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Q16620 (NTRK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 167. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length822 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 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. 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

Obesity hyperphagia and developmental delay (OHPDD) [MIM:613886]: A disorder characterized by early-onset obesity, hyperphagia, and severe developmental delay in motor function, speech, and language.
Note: The disease is caused by mutations affecting the gene represented in this entry. 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 processDifferentiation
Neurogenesis
   Cellular componentCell membrane
Endosome
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
Obesity
   DomainImmunoglobulin domain
Leucine-rich repeat
Repeat
Signal
Transmembrane
Transmembrane helix
   LigandATP-binding
Nucleotide-binding
   Molecular functionDevelopmental protein
Kinase
Receptor
Transferase
Tyrosine-protein kinase
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of adenylate cyclase activity

Traceable author statement. Source: Reactome

aging

Inferred from electronic annotation. Source: Ensembl

brain-derived neurotrophic factor receptor signaling pathway

Inferred from mutant phenotype Ref.17. Source: UniProtKB

calcium-mediated signaling using intracellular calcium source

Inferred from electronic annotation. Source: Ensembl

central nervous system neuron development

Inferred from sequence or structural similarity. Source: UniProtKB

cerebral cortex development

Inferred from sequence or structural similarity. Source: UniProtKB

feeding behavior

Inferred from electronic annotation. Source: Ensembl

glutamate secretion

Inferred from electronic annotation. Source: Ensembl

learning

Inferred from sequence or structural similarity. Source: UniProtKB

long-term memory

Inferred from electronic annotation. Source: Ensembl

long-term synaptic potentiation

Inferred from electronic annotation. Source: Ensembl

mechanoreceptor differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of anoikis

Inferred from electronic annotation. Source: Ensembl

negative regulation of neuron apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

neuromuscular junction development

Inferred from electronic annotation. Source: Ensembl

neuron differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

neuron migration

Inferred from sequence or structural similarity. Source: UniProtKB

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

oligodendrocyte differentiation

Inferred from electronic annotation. Source: Ensembl

peripheral nervous system neuron development

Inferred from electronic annotation. Source: Ensembl

positive regulation of MAPK cascade

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of axonogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of gene expression

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of neuron projection development

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of phosphatidylinositol 3-kinase signaling

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of synaptic transmission, glutamatergic

Inferred from electronic annotation. Source: Ensembl

protein autophosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of Rac GTPase activity

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of dendrite development

Inferred from electronic annotation. Source: Ensembl

regulation of neurotransmitter secretion

Inferred from electronic annotation. Source: Ensembl

regulation of protein kinase B signaling

Inferred from electronic annotation. Source: Ensembl

response to auditory stimulus

Inferred from electronic annotation. Source: Ensembl

retinal rod cell development

Inferred from electronic annotation. Source: Ensembl

transmembrane receptor protein tyrosine kinase signaling pathway

Traceable author statement. Source: Reactome

vasculogenesis

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcell surface

Inferred from electronic annotation. Source: Ensembl

cytosol

Inferred from electronic annotation. Source: Ensembl

dendritic spine

Inferred from electronic annotation. Source: Ensembl

endosome membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

excitatory synapse

Inferred from electronic annotation. Source: Ensembl

growth cone

Inferred from electronic annotation. Source: Ensembl

integral component of plasma membrane

Inferred from direct assay Ref.17. Source: UniProtKB

neuronal cell body

Inferred from electronic annotation. Source: Ensembl

postsynaptic density

Inferred from electronic annotation. Source: Ensembl

postsynaptic membrane

Inferred from electronic annotation. Source: Ensembl

presynaptic active zone

Inferred from electronic annotation. Source: Ensembl

receptor complex

Inferred from direct assay PubMed 23382219. Source: MGI

terminal bouton

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

brain-derived neurotrophic factor binding

Inferred from sequence or structural similarity. Source: UniProtKB

brain-derived neurotrophic factor-activated receptor activity

Inferred from mutant phenotype Ref.17. Source: UniProtKB

neurotrophin binding

Inferred from direct assay Ref.16. Source: UniProtKB

protein homodimerization activity

Inferred from sequence or structural similarity. Source: UniProtKB

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3131
Chain32 – 822791BDNF/NT-3 growth factors receptor
PRO_0000016727

