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Protein

BDNF/NT-3 growth factors receptor

Gene

NTRK2

Organism
Homo sapiens (Human)
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 and mediate communication between neurons and glia.1 Publication

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.

Catalytic activityi

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

Activity 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 (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei572ATPPROSITE-ProRule annotation1
Active sitei676Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi544 – 552ATPPROSITE-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
  • protein homodimerization activity Source: UniProtKB

GO - Biological processi

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 2681
ReactomeiR-HSA-187024 NGF-independant TRKA activation
R-HSA-9024909 BDNF activates NTRK2 (TRKB) signaling
R-HSA-9025046 NTF3 activates NTRK2 (TRKB) signaling
R-HSA-9026357 NTF4 activates NTRK2 (TRKB) signaling
R-HSA-9026519 Activated NTRK2 signals through RAS
R-HSA-9026527 Activated NTRK2 signals through PLCG1
R-HSA-9028335 Activated NTRK2 signals through PI3K
R-HSA-9028731 Activated NTRK2 signals through FRS2 and FRS3
R-HSA-9032500 Activated NTRK2 signals through FYN
R-HSA-9032759 NTRK2 activates RAC1
R-HSA-9032845 Activated NTRK2 signals through CDK5
SignaLinkiQ16620
SIGNORiQ16620

Names & Taxonomyi

Protein namesi
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 namesi
Name:NTRK2
Synonyms:TRKB
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000148053.15
HGNCiHGNC:8032 NTRK2
MIMi600456 gene
neXtProtiNX_Q16620

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 – 430ExtracellularSequence analysisAdd BLAST399
Transmembranei431 – 454HelicalSequence analysisAdd BLAST24
Topological domaini455 – 822CytoplasmicSequence analysisAdd BLAST368

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Endosome, Membrane

Pathology & Biotechi

Involvement in diseasei

Epileptic encephalopathy, early infantile, 58 (EIEE58)1 Publication
The disease may be caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. EIEE58 is an autosomal dominant condition characterized by onset of refractory seizures in the first days or months of life.
See also OMIM:617830
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_080659434Y → C in EIEE58; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs886041091EnsemblClinVar.1
Obesity, hyperphagia, and developmental delay (OBHD)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by early-onset obesity, hyperphagia, and severe developmental delay in motor function, speech, and language.
See also OMIM:613886
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_080660444 – 822Missing in OBHD. 1 PublicationAdd BLAST379
Natural variantiVAR_080661704T → I in OBHD; unknown pathological significance. 1 Publication1
Natural variantiVAR_065890706Y → C in OBHD; expressed normally on the cell surface; results in markedly impaired ligand-induced phosphorylation as well as impaired downstream MAPK1 phosphorylation. 1 PublicationCorresponds to variant dbSNP:rs121434633Ensembl.1

Keywords - Diseasei

Disease mutation, Epilepsy, Obesity

Organism-specific databases

DisGeNETi4915
MalaCardsiNTRK2
MIMi613886 phenotype
617830 phenotype
OpenTargetsiENSG00000148053
Orphaneti251612 Pilocytic astrocytoma
PharmGKBiPA31818

Chemistry databases

ChEMBLiCHEMBL4898
DrugBankiDB00321 Amitriptyline
GuidetoPHARMACOLOGYi1818

Polymorphism and mutation databases

BioMutaiNTRK2
DMDMi2497560

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 31Add BLAST31
ChainiPRO_000001672732 – 822BDNF/NT-3 growth factors receptorAdd BLAST791

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi32 ↔ 38PROSITE-ProRule annotation1 Publication
Disulfide bondi36 ↔ 45PROSITE-ProRule annotation1 Publication
Glycosylationi67N-linked (GlcNAc...) asparagine2 Publications1
Glycosylationi95N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi121N-linked (GlcNAc...) asparagine2 Publications1
Disulfide bondi152 ↔ 176PROSITE-ProRule annotation1 Publication
Disulfide bondi154 ↔ 194PROSITE-ProRule annotation1 Publication
Glycosylationi178N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi205N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi218 ↔ 266PROSITE-ProRule annotation1 Publication
Glycosylationi241N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi254N-linked (GlcNAc...) asparagine2 Publications1
Glycosylationi280N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi302 ↔ 345PROSITE-ProRule annotation1 Publication
Glycosylationi325N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi338N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi412N-linked (GlcNAc...) asparagine1 Publication1
Modified residuei516Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei702Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei706Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei707Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei817Phosphotyrosine; by autocatalysisBy similarity1

Post-translational modificationi

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.1 Publication
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

