LOCUS       NP_006171                838 aa            linear   PRI 30-APR-2025
DEFINITION  BDNF/NT-3 growth factors receptor isoform a precursor [Homo
            sapiens].
ACCESSION   NP_006171 NP_001368857 XP_005252059
VERSION     NP_006171.2
DBSOURCE    REFSEQ: accession NM_006180.6
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 838)
  AUTHORS   Gupta,R., Dittmeier,M., Wohlleben,G., Nickl,V., Bischler,T.,
            Luzak,V., Wegat,V., Doll,D., Sodmann,A., Bady,E., Langlhofer,G.,
            Wachter,B., Havlicek,S., Gupta,J., Horn,E., Luningschror,P.,
            Villmann,C., Polat,B., Wischhusen,J., Monoranu,C.M., Kuper,J. and
            Blum,R.
  TITLE     Atypical cellular responses mediated by intracellular constitutive
            active TrkB (NTRK2) kinase domains and a solely intracellular
            NTRK2-fusion oncogene
  JOURNAL   Cancer Gene Ther 31 (9), 1357-1379 (2024)
   PUBMED   39039193
  REMARK    GeneRIF: Atypical cellular responses mediated by intracellular
            constitutive active TrkB (NTRK2) kinase domains and a solely
            intracellular NTRK2-fusion oncogene.
REFERENCE   2  (residues 1 to 838)
  AUTHORS   Zhang,X., Zhang,Y., Yan,H., Yu,H., Zhang,D., Mattay,V.S., Tan,H.Y.
            and Yue,W.
  TITLE     Childhood urbanicity is associated with emotional episodic
            memory-related striatal function and common variation in NTRK2
  JOURNAL   BMC Med 22 (1), 146 (2024)
   PUBMED   38561734
  REMARK    GeneRIF: Childhood urbanicity is associated with emotional episodic
            memory-related striatal function and common variation in NTRK2.
            Publication Status: Online-Only
REFERENCE   3  (residues 1 to 838)
  AUTHORS   Ikhlef,L., Yassine,M., Chandouri,B., Riviere,L., Naves,T.,
            Dmytruk,N., Gachard,N., Jauberteau,M.O. and Gallet,P.F.
  TITLE     Targeting the NTSR2/TrkB oncogenic pathway in chronic lymphocytic
            leukemia
  JOURNAL   Sci Rep 14 (1), 6084 (2024)
   PUBMED   38480783
  REMARK    GeneRIF: Targeting the NTSR2/TrkB oncogenic pathway in chronic
            lymphocytic leukemia.
            Publication Status: Online-Only
REFERENCE   4  (residues 1 to 838)
  AUTHORS   Wang,Y., Liang,J., Xu,B., Yang,J., Wu,Z. and Cheng,L.
  TITLE     TrkB/BDNF signaling pathway and its small molecular agonists in CNS
            injury
  JOURNAL   Life Sci 336, 122282 (2024)
   PUBMED   38008209
  REMARK    GeneRIF: TrkB/BDNF signaling pathway and its small molecular
            agonists in CNS injury.
            Review article
REFERENCE   5  (residues 1 to 838)
  AUTHORS   Luberg,K., Wong,J., Weickert,C.S. and Timmusk,T.
  TITLE     Human TrkB gene: novel alternative transcripts, protein isoforms
            and expression pattern in the prefrontal cerebral cortex during
            postnatal development
  JOURNAL   J Neurochem 113 (4), 952-964 (2010)
   PUBMED   20193039
  REMARK    GeneRIF: Identification of 36 potential TrkB protein isoforms
            suggests high complexity in the synthesis, regulation and function
            of this important neurotrophin receptor emphasizing the need for
            further study of these novel TrkB variants.
REFERENCE   6  (residues 1 to 838)
  AUTHORS   Stoilov,P., Castren,E. and Stamm,S.
  TITLE     Analysis of the human TrkB gene genomic organization reveals novel
            TrkB isoforms, unusual gene length, and splicing mechanism
  JOURNAL   Biochem Biophys Res Commun 290 (3), 1054-1065 (2002)
   PUBMED   11798182
  REMARK    GeneRIF: analysis of TrkB gene reveals novel gene length and
            splicing mechanism
REFERENCE   7  (residues 1 to 838)
  AUTHORS   Haniu,M., Talvenheimo,J., Le,J., Katta,V., Welcher,A. and
            Rohde,M.F.