Regions

Topological domain32 – 430399Extracellular Potential
Transmembrane431 – 45424Helical; Potential
Topological domain455 – 822368Cytoplasmic Potential
Domain32 – 6130LRRNT
Repeat92 – 11322LRR 1
Repeat116 – 13722LRR 2
Domain148 – 19649LRRCT
Domain197 – 28286Ig-like C2-type 1
Domain295 – 36571Ig-like C2-type 2
Domain538 – 807270Protein kinase
Nucleotide binding544 – 5529ATP By similarity

Sites

Active site6761Proton acceptor By similarity
Binding site5721ATP By similarity
Site5161Interaction with SHC1 By similarity
Site7061Interaction with SH2D1A By similarity
Site8171Interaction with PLCG1 By similarity

Amino acid modifications

Modified residue5161Phosphotyrosine; by autocatalysis By similarity
Modified residue7021Phosphotyrosine; by autocatalysis By similarity
Modified residue7061Phosphotyrosine; by autocatalysis By similarity
Modified residue7071Phosphotyrosine; by autocatalysis By similarity
Modified residue8171Phosphotyrosine; by autocatalysis By similarity
Glycosylation671N-linked (GlcNAc...) Ref.11 Ref.13
Glycosylation951N-linked (GlcNAc...) Ref.11
Glycosylation1211N-linked (GlcNAc...) Ref.11 Ref.13
Glycosylation1781N-linked (GlcNAc...) Ref.11
Glycosylation2051N-linked (GlcNAc...) Ref.11
Glycosylation2411N-linked (GlcNAc...) Ref.11
Glycosylation2541N-linked (GlcNAc...) Ref.11 Ref.13
Glycosylation2801N-linked (GlcNAc...) Ref.11
Glycosylation3251N-linked (GlcNAc...) Potential
Glycosylation3381N-linked (GlcNAc...) Ref.11
Glycosylation4121N-linked (GlcNAc...) Ref.11
Disulfide bond32 ↔ 38 Ref.11
Disulfide bond36 ↔ 45 Ref.11
Disulfide bond152 ↔ 176 Ref.11
Disulfide bond154 ↔ 194 Ref.11
Disulfide bond218 ↔ 266 Ref.11
Disulfide bond302 ↔ 345 Ref.11

Natural variations

Alternative sequence1 – 156156Missing in isoform TrkB-N-T1.
VSP_042177
Alternative sequence4651K → KDFSWFGFGKVKSRQGV in isoform 4 and isoform 5.
VSP_041942
Alternative sequence467 – 47711PASVISNDDDS → FVLFHKIPLDG in isoform TrkB-T1 and isoform TrkB-N-T1.
VSP_002901
Alternative sequence478 – 822345Missing in isoform TrkB-T1 and isoform TrkB-N-T1.
VSP_002902
Alternative sequence529 – 5379FVQHIKRHN → WPRGSPKTA in isoform TrkB-T-Shc and isoform 5.
VSP_002903
Alternative sequence538 – 822285Missing in isoform TrkB-T-Shc and isoform 5.
VSP_002904
Alternative sequence710 – 73526GGHTM…TTESD → SSCADQRPQGPLSLRDPCCI CLLRLS in isoform TrkB-T-TK.
VSP_042178
Alternative sequence736 – 82287Missing in isoform TrkB-T-TK.
VSP_042179
Natural variant1381L → F in a lung adenocarcinoma sample; somatic mutation. Ref.18
VAR_041470
Natural variant3091G → R. Ref.5
VAR_016320
Natural variant3381N → Y.
Corresponds to variant rs1047856 [ dbSNP | Ensembl ].
VAR_011973
Natural variant5451G → V.
Corresponds to variant rs1075108 [ dbSNP | Ensembl ].
VAR_049715
Natural variant6971M → I in a lung carcinoma sample; somatic mutation. Ref.19
VAR_046518
Natural variant6991R → G in a lung carcinoma sample; somatic mutation. Ref.19
VAR_046519
Natural variant7061Y → 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
Natural variant7181R → C in a lung carcinoma sample; somatic mutation. Ref.19
VAR_046520

Secondary structure

.............................................................................. 822
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform TrkB (gp145-TrkB) [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 2FEB9159948F0D13

FASTA82291,999
        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 

« Hide

Isoform TrkB-T1 [UniParc].

Checksum: C4A7F565BC88372F
Show »

FASTA47753,051
Isoform TrkB-T-Shc [UniParc].

Checksum: 5A8FA252A3871CC1
Show »

FASTA53759,167
Isoform 4 [UniParc].

Checksum: 130C95A9D8895432
Show »

FASTA83893,826
Isoform 5 [UniParc].

Checksum: BD98221B9EE1A6C1
Show »

FASTA55360,994
Isoform TrkB-T-TK [UniParc].