PaxDbiQ16620
PeptideAtlasiQ16620
PRIDEiQ16620
ProteomicsDBi60955
60956 [Q16620-2]
60957 [Q16620-3]
60958 [Q16620-4]
60959 [Q16620-5]
60960 [Q16620-6]
60961 [Q16620-7]

PTM databases

GlyConnecti1029
iPTMnetiQ16620
PhosphoSitePlusiQ16620

Expressioni

Tissue specificityi

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 ophthalmic 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.2 Publications

Developmental stagei

Widely expressed in fetal brain.1 Publication

Gene expression databases

BgeeiENSG00000148053 Expressed in 222 organ(s), highest expression level in hypothalamus
CleanExiHS_NTRK2
ExpressionAtlasiQ16620 baseline and differential
GenevisibleiQ16620 HS

Organism-specific databases

HPAiCAB010346
HPA007637

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 (By similarity). Interacts (phosphorylated upon ligand-binding) with FRS2; activates the MAPK signaling pathway. Interacts with APPL1 (By similarity). Interacts with MAPK8IP3/JIP3 and KLC1; interaction with KLC1 is mediated by MAPK8IP3/JIP3 (By similarity).By similarity2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei516Interaction with SHC1By similarity1
Sitei706Interaction with SH2D1ABy similarity1
Sitei817Interaction with PLCG1By similarity1

Binary interactionsi

WithEntry#Exp.IntActNotes
Cdk5Q031143EBI-3904881,EBI-2008531From Rattus norvegicus.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi110970, 24 interactors
DIPiDIP-5720N
IntActiQ16620, 11 interactors
STRINGi9606.ENSP00000277120

Chemistry databases

BindingDBiQ16620

Structurei

Secondary structure

1822
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ16620
SMRiQ16620
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ16620

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
Domaini538 – 807Protein kinasePROSITE-ProRule annotationAdd BLAST270

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni455 – 466Interaction with MAPK8IP3/JIP3By similarityAdd BLAST12

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
InParanoidiQ16620
KOiK04360
OMAiCSCEIMW
PhylomeDBiQ16620
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
PF01462 LRRNT, 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 (7)i

Sequence statusi: Complete.

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

This entry describes 7 isoformsi produced by alternative splicing. AlignAdd to basket
Note: Additional isoforms seem to exist.
Isoform TrkB (identifier: Q16620-1) [UniParc]FASTAAdd to basket
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.

« Hide
        10         20         30         40         50
MSSWIRWHGP AMARLWGFCW LVVGFWRAAF ACPTSCKCSA SRIWCSDPSP
60 70 80 90 100
GIVAFPRLEP NSVDPENITE IFIANQKRLE IINEDDVEAY VGLRNLTIVD
110 120 130 140 150
SGLKFVAHKA FLKNSNLQHI NFTRNKLTSL SRKHFRHLDL SELILVGNPF
160 170 180 190 200
TCSCDIMWIK TLQEAKSSPD TQDLYCLNES SKNIPLANLQ IPNCGLPSAN
210 220 230 240 250
LAAPNLTVEE GKSITLSCSV AGDPVPNMYW DVGNLVSKHM NETSHTQGSL
260 270 280 290 300
RITNISSDDS GKQISCVAEN LVGEDQDSVN LTVHFAPTIT FLESPTSDHH
310 320 330 340 350
WCIPFTVKGN PKPALQWFYN GAILNESKYI CTKIHVTNHT EYHGCLQLDN
360 370 380 390 400
PTHMNNGDYT LIAKNEYGKD EKQISAHFMG WPGIDDGANP NYPDVIYEDY
410 420 430 440 450
GTAANDIGDT TNRSNEIPST DVTDKTGREH LSVYAVVVIA SVVGFCLLVM
460 470 480 490 500
LFLLKLARHS KFGMKGPASV ISNDDDSASP LHHISNGSNT PSSSEGGPDA
510 520 530 540 550
VIIGMTKIPV IENPQYFGIT NSQLKPDTFV QHIKRHNIVL KRELGEGAFG
560 570 580 590 600
KVFLAECYNL CPEQDKILVA VKTLKDASDN ARKDFHREAE LLTNLQHEHI
610 620 630 640 650
VKFYGVCVEG DPLIMVFEYM KHGDLNKFLR AHGPDAVLMA EGNPPTELTQ
660 670 680 690 700
SQMLHIAQQI AAGMVYLASQ HFVHRDLATR NCLVGENLLV KIGDFGMSRD
710 720 730 740 750
VYSTDYYRVG GHTMLPIRWM PPESIMYRKF TTESDVWSLG VVLWEIFTYG
760 770 780 790 800
KQPWYQLSNN EVIECITQGR VLQRPRTCPQ EVYELMLGCW QREPHMRKNI
810 820
KGIHTLLQNL AKASPVYLDI LG
Length:822
Mass (Da):91,999
Last modified:November 1, 1996 - v1
Checksum:i2FEB9159948F0D13
GO
Isoform TrkB-T1 (identifier: Q16620-2) [UniParc]FASTAAdd to basket

