NTRK1_CHICK
ID NTRK1_CHICK Reviewed; 778 AA.
AC Q91009;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=High affinity nerve growth factor receptor;
DE EC=2.7.10.1;
DE AltName: Full=Neurotrophic tyrosine kinase receptor type 1;
DE Short=Trk-A;
DE Flags: Precursor; Fragment;
GN Name=NTRK1; Synonyms=TRKA;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RC TISSUE=Sympathetic ganglion;
RX PubMed=8892107;
RX DOI=10.1002/(sici)1097-4547(19961001)46:1<67::aid-jnr9>3.0.co;2-d;
RA Backstrom A., Soderstrom S., Kylberg A., Ebendal T.;
RT "Molecular cloning of the chicken trkA and its expression in early
RT peripheral ganglia.";
RL J. Neurosci. Res. 46:67-81(1996).
RN [2]
RP INTERACTION WITH PTPRS.
RX PubMed=17967490; DOI=10.1016/j.bbamcr.2007.06.008;
RA Faux C., Hawadle M., Nixon J., Wallace A., Lee S., Murray S., Stoker A.;
RT "PTPsigma binds and dephosphorylates neurotrophin receptors and can
RT suppress NGF-dependent neurite outgrowth from sensory neurons.";
RL Biochim. Biophys. Acta 1773:1689-1700(2007).
CC -!- FUNCTION: Receptor tyrosine kinase involved in the development and the
CC maturation of the central and peripheral nervous systems through
CC regulation of proliferation, differentiation and survival of
CC sympathetic and nervous neurons. High affinity receptor for NGF which
CC is its primary ligand, it can also bind and be activated by
CC NTF3/neurotrophin-3. Upon dimeric NGF ligand-binding, undergoes
CC homodimerization, autophosphorylation and activation. Recruits,
CC phosphorylates and/or activates several downstream effectors that
CC regulate distinct overlapping signaling cascades driving cell survival
CC and differentiation. In absence of ligand and activation, may promote
CC cell death, making the survival of neurons dependent on trophic
CC factors.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC -!- ACTIVITY REGULATION: The pro-survival signaling effect of NTRK1 in
CC neurons requires its endocytosis into signaling early endosomes and its
CC retrograde axonal transport. {ECO:0000250}.
CC -!- SUBUNIT: Exists in a dynamic equilibrium between monomeric (low
CC affinity) and dimeric (high affinity) structures. Homodimerization is
CC induced by NGF dimer binding (By similarity). Interacts with PTPRS
CC (PubMed:17967490). {ECO:0000250, ECO:0000269|PubMed:17967490}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P35739};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:P35739}.
CC Early endosome membrane {ECO:0000250|UniProtKB:P35739}; Single-pass
CC type I membrane protein {ECO:0000250|UniProtKB:P35739}. Late endosome
CC membrane {ECO:0000250|UniProtKB:P35739}; Single-pass type I membrane
CC protein {ECO:0000250|UniProtKB:P35739}. Recycling endosome membrane
CC {ECO:0000250|UniProtKB:P35739}; Single-pass type I membrane protein
CC {ECO:0000250|UniProtKB:P35739}. Note=Internalized to endosomes upon
CC binding of NGF or NTF3 and further transported to the cell body via a
CC retrograde axonal transport. Localized at cell membrane and early
CC endosomes before nerve growth factor (NGF) stimulation. Recruited to
CC late endosomes after NGF stimulation. Colocalized with RAPGEF2 at late
CC endosomes. {ECO:0000250|UniProtKB:P35739}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=1;
CC Comment=2 isoforms are produced.;
CC Name=1;
CC IsoId=Q91009-1; Sequence=Displayed;
CC -!- DEVELOPMENTAL STAGE: Expressed in the condensing dorsal root ganglia at
CC embryonal day 3, and in the primary sympathetic chain ganglia at
CC embryonal day 4. {ECO:0000269|PubMed:8892107}.
CC -!- PTM: Ligand-mediated auto-phosphorylation. {ECO:0000250}.
CC -!- PTM: Ubiquitinated. Undergoes polyubiquitination upon activation;
CC regulated by NGFR. Ubiquitination regulates the internalization of the
CC receptor. {ECO:0000250|UniProtKB:Q3UFB7}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Insulin receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; X93581; CAA63785.1; -; mRNA.
DR AlphaFoldDB; Q91009; -.
DR SMR; Q91009; -.
DR STRING; 9031.ENSGALP00000021606; -.
DR PaxDb; Q91009; -.
DR VEuPathDB; HostDB:geneid_396337; -.
DR eggNOG; KOG1026; Eukaryota.
DR InParanoid; Q91009; -.
DR PhylomeDB; Q91009; -.
DR Proteomes; UP000000539; Unplaced.
DR GO; GO:0030424; C:axon; IBA:GO_Central.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0055038; C:recycling endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0048406; F:nerve growth factor binding; ISS:UniProtKB.
DR GO; GO:0010465; F:nerve growth factor receptor activity; ISS:UniProtKB.
DR GO; GO:0043121; F:neurotrophin binding; IBA:GO_Central.
DR GO; GO:0005030; F:neurotrophin receptor activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; ISS:UniProtKB.