Checksum: 5E0746BCCA281069
Show »

FASTA73581,569
Isoform TrkB-N-T1 [UniParc].

Checksum: 64C146AAB494744E
Show »

FASTA32135,332

References

« Hide '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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-67; ASN-121 AND ASN-254.
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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: VARIANT OHPDD CYS-706, CHARACTERIZATION OF VARIANT OHPDD CYS-706, 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. expand/collapse author list , 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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: VARIANTS ILE-697; GLY-699 AND CYS-718.
+Additional computationally mapped references.

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.
CCDSCCDS35050.1. [Q16620-1]
CCDS35051.1. [Q16620-5]
CCDS35052.1. [Q16620-3]
CCDS35053.1. [Q16620-2]
CCDS6671.1. [Q16620-4]
PIRA56853.
I73631.
RefSeqNP_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_005252001.1. [Q16620-4]
XP_005252060.1. XM_005252003.1. [Q16620-4]
XP_005252061.1. XM_005252004.1. [Q16620-4]
XP_005252063.1. XM_005252006.2. [Q16620-5]
XP_005252064.1. XM_005252007.1. [Q16620-2]
UniGeneHs.494312.
Hs.712776.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
ProteinModelPortalQ16620.
SMRQ16620. Positions 29-385, 527-822.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110970. 22 interactions.
DIPDIP-5720N.
IntActQ16620. 4 interactions.
MINTMINT-156841.
STRING9606.ENSP00000277120.

Chemistry

BindingDBQ16620.
ChEMBLCHEMBL4898.
GuidetoPHARMACOLOGY1818.

PTM databases

PhosphoSiteQ16620.

Polymorphism databases

DMDM2497560.

Proteomic databases

PaxDbQ16620.
PRIDEQ16620.

Protocols and materials databases

DNASU4915.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000277120; 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]
ENST00000395866; ENSP00000379207; ENSG00000148053. [Q16620-7]
ENST00000395882; ENSP00000379221; ENSG00000148053. [Q16620-2]
GeneID4915.
KEGGhsa:4915.
UCSCuc004any.1. human. [Q16620-6]
uc004anz.1. human. [Q16620-4]
uc004aoa.1. human. [Q16620-1]
uc011lsz.2. human. [Q16620-5]
uc011lta.2. human. [Q16620-3]
uc011ltb.1. human. [Q16620-7]

Organism-specific databases

CTD4915.
GeneCardsGC09P087283.
HGNCHGNC:8032. NTRK2.
HPACAB010346.
HPA007637.
MIM600456. gene.
613886. phenotype.
neXtProtNX_Q16620.
Orphanet251612. Pilocytic astrocytoma.
PharmGKBPA31818.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000264255.
HOVERGENHBG056735.
KOK04360.
OMACEIMWIK.
OrthoDBEOG7QG43C.
PhylomeDBQ16620.
TreeFamTF106465.

Enzyme and pathway databases

BRENDA2.7.10.1. 2681.
ReactomeREACT_111102. Signal Transduction.
SignaLinkQ16620.

Gene expression databases

ArrayExpressQ16620.
BgeeQ16620.
CleanExHS_NTRK2.
GenevestigatorQ16620.

Family and domain databases

Gene3D2.60.40.10. 2 hits.
InterProIPR000483. Cys-rich_flank_reg_C.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003598. Ig_sub2.
IPR011009. Kinase-like_dom.
IPR001611. Leu-rich_rpt.
IPR000372. LRR-contain_N.
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.
[Graphical view]
PfamPF07679. I-set. 2 hits.
PF13855. LRR_8. 1 hit.
PF01462. LRRNT. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSPR01939. NTKRECEPTOR.
PR01941. NTKRECEPTOR2.
PR00109. TYRKINASE.
SMARTSM00408. IGc2. 1 hit.
SM00082. LRRCT. 1 hit.
SM00013. LRRNT. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS50835. 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]
ProtoNetSearch...

Other

EvolutionaryTraceQ16620.
GeneWikiTrkB_receptor.
GenomeRNAi4915.
NextBio18915.
PROQ16620.
SOURCESearch...

Entry information

Entry nameNTRK2_HUMAN
AccessionPrimary (citable) accession number: Q16620
Secondary accession number(s): B1ANZ4 expand/collapse secondary AC list , B4DFV9, Q16675, Q59GJ1, Q8WXJ5, Q8WXJ6, Q8WXJ7
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: July 9, 2014
This is version 167 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM