NTRK1_HUMAN
ID NTRK1_HUMAN Reviewed; 796 AA.
AC P04629; B2R6T5; B7ZM34; P08119; Q15655; Q15656; Q5D056; Q5VZS2; Q7Z5C3;
AC Q9UIU7;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 02-MAY-2006, sequence version 4.
DT 03-AUG-2022, entry version 263.
DE RecName: Full=High affinity nerve growth factor receptor;
DE EC=2.7.10.1 {ECO:0000269|PubMed:1281417, ECO:0000269|PubMed:2927393};
DE AltName: Full=Neurotrophic tyrosine kinase receptor type 1;
DE AltName: Full=TRK1-transforming tyrosine kinase protein;
DE AltName: Full=Tropomyosin-related kinase A;
DE AltName: Full=Tyrosine kinase receptor;
DE AltName: Full=Tyrosine kinase receptor A;
DE Short=Trk-A;
DE AltName: Full=gp140trk {ECO:0000303|PubMed:2927393};
DE AltName: Full=p140-TrkA;
DE Flags: Precursor;
GN Name=NTRK1;
GN Synonyms=MTC, TRK {ECO:0000303|PubMed:2927393},
GN TRKA {ECO:0000303|PubMed:9290260};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TRKA-I), CATALYTIC ACTIVITY,
RP PHOSPHORYLATION, GLYCOSYLATION, AND SUBCELLULAR LOCATION.
RC TISSUE=Colon;
RX PubMed=2927393; DOI=10.1128/mcb.9.1.24-33.1989;
RA Martin-Zanca D., Oskam R., Mitra G., Copeland T.D., Barbacid M.;
RT "Molecular and biochemical characterization of the human trk proto-
RT oncogene.";
RL Mol. Cell. Biol. 9:24-33(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=7823156; DOI=10.1523/jneurosci.15-01-00477.1995;
RA Shelton D.L., Sutherland J., Gripp J., Camerato T., Armanini M.P.,
RA Phillips H.S., Carroll K., Spencer S.D., Levinson A.D.;
RT "Human trks: molecular cloning, tissue distribution, and expression of
RT extracellular domain immunoadhesins.";
RL J. Neurosci. 15:477-491(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9290260; DOI=10.1007/bf02766957;
RA Indo Y., Mardy S., Tsuruta M., Karim M.A., Matsuda I.;
RT "Structure and organization of the human TRKA gene encoding a high affinity
RT receptor for nerve growth factor.";
RL Jpn. J. Hum. Genet. 42:343-351(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM TRKA-II), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 1-175 (ISOFORM 3).
RC TISSUE=Uterus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS TRKA-I AND TRKA-II).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-71.
RX PubMed=15870692; DOI=10.1038/sj.onc.1208697;
RA Fujimoto M., Kitazawa R., Maeda S., Kitazawa S.;
RT "Methylation adjacent to negatively regulating AP-1 site reactivates TrkA
RT gene expression during cancer progression.";
RL Oncogene 24:5108-5118(2005).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 399-796, AND CHROMOSOMAL TRANSLOCATION WITH
RP TPM3.
RX PubMed=2869410; DOI=10.1038/319743a0;
RA Martin-Zanca D., Hughes S.H., Barbacid M.;
RT "A human oncogene formed by the fusion of truncated tropomyosin and protein
RT tyrosine kinase sequences.";
RL Nature 319:743-748(1986).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 399-796.
RX PubMed=2966065; DOI=10.1002/j.1460-2075.1988.tb02794.x;
RA Kozma S.C., Redmond S.M.S., Saurer S.M., Groner B., Hynes N.E.;
RT "Activation of the receptor kinase domain of the trk oncogene by
RT recombination with two different cellular sequences.";
RL EMBO J. 7:147-154(1988).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 399-796, AND CHROMOSOMAL TRANSLOCATION WITH
RP TFG.
RX PubMed=7565764; DOI=10.1128/mcb.15.11.6118;
RA Greco A., Mariani C., Miranda C., Lupas A., Pagliardini S., Pomati M.,
RA Pierotti M.A.;
RT "The DNA rearrangement that generates the TRK-T3 oncogene involves a novel
RT gene on chromosome 3 whose product has a potential coiled-coil domain.";
RL Mol. Cell. Biol. 15:6118-6127(1995).
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 486-796, AND CHROMOSOMAL REARRANGEMENT WITH
RP TPR.
RX PubMed=1532241;
RA Greco A., Pierotti M.A., Bongarzone I., Pagliardini S., Lanzi C.,
RA Della Porta G.;
RT "TRK-T1 is a novel oncogene formed by the fusion of TPR and TRK genes in
RT human papillary thyroid carcinomas.";
RL Oncogene 7:237-242(1992).
RN [12]
RP FUNCTION AS RECEPTOR FOR NGF.
RX PubMed=1850821; DOI=10.1038/350678a0;
RA Hempstead B.L., Martin-Zanca D., Kaplan D.R., Parada L.F., Chao M.V.;
RT "High-affinity NGF binding requires coexpression of the trk proto-oncogene
RT and the low-affinity NGF receptor.";
RL Nature 350:678-683(1991).
RN [13]
RP FUNCTION IN NGF SIGNALING, AND IDENTIFICATION AS THE HIGH AFFINITY NGF
RP RECEPTOR.
RX PubMed=1849459; DOI=10.1016/0092-8674(91)90419-y;
RA Klein R., Jing S., Nanduri V., O'Rourke E., Barbacid M.;
RT "The trk proto-oncogene encodes a receptor for nerve growth factor.";
RL Cell 65:189-197(1991).
RN [14]
RP FUNCTION, SUBUNIT, CATALYTIC ACTIVITY, PHOSPHORYLATION, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF LYS-544.
RX PubMed=1281417; DOI=10.1016/0896-6273(92)90066-m;
RA Jing S., Tapley P., Barbacid M.;
RT "Nerve growth factor mediates signal transduction through trk homodimer
RT receptors.";
RL Neuron 9:1067-1079(1992).
RN [15]
RP ALTERNATIVE SPLICING (ISOFORMS TRKA-I AND TRKA-II), FUNCTION IN CELL
RP SURVIVAL, NGF-BINDING, PHOSPHORYLATION, AND TISSUE SPECIFICITY.
RX PubMed=8325889; DOI=10.1016/s0021-9258(18)82449-8;
RA Barker P.A., Lomen-Hoerth C., Gensch E.M., Meakin S.O., Glass D.J.,
RA Shooter E.M.;
RT "Tissue-specific alternative splicing generates two isoforms of the trkA
RT receptor.";
RL J. Biol. Chem. 268:15150-15157(1993).
RN [16]
RP PHOSPHORYLATION AT TYR-791, INTERACTION WITH PLCG1, AND MUTAGENESIS OF
RP TYR-791.
RX PubMed=7510697; DOI=10.1016/s0021-9258(17)37053-9;
RA Loeb D.M., Stephens R.M., Copeland T.D., Kaplan D.R., Greene L.A.;
RT "A Trk nerve growth factor (NGF) receptor point mutation affecting
RT interaction with phospholipase C-gamma 1 abolishes NGF-promoted peripherin
RT induction but not neurite outgrowth.";
RL J. Biol. Chem. 269:8901-8910(1994).
RN [17]
RP FUNCTION IN NEURONAL DIFFERENTIATION, FUNCTION IN PHOSPHORYLATION OF SHC1
RP AND PLCG1, INTERACTION WITH SHC1, MUTAGENESIS OF TYR-496; LYS-544 AND
RP TYR-791, AND PHOSPHORYLATION AT TYR-496; TYR-676; TYR-680; TYR-681 AND
RP TYR-791.
RX PubMed=8155326; DOI=10.1016/0896-6273(94)90223-2;
RA Stephens R.M., Loeb D.M., Copeland T.D., Pawson T., Greene L.A.,
RA Kaplan D.R.;
RT "Trk receptors use redundant signal transduction pathways involving SHC and
RT PLC-gamma 1 to mediate NGF responses.";
RL Neuron 12:691-705(1994).