DR GO; GO:0060385; P:axonogenesis involved in innervation; ISS:UniProtKB.
DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IBA:GO_Central.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISS:UniProtKB.
DR GO; GO:0038180; P:nerve growth factor signaling pathway; IBA:GO_Central.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0043547; P:positive regulation of GTPase activity; ISS:UniProtKB.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISS:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IBA:GO_Central.
DR GO; GO:0046579; P:positive regulation of Ras protein signal transduction; ISS:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0051896; P:regulation of protein kinase B signaling; IBA:GO_Central.
DR GO; GO:0048485; P:sympathetic nervous system development; ISS:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR Gene3D; 2.60.40.10; -; 2.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR000483; Cys-rich_flank_reg_C.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013098; Ig_I-set.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR020777; NTRK.
DR InterPro; IPR020461; NTRK1.
DR InterPro; IPR031635; NTRK_LRRCT.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR040665; TrkA_TMD.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR002011; Tyr_kinase_rcpt_2_CS.
DR Pfam; PF07679; I-set; 1.
DR Pfam; PF13855; LRR_8; 1.
DR Pfam; PF16920; LRRCT_2; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF18613; TrkA_TMD; 1.
DR PRINTS; PR01939; NTKRECEPTOR.
DR PRINTS; PR01940; NTKRECEPTOR1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00409; IG; 1.
DR SMART; SM00082; LRRCT; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF48726; SSF48726; 2.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS00239; RECEPTOR_TYR_KIN_II; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cell membrane; Developmental protein;
KW Differentiation; Disulfide bond; Endosome; Glycoprotein;
KW Immunoglobulin domain; Kinase; Leucine-rich repeat; Membrane; Neurogenesis;
KW Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome; Repeat;
KW Signal; Transferase; Transmembrane; Transmembrane helix;
KW Tyrosine-protein kinase; Ubl conjugation.
FT SIGNAL <1..14
FT /evidence="ECO:0000255"
FT CHAIN 15..778
FT /note="High affinity nerve growth factor receptor"
FT /id="PRO_0000016726"
FT TOPO_DOM 15..400
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 401..421
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 422..778
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 71..92
FT /note="LRR 1"
FT REPEAT 95..116
FT /note="LRR 2"
FT DOMAIN 127..175
FT /note="LRRCT"
FT DOMAIN 175..262
FT /note="Ig-like C2-type 1"
FT DOMAIN 281..347
FT /note="Ig-like C2-type 2"
FT DOMAIN 493..763
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 633
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 499..507
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 527
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 479
FT /note="Interaction with SHC1"
FT /evidence="ECO:0000250"
FT SITE 773
FT /note="Interaction with PLC-gamma-1"
FT /evidence="ECO:0000250"
FT MOD_RES 479
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P04629"
FT MOD_RES 659
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P04629"
FT MOD_RES 663
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P04629"
FT MOD_RES 664
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P04629"
FT MOD_RES 773
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P04629"
FT CARBOHYD 100
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 130
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 143
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 151
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 194
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 234
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 262
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 300
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 320
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 340
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 384
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 18..20
FT /evidence="ECO:0000250|UniProtKB:P04629"
FT DISULFID 133..173
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 282..327
FT /evidence="ECO:0000250|UniProtKB:P04629"
FT NON_TER 1
SQ SEQUENCE 778 AA; 87339 MW; 4B30CD9289A3C300 CRC64;
WGCLRLPLPL CHALAAHCRC PASHTLRCRE PLTVSSLSAL LLGAHRPTDV IIENQALLTS
LTRDDTRMLW DLRHLTISNS GLQYISDDAF QDNHRLSHVN LSFNALTSLS WKTFQHLPLQ
ELTLEGNPFN CSCGIRWLQL WQNGSRAELG NQSLLCWEGS MLVALDSHPL HDCEPPTARI
EHPDVVLRQG DSVNLTCHIW GEPSATGEWV LPHVGSEPSV TKLSEWELVL EINNISSSLN
HKDLTCRAEN SVGLAEDSVM LNVTFPPVIL LLSEAIPQHF WCIPFSVDSN PTPRILWLFN
GSMLPEGPYI HTRIVEYEPN STVLHGCLQL NRPTHVNNGN YTLVVQNPLG RAARSIQGRF
MDNPFSFSPE EPIPVSISPL GTRNSSLEGP VETADEHTFG VSVAVALAVF ASLFLSVMLI
ALNKCGHRSK FGINRSAVLA PEDGLAMSLH FMTLGSSPVS STESKLDGLK SNFIENPQYF
CNACVHHVQR RDIVLKWELG EGAFGKVFLA ECSHLLPEQE KTLVAVKALK EVTENARLDF
QREAELLTVL QHEHIVKFYG VCTEGDPLIM VFEYMKHGDL NRFLRSHGPD AKILDQGQGQ
PCGQLTLSHM LQIATQIASG MVYLASLHFV HRDLATRNCL VGHDLVVKIG DFGMSRDIYS
TDYYRVGGRT MLPIRWMPPE SILYRKFTTE SDIWSFGVVL WEIFTYGKQP WYQLSNTEAI
ECITQGRELE RPRTCPSEVY DIMQSCWQRE PQQRSIQDIH SRLQALVKTP PIYLDILG
