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Reviewed, UniProtKB/Swiss-Prot Q16620 (NTRK2_HUMAN)

Last modified November 25, 2008. Version 105. Feed History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    BDNF/NT-3 growth factors receptor
    EC=2.7.10.1
Alternative name(s):
    Neurotrophic tyrosine kinase receptor type 2
    TrkB tyrosine kinase
    GP145-TrkB
      Short name=Trk-B
Gene names
Name: NTRK2
Synonyms: TRKB
OrganismHomo sapiens (Human)
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 for brain-derived neurotrophic factor (BDNF), neurotrophin-3 and neurotrophin-4/5 but not nerve growth factor (NGF). Involved in the development and/or maintenance of the nervous system. This is a tyrosine-protein kinase receptor. Known substrates for the TRK receptors are SHC1, PI-3 kinase, and PLC-gamma-1.

Catalytic activity

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

Subunit structure

Exists in a dynamic equilibrium between monomeric (low affinity) and dimeric (high affinity) structures. Binds SH2B2. Interacts with SQSTM1 and ARMS By similarity.

Subcellular location

Membrane; Single-pass type I membrane protein.

Tissue specificity

Isoform TrkB is widely expressed, mainly in the nervous tissue. In the CNS, expression is observed in the cerebral cortex, hippocampus, thalamus, choroid plexus, granular layer of the cerebellum, brain stem, and spinal cord. In the peripheral nervous system, it is expressed in many cranial ganglia, the ophtalmic nerve, the vestibular system, multiple facial structures, the submaxillary glands, and dorsal root ganglia. Isoform TrkB-T1 is expressed in multiple tissues, mainly in brain, pancreas, kidney and heart. Isoform TrkB-T-Shc is predominantly expressed in brain.

Post-translational modification

Ligand-mediated auto-phosphorylation.

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.

Contains 2 Ig-like C2-type (immunoglobulin-like) domains.

Contains 2 LRR (leucine-rich) repeats.

Contains 1 protein kinase domain.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Notes: Additional isoforms seem to exist.
Isoform TrkB (identifier: Q16620-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform TrkB-T1 (identifier: Q16620-2)

The sequence of this isoform differs from the canonical sequence as follows:
     467-477: PASVISNDDDS → FVLFHKIPLDG
     478-822: Missing.
Isoform TrkB-T-Shc (identifier: Q16620-3)

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

Sequence annotation (Features)

Feature 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 – 45424 Potential
Topological domain455 – 822368Cytoplasmic Potential
Repeat72 – 9322LRR 1
Repeat96 – 11722LRR 2
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
Site8171Interaction with PLC-gamma-1 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...)
Glycosylation951N-linked (GlcNAc...) Potential
Glycosylation1211N-linked (GlcNAc...)
Glycosylation1781N-linked (GlcNAc...) Potential
Glycosylation2051N-linked (GlcNAc...) Potential
Glycosylation2411N-linked (GlcNAc...) Potential
Glycosylation2541N-linked (GlcNAc...)
Glycosylation2801N-linked (GlcNAc...) Potential
Glycosylation3251N-linked (GlcNAc...) Potential
Glycosylation3381N-linked (GlcNAc...) Potential
Glycosylation4121N-linked (GlcNAc...) Potential
Disulfide bond32 ↔ 38
Disulfide bond36 ↔ 45
Disulfide bond152 ↔ 176
Disulfide bond154 ↔ 194
Disulfide bond218 ↔ 266
Disulfide bond302 ↔ 345

Natural variations

Alternative sequence467 – 47711PASVISNDDDS → FVLFHKIPLDG in isoform TrkB-T1.
VSP_002901
Alternative sequence478 – 822345Missing in isoform TrkB-T1.
VSP_002902
Alternative sequence529 – 5379FVQHIKRHN → WPRGSPKTA in isoform TrkB-T-Shc.
VSP_002903
Alternative sequence538 – 822285Missing in isoform TrkB-T-Shc.
VSP_002904
Natural variant1381L → F in a lung adenocarcinoma sample; somatic mutation.
VAR_041470
Natural variant3091G → R
VAR_016320
Natural variant3381N → Y: dbSNP rs1047856.
VAR_011973
Natural variant6971M → I in a lung carcinoma sample; somatic mutation.
VAR_046518
Natural variant6991R → G in a lung carcinoma sample; somatic mutation.
VAR_046519
Natural variant7181R → C in a lung carcinoma sample; somatic mutation.
VAR_046520

Secondary structure

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

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 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 »

47753,051
Isoform TrkB-T-Shc [UniParc].

Checksum: 5A8FA252A3871CC1
Show »

53759,167

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: 7789988] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TRKB).
Tissue: Hippocampus.
[2]"Human trks: molecular cloning, tissue distribution, and expression of extracellular domain immunoadhesins."
Shelton D.L., Sutherland J., Gripp J., Camerato T., Armanini M.P., Phillips H.S., Carroll K., Spencer S.D., Levinson A.D.
J. Neurosci. 15:477-491(1995) [PubMed: 7823156] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS TRKB AND TRKB-T1).
Tissue: Brain.
[3]"Cloning of a non-catalytic form of human trkB and distribution of messenger RNA for trkB in human brain."
Allen S.J., Dawbarn D., Eckford S.D., Wilcock G.K., Ashcroft M., Colebrook S.M., Feeney R., Macgowan S.H.
Neuroscience 60:825-834(1994) [PubMed: 7936202] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TRKB-T1).
Tissue: Hippocampus.
[4]"Analysis of the human TrkB gene genomic organization reveals novel TrkB isoforms, unusual gene length, and splicing mechanism."
Stoilov P., Castren E., Stamm S.
Biochem. Biophys. Res. Commun. 290:1054-1065(2002) [PubMed: 11798182] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS TRKB; TRKB-T1 AND TRKB-T-SHC).
[5]"Full length truncated TrkB sequence identified in a screen for genes regulated by ischemic preconditioning."
Steinbeck J.A., Thomsen S., Wessig J., Leypoldt F., Lewerenz J., Methner A.
Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TRKB-T1), VARIANT ARG-309.
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM TRKB-T1).
Tissue: Brain.
[7]"Extracellular domain of neurotrophin receptor trkB: disulfide structure, N-glycosylation sites, and ligand binding."
Haniu M., Talvenheimo J., Le J., Katta V., Welcher A., Rohde M.F.
Arch. Biochem. Biophys. 322:256-264(1995) [PubMed: 7574684] [Abstract]
Cited for: DISULFIDE BONDS.
[8]"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
J. Proteome Res. 4:2070-2080(2005) [PubMed: 16335952] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-67; ASN-121 AND ASN-254, MASS SPECTROMETRY.
Tissue: Plasma.
[9]"Crystal structures of the neurotrophin-binding domain of TrkA, TrkB and TrkC."
Ultsch M.H., Wiesmann C., Simmons L.C., Henrich J., Yang M., Reilly D., Bass S.H., de Vos A.M.
J. Mol. Biol. 290:149-159(1999) [PubMed: 10388563] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 283-385.
[10]"Specificity in Trk receptor:neurotrophin interactions: the crystal structure of TrkB-d5 in complex with neurotrophin-4/5."
Banfield M.J., Naylor R.L., Robertson A.G., Allen S.J., Dawbarn D., Brady R.L.
Structure 9:1191-1199(2001) [PubMed: 11738045] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 284-383.
[11]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. 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.,