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

Note: Non-catalytic isoform.
Show »
Length:477
Mass (Da):53,051
Checksum:iC4A7F565BC88372F
GO
Isoform TrkB-T-Shc (identifier: Q16620-3) [UniParc]FASTAAdd to basket

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

Show »
Length:537
Mass (Da):59,167
Checksum:i5A8FA252A3871CC1
GO
Isoform 4 (identifier: Q16620-4) [UniParc]FASTAAdd to basket

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

Show »
Length:838
Mass (Da):93,826
Checksum:i130C95A9D8895432
GO
Isoform 5 (identifier: Q16620-5) [UniParc]FASTAAdd to basket

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

Show »
Length:553
Mass (Da):60,994
Checksum:iBD98221B9EE1A6C1
GO
Isoform TrkB-T-TK (identifier: Q16620-6) [UniParc]FASTAAdd to basket

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

Show »
Length:735
Mass (Da):81,569
Checksum:i5E0746BCCA281069
GO
Isoform TrkB-N-T1 (identifier: Q16620-7) [UniParc]FASTAAdd to basket

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

Show »
Length:321
Mass (Da):35,332
Checksum:i64C146AAB494744E
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_041470138L → F in a lung adenocarcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_016320309G → R1 Publication1
Natural variantiVAR_011973338N → Y. Corresponds to variant dbSNP:rs1047856Ensembl.1
Natural variantiVAR_080659434Y → C in EIEE58; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs886041091EnsemblClinVar.1
Natural variantiVAR_080660444 – 822Missing in OBHD. 1 PublicationAdd BLAST379
Natural variantiVAR_049715545G → V. Corresponds to variant dbSNP:rs1075108Ensembl.1
Natural variantiVAR_046518697M → I in a lung carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_046519699R → G in a lung carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_080661704T → I in OBHD; unknown pathological significance. 1 Publication1
Natural variantiVAR_065890706Y → C in OBHD; expressed normally on the cell surface; results in markedly impaired ligand-induced phosphorylation as well as impaired downstream MAPK1 phosphorylation. 1 PublicationCorresponds to variant dbSNP:rs121434633Ensembl.1
Natural variantiVAR_046520718R → C in a lung carcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs1324578301Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0421771 – 156Missing in isoform TrkB-N-T1. 1 PublicationAdd BLAST156
Alternative sequenceiVSP_041942465K → KDFSWFGFGKVKSRQGV in isoform 4 and isoform 5. 1 Publication1
Alternative sequenceiVSP_002901467 – 477PASVISNDDDS → FVLFHKIPLDG in isoform TrkB-T1 and isoform TrkB-N-T1. 6 PublicationsAdd BLAST11
Alternative sequenceiVSP_002902478 – 822Missing in isoform TrkB-T1 and isoform TrkB-N-T1. 6 PublicationsAdd BLAST345
Alternative sequenceiVSP_002903529 – 537FVQHIKRHN → WPRGSPKTA in isoform TrkB-T-Shc and isoform 5. 1 Publication9
Alternative sequenceiVSP_002904538 – 822Missing in isoform TrkB-T-Shc and isoform 5. 1 PublicationAdd BLAST285
Alternative sequenceiVSP_042178710 – 735GGHTM…TTESD → SSCADQRPQGPLSLRDPCCI CLLRLS in isoform TrkB-T-TK. 1 PublicationAdd BLAST26
Alternative sequenceiVSP_042179736 – 822Missing in isoform TrkB-T-TK. 1 PublicationAdd BLAST87

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
AL390777 Genomic DNA No translation available.
AL445532 Genomic DNA No translation available.
AL596132 Genomic DNA No translation available.
CH471089 Genomic DNA Translation: EAW62688.1
BC031835 mRNA Translation: AAH31835.1
CCDSiCCDS35050.1 [Q16620-1]
CCDS35051.1 [Q16620-5]
CCDS35052.1 [Q16620-3]
CCDS35053.1 [Q16620-2]
CCDS6671.1 [Q16620-4]
PIRiA56853
I73631
RefSeqiNP_001007098.1, NM_001007097.2 [Q16620-2]
NP_001018074.1, NM_001018064.2 [Q16620-1]
NP_001018075.1, NM_001018065.2 [Q16620-5]
NP_001018076.1, NM_001018066.2 [Q16620-3]
NP_006171.2, NM_006180.4 [Q16620-4]
XP_005252058.1, XM_005252001.2 [Q16620-4]
XP_005252060.1, XM_005252003.2 [Q16620-4]
XP_005252061.1, XM_005252004.2 [Q16620-4]
XP_005252063.1, XM_005252006.3 [Q16620-5]
XP_005252064.1, XM_005252007.3 [Q16620-2]
XP_011517020.1, XM_011518718.2 [Q16620-1]
XP_011517022.1, XM_011518720.2 [Q16620-3]
XP_016870240.1, XM_017014751.1 [Q16620-4]
XP_016870241.1, XM_017014752.1 [Q16620-1]
XP_016870242.1, XM_017014753.1 [Q16620-1]
XP_016870243.1, XM_017014754.1 [Q16620-1]
XP_016870244.1, XM_017014755.1 [Q16620-5]
XP_016870245.1, XM_017014756.1 [Q16620-5]
XP_016870246.1, XM_017014757.1 [Q16620-3]
XP_016870247.1, XM_017014758.1 [Q16620-2]
XP_016870248.1, XM_017014759.1 [Q16620-2]
XP_016870249.1, XM_017014760.1 [Q16620-2]
XP_016870250.1, XM_017014761.1 [Q16620-2]
UniGeneiHs.494312
Hs.712776

Genome annotation databases

EnsembliENST00000277120; ENSP00000277120; ENSG00000148053 [Q16620-4]
ENST00000304053; ENSP00000306167; ENSG00000148053 [Q16620-5]
ENST00000323115; ENSP00000314586; ENSG00000148053 [Q16620-1]
ENST00000359847; ENSP00000352906; ENSG00000148053 [Q16620-2]
ENST00000376208; ENSP00000365381; ENSG00000148053 [Q16620-3]
ENST00000376213; ENSP00000365386; ENSG00000148053 [Q16620-1]
ENST00000376214; ENSP00000365387; ENSG00000148053 [Q16620-4]
ENST00000395882; ENSP00000379221; ENSG00000148053 [Q16620-2]
GeneIDi4915
KEGGihsa:4915
UCSCiuc004anz.1 human [Q16620-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
AL390777 Genomic DNA No translation available.
AL445532 Genomic DNA No translation available.
AL596132 Genomic DNA No translation available.
CH471089 Genomic DNA Translation: EAW62688.1
BC031835 mRNA Translation: AAH31835.1
CCDSiCCDS35050.1 [Q16620-1]
CCDS35051.1 [Q16620-5]
CCDS35052.1 [Q16620-3]
CCDS35053.1 [Q16620-2]
CCDS6671.1 [Q16620-4]
PIRiA56853
I73631
RefSeqiNP_001007098.1, NM_001007097.2 [Q16620-2]
NP_001018074.1, NM_001018064.2 [Q16620-1]
NP_001018075.1, NM_001018065.2 [Q16620-5]
NP_001018076.1, NM_001018066.2 [Q16620-3]
NP_006171.2, NM_006180.4 [Q16620-4]
XP_005252058.1, XM_005252001.2 [Q16620-4]
XP_005252060.1, XM_005252003.2 [Q16620-4]
XP_005252061.1, XM_005252004.2 [Q16620-4]
XP_005252063.1, XM_005252006.3 [Q16620-5]
XP_005252064.1, XM_005252007.3 [Q16620-2]
XP_011517020.1, XM_011518718.2 [Q16620-1]
XP_011517022.1, XM_011518720.2 [Q16620-3]
XP_016870240.1, XM_017014751.1 [Q16620-4]
XP_016870241.1, XM_017014752.1 [Q16620-1]
XP_016870242.1, XM_017014753.1 [Q16620-1]
XP_016870243.1, XM_017014754.1 [Q16620-1]
XP_016870244.1, XM_017014755.1 [Q16620-5]
XP_016870245.1, XM_017014756.1 [Q16620-5]
XP_016870246.1, XM_017014757.1 [Q16620-3]
XP_016870247.1, XM_017014758.1 [Q16620-2]
XP_016870248.1, XM_017014759.1 [Q16620-2]
XP_016870249.1, XM_017014760.1 [Q16620-2]
XP_016870250.1, XM_017014761.1 [Q16620-2]
UniGeneiHs.494312
Hs.712776

