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UniProtKB - Q63604 (NTRK2_RAT)

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Protein

BDNF/NT-3 growth factors receptor

Gene

Ntrk2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.4 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

Enzyme regulationi

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.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei571ATPPROSITE-ProRule annotation1
Active sitei675Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi543 – 551ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • brain-derived neurotrophic factor-activated receptor activity Source: UniProtKB
  • brain-derived neurotrophic factor binding Source: UniProtKB
  • neurotrophin binding Source: UniProtKB
  • neurotrophin receptor activity Source: RGD
  • protein homodimerization activity Source: UniProtKB
  • protein tyrosine kinase activity Source: Reactome
  • transmembrane receptor protein serine/threonine kinase activity Source: Reactome
  • transmembrane receptor protein tyrosine kinase activity Source: RGD
View the complete GO annotation on QuickGO ...

GO - Biological processi

  • aging Source: RGD
  • brain-derived neurotrophic factor receptor signaling pathway Source: UniProtKB
  • cellular response to brain-derived neurotrophic factor stimulus Source: RGD
  • cellular response to nerve growth factor stimulus Source: RGD
  • cellular response to tumor necrosis factor Source: RGD
  • central nervous system neuron development Source: UniProtKB
  • cerebral cortex development Source: UniProtKB
  • inflammatory response Source: RGD
  • learning Source: UniProtKB
  • long-term memory Source: RGD
  • negative regulation of neuron apoptotic process Source: UniProtKB
  • neuron differentiation Source: UniProtKB
  • neuron migration Source: UniProtKB
  • positive regulation of axonogenesis Source: UniProtKB
  • positive regulation of cell proliferation Source: UniProtKB
  • positive regulation of gene expression Source: UniProtKB
  • positive regulation of glucocorticoid receptor signaling pathway Source: MGI
  • positive regulation of MAPK cascade Source: UniProtKB
  • positive regulation of neuron projection development Source: UniProtKB
  • positive regulation of phosphatidylinositol 3-kinase signaling Source: UniProtKB
  • positive regulation of synaptic transmission, glutamatergic Source: RGD
  • protein autophosphorylation Source: UniProtKB
  • regulation of dendrite development Source: RGD
  • regulation of GTPase activity Source: UniProtKB
  • regulation of MAPK cascade Source: UniProtKB
  • regulation of neurotransmitter secretion Source: RGD
  • response to auditory stimulus Source: RGD
  • response to light stimulus Source: RGD
View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionDevelopmental protein, Kinase, Receptor, Transferase, Tyrosine-protein kinase
Biological processDifferentiation, Neurogenesis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1 5301
ReactomeiR-RNO-9026527 Activated NTRK2 signals through PLCG1
R-RNO-9028731 Activated NTRK2 signals through FRS2 and FRS3

Names & Taxonomyi

Protein namesi
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
Short name:
Trk-B
Gene namesi
Name:Ntrk2
Synonyms:Trkb
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus
Proteomesi
  • UP000002494 Componenti: Chromosome 17

Organism-specific databases

RGDi3213 Ntrk2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini32 – 429ExtracellularSequence analysisAdd BLAST398
Transmembranei430 – 453HelicalSequence analysisAdd BLAST24
Topological domaini454 – 821CytoplasmicSequence analysisAdd BLAST368

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi515Y → F: Loss of interaction with SHC1. 1 Publication1
Mutagenesisi571K → A: Loss of kinase activity. 1 Publication1
Mutagenesisi701Y → F: Loss of autophosphorylation and altered interaction with SHC1 and PLCG1; when associated with F-705 and F-706. 1 Publication1
Mutagenesisi705Y → F: Loss of autophosphorylation; when associated with F-701 and F-706. 2 Publications1
Mutagenesisi706Y → F: Loss of autophosphorylation; when associated with F-701 and F-705. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL1795111

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 31By similarityAdd BLAST31
ChainiPRO_000001672932 – 821BDNF/NT-3 growth factors receptorAdd BLAST790