RN [18]
RP FUNCTION IN NF-KAPPA-B ACTIVATION, AND INTERACTION WITH SQSTM1.
RX PubMed=11244088; DOI=10.1074/jbc.c000869200;
RA Wooten M.W., Seibenhener M.L., Mamidipudi V., Diaz-Meco M.T., Barker P.A.,
RA Moscat J.;
RT "The atypical protein kinase C-interacting protein p62 is a scaffold for
RT NF-kappaB activation by nerve growth factor.";
RL J. Biol. Chem. 276:7709-7712(2001).
RN [19]
RP FUNCTION IN NEURONAL CELL PROLIFERATION AND DIFFERENTIATION, FUNCTION IN
RP SIGNALING CASCADE ACTIVATION, NGF-BINDING, SUBCELLULAR LOCATION,
RP ALTERNATIVE SPLICING (ISOFORM TRKA-III), CHARACTERIZATION OF ISOFORM
RP TRKA-III, PHOSPHORYLATION AT TYR-496; TYR-680; TYR-681 AND TYR-791,
RP INTERACTION WITH FRS2; GRB2; PIK3R1; PLCG1; SHC1, GLYCOSYLATION, TISSUE
RP SPECIFICITY, AND INDUCTION BY HYPOXIA.
RX PubMed=15488758; DOI=10.1016/j.ccr.2004.09.011;
RA Tacconelli A., Farina A.R., Cappabianca L., Desantis G., Tessitore A.,
RA Vetuschi A., Sferra R., Rucci N., Argenti B., Screpanti I., Gulino A.,
RA Mackay A.R.;
RT "TrkA alternative splicing: a regulated tumor-promoting switch in human
RT neuroblastoma.";
RL Cancer Cell 6:347-360(2004).
RN [20]
RP INTERACTION WITH SORT1, AND ACTIVITY REGULATION.
RX PubMed=21102451; DOI=10.1038/nn.2689;
RA Vaegter C.B., Jansen P., Fjorback A.W., Glerup S., Skeldal S., Kjolby M.,
RA Richner M., Erdmann B., Nyengaard J.R., Tessarollo L., Lewin G.R.,
RA Willnow T.E., Chao M.V., Nykjaer A.;
RT "Sortilin associates with Trk receptors to enhance anterograde transport
RT and neurotrophin signaling.";
RL Nat. Neurosci. 14:54-61(2011).
RN [21]
RP FUNCTION, AND INTERACTION WITH NGF.
RX PubMed=22649032; DOI=10.1096/fj.12-207316;
RA Tong Q., Wang F., Zhou H.Z., Sun H.L., Song H., Shu Y.Y., Gong Y.,
RA Zhang W.T., Cai T.X., Yang F.Q., Tang J., Jiang T.;
RT "Structural and functional insights into lipid-bound nerve growth
RT factors.";
RL FASEB J. 26:3811-3821(2012).
RN [22]
RP INTERACTION WITH GGA3, AND MUTAGENESIS OF 540-LEU-VAL-541; LYS-544 AND
RP 610-LEU-LEU-611.
RX PubMed=26446845; DOI=10.1091/mbc.e15-02-0087;
RA Li X., Lavigne P., Lavoie C.;
RT "GGA3 mediates TrkA endocytic recycling to promote sustained Akt
RT phosphorylation and cell survival.";
RL Mol. Biol. Cell 26:4412-4426(2015).
RN [23]
RP FUNCTION, UBIQUITINATION BY NEDD4L, AND INTERACTION WITH USP36.
RX PubMed=27445338; DOI=10.1074/jbc.m116.722637;
RA Anta B., Martin-Rodriguez C., Gomis-Perez C., Calvo L., Lopez-Benito S.,
RA Calderon-Garcia A.A., Vicente-Garcia C., Villarroel A., Arevalo J.C.;
RT "Ubiquitin-specific Protease 36 (USP36) Controls Neuronal Precursor Cell-
RT expressed Developmentally Down-regulated 4-2 (Nedd4-2) Actions over the
RT Neurotrophin Receptor TrkA and Potassium Voltage-gated Channels 7.2/3
RT (Kv7.2/3).";
RL J. Biol. Chem. 291:19132-19145(2016).
RN [24]
RP PHOSPHORYLATION, VARIANTS CIPA 235-SER--GLY-796 DEL; ASN-596 AND TYR-674,
RP AND CHARACTERIZATION OF VARIANTS CIPA 235-SER--GLY-796 DEL AND ASN-596.
RX PubMed=28177573; DOI=10.1111/jns.12205;
RA Nam T.S., Li W., Yoon S., Eom G.H., Kim M.K., Jung S.T., Choi S.Y.;
RT "Novel NTRK1 mutations associated with congenital insensitivity to pain
RT with anhidrosis verified by functional studies.";
RL J. Peripher. Nerv. Syst. 22:92-99(2017).
RN [25]
RP STRUCTURE BY NMR OF 489-500.
RX PubMed=8524391; DOI=10.1038/378584a0;
RA Zhou M.-M., Ravichandran K.S., Olejniczak E.F., Petros A.M., Meadows R.P.,
RA Sattler M., Harlan J.E., Wade W.S., Burakoff S.J., Fesik S.W.;
RT "Structure and ligand recognition of the phosphotyrosine binding domain of
RT Shc.";
RL Nature 378:584-592(1995).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 278-386, AND DISULFIDE BONDS.
RX PubMed=10388563; DOI=10.1006/jmbi.1999.2816;
RA Ultsch M.H., Wiesmann C., Simmons L.C., Henrich J., Yang M., Reilly D.,
RA Bass S.H., de Vos A.M.;
RT "Crystal structures of the neurotrophin-binding domain of TrkA, TrkB and
RT TrkC.";
RL J. Mol. Biol. 290:149-159(1999).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 282-382 IN COMPLEX WITH NGF,
RP SUBUNIT, AND DISULFIDE BONDS.
RX PubMed=10490030; DOI=10.1038/43705;
RA Wiesmann C., Ultsch M.H., Bass S.H., de Vos A.M.;
RT "Crystal structure of nerve growth factor in complex with the ligand-
RT binding domain of the TrkA receptor.";
RL Nature 401:184-188(1999).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS) OF 36-382 IN COMPLEX WITH NGF,
RP HOMODIMERIZATION, SUBUNIT, SUBCELLULAR LOCATION, DISULFIDE BONDS, AND
RP GLYCOSYLATION AT ASN-95; ASN-121; ASN-188; ASN-262; ASN-281 AND ASN-358.
RX PubMed=17196528; DOI=10.1016/j.neuron.2006.09.034;
RA Wehrman T., He X., Raab B., Dukipatti A., Blau H., Garcia K.C.;
RT "Structural and mechanistic insights into nerve growth factor interactions
RT with the TrkA and p75 receptors.";
RL Neuron 53:25-38(2007).
RN [29]
RP VARIANT CIPA ARG-577.
RX PubMed=8696348; DOI=10.1038/ng0896-485;
RA Indo Y., Tsuruta M., Hayashida Y., Karim M.A., Ohta K., Kawano T.,
RA Mitsubuchi H., Tonoki H., Awaya Y., Matsuda I.;
RT "Mutations in the TRKA/NGF receptor gene in patients with congenital
RT insensitivity to pain with anhidrosis.";
RL Nat. Genet. 13:485-488(1996).
RN [30]
RP VARIANT CIPA PRO-780.
RX PubMed=10090906; DOI=10.1086/302319;
RA Greco A., Villa R., Tubino B., Romano L., Penso D., Pierotti M.A.;
RT "A novel NTRK1 mutation associated with congenital insensitivity to pain
RT with anhidrosis.";
RL Am. J. Hum. Genet. 64:1207-1210(1999).