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1HCFX-ray2.70X/Y286-383[»]
1WWBX-ray2.10X283-385[»]
2MFQNMR-B497-519[»]
4ASZX-ray1.70A527-822[»]
4AT3X-ray1.77A527-822[»]
4AT4X-ray2.36A527-822[»]
4AT5X-ray1.71A527-822[»]
5MO9X-ray2.59X278-426[»]
ProteinModelPortaliQ16620
SMRiQ16620
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110970, 24 interactors
DIPiDIP-5720N
IntActiQ16620, 11 interactors
STRINGi9606.ENSP00000277120

Chemistry databases

BindingDBiQ16620
ChEMBLiCHEMBL4898
DrugBankiDB00321 Amitriptyline
GuidetoPHARMACOLOGYi1818

PTM databases

GlyConnecti1029
iPTMnetiQ16620
PhosphoSitePlusiQ16620

Polymorphism and mutation databases

BioMutaiNTRK2
DMDMi2497560

Proteomic databases

PaxDbiQ16620
PeptideAtlasiQ16620
PRIDEiQ16620
ProteomicsDBi60955
60956 [Q16620-2]
60957 [Q16620-3]
60958 [Q16620-4]
60959 [Q16620-5]
60960 [Q16620-6]
60961 [Q16620-7]

Protocols and materials databases

DNASUi4915
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000277120; ENSP00000277120; ENSG00000148053 [Q16620-4]
ENST00000304053; ENSP00000306167; ENSG00000148053 [Q16620-5]
ENST00000323115; ENSP00000314586; ENSG00000148053 [Q16620-1]
ENST00000359847; ENSP00000352906; ENSG00000148053 [Q16620-2]
ENST00000376208; ENSP00000365381; ENSG00000148053 [Q16620-3]
ENST00000376213; ENSP00000365386; ENSG00000148053 [Q16620-1]
ENST00000376214; ENSP00000365387; ENSG00000148053 [Q16620-4]
ENST00000395882; ENSP00000379221; ENSG00000148053 [Q16620-2]
GeneIDi4915
KEGGihsa:4915
UCSCiuc004anz.1 human [Q16620-1]

Organism-specific databases

CTDi4915
DisGeNETi4915
EuPathDBiHostDB:ENSG00000148053.15
GeneCardsiNTRK2
HGNCiHGNC:8032 NTRK2
HPAiCAB010346
HPA007637
MalaCardsiNTRK2
MIMi600456 gene
613886 phenotype
617830 phenotype
neXtProtiNX_Q16620
OpenTargetsiENSG00000148053
Orphaneti251612 Pilocytic astrocytoma
PharmGKBiPA31818
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1026 Eukaryota
ENOG410YGKQ LUCA
GeneTreeiENSGT00760000118818
HOGENOMiHOG000264255
HOVERGENiHBG056735
InParanoidiQ16620
KOiK04360
OMAiCSCEIMW
PhylomeDBiQ16620
TreeFamiTF106465

Enzyme and pathway databases

BRENDAi2.7.10.1 2681
ReactomeiR-HSA-187024 NGF-independant TRKA activation
R-HSA-9024909 BDNF activates NTRK2 (TRKB) signaling
R-HSA-9025046 NTF3 activates NTRK2 (TRKB) signaling
R-HSA-9026357 NTF4 activates NTRK2 (TRKB) signaling
R-HSA-9026519 Activated NTRK2 signals through RAS
R-HSA-9026527 Activated NTRK2 signals through PLCG1
R-HSA-9028335 Activated NTRK2 signals through PI3K
R-HSA-9028731 Activated NTRK2 signals through FRS2 and FRS3
R-HSA-9032500 Activated NTRK2 signals through FYN
R-HSA-9032759 NTRK2 activates RAC1
R-HSA-9032845 Activated NTRK2 signals through CDK5
SignaLinkiQ16620
SIGNORiQ16620

Miscellaneous databases

ChiTaRSiNTRK2 human
EvolutionaryTraceiQ16620
GeneWikiiTrkB_receptor
GenomeRNAii4915
PROiPR:Q16620
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000148053 Expressed in 222 organ(s), highest expression level in hypothalamus
CleanExiHS_NTRK2
ExpressionAtlasiQ16620 baseline and differential
GenevisibleiQ16620 HS

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
PF01462 LRRNT, 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
ProtoNetiSearch...

Entry informationi

Entry nameiNTRK2_HUMAN
AccessioniPrimary (citable) accession number: Q16620
Secondary accession number(s): B1ANZ4
, B4DFV9, Q16675, Q59GJ1, Q8WXJ5, Q8WXJ6, Q8WXJ7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: October 10, 2018
This is version 207 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  7. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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