  TITLE     Extracellular domain of neurotrophin receptor trkB: disulfide
            structure, N-glycosylation sites, and ligand binding
  JOURNAL   Arch Biochem Biophys 322 (1), 256-264 (1995)
   PUBMED   7574684
REFERENCE   8  (residues 1 to 838)
  AUTHORS   Nakagawara,A., Liu,X.G., Ikegaki,N., White,P.S., Yamashiro,D.J.,
            Nycum,L.M., Biegel,J.A. and Brodeur,G.M.
  TITLE     Cloning and chromosomal localization of the human TRK-B tyrosine
            kinase receptor gene (NTRK2)
  JOURNAL   Genomics 25 (2), 538-546 (1995)
   PUBMED   7789988
REFERENCE   9  (residues 1 to 838)
  AUTHORS   Squinto,S.P., Stitt,T.N., Aldrich,T.H., Davis,S., Blanco,S.M.,
            RadzieJewski,C., Glass,D.J., Masiakowski,P., Furth,M.E.,
            Valenzuela,D.M., Distefano,P.S. and Yancopoulos,G.D.
  TITLE     trkB encodes a functional receptor for brain-derived neurotrophic
            factor and neurotrophin-3 but not nerve growth factor
  JOURNAL   Cell 65 (5), 885-893 (1991)
   PUBMED   1710174
REFERENCE   10 (residues 1 to 838)
  AUTHORS   Soppet,D., Escandon,E., Maragos,J., Middlemas,D.S., Reid,S.W.,
            Blair,J., Burton,L.E., Stanton,B.R., Kaplan,D.R., Hunter,T.,
            Nikolics,K. and Parada,L.F.
  TITLE     The neurotrophic factors brain-derived neurotrophic factor and
            neurotrophin-3 are ligands for the trkB tyrosine kinase receptor
  JOURNAL   Cell 65 (5), 895-903 (1991)
   PUBMED   1645620
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL390777.13, AL596132.7 and
            AL445532.8.
            This sequence is a reference standard in the RefSeqGene project.
            
            On or before Apr 20, 2020 this sequence version replaced
            NP_001368857.1, XP_005252059.1, NP_006171.1.
            
            Summary: This gene encodes a member of the neurotrophic tyrosine
            receptor kinase (NTRK) family. This kinase is a membrane-bound
            receptor that, upon neurotrophin binding, phosphorylates itself and
            members of the MAPK pathway. Signalling through this kinase leads
            to cell differentiation. Mutations in this gene have been
            associated with obesity and mood disorders. Alternative splicing
            results in multiple transcript variants. [provided by RefSeq, May
            2014].
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: AF410899.1, SRR1803616.57704.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA2154665, SAMEA2157437
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000277120.8/ ENSP00000277120.3
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      longest protein
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..838
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="9"
                     /map="9q21.33"
     Protein         1..838
                     /product="BDNF/NT-3 growth factors receptor isoform a
                     precursor"
                     /EC_number="2.7.10.1"
                     /note="BDNF/NT-3 growth factors receptor; tyrosine kinase
                     receptor B; BDNF-tropomyosine receptor kinase B;
                     tropomyosin-related kinase B; neurotrophic tyrosine kinase
                     receptor type 2"
                     /calculated_mol_wt=90147
     sig_peptide     1..31
                     /inference="COORDINATES: ab initio prediction:SignalP:6.0"
                     /calculated_mol_wt=3697
     Site            67
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:16335952,
                     ECO:0000269|PubMed:7574684; propagated from
                     UniProtKB/Swiss-Prot (Q16620.1)"
     Region          92..150
                     /region_name="LRR_8"
                     /note="Leucine rich repeat; pfam13855"
                     /db_xref="CDD:404697"
     Region          92..113
                     /region_name="LRR 1"
                     /note="propagated from UniProtKB/Swiss-Prot (Q16620.1)"
     Site            95
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:7574684; propagated from
                     UniProtKB/Swiss-Prot (Q16620.1)"
     Region          116..137
                     /region_name="LRR 2"
                     /note="propagated from UniProtKB/Swiss-Prot (Q16620.1)"
     Site            121
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:16335952,
                     ECO:0000269|PubMed:7574684; propagated from
                     UniProtKB/Swiss-Prot (Q16620.1)"
     Region          151..195
                     /region_name="LRRCT_2"
                     /note="Leucine rich repeat C-terminal motif; pfam16920"
                     /db_xref="CDD:465313"
     Site            178
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:7574684; propagated from
                     UniProtKB/Swiss-Prot (Q16620.1)"
     Region          205..283
                     /region_name="Ig"