RN [31]
RP VARIANTS CIPA PRO-213; TRP-649 AND SER-714, AND VARIANTS SER-85; TYR-604
RP AND VAL-613.
RX PubMed=10330344; DOI=10.1086/302422;
RA Mardy S., Miura Y., Endo F., Matsuda I., Sztriha L., Frossard P., Moosa A.,
RA Ismail E.A.R., Macaya A., Andria G., Toscano E., Gibson W., Graham G.E.,
RA Indo Y.;
RT "Congenital insensitivity to pain with anhidrosis: novel mutations in the
RT TRKA (NTRK1) gene encoding a high-affinity receptor for nerve growth
RT factor.";
RL Am. J. Hum. Genet. 64:1570-1579(1999).
RN [32]
RP VARIANTS TYR-604; VAL-613 AND GLN-780.
RX PubMed=10443680; DOI=10.1210/jcem.84.8.5901;
RA Gimm O., Greco A., Hoang-Vu C., Dralle H., Pierotti M.A., Eng C.;
RT "Mutation analysis reveals novel sequence variants in NTRK1 in sporadic
RT human medullary thyroid carcinoma.";
RL J. Clin. Endocrinol. Metab. 84:2784-2787(1999).
RN [33]
RP VARIANT CIPA VAL-587.
RX PubMed=10233776; DOI=10.1046/j.1523-1747.1999.00569.x;
RA Yotsumoto S., Setoyama M., Hozumi H., Mizoguchi S., Fukumaru S.,
RA Kobayashi K., Saheki T., Kanzaki T.;
RT "A novel point mutation affecting the tyrosine kinase domain of the TRKA
RT gene in a family with congenital insensitivity to pain with anhidrosis.";
RL J. Invest. Dermatol. 112:810-814(1999).
RN [34]
RP VARIANTS TYR-604 AND VAL-613.
RX PubMed=10391209; DOI=10.1038/10290;
RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA Lander E.S.;
RT "Characterization of single-nucleotide polymorphisms in coding regions of
RT human genes.";
RL Nat. Genet. 22:231-238(1999).
RN [35]
RP ERRATUM OF PUBMED:10391209.
RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA Lander E.S.;
RL Nat. Genet. 23:373-373(1999).
RN [36]
RP VARIANT CIPA LEU-695, AND VARIANT VAL-613.
RC TISSUE=Peripheral blood;
RX PubMed=10861667;
RX DOI=10.1002/1096-8628(20000619)92:5<353::aid-ajmg12>3.0.co;2-c;
RA Shatzky S., Moses S., Levy J., Pinsk V., Hershkovitz E., Herzog L.,
RA Shorer Z., Luder A., Parvari R.;
RT "Congenital insensitivity to pain with anhidrosis (CIPA) in Israeli-
RT Bedouins: genetic heterogeneity, novel mutations in the TRKA/NGF receptor
RT gene, clinical findings, and results of nerve conduction studies.";
RL Am. J. Med. Genet. 92:353-360(2000).
RN [37]
RP VARIANTS CIPA PRO-93; ARG-522; ARG-577; CYS-654 AND TYR-674.
RX PubMed=10982191; DOI=10.1007/s004390051018;
RA Miura Y., Mardy S., Awaya Y., Nihei K., Endo F., Matsuda I., Indo Y.;
RT "Mutation and polymorphism analysis of the TRKA (NTRK1) gene encoding a
RT high-affinity receptor for nerve growth factor in congenital insensitivity
RT to pain with anhidrosis (CIPA) families.";
RL Hum. Genet. 106:116-124(2000).
RN [38]
RP VARIANT CIPA ARG-577.
RX PubMed=10567924;
RX DOI=10.1002/(sici)1097-4652(200001)182:1<127::aid-jcp14>3.0.co;2-0;
RA Greco A., Villa R., Fusetti L., Orlandi R., Pierotti M.A.;
RT "The Gly571Arg mutation, associated with the autonomic and sensory disorder
RT congenital insensitivity to pain with anhidrosis, causes the inactivation
RT of the NTRK1/nerve growth factor receptor.";
RL J. Cell. Physiol. 182:127-133(2000).
RN [39]
RP VARIANT CIPA CYS-359, AND VARIANTS TYR-604 AND VAL-613.
RX PubMed=11310631; DOI=10.1002/ana.103;
RA Houlden H., King R.H., Hashemi-Nejad A., Wood N.W., Mathias C.J.,
RA Reilly M., Thomas P.K.;
RT "A novel TRK A (NTRK1) mutation associated with hereditary sensory and
RT autonomic neuropathy type V.";
RL Ann. Neurol. 49:521-525(2001).
RN [40]
RP CHARACTERIZATION OF VARIANTS CIPA PRO-93; PRO-213; ARG-522; ARG-577;
RP TRP-649; CYS-654 AND SER-714, AND CHARACTERIZATION OF VARIANTS SER-85;
RP TYR-604; VAL-613 AND TYR-674.
RX PubMed=11159935; DOI=10.1093/hmg/10.3.179;
RA Mardy S., Miura Y., Endo F., Matsuda I., Indo Y.;
RT "Congenital insensitivity to pain with anhidrosis (CIPA): effect of TRKA
RT (NTRK1) missense mutations on autophosphorylation of the receptor tyrosine
RT kinase for nerve growth factor.";
RL Hum. Mol. Genet. 10:179-188(2001).
RN [41]
RP VARIANTS [LARGE SCALE ANALYSIS] ARG-80; VAL-107; MET-237; GLY-238; GLY-260;
RP GLN-444; CYS-452; THR-566; TYR-604; VAL-613; GLN-780 AND ILE-790.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
RN [42]
RP VARIANTS CIPA SER-572 AND ARG-717.
RX PubMed=18077166; DOI=10.1016/j.nmd.2007.10.005;
RA Huehne K., Zweier C., Raab K., Odent S., Bonnaure-Mallet M., Sixou J.L.,
RA Landrieu P., Goizet C., Sarlangue J., Baumann M., Eggermann T., Rauch A.,
RA Ruppert S., Stettner G.M., Rautenstrauss B.;
RT "Novel missense, insertion and deletion mutations in the neurotrophic
RT tyrosine kinase receptor type 1 gene (NTRK1) associated with congenital
RT insensitivity to pain with anhidrosis.";
RL Neuromuscul. Disord. 18:159-166(2008).
RN [43]
RP VARIANTS CIPA LYS-492 AND CYS-654, AND VARIANT TRP-6.
RX PubMed=22302274; DOI=10.1007/s00415-011-6397-y;
RA Davidson G.L., Murphy S.M., Polke J.M., Laura M., Salih M.A., Muntoni F.,
RA Blake J., Brandner S., Davies N., Horvath R., Price S., Donaghy M.,
RA Roberts M., Foulds N., Ramdharry G., Soler D., Lunn M.P., Manji H.,
RA Davis M.B., Houlden H., Reilly M.M.;
RT "Frequency of mutations in the genes associated with hereditary sensory and
RT autonomic neuropathy in a UK cohort.";
RL J. Neurol. 259:1673-1685(2012).
RN [44]
RP VARIANTS CIPA ASP-110; 146-SER--GLY-796 DEL; 176-GLN--GLY-796 DEL;
RP 476-LEU--GLY-796 DEL; GLN-649 AND PRO-700.
RX PubMed=28328124; DOI=10.1002/ajmg.a.38120;
RA Altassan R., Saud H.A., Masoodi T.A., Dosssari H.A., Khalifa O.,
RA Al-Zaidan H., Sakati N., Rhabeeni Z., Al-Hassnan Z., Binamer Y.,
RA Alhashemi N., Wade W., Al-Zayed Z., Al-Sayed M., Al-Muhaizea M.A.,
RA Meyer B., Al-Owain M., Wakil S.M.;
RT "Exome sequencing identifies novel NTRK1 mutations in patients with HSAN-IV
RT phenotype.";
RL Am. J. Med. Genet. A 173:1009-1016(2017).