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi32 ↔ 38PROSITE-ProRule annotation
Disulfide bondi36 ↔ 45PROSITE-ProRule annotation
Glycosylationi67N-linked (GlcNAc...) asparagineBy similarity1
Glycosylationi95N-linked (GlcNAc...) asparagine; alternateBy similarity1
Glycosylationi95N-linked (HexNAc...) asparagine; alternateCombined sources1
Glycosylationi121N-linked (GlcNAc...) asparagineBy similarity1
Disulfide bondi152 ↔ 176PROSITE-ProRule annotation
Disulfide bondi154 ↔ 194PROSITE-ProRule annotation
Glycosylationi178N-linked (GlcNAc...) asparagineBy similarity1
Glycosylationi205N-linked (GlcNAc...) asparagineBy similarity1
Disulfide bondi218 ↔ 266PROSITE-ProRule annotation
Glycosylationi241N-linked (GlcNAc...) asparagine; alternateBy similarity1
Glycosylationi241N-linked (HexNAc...) asparagine; alternateCombined sources1
Glycosylationi254N-linked (GlcNAc...) asparagineBy similarity1
Glycosylationi280N-linked (GlcNAc...) asparagineBy similarity1
Disulfide bondi302 ↔ 345PROSITE-ProRule annotation
Glycosylationi325N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi338N-linked (GlcNAc...) asparagineBy similarity1
Glycosylationi411N-linked (GlcNAc...) asparagineBy similarity1
Modified residuei515Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei701Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei705Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei706Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei816Phosphotyrosine; by autocatalysis1 Publication1

Post-translational modificationi

Phosphorylated. Undergoes ligand-mediated autophosphorylation that is required for interaction with SHC1 and PLCG1 and other downstream effectors. Some isoforms are not phosphorylated.2 Publications
Ubiquitinated. Undergoes polyubiquitination upon activation; regulated by NGFR. Ubiquitination regulates the internalization of the receptor (By similarity).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ63604
PRIDEiQ63604

PTM databases

iPTMnetiQ63604
PhosphoSitePlusiQ63604
UniCarbKBiQ63604

Expressioni

Tissue specificityi

Widely expressed in the central and peripheral nervous system. The different forms are differentially expressed in various cell types. Isoform T2 is primarily expressed in neurons.

Gene expression databases

BgeeiENSRNOG00000018839
ExpressionAtlasiQ63604 baseline and differential
GenevisibleiQ63604 RN

Interactioni

Subunit structurei

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. Interacts (phosphorylated upon ligand-binding) with FRS2; activates the MAPK signaling pathway. Interacts with APPL1 (By similarity).By similarity8 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei515Interaction with SHC11
Sitei705Interaction with SH2D1A1
Sitei816Interaction with PLCG1By similarity1

Binary interactionsi

Show more details

GO - Molecular functioni

  • brain-derived neurotrophic factor binding Source: UniProtKB
  • neurotrophin binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi247131, 8 interactors
CORUMiQ63604
DIPiDIP-5717N
IntActiQ63604, 11 interactors
MINTiQ63604
STRINGi10116.ENSRNOP00000045635

Structurei

3D structure databases

ProteinModelPortaliQ63604
SMRiQ63604
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini32 – 61LRRNTAdd BLAST30
Repeati92 – 113LRR 1Add BLAST22
Repeati116 – 137LRR 2Add BLAST22
Domaini148 – 196LRRCTAdd BLAST49
Domaini197 – 282Ig-like C2-type 1Add BLAST86
Domaini295 – 365Ig-like C2-type 2Add BLAST71
Domaini537 – 806Protein kinasePROSITE-ProRule annotationAdd BLAST270

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Immunoglobulin domain, Leucine-rich repeat, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1026 Eukaryota
ENOG410YGKQ LUCA
GeneTreeiENSGT00760000118818
HOGENOMiHOG000264255
HOVERGENiHBG056735
InParanoidiQ63604
KOiK04360
PhylomeDBiQ63604
TreeFamiTF106465

Family and domain databases

Gene3Di2.60.40.10, 2 hits
3.80.10.10, 1 hit
InterProiView protein in InterPro
IPR000483 Cys-rich_flank_reg_C
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR013098 Ig_I-set
IPR003599 Ig_sub
IPR003598 Ig_sub2
IPR011009 Kinase-like_dom_sf
IPR001611 Leu-rich_rpt
IPR032675 LRR_dom_sf
IPR000372 LRRNT
IPR031635 NTRK_C2
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
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
PfamiView protein in Pfam
PF07679 I-set, 2 hits
PF13855 LRR_8, 1 hit
PF07714 Pkinase_Tyr, 1 hit
PF16920 TPKR_C2, 1 hit
PRINTSiPR01939 NTKRECEPTOR
PR01941 NTKRECEPTOR2
PR00109 TYRKINASE
SMARTiView protein in SMART
SM00409 IG, 1 hit
SM00408 IGc2, 1 hit
SM00082 LRRCT, 1 hit
SM00013 LRRNT, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF48726 SSF48726, 2 hits
SSF56112 SSF56112, 1 hit
PROSITEiView protein in 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

