for tropomyosin-related kinase since the first Trk was isolated as an oncogenic protein which was the result of a fusion between the tropomyosin gene TPM3 and NTRK1.
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 LRRNT domain. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Differentiation Neurogenesis
Cellular component	Cell membrane Endosome Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Obesity
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 Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	activation of adenylate cyclase activity Traceable author statement. Source: Reactome cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome nervous system development Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	integral to plasma membrane Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW neurotrophin binding Traceable author statement. Source: ProtInc neurotrophin receptor activity Inferred from electronic annotation. Source: InterPro transmembrane receptor protein tyrosine kinase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

This entry describes 7 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform TrkB (identifier: Q16620-1)

Also known as: gp145-TrkB;

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.

Note: Non-catalytic isoform.

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.

Isoform 4 (identifier: Q16620-4)

The sequence of this isoform differs from the canonical sequence as follows:
     465-465: K → KDFSWFGFGKVKSRQGV

Isoform 5 (identifier: Q16620-5)

The sequence of this isoform differs from the canonical sequence as follows:
     465-465: K → KDFSWFGFGKVKSRQGV
     529-537: FVQHIKRHN → WPRGSPKTA
     538-822: Missing.

Isoform TrkB-T-TK (identifier: Q16620-6)

The sequence of this isoform differs from the canonical sequence as follows:
     710-735: GGHTMLPIRWMPPESIMYRKFTTESD → SSCADQRPQGPLSLRDPCCICLLRLS
     736-822: Missing.

Isoform TrkB-N-T1 (identifier: Q16620-7)

The sequence of this isoform differs from the canonical sequence as follows:
     1-156: Missing.
     467-477: PASVISNDDDS → FVLFHKIPLDG
     478-822: 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

Helical; Potential

Topological domain

455 – 822

368

Cytoplasmic Potential

Domain

32 – 61

30

LRRNT

Repeat

92 – 113

22

LRR 1

Repeat

116 – 137

22

LRR 2

Domain

148 – 196

49

LRRCT

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

706

1

Interaction with SH2D1A By similarity

Site

817

1

Interaction with PLCG1 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...) Ref.11 Ref.13

Glycosylation

95

1

N-linked (GlcNAc...) Ref.11

Glycosylation

121

1

N-linked (GlcNAc...) Ref.11 Ref.13

Glycosylation

178

1

N-linked (GlcNAc...) Ref.11

Glycosylation

205

1

N-linked (GlcNAc...) Ref.11

Glycosylation

241

1

N-linked (GlcNAc...) Ref.11

Glycosylation

254

1

N-linked (GlcNAc...) Ref.11 Ref.13

Glycosylation

280

1

N-linked (GlcNAc...) Ref.11

Glycosylation

325

1

N-linked (GlcNAc...) Potential

Glycosylation

338

1

N-linked (GlcNAc...) Ref.11

Glycosylation

412

1

N-linked (GlcNAc...) Ref.11

Disulfide bond

32 ↔ 38

Ref.11

Disulfide bond

36 ↔ 45

Ref.11

Disulfide bond

152 ↔ 176

Ref.11

Disulfide bond

154 ↔ 194

Ref.11

Disulfide bond

218 ↔ 266

Ref.11

Disulfide bond

302 ↔ 345

Ref.11

Natural variations

Alternative sequence

1 – 156

156

Missing in isoform TrkB-N-T1.

VSP_042177

Alternative sequence

465

1

K → KDFSWFGFGKVKSRQGV in isoform 4 and isoform 5.

VSP_041942

Alternative sequence

467 – 477

11

PASVISNDDDS → FVLFHKIPLDG in isoform TrkB-T1 and isoform TrkB-N-T1.

VSP_002901

Alternative sequence

478 – 822

345

Missing in isoform TrkB-T1 and isoform TrkB-N-T1.

VSP_002902

Alternative sequence

529 – 537

9

FVQHIKRHN → WPRGSPKTA in isoform TrkB-T-Shc and isoform 5.