RN [45]
RP VARIANTS CIPA GLU-517; GLU-522; PRO-657; THR-699; SER-752; SER-763 AND
RP CYS-771, CHARACTERIZATION OF VARIANTS CIPA GLU-517; GLU-522; PRO-657;
RP THR-699; SER-752; SER-763 AND CYS-771, GLYCOSYLATION, SUBCELLULAR LOCATION,
RP AUTOPHOSPHORYLATION AFTER NGF STIMULATION, AND FUNCTION.
RX PubMed=27676246; DOI=10.1002/humu.23123;
RA Shaikh S.S., Chen Y.C., Halsall S.A., Nahorski M.S., Omoto K., Young G.T.,
RA Phelan A., Woods C.G.;
RT "A comprehensive functional analysis of NTRK1 missense mutations causing
RT hereditary sensory and autonomic neuropathy type IV (HSAN IV).";
RL Hum. Mutat. 38:55-63(2017).
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 (PubMed:1850821, PubMed:1849459, PubMed:1281417,
CC PubMed:8325889, PubMed:15488758, PubMed:22649032, PubMed:17196528,
CC PubMed:27445338). Can also bind and be activated by NTF3/neurotrophin-
CC 3. However, NTF3 only supports axonal extension through NTRK1 but has
CC no effect on neuron survival (By similarity). Upon dimeric NGF ligand-
CC binding, undergoes homodimerization, autophosphorylation and activation
CC (PubMed:1281417). Recruits, phosphorylates and/or activates several
CC downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that
CC regulate distinct overlapping signaling cascades driving cell survival
CC and differentiation. Through SHC1 and FRS2 activates a GRB2-Ras-MAPK
CC cascade that regulates cell differentiation and survival. Through PLCG1
CC controls NF-Kappa-B activation and the transcription of genes involved
CC in cell survival. Through SHC1 and SH2B1 controls a Ras-PI3 kinase-AKT1
CC signaling cascade that is also regulating survival. In absence of
CC ligand and activation, may promote cell death, making the survival of
CC neurons dependent on trophic factors. {ECO:0000250|UniProtKB:P35739,
CC ECO:0000250|UniProtKB:Q3UFB7, ECO:0000269|PubMed:11244088,
CC ECO:0000269|PubMed:1281417, ECO:0000269|PubMed:15488758,
CC ECO:0000269|PubMed:17196528, ECO:0000269|PubMed:1849459,
CC ECO:0000269|PubMed:1850821, ECO:0000269|PubMed:22649032,
CC ECO:0000269|PubMed:27445338, ECO:0000269|PubMed:27676246,
CC ECO:0000269|PubMed:8155326, ECO:0000269|PubMed:8325889}.
CC -!- FUNCTION: [Isoform TrkA-III]: Resistant to NGF, it constitutively
CC activates AKT1 and NF-kappa-B and is unable to activate the Ras-MAPK
CC signaling cascade. Antagonizes the anti-proliferative NGF-NTRK1
CC signaling that promotes neuronal precursors differentiation. Isoform
CC TrkA-III promotes angiogenesis and has oncogenic activity when
CC overexpressed. {ECO:0000269|PubMed:15488758}.
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 ECO:0000269|PubMed:1281417, ECO:0000269|PubMed:2927393};
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. This is regulated by different proteins
CC including CFL1, RAC1 and SORT1. NTF3 is unable to induce this signaling
CC probably due to the lability of the NTF3-NTRK1 complex in endosomes.
CC SH2D1A inhibits the autophosphorylation of the receptor, and alters the
CC recruitment and activation of downstream effectors and signaling
CC cascades (By similarity). Regulated by NGFR (By similarity).
CC {ECO:0000250|UniProtKB:Q3UFB7}.
CC -!- SUBUNIT: Exists in a dynamic equilibrium between monomeric (low
CC affinity) and dimeric (high affinity) structures. Homodimerization is
CC induced by binding of a NGF dimer (PubMed:1281417, PubMed:10490030,
CC PubMed:17196528). Interacts with SQSTM1; bridges NTRK1 to NGFR
CC (PubMed:11244088). Forms a ternary complex with NGFR and KIDINS220;
CC this complex is affected by the expression levels of KIDINS220 and an
CC increase in KIDINS220 expression leads to a decreased association of
CC NGFR and NTRK1 (By similarity). Interacts with SH2D1A; regulates NTRK1
CC (By similarity). Interacts (phosphorylated upon activation by NGF) with
CC SHC1; mediates SHC1 phosphorylation and activation (PubMed:8155326,
CC PubMed:15488758). Interacts (phosphorylated upon activation by NGF)
CC with PLCG1; mediates PLCG1 phosphorylation and activation
CC (PubMed:7510697, PubMed:15488758). Interacts (phosphorylated) with
CC SH2B1 and SH2B2 (By similarity). Interacts with GRB2 (PubMed:15488758).
CC Interacts with PIK3R1 (PubMed:15488758). Interacts with FRS2
CC (PubMed:15488758). Interacts with SORT1; may regulate NTRK1 anterograde
CC axonal transport (PubMed:21102451). Interacts with RAB7A (By
CC similarity). Found in a complex, at least composed of KIDINS220, MAGI2,
CC NTRK1 and RAPGEF2; the complex is mainly formed at late endosomes in a
CC nerve growth factor (NGF)-dependent manner (By similarity). Interacts
CC with RAPGEF2; the interaction is strengthened after NGF stimulation (By
CC similarity). Interacts with PTPRS (By similarity). Interacts with
CC USP36; USP36 does not deubiquitinate NTRK1 (PubMed:27445338). Interacts
CC with GGA3 (PubMed:26446845). {ECO:0000250,
CC ECO:0000250|UniProtKB:P35739, ECO:0000269|PubMed:10490030,
CC ECO:0000269|PubMed:11244088, ECO:0000269|PubMed:1281417,
CC ECO:0000269|PubMed:15488758, ECO:0000269|PubMed:17196528,
CC ECO:0000269|PubMed:21102451, ECO:0000269|PubMed:22649032,
CC ECO:0000269|PubMed:26446845, ECO:0000269|PubMed:27445338,
CC ECO:0000269|PubMed:7510697, ECO:0000269|PubMed:8155326,
CC ECO:0000269|PubMed:8325889}.
CC -!- INTERACTION:
CC P04629; P05067-4: APP; NbExp=7; IntAct=EBI-1028226, EBI-302641;
CC P04629; P22681: CBL; NbExp=2; IntAct=EBI-1028226, EBI-518228;
CC P04629; P01138: NGF; NbExp=3; IntAct=EBI-1028226, EBI-1028250;
CC P04629; PRO_0000019600 [P01138]: NGF; NbExp=2; IntAct=EBI-1028226, EBI-9249861;
CC P04629; P04629: NTRK1; NbExp=3; IntAct=EBI-1028226, EBI-1028226;
CC P04629; P18031: PTPN1; NbExp=2; IntAct=EBI-1028226, EBI-968788;
CC P04629; Q99523: SORT1; NbExp=3; IntAct=EBI-1028226, EBI-1057058;
CC P04629; Q13501: SQSTM1; NbExp=2; IntAct=EBI-1028226, EBI-307104;
CC P04629; O75385: ULK1; NbExp=2; IntAct=EBI-1028226, EBI-908831;
CC P04629; Q8K4V6: Pirb; Xeno; NbExp=2; IntAct=EBI-1028226, EBI-8602514;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1281417,
CC ECO:0000269|PubMed:15488758, ECO:0000269|PubMed:17196528,
CC ECO:0000269|PubMed:27676246, ECO:0000269|PubMed:2927393}; Single-pass
CC type I membrane protein {ECO:0000269|PubMed:1281417,
CC ECO:0000269|PubMed:15488758}. Early endosome membrane
CC {ECO:0000250|UniProtKB:P35739}; Single-pass type I membrane protein
CC {ECO:0000250|UniProtKB:P35739}. Late endosome membrane
CC {ECO:0000250|UniProtKB:P35739}; Single-pass type I membrane protein
CC {ECO:0000250|UniProtKB:P35739}. Recycling endosome membrane
CC {ECO:0000250|UniProtKB:P35739}; Single-pass type I membrane protein
CC {ECO:0000250|UniProtKB:P35739}. Note=Rapidly internalized after NGF
CC binding (PubMed:1281417). Internalized to endosomes upon binding of NGF
CC or NTF3 and further transported to the cell body via a retrograde
CC axonal transport. Localized at cell membrane and early endosomes before
CC nerve growth factor (NGF) stimulation. Recruited to late endosomes
CC after NGF stimulation. Colocalized with RAPGEF2 at late endosomes.