                     /note="Immunoglobulin domain; cl11960"
                     /db_xref="CDD:472250"
     Site            205
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:7574684; propagated from
                     UniProtKB/Swiss-Prot (Q16620.1)"
     Region          214..218
                     /region_name="Ig strand B"
                     /note="Ig strand B [structural motif]"
                     /db_xref="CDD:409353"
     Region          227..230
                     /region_name="Ig strand C"
                     /note="Ig strand C [structural motif]"
                     /db_xref="CDD:409353"
     Site            241
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:7574684; propagated from
                     UniProtKB/Swiss-Prot (Q16620.1)"
     Region          245..252
                     /region_name="Ig strand E"
                     /note="Ig strand E [structural motif]"
                     /db_xref="CDD:409353"
     Site            254
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:16335952,
                     ECO:0000269|PubMed:7574684; propagated from
                     UniProtKB/Swiss-Prot (Q16620.1)"
     Region          262..268
                     /region_name="Ig strand F"
                     /note="Ig strand F [structural motif]"
                     /db_xref="CDD:409353"
     Region          276..279
                     /region_name="Ig strand G"
                     /note="Ig strand G [structural motif]"
                     /db_xref="CDD:409353"
     Site            280
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:7574684; propagated from
                     UniProtKB/Swiss-Prot (Q16620.1)"
     Region          286..379
                     /region_name="IgI_TrkB_d5"
                     /note="Fifth domain (immunoglobulin-like) of Trk receptor
                     TrkB; member of the I-set of Ig superfamily (IgSF)
                     domains; cd05855"
                     /db_xref="CDD:409441"
     Region          286..294
                     /region_name="Ig strand A"
                     /note="Ig strand A [structural motif]"
                     /db_xref="CDD:409441"
     Region          295..298
                     /region_name="Ig strand A'"
                     /note="Ig strand A' [structural motif]"
                     /db_xref="CDD:409441"
     Region          301..309
                     /region_name="Ig strand B"
                     /note="Ig strand B [structural motif]"
                     /db_xref="CDD:409441"
     Site            310
                     /site_type="other"
                     /note="interdomain interface [polypeptide binding]"
                     /db_xref="CDD:409441"
     Region          312..319
                     /region_name="Ig strand C"
                     /note="Ig strand C [structural motif]"
                     /db_xref="CDD:409441"
     Region          322..325
                     /region_name="Ig strand C'"
                     /note="Ig strand C' [structural motif]"
                     /db_xref="CDD:409441"
     Site            325
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (Q16620.1)"
     Region          330..335
                     /region_name="Ig strand D"
                     /note="Ig strand D [structural motif]"
                     /db_xref="CDD:409441"
     Site            order(335,349..350,353)
                     /site_type="other"
                     /note="receptor binding site [polypeptide binding]"
                     /db_xref="CDD:409441"
     Site            338
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:7574684; propagated from
                     UniProtKB/Swiss-Prot (Q16620.1)"
     Region          341..349
                     /region_name="Ig strand E"
                     /note="Ig strand E [structural motif]"
                     /db_xref="CDD:409441"
     Region          357..365
                     /region_name="Ig strand F"
                     /note="Ig strand F [structural motif]"
                     /db_xref="CDD:409441"
     Region          368..376
                     /region_name="Ig strand G"
                     /note="Ig strand G [structural motif]"
                     /db_xref="CDD:409441"
     Site            412
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:7574684; propagated from
                     UniProtKB/Swiss-Prot (Q16620.1)"
     Site            431..454
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (Q16620.1)"
     Region          491..514
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (Q16620.1)"
     Site            532
                     /site_type="other"
                     /note="Interaction with SHC1. /evidence=ECO:0000250;
                     propagated from UniProtKB/Swiss-Prot (Q16620.1)"
     Site            532
                     /site_type="phosphorylation"
                     /note="Phosphotyrosine, by autocatalysis.