VSP_002903

Alternative sequence

538 – 822

285

Missing in isoform TrkB-T-Shc and isoform 5.

VSP_002904

Alternative sequence

710 – 735

26

GGHTM…TTESD → SSCADQRPQGPLSLRDPCCI CLLRLS in isoform TrkB-T-TK.

VSP_042178

Alternative sequence

736 – 822

87

Missing in isoform TrkB-T-TK.

VSP_042179

Natural variant

138

1

L → F in a lung adenocarcinoma sample; somatic mutation. Ref.18

VAR_041470

Natural variant

309

1

G → R. Ref.5

VAR_016320

Natural variant

338

1

N → Y.
Corresponds to variant rs1047856 [ dbSNP | Ensembl ].

VAR_011973

Natural variant

545

1

G → V.
Corresponds to variant rs1075108 [ dbSNP | Ensembl ].

VAR_049715

Natural variant

697

1

M → I in a lung carcinoma sample; somatic mutation. Ref.19

VAR_046518

Natural variant

699

1

R → G in a lung carcinoma sample; somatic mutation. Ref.19

VAR_046519

Natural variant

718

1

R → C in a lung carcinoma sample; somatic mutation. Ref.19

VAR_046520

Natural variant

783

1

Y → C in OHPDD; expressed normally on the cell surface; results in markedly impaired ligand-induced phosphorylation as well as impaired downstream MAPK1 phosphorylation. Ref.17

VAR_065890

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 (gp145-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	FASTA	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	FASTA	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
	Isoform 4 [UniParc]. Checksum: 130C95A9D8895432	FASTA	838	93,826
	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 KFGMKDFSWF GFGKVKSRQG 490 500 510 520 530 540 VGPASVISND DDSASPLHHI SNGSNTPSSS EGGPDAVIIG MTKIPVIENP QYFGITNSQL 550 560 570 580 590 600 KPDTFVQHIK RHNIVLKREL GEGAFGKVFL AECYNLCPEQ DKILVAVKTL KDASDNARKD 610 620 630 640 650 660 FHREAELLTN LQHEHIVKFY GVCVEGDPLI MVFEYMKHGD LNKFLRAHGP DAVLMAEGNP 670 680 690 700 710 720 PTELTQSQML HIAQQIAAGM VYLASQHFVH RDLATRNCLV GENLLVKIGD FGMSRDVYST 730 740 750 760 770 780 DYYRVGGHTM LPIRWMPPES IMYRKFTTES DVWSLGVVLW EIFTYGKQPW YQLSNNEVIE 790 800 810 820 830 CITQGRVLQR PRTCPQEVYE LMLGCWQREP HMRKNIKGIH TLLQNLAKAS PVYLDILG
	Isoform 5 [UniParc]. Checksum: BD98221B9EE1A6C1	FASTA	553	60,994
	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 KFGMKDFSWF GFGKVKSRQG 490 500 510 520 530 540 VGPASVISND DDSASPLHHI SNGSNTPSSS EGGPDAVIIG MTKIPVIENP QYFGITNSQL 550 KPDTWPRGSP KTA
	Isoform TrkB-T-TK [UniParc]. Checksum: 5E0746BCCA281069	FASTA	735	81,569
	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 VYSTDYYRVS SCADQRPQGP 730 LSLRDPCCIC LLRLS
	Isoform TrkB-N-T1 [UniParc]. Checksum: 64C146AAB494744E	FASTA	321	35,332
	10 20 30 40 50 60 MWIKTLQEAK SSPDTQDLYC LNESSKNIPL ANLQIPNCGL PSANLAAPNL TVEEGKSITL 70 80 90 100 110 120 SCSVAGDPVP NMYWDVGNLV SKHMNETSHT QGSLRITNIS SDDSGKQISC VAENLVGEDQ 130 140 150 160 170 180 DSVNLTVHFA PTITFLESPT SDHHWCIPFT VKGNPKPALQ WFYNGAILNE SKYICTKIHV 190 200 210 220 230 240 TNHTEYHGCL QLDNPTHMNN GDYTLIAKNE YGKDEKQISA HFMGWPGIDD GANPNYPDVI 250 260 270 280 290 300 YEDYGTAAND IGDTTNRSNE IPSTDVTDKT GREHLSVYAV VVIASVVGFC LLVMLFLLKL 310 320 ARHSKFGMKG FVLFHKIPLD G

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 SPECIFICITY, DEVELOPMENTAL STAGE. 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; TRKB-T-SHC; 4 AND 5), ALTERNATIVE SPLICING, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[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]	"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 TRKB-N-T1). Tissue: Amygdala.
[7]	"Homo sapiens protein coding cDNA." Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM TRKB-T-TK). Tissue: Brain.
[8]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	"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.
[11]	"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, GLYCOSYLATION AT ASN-67; ASN-95; ASN-121; ASN-178; ASN-205; ASN-241; ASN-254; ASN-280; ASN-338 AND ASN-412.
[12]	"The signaling adapter FRS-2 competes with Shc for binding to the nerve growth factor receptor TrkA. A model for discriminating proliferation and differentiation." Meakin S.O., MacDonald J.I.S., Gryz E.A., Kubu C.J., Verdi J.M. J. Biol. Chem. 274:9861-9870(1999) [PubMed: 10092678] [Abstract] Cited for: INTERACTION WITH FRS2.
[13]	"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.
[14]	"Human TrkB gene: novel alternative transcripts, protein isoforms and expression pattern in the prefrontal cerebral cortex during postnatal development." Luberg K., Wong J., Weickert C.S., Timmusk T. J. Neurochem. 113:952-964(2010) [PubMed: 20193039] [Abstract] Cited for: ALTERNATIVE SPLICING (ISOFORMS TRKB-T-TK AND TRKB-N-T1).
[15]	"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.
[16]	"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 IN COMPLEX WITH NTF4.
[17]	"A de novo mutation affecting human TrkB associated with severe obesity and developmental delay." Yeo G.S., Connie Hung C.C., Rochford J., Keogh J., Gray J., Sivaramakrishnan S., O'Rahilly S., Farooqi I.S. Nat. Neurosci. 7:1187-1189(2004) [PubMed: 15494731] [Abstract] Cited for: VARIANT OHPDD CYS-783, CHARACTERIZATION OF VARIANT OHPDD CYS-783, FUNCTION AS A BDNF-ACTIVATED RECEPTOR, PHOSPHORYLATION, SUBCELLULAR LOCATION.
[18]	"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: VARIANT [LARGE SCALE ANALYSIS] PHE-138.
[19]	"Frequent mutations in the neurotrophic tyrosine receptor kinase gene family in large cell neuroendocrine carcinoma of the lung." Marchetti A., Felicioni L., Pelosi G., Del Grammastro M., Fumagalli C., Sciarrotta M., Malatesta S., Chella A., Barassi F., Mucilli F., Camplese P., D'Antuono T., Sacco R., Buttitta F. Hum. Mutat. 29:609-616(2008) [PubMed: 18293376] [Abstract] Cited for: VARIANTS ILE-697; GLY-699 AND CYS-718.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U12140 mRNA. Translation: AAC51371.1.
S76473 mRNA. Translation: AAB33109.1.
S76474 mRNA. Translation: AAB33110.1.
X75958 mRNA. Translation: CAA53571.1.
AF410899 mRNA. Translation: AAL67965.1.
AF410900 mRNA. Translation: AAL67966.1.
AF410901 mRNA. Translation: AAL67967.1.
AF508964 mRNA. Translation: AAM77876.1.
AB209118 mRNA. Translation: BAD92355.1.
AK294285 mRNA. Translation: BAG57570.1.
AL445532, AL390777, AL596132 Genomic DNA. Translation: CAH71816.1.
AL390777, AL596132 Genomic DNA. Translation: CAH72193.1.
AL390777, AL596132 Genomic DNA. Translation: CAH72194.1.
AL390777, AL445532, AL596132 Genomic DNA. Translation: CAH72195.1.
AL596132, AL390777 Genomic DNA. Translation: CAH72313.1.
AL596132, AL390777 Genomic DNA. Translation: CAH72314.1.
AL596132, AL390777, AL445532 Genomic DNA. Translation: CAH72316.1.
CH471089 Genomic DNA. Translation: EAW62688.1.
BC031835 mRNA. Translation: AAH31835.1.

IPI

IPI00003366.
IPI00179433.
IPI00478527.
IPI00604575.
IPI01010072.

PIR

A56853.
I73631.

RefSeq

NP_001007098.1. NM_001007097.1.
NP_001018074.1. NM_001018064.1.
NP_001018075.1. NM_001018065.2.
NP_001018076.1. NM_001018066.2.
NP_006171.2. NM_006180.3.

UniGene

Hs.494312.
Hs.712776.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1HCF	X-ray	2.70	X/Y	286-383	[»]
1WWB	X-ray	2.10	X	283-385	[»]

ProteinModelPortal

Q16620.

SMR

Q16620. Positions 31-385, 530-812.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-5720N.

IntAct

Q16620. 3 interactions.

STRING

Q16620.

PTM databases

PhosphoSite

Q16620.

Polymorphism databases

DMDM

2497560.

Proteomic databases

PRIDE

Q16620.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000323115; ENSP00000314586; ENSG00000148053.
ENST00000376213; ENSP00000365386; ENSG00000148053.
ENST00000395866; ENSP00000379207; ENSG00000148053.

GeneID

4915.

KEGG

hsa:4915.

UCSC

uc004anx.1. human.
uc004any.1. human.
uc004aoa.1. human.

Organism-specific databases

CTD

4915.

GeneCards

GC09P087283.

HGNC

HGNC:8032. NTRK2.

HPA

CAB010346.
HPA007637.

MIM

600456. gene.
613886. phenotype.

neXtProt

NX_Q16620.

PharmGKB

PA31818.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG08108.

HOVERGEN

HBG056735.

Enzyme and pathway databases

BRENDA

2.7.10.1. 2681.

Pathway_Interaction_DB

trkrpathway. Neurotrophic factor-mediated Trk receptor signaling.

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

Q16620.

Bgee

Q16620.

CleanEx

HS_NTRK2.

Genevestigator

Q16620.

GermOnline

ENSG00000148053. Homo sapiens.

Family and domain databases

InterPro

IPR000483. Cys-rich_flank_reg_C.
IPR007110. Ig-like.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003598. Ig_sub2.
IPR011009. Kinase-like_dom.
IPR000372. LRR-contain_N.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase.
IPR020455. Tyr_kin_neurotrophic_rcpt_2.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR020777. Tyr_kinase_NGF_rcpt.
IPR002011. Tyr_kinase_rcpt_2_CS.
[Graphical view]

Gene3D

G3DSA:2.60.40.10. Ig-like_fold. 2 hits.

KO

K04360.

Pfam

PF07679. I-set. 2 hits.
PF01462. LRRNT. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]

PRINTS

PR01939. NTKRECEPTOR.
PR01941. NTKRECEPTOR2.
PR00109. TYRKINASE.

SMART

SM00408. IGc2. 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.
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

NextBio

18915.

SOURCE

Search...

Entry information

Entry name

NTRK2_HUMAN

Accession

Primary (citable) accession number: Q16620
Secondary accession number(s): B1ANZ4 , B4DFV9, Q16675, Q59GJ1, Q8WXJ5, Q8WXJ6, Q8WXJ7

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	January 25, 2012
This is version 140 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.