CC {ECO:0000250|UniProtKB:P35739, ECO:0000269|PubMed:1281417}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Comment=TrkA-I and TrkA-II isoforms have similar biological
CC properties but are differentially expressed.;
CC Name=TrkA-II; Synonyms=TrkAII;
CC IsoId=P04629-1; Sequence=Displayed;
CC Name=TrkA-I; Synonyms=TrkAI;
CC IsoId=P04629-2; Sequence=VSP_002899;
CC Name=3;
CC IsoId=P04629-3; Sequence=VSP_041905, VSP_002899;
CC Name=TrkA-III; Synonyms=TrkAIII;
CC IsoId=P04629-4; Sequence=VSP_042152, VSP_002899;
CC -!- TISSUE SPECIFICITY: Isoform TrkA-I is found in most non-neuronal
CC tissues. Isoform TrkA-II is primarily expressed in neuronal cells.
CC TrkA-III is specifically expressed by pluripotent neural stem and
CC neural crest progenitors. {ECO:0000269|PubMed:15488758,
CC ECO:0000269|PubMed:8325889}.
CC -!- INDUCTION: Isoform TrkA-III is up-regulated upon hypoxia in cells
CC normally expressing it. {ECO:0000269|PubMed:15488758}.
CC -!- DOMAIN: The transmembrane domain mediates interaction with KIDINS220.
CC {ECO:0000250|UniProtKB:P35739}.
CC -!- DOMAIN: The extracellular domain mediates interaction with NGFR.
CC {ECO:0000250|UniProtKB:P35739}.
CC -!- PTM: Ligand-mediated autophosphorylation (PubMed:2927393,
CC PubMed:1281417, PubMed:15488758, PubMed:7510697, PubMed:8155326,
CC PubMed:8325889, PubMed:27676246, PubMed:28177573). Interaction with
CC SQSTM1 is phosphotyrosine-dependent. Autophosphorylation at Tyr-496
CC mediates interaction and phosphorylation of SHC1 (PubMed:15488758,
CC PubMed:7510697, PubMed:8155326, PubMed:8325889).
CC {ECO:0000269|PubMed:1281417, ECO:0000269|PubMed:15488758,
CC ECO:0000269|PubMed:27676246, ECO:0000269|PubMed:28177573,
CC ECO:0000269|PubMed:2927393, ECO:0000269|PubMed:7510697,
CC ECO:0000269|PubMed:8155326, ECO:0000269|PubMed:8325889}.
CC -!- PTM: N-glycosylated (PubMed:2927393). Isoform TrkA-I and isoform TrkA-
CC II are N-glycosylated. {ECO:0000269|PubMed:15488758,
CC ECO:0000269|PubMed:17196528, ECO:0000269|PubMed:27676246,
CC ECO:0000269|PubMed:2927393}.
CC -!- PTM: Ubiquitinated (PubMed:27445338). Undergoes polyubiquitination upon
CC activation; regulated by NGFR (PubMed:27445338). Ubiquitination by
CC NEDD4L leads to degradation (PubMed:27445338). Ubiquitination regulates
CC the internalization of the receptor (By similarity).
CC {ECO:0000250|UniProtKB:Q3UFB7, ECO:0000269|PubMed:27445338}.
CC -!- DISEASE: Congenital insensitivity to pain with anhidrosis (CIPA)
CC [MIM:256800]: Characterized by a congenital insensitivity to pain,
CC anhidrosis (absence of sweating), absence of reaction to noxious
CC stimuli, self-mutilating behavior, and intellectual disability. This
CC rare autosomal recessive disorder is also known as congenital sensory
CC neuropathy with anhidrosis or hereditary sensory and autonomic
CC neuropathy type IV or familial dysautonomia type II.
CC {ECO:0000269|PubMed:10090906, ECO:0000269|PubMed:10233776,
CC ECO:0000269|PubMed:10330344, ECO:0000269|PubMed:10567924,
CC ECO:0000269|PubMed:10861667, ECO:0000269|PubMed:10982191,
CC ECO:0000269|PubMed:11159935, ECO:0000269|PubMed:11310631,
CC ECO:0000269|PubMed:18077166, ECO:0000269|PubMed:22302274,
CC ECO:0000269|PubMed:27676246, ECO:0000269|PubMed:28177573,
CC ECO:0000269|PubMed:28328124, ECO:0000269|PubMed:8696348}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Note=Chromosomal aberrations involving NTRK1 are found in
CC papillary thyroid carcinomas (PTCs) (PubMed:2869410, PubMed:7565764,
CC PubMed:1532241). Translocation t(1;3)(q21;q11) with TFG generates the
CC TRKT3 (TRK-T3) transcript by fusing TFG to the 3'-end of NTRK1
CC (PubMed:7565764). A rearrangement with TPM3 generates the TRK
CC transcript by fusing TPM3 to the 3'-end of NTRK1 (PubMed:2869410). An
CC intrachromosomal rearrangement that links the protein kinase domain of
CC NTRK1 to the 5'-end of the TPR gene forms the fusion protein TRK-T1.
CC TRK-T1 is a 55 kDa protein reacting with antibodies against the C-
CC terminus of the NTRK1 protein (PubMed:1532241).
CC {ECO:0000269|PubMed:1532241, ECO:0000269|PubMed:2869410,
CC ECO:0000269|PubMed:7565764}.
CC -!- MISCELLANEOUS: Trk also stands for tropomyosin-related kinase since it
CC was first isolated as an oncogenic protein which was the result of a
CC fusion between the tropomyosin gene TPM3 and NTRK1.
CC -!- MISCELLANEOUS: [Isoform TrkA-II]: Major isoform.
CC -!- MISCELLANEOUS: [Isoform TrkA-I]: Has enhanced responsiveness to NTF3
CC neurotrophin. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform TrkA-III]: Constitutively active. Does not bind
CC NGF and does not interact with GRB2 and FRS2. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Insulin receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA27243.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
CC Sequence=CAA27243.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAA27243.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305};
CC Sequence=CAA29888.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305};
CC Sequence=CAA44719.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305};
CC Sequence=CAA59936.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305};
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DR EMBL; M23102; AAA36770.1; -; mRNA.
DR EMBL; AB019488; BAA34355.1; -; Genomic_DNA.
DR EMBL; AK312704; BAG35582.1; -; mRNA.
DR EMBL; DB265639; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AL158169; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC062580; AAH62580.1; -; mRNA.
DR EMBL; BC136554; AAI36555.1; -; mRNA.
DR EMBL; BC144239; AAI44240.1; -; mRNA.
DR EMBL; AY321513; AAP88292.1; -; Genomic_DNA.
DR EMBL; X03541; CAA27243.1; ALT_SEQ; mRNA.
DR EMBL; X06704; CAA29888.1; ALT_SEQ; mRNA.
DR EMBL; X85960; CAA59936.1; ALT_SEQ; mRNA.
DR EMBL; X62947; CAA44719.1; ALT_SEQ; mRNA.
DR CCDS; CCDS1161.1; -. [P04629-1]
DR CCDS; CCDS30890.1; -. [P04629-3]
DR CCDS; CCDS30891.1; -. [P04629-2]
DR PIR; A30124; TVHUTT.
DR PIR; S23741; S23741.
DR RefSeq; NP_001007793.1; NM_001007792.1. [P04629-3]
DR RefSeq; NP_001012331.1; NM_001012331.1. [P04629-2]
DR RefSeq; NP_002520.2; NM_002529.3. [P04629-1]
DR PDB; 1HE7; X-ray; 2.00 A; A=285-413.
DR PDB; 1SHC; NMR; -; B=489-500.
DR PDB; 1WWA; X-ray; 2.50 A; X/Y=278-386.
DR PDB; 1WWW; X-ray; 2.20 A; X/Y=282-382.
DR PDB; 2IFG; X-ray; 3.40 A; A/B=36-382.
DR PDB; 2N90; NMR; -; A/B=410-447.
DR PDB; 4AOJ; X-ray; 2.75 A; A/B/C=473-796.
DR PDB; 4CRP; NMR; -; A=282-383.
DR PDB; 4F0I; X-ray; 2.30 A; A/B=498-796.
DR PDB; 4GT5; X-ray; 2.40 A; A=498-796.
DR PDB; 4PMM; X-ray; 2.00 A; A=501-787.
DR PDB; 4PMP; X-ray; 1.80 A; A=501-787.
DR PDB; 4PMS; X-ray; 2.80 A; A=501-787.
DR PDB; 4PMT; X-ray; 2.10 A; A=501-787.
DR PDB; 4YNE; X-ray; 2.02 A; A=502-796.
DR PDB; 4YPS; X-ray; 2.10 A; A=502-796.
DR PDB; 5H3Q; X-ray; 2.10 A; A=473-796.
DR PDB; 5I8A; X-ray; 2.33 A; A=498-787.
DR PDB; 5JFS; X-ray; 2.07 A; A=502-796.
DR PDB; 5JFV; X-ray; 1.59 A; A=502-796.
DR PDB; 5JFW; X-ray; 1.52 A; A=502-796.
DR PDB; 5JFX; X-ray; 1.63 A; A=502-796.
DR PDB; 5KMI; X-ray; 1.87 A; A=474-796.
DR PDB; 5KMJ; X-ray; 2.04 A; A=474-796.
DR PDB; 5KMK; X-ray; 2.24 A; A=474-796.
DR PDB; 5KML; X-ray; 2.01 A; A=474-796.
DR PDB; 5KMM; X-ray; 2.12 A; A=474-796.
DR PDB; 5KMN; X-ray; 2.14 A; A=474-796.
DR PDB; 5KMO; X-ray; 2.67 A; A=474-796.
DR PDB; 5KVT; X-ray; 2.45 A; A=501-787.
DR PDB; 5WR7; X-ray; 2.76 A; A=489-792.
DR PDB; 6D1Y; X-ray; 1.93 A; A=479-796.
DR PDB; 6D1Z; X-ray; 1.87 A; A=479-796.
DR PDB; 6D20; X-ray; 1.94 A; A=479-796.
DR PDB; 6D22; X-ray; 2.46 A; A=502-796.
DR PDB; 6DKB; X-ray; 2.68 A; A=479-796.
DR PDB; 6DKG; X-ray; 2.53 A; A=479-796.
DR PDB; 6DKI; X-ray; 2.11 A; A=479-796.
DR PDB; 6DKW; X-ray; 2.91 A; A/B=502-796.
DR PDB; 6IQN; X-ray; 2.54 A; A/B=502-796.
DR PDB; 6J5L; X-ray; 2.30 A; A=502-796.
DR PDB; 6NPT; X-ray; 2.19 A; A=491-795.
DR PDB; 6NSP; X-ray; 2.31 A; A=500-796.
DR PDB; 6NSS; X-ray; 1.97 A; A=485-795.
DR PDB; 6PL1; X-ray; 2.03 A; A=485-795.
DR PDB; 6PL2; X-ray; 2.59 A; A=485-795.
DR PDB; 6PL3; X-ray; 3.00 A; A=485-795.
DR PDB; 6PL4; X-ray; 2.06 A; A=485-795.
DR PDB; 6PMA; X-ray; 2.53 A; A=485-795.
DR PDB; 6PMB; X-ray; 2.81 A; A=485-795.
DR PDB; 6PMC; X-ray; 2.19 A; A=485-795.
DR PDB; 6PME; X-ray; 3.00 A; A/B/C=485-795.
DR PDBsum; 1HE7; -.
DR PDBsum; 1SHC; -.
DR PDBsum; 1WWA; -.
DR PDBsum; 1WWW; -.
DR PDBsum; 2IFG; -.
DR PDBsum; 2N90; -.
DR PDBsum; 4AOJ; -.
DR PDBsum; 4CRP; -.
DR PDBsum; 4F0I; -.
DR PDBsum; 4GT5; -.
DR PDBsum; 4PMM; -.
DR PDBsum; 4PMP; -.
DR PDBsum; 4PMS; -.
DR PDBsum; 4PMT; -.
DR PDBsum; 4YNE; -.
DR PDBsum; 4YPS; -.
DR PDBsum; 5H3Q; -.
DR PDBsum; 5I8A; -.
DR PDBsum; 5JFS; -.
DR PDBsum; 5JFV; -.
DR PDBsum; 5JFW; -.
DR PDBsum; 5JFX; -.
DR PDBsum; 5KMI; -.
DR PDBsum; 5KMJ; -.
DR PDBsum; 5KMK; -.
DR PDBsum; 5KML; -.
DR PDBsum; 5KMM; -.
DR PDBsum; 5KMN; -.
DR PDBsum; 5KMO; -.
DR PDBsum; 5KVT; -.
DR PDBsum; 5WR7; -.
DR PDBsum; 6D1Y; -.
DR PDBsum; 6D1Z; -.
DR PDBsum; 6D20; -.
DR PDBsum; 6D22; -.
DR PDBsum; 6DKB; -.
DR PDBsum; 6DKG; -.
DR PDBsum; 6DKI; -.
DR PDBsum; 6DKW; -.
DR PDBsum; 6IQN; -.
DR PDBsum; 6J5L; -.
DR PDBsum; 6NPT; -.
DR PDBsum; 6NSP; -.
DR PDBsum; 6NSS; -.
DR PDBsum; 6PL1; -.
DR PDBsum; 6PL2; -.
DR PDBsum; 6PL3; -.
DR PDBsum; 6PL4; -.
DR PDBsum; 6PMA; -.
DR PDBsum; 6PMB; -.
DR PDBsum; 6PMC; -.
DR PDBsum; 6PME; -.
DR AlphaFoldDB; P04629; -.
DR BMRB; P04629; -.
DR SMR; P04629; -.
DR BioGRID; 110969; 1963.
DR CORUM; P04629; -.
DR DIP; DIP-5714N; -.
DR ELM; P04629; -.
DR IntAct; P04629; 30.
DR MINT; P04629; -.
DR STRING; 9606.ENSP00000431418; -.
DR BindingDB; P04629; -.
DR ChEMBL; CHEMBL2815; -.
DR DrugBank; DB00321; Amitriptyline.
DR DrugBank; DB13926; Cenegermin.
DR DrugBank; DB11986; Entrectinib.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB00619; Imatinib.
DR DrugBank; DB14723; Larotrectinib.
DR DrugBank; DB15822; Pralsetinib.
DR DrugBank; DB08896; Regorafenib.
DR DrugCentral; P04629; -.
DR GuidetoPHARMACOLOGY; 1817; -.
DR GlyGen; P04629; 13 sites.
DR iPTMnet; P04629; -.
DR PhosphoSitePlus; P04629; -.
DR BioMuta; NTRK1; -.
DR DMDM; 94730402; -.
DR MassIVE; P04629; -.
DR PaxDb; P04629; -.
DR PeptideAtlas; P04629; -.
DR PRIDE; P04629; -.
DR ProteomicsDB; 51723; -. [P04629-1]
DR ProteomicsDB; 51724; -. [P04629-2]
DR ProteomicsDB; 51725; -. [P04629-3]
DR ProteomicsDB; 51726; -. [P04629-4]
DR ABCD; P04629; 33 sequenced antibodies.
DR Antibodypedia; 3896; 1600 antibodies from 45 providers.
DR DNASU; 4914; -.
DR Ensembl; ENST00000368196.7; ENSP00000357179.3; ENSG00000198400.13. [P04629-2]
DR Ensembl; ENST00000524377.7; ENSP00000431418.1; ENSG00000198400.13. [P04629-1]
DR GeneID; 4914; -.
DR KEGG; hsa:4914; -.
DR MANE-Select; ENST00000524377.7; ENSP00000431418.1; NM_002529.4; NP_002520.2.
DR UCSC; uc001fqf.2; human. [P04629-1]
DR CTD; 4914; -.
DR DisGeNET; 4914; -.
DR GeneCards; NTRK1; -.
DR GeneReviews; NTRK1; -.
DR HGNC; HGNC:8031; NTRK1.
DR HPA; ENSG00000198400; Group enriched (adrenal gland, brain).
DR MalaCards; NTRK1; -.
DR MIM; 164970; gene.
DR MIM; 191315; gene.
DR MIM; 256800; phenotype.
DR neXtProt; NX_P04629; -.
DR OpenTargets; ENSG00000198400; -.
DR Orphanet; 146; Differentiated thyroid carcinoma.
DR Orphanet; 99361; Familial medullary thyroid carcinoma.
DR Orphanet; 642; Hereditary sensory and autonomic neuropathy type 4.
DR Orphanet; 64752; Hereditary sensory and autonomic neuropathy type 5.
DR PharmGKB; PA31817; -.
DR VEuPathDB; HostDB:ENSG00000198400; -.
DR eggNOG; KOG1026; Eukaryota.
DR GeneTree; ENSGT00940000159412; -.
DR HOGENOM; CLU_000288_74_1_1; -.
DR InParanoid; P04629; -.
DR OMA; IMLKWEL; -.
DR OrthoDB; 295510at2759; -.
DR PhylomeDB; P04629; -.
DR TreeFam; TF106465; -.
DR BRENDA; 2.7.10.1; 2681.
DR PathwayCommons; P04629; -.
DR Reactome; R-HSA-167021; PLC-gamma1 signalling.
DR Reactome; R-HSA-167044; Signalling to RAS.
DR Reactome; R-HSA-170968; Frs2-mediated activation. [P04629-1]
DR Reactome; R-HSA-170984; ARMS-mediated activation.
DR Reactome; R-HSA-177504; Retrograde neurotrophin signalling.
DR Reactome; R-HSA-187024; NGF-independant TRKA activation.
DR Reactome; R-HSA-187042; TRKA activation by NGF.
DR Reactome; R-HSA-187706; Signalling to p38 via RIT and RIN.
DR Reactome; R-HSA-198203; PI3K/AKT activation.
DR Reactome; R-HSA-198745; Signalling to STAT3.
DR SignaLink; P04629; -.
DR SIGNOR; P04629; -.
DR BioGRID-ORCS; 4914; 14 hits in 1111 CRISPR screens.
DR ChiTaRS; NTRK1; human.
DR EvolutionaryTrace; P04629; -.
DR GenomeRNAi; 4914; -.
DR Pharos; P04629; Tclin.
DR PRO; PR:P04629; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P04629; protein.
DR Bgee; ENSG00000198400; Expressed in dorsal root ganglion and 94 other tissues.
DR ExpressionAtlas; P04629; baseline and differential.
DR Genevisible; P04629; HS.
DR GO; GO:0030424; C:axon; IBA:GO_Central.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0005769; C:early endosome; ISS:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0010008; C:endosome membrane; TAS:Reactome.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005770; C:late endosome; ISS:UniProtKB.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISS:UniProtKB.
DR GO; GO:0043235; C:receptor complex; IDA:MGI.
DR GO; GO:0055038; C:recycling endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005004; F:GPI-linked ephrin receptor activity; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0019900; F:kinase binding; IEA:Ensembl.
DR GO; GO:0048406; F:nerve growth factor binding; IDA:UniProtKB.
DR GO; GO:0010465; F:nerve growth factor receptor activity; IDA:UniProtKB.
DR GO; GO:0043121; F:neurotrophin binding; IBA:GO_Central.
DR GO; GO:0005166; F:neurotrophin p75 receptor binding; IEA:Ensembl.
DR GO; GO:0005030; F:neurotrophin receptor activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IDA:MGI.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0007411; P:axon guidance; IEA:Ensembl.
DR GO; GO:0060385; P:axonogenesis involved in innervation; ISS:UniProtKB.
DR GO; GO:0030183; P:B cell differentiation; IEA:Ensembl.
DR GO; GO:0061368; P:behavioral response to formalin induced pain; IEA:Ensembl.
DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IMP:UniProtKB.
DR GO; GO:0071316; P:cellular response to nicotine; IEA:Ensembl.
DR GO; GO:0007623; P:circadian rhythm; IEA:Ensembl.
DR GO; GO:0050966; P:detection of mechanical stimulus involved in sensory perception of pain; IEA:Ensembl.
DR GO; GO:0050965; P:detection of temperature stimulus involved in sensory perception of pain; IEA:Ensembl.
DR GO; GO:0007611; P:learning or memory; IEA:Ensembl.
DR GO; GO:0042490; P:mechanoreceptor differentiation; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:ARUK-UCL.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISS:UniProtKB.
DR GO; GO:0038180; P:nerve growth factor signaling pathway; IMP:UniProtKB.
DR GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0048666; P:neuron development; IDA:MGI.
DR GO; GO:0031175; P:neuron projection development; IDA:MGI.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0021553; P:olfactory nerve development; IEA:Ensembl.
DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; IDA:MGI.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IDA:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IDA: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; IDA:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IBA:GO_Central.
DR GO; GO:0043068; P:positive regulation of programmed cell death; ISS:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; TAS:BHF-UCL.
DR GO; GO:0046579; P:positive regulation of Ras protein signal transduction; IDA:UniProtKB.
DR GO; GO:0051965; P:positive regulation of synapse assembly; IEA:Ensembl.
DR GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; IEA:Ensembl.
DR GO; GO:0010623; P:programmed cell death involved in cell development; ISS:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0051896; P:regulation of protein kinase B signaling; IBA:GO_Central.
DR GO; GO:0048678; P:response to axon injury; IEA:Ensembl.
DR GO; GO:0051602; P:response to electrical stimulus; IEA:Ensembl.
DR GO; GO:0051599; P:response to hydrostatic pressure; IEA:Ensembl.
DR GO; GO:0031667; P:response to nutrient levels; IEA:Ensembl.
DR GO; GO:0009314; P:response to radiation; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0060009; P:Sertoli cell development; IEA:Ensembl.
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 IDEAL; IID00535; -.
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; 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; 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; 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 3D-structure; Alternative splicing; ATP-binding; Cell membrane;
KW Chromosomal rearrangement; Developmental protein; Differentiation;
KW Disease variant; Disulfide bond; Endosome; Glycoprotein;
KW Immunoglobulin domain; Kinase; Leucine-rich repeat; Membrane; Neurogenesis;
KW Nucleotide-binding; Phosphoprotein; Proto-oncogene; Receptor;
KW Reference proteome; Repeat; Signal; Transferase; Transmembrane;
KW Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation.