                     /evidence=ECO:0000250|UniProtKB:P15209; propagated from
                     UniProtKB/Swiss-Prot (Q16620.1)"
     Region          548..835
                     /region_name="PTKc_TrkB"
                     /note="Catalytic domain of the Protein Tyrosine Kinase,
                     Tropomyosin Related Kinase B; cd05093"
                     /db_xref="CDD:270675"
     Site            order(560..564,568,586,588,633..636,639..640,692,696..697,
                     699,710,728..732,741,775)
                     /site_type="active"
                     /db_xref="CDD:270675"
     Site            order(560..561,563..564,568,586,588,633..636,639..640,
                     696..697,699,710)
                     /site_type="other"
                     /note="ATP binding site [chemical binding]"
                     /db_xref="CDD:270675"
     Site            order(692,696,728..732,741,775)
                     /site_type="other"
                     /note="polypeptide substrate binding site [polypeptide
                     binding]"
                     /db_xref="CDD:270675"
     Site            709..734
                     /site_type="other"
                     /note="activation loop (A-loop)"
                     /db_xref="CDD:270675"
     Site            718
                     /site_type="phosphorylation"
                     /note="Phosphotyrosine, by autocatalysis.
                     /evidence=ECO:0000250|UniProtKB:Q63604; propagated from
                     UniProtKB/Swiss-Prot (Q16620.1)"
     Site            722
                     /site_type="other"
                     /note="Interaction with SH2D1A. /evidence=ECO:0000250;
                     propagated from UniProtKB/Swiss-Prot (Q16620.1)"
     Site            722
                     /site_type="phosphorylation"
                     /note="Phosphotyrosine, by autocatalysis.
                     /evidence=ECO:0000250|UniProtKB:Q63604; propagated from
                     UniProtKB/Swiss-Prot (Q16620.1)"
     Site            723
                     /site_type="phosphorylation"
                     /note="Phosphotyrosine, by autocatalysis.
                     /evidence=ECO:0000250|UniProtKB:Q63604; propagated from
                     UniProtKB/Swiss-Prot (Q16620.1)"
     Site            833
                     /site_type="other"
                     /note="Interaction with PLCG1. /evidence=ECO:0000250;
                     propagated from UniProtKB/Swiss-Prot (Q16620.1)"
     Site            833
                     /site_type="phosphorylation"
                     /note="Phosphotyrosine, by autocatalysis.
                     /evidence=ECO:0000250|UniProtKB:Q63604; propagated from
                     UniProtKB/Swiss-Prot (Q16620.1)"
     CDS             1..838
                     /gene="NTRK2"
                     /gene_synonym="DEE58; EIEE58; GP145-TrkB; OBHD; trk-B;
                     TRKB"
                     /coded_by="NM_006180.6:533..3049"
                     /note="isoform a precursor is encoded by transcript
                     variant a"
                     /db_xref="CCDS:CCDS6671.1"
                     /db_xref="GeneID:4915"
                     /db_xref="HGNC:HGNC:8032"
                     /db_xref="MIM:600456"
ORIGIN      
        1 msswirwhgp amarlwgfcw lvvgfwraaf acptsckcsa sriwcsdpsp givafprlep
       61 nsvdpenite ifianqkrle iineddveay vglrnltivd sglkfvahka flknsnlqhi
      121 nftrnkltsl srkhfrhldl selilvgnpf tcscdimwik tlqeaksspd tqdlyclnes
      181 skniplanlq ipncglpsan laapnltvee gksitlscsv agdpvpnmyw dvgnlvskhm
      241 netshtqgsl ritnissdds gkqiscvaen lvgedqdsvn ltvhfaptit flesptsdhh
      301 wcipftvkgn pkpalqwfyn gailneskyi ctkihvtnht eyhgclqldn pthmnngdyt
      361 liakneygkd ekqisahfmg wpgiddganp nypdviyedy gtaandigdt tnrsneipst
      421 dvtdktgreh lsvyavvvia svvgfcllvm lfllklarhs kfgmkdfswf gfgkvksrqg
      481 vgpasvisnd ddsasplhhi sngsntpsss eggpdaviig mtkipvienp qyfgitnsql
      541 kpdtfvqhik rhnivlkrel gegafgkvfl aecynlcpeq dkilvavktl kdasdnarkd
      601 fhreaelltn lqhehivkfy gvcvegdpli mvfeymkhgd lnkflrahgp davlmaegnp
      661 pteltqsqml hiaqqiaagm vylasqhfvh rdlatrnclv genllvkigd fgmsrdvyst
      721 dyyrvgghtm lpirwmppes imyrkfttes dvwslgvvlw eiftygkqpw yqlsnnevie
      781 citqgrvlqr prtcpqevye lmlgcwqrep hmrknikgih tllqnlakas pvyldilg
//