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform GP145-TrkB (identifier: Q63604-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MSPWPRWHGP AMARLWGLCL LVLGFWRASL ACPMSCKCST TRIWCTEPSP 
        60         70         80         90        100
GIVAFPRLEP NSIDPENITE ILIANQKRLE IINEDDVEAY VGLKNLTIVD 
       110        120        130        140        150
SGLKFVAYKA FLKNGNLRHI NFTRNKLTSL SRRHFRHLDL SDLILTGNPF 
       160        170        180        190        200
TCSCDIMWLK TLQETKSSPD TQDLYCLNES SKNTPLANLQ IPNCGLPSAR 
       210        220        230        240        250
LAAPNLTVEE GKSVTISCSV GGDPLPTLYW DVGNLVSKHM NETSHTQGSL 
       260        270        280        290        300
RITNISSDDS GKQISCVAEN LVGEDQDSVN LTVHFAPTIT FLESPTSDHH 
       310        320        330        340        350
WCIPFTVRGN PKPALQWFYN GAILNESKYI CTKIHVTNHT EYHGCLQLDN 
       360        370        380        390        400
PTHMNNGDYT LMAKNEYGKD ERQISAHFMG RPGVDYETNP NYPEVLYEDW 
       410        420        430        440        450
TTPTDIGDTT NKSNEIPSTD VADQTNREHL SVYAVVVIAS VVGFCLLVML 
       460        470        480        490        500
LLLKLARHSK FGMKGPASVI SNDDDSASPL HHISNGSNTP SSSEGGPDAV 
       510        520        530        540        550
IIGMTKIPVI ENPQYFGITN SQLKPDTFVQ HIKRHNIVLK RELGEGAFGK 
       560        570        580        590        600
VFLAECYNLC PEQDKILVAV KTLKDASDNA RKDFHREAEL LTNLQHEHIV 
       610        620        630        640        650
KFYGVCVEGD PLIMVFEYMK HGDLNKFLRA HGPDAVLMAE GNPPTELTQS 
       660        670        680        690        700
QMLHIAQQIA AGMVYLASQH FVHRDLATRN CLVGENLLVK IGDFGMSRDV 
       710        720        730        740        750
YSTDYYRVGG HTMLPIRWMP PESIMYRKFT TESDVWSLGV VLWEIFTYGK 
       760        770        780        790        800
QPWYQLSNNE VIECITQGRV LQRPRTCPQE VYELMLGCWQ REPHTRKNIK 
       810        820 
NIHTLLQNLA KASPVYLDIL G
Length:821
Mass (Da):92,186
Last modified:November 1, 1996 - v1
Checksum:i0DDACDA212CDAA0E
GO
Isoform T1 (identifier: Q63604-2) [UniParc]FASTAAdd to basket
Also known as: GP95-TrkB

The sequence of this isoform differs from the canonical sequence as follows:
     466-476: PASVISNDDDS → FVLFHKIPLDG
     477-821: Missing.

Note: Non-catalytic isoform.
Show »
Length:476
Mass (Da):53,212
Checksum:i79AFCD9CA0AB13A8
GO
Isoform T2 (identifier: Q63604-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     466-474: PASVISNDD → KQKCAYFAS
     475-821: Missing.

Note: Non-catalytic isoform.
Show »
Length:474
Mass (Da):52,971
Checksum:i2A6F19237F9F692A
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_002910466 – 476PASVISNDDDS → FVLFHKIPLDG in isoform T1. CuratedAdd BLAST11
Alternative sequenceiVSP_002912466 – 474PASVISNDD → KQKCAYFAS in isoform T2. Curated9
Alternative sequenceiVSP_002913475 – 821Missing in isoform T2. CuratedAdd BLAST347
Alternative sequenceiVSP_002911477 – 821Missing in isoform T1. CuratedAdd BLAST345

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M55291 mRNA Translation: AAA42279.1
M55292 mRNA Translation: AAA42280.1
M55293 mRNA Translation: AAA42281.1
PIRiA39667
B39667
C39667
RefSeqiNP_001156640.1, NM_001163168.2 [Q63604-2]
NP_036863.1, NM_012731.2 [Q63604-1]
UniGeneiRn.11246

Genome annotation databases

EnsembliENSRNOT00000042145; ENSRNOP00000045635; ENSRNOG00000018839 [Q63604-1]
ENSRNOT00000090914; ENSRNOP00000070128; ENSRNOG00000018839 [Q63604-2]
GeneIDi25054
KEGGirno:25054
UCSCiRGD:3213 rat [Q63604-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiNTRK2_RAT
AccessioniPrimary (citable) accession number: Q63604
Secondary accession number(s): Q63605, Q63606
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: May 23, 2018
This is version 172 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

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