FT SIGNAL 1..32
FT /evidence="ECO:0000255"
FT CHAIN 33..796
FT /note="High affinity nerve growth factor receptor"
FT /id="PRO_0000016724"
FT TOPO_DOM 33..423
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 424..439
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 440..796
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 90..113
FT /note="LRR 1"
FT REPEAT 116..137
FT /note="LRR 2"
FT DOMAIN 148..193
FT /note="LRRCT"
FT DOMAIN 194..283
FT /note="Ig-like C2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DOMAIN 299..365
FT /note="Ig-like C2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DOMAIN 510..781
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 469..490
FT /note="Interaction with SQSTM1"
FT /evidence="ECO:0000250"
FT MOTIF 537..541
FT /note="DXXLL"
FT /evidence="ECO:0000269|PubMed:26446845"
FT MOTIF 607..611
FT /note="DXXLL"
FT /evidence="ECO:0000269|PubMed:26446845"
FT ACT_SITE 650
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 516..524
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 544
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 398..399
FT /note="Breakpoint for translocation to form TRK and TRK-T3"
FT SITE 486
FT /note="Breakpoint for translocation to form TRK-T1"
FT SITE 496
FT /note="Interaction with SHC1"
FT SITE 791
FT /note="Interaction with PLCG1"
FT MOD_RES 496
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15488758,
FT ECO:0000269|PubMed:27676246, ECO:0000269|PubMed:8155326"
FT MOD_RES 676
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:8155326"
FT MOD_RES 680
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15488758,
FT ECO:0000269|PubMed:8155326"
FT MOD_RES 681
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15488758,
FT ECO:0000269|PubMed:8155326"
FT MOD_RES 791
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15488758,
FT ECO:0000269|PubMed:7510697, ECO:0000269|PubMed:8155326"
FT CARBOHYD 67
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 95
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17196528"
FT CARBOHYD 121
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17196528"
FT CARBOHYD 188
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17196528,
FT ECO:0007744|PDB:2IFG"
FT CARBOHYD 202
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 253
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 262
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17196528,
FT ECO:0007744|PDB:2IFG"
FT CARBOHYD 281
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17196528,
FT ECO:0007744|PDB:2IFG"
FT CARBOHYD 318
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 323
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 338
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 358
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17196528,
FT ECO:0007744|PDB:2IFG"
FT CARBOHYD 401
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 36..41
FT /evidence="ECO:0007744|PDB:2IFG"
FT DISULFID 40..50
FT /evidence="ECO:0007744|PDB:2IFG"
FT DISULFID 154..191
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:17196528, ECO:0007744|PDB:2IFG"
FT DISULFID 215..265
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:17196528, ECO:0007744|PDB:2IFG"
FT DISULFID 300..345
FT /evidence="ECO:0007744|PDB:1HE7, ECO:0007744|PDB:1WWA,
FT ECO:0007744|PDB:1WWW, ECO:0007744|PDB:2IFG,
FT ECO:0007744|PDB:4CRP"
FT VAR_SEQ 1..71
FT /note="MLRGGRRGQLGWHSWAAGPGSLLAWLILASAGAAPCPDACCPHGSSGLRCTR
FT DGALDSLHHLPGAENLTEL -> MKEAALICLAPSVPPILTVKSWDTMQLRAARSRCTN
FT LLAAS (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_041905"
FT VAR_SEQ 192..284
FT /note="GVPTLKVQVPNASVDVGDDVLLRCQVEGRGLEQAGWILTELEQSATVMKSGG
FT LPSLGLTLANVTSDLNRKNVTCWAENDVGRAEVSVQVNVSF -> V (in isoform
FT TrkA-III)"
FT /evidence="ECO:0000305"
FT /id="VSP_042152"
FT VAR_SEQ 393..398
FT /note="Missing (in isoform TrkA-I, isoform 3 and isoform
FT TrkA-III)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:2927393"
FT /id="VSP_002899"
FT VARIANT 6
FT /note="R -> W (in dbSNP:rs201472270)"
FT /evidence="ECO:0000269|PubMed:22302274"
FT /id="VAR_068480"
FT VARIANT 18
FT /note="G -> E (in dbSNP:rs1007211)"
FT /id="VAR_049714"
FT VARIANT 80
FT /note="Q -> R (in dbSNP:rs55891455)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041461"
FT VARIANT 85
FT /note="R -> S (in dbSNP:rs543320028)"
FT /evidence="ECO:0000269|PubMed:10330344,
FT ECO:0000269|PubMed:11159935"
FT /id="VAR_009623"
FT VARIANT 93
FT /note="L -> P (in CIPA; aberrantly processed; shows
FT diminished autophosphorylation in neuronal cells)"
FT /evidence="ECO:0000269|PubMed:10982191,
FT ECO:0000269|PubMed:11159935"
FT /id="VAR_009624"
FT VARIANT 107
FT /note="A -> V (in an ovarian serous carcinoma sample;
FT somatic mutation; dbSNP:rs540521894)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041462"
FT VARIANT 110
FT /note="A -> D (in CIPA)"
FT /evidence="ECO:0000269|PubMed:28328124"
FT /id="VAR_079399"
FT VARIANT 146..796
FT /note="Missing (in CIPA)"
FT /evidence="ECO:0000269|PubMed:28328124"
FT /id="VAR_079400"
FT VARIANT 176..796
FT /note="Missing (in CIPA)"
FT /evidence="ECO:0000269|PubMed:28328124"
FT /id="VAR_079401"
FT VARIANT 213
FT /note="L -> P (in CIPA; aberrantly processed; shows
FT diminished autophosphorylation in neuronal cells;
FT dbSNP:rs747711259)"
FT /evidence="ECO:0000269|PubMed:10330344,
FT ECO:0000269|PubMed:11159935"
FT /id="VAR_009625"
FT VARIANT 235..796
FT /note="Missing (in CIPA; loss of protein)"
FT /evidence="ECO:0000269|PubMed:28177573"
FT /id="VAR_079402"
FT VARIANT 237
FT /note="T -> M (in dbSNP:rs55909005)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041463"
FT VARIANT 238
FT /note="V -> G (in dbSNP:rs56000394)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041464"
FT VARIANT 260
FT /note="R -> G (in dbSNP:rs35116695)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041465"
FT VARIANT 359
FT /note="Y -> C (in CIPA; dbSNP:rs121964869)"
FT /evidence="ECO:0000269|PubMed:11310631"
FT /id="VAR_068481"
FT VARIANT 444
FT /note="R -> Q (in dbSNP:rs56320207)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041466"
FT VARIANT 452
FT /note="R -> C (in dbSNP:rs34900547)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041467"
FT VARIANT 476..796
FT /note="Missing (in CIPA)"
FT /evidence="ECO:0000269|PubMed:28328124"
FT /id="VAR_079403"
FT VARIANT 492
FT /note="E -> K (in CIPA; dbSNP:rs144901788)"
FT /evidence="ECO:0000269|PubMed:22302274"
FT /id="VAR_068482"
FT VARIANT 517
FT /note="G -> E (in CIPA; following transfection in
FT neuroblastoma cells and NGF treatment, small decrease in
FT the percentage of cells differentiated into neuronal
FT phenotype, but in differentiated cells, the average neurite
FT length is comparable to wild-type; no effect on N-
FT glycosylation, subcellular location, nor on basal and NGF-
FT induced autophosphorylation; loss of NGF-stimulated calcium
FT flux; dbSNP:rs606231467)"
FT /evidence="ECO:0000269|PubMed:27676246"
FT /id="VAR_077472"
FT VARIANT 522
FT /note="G -> E (in CIPA; no effect on N-glycosylation, nor
FT on subcellular location; reduced basal autophosphorylation
FT and complete loss of NGF-induced autophosphorylation; loss
FT of NGF-stimulated calcium flux)"
FT /evidence="ECO:0000269|PubMed:27676246"
FT /id="VAR_077473"
FT VARIANT 522
FT /note="G -> R (in CIPA; processed as wild-type but shows
FT significantly diminished autophosphorylation in both
FT neuronal and non-neuronal cells; dbSNP:rs1571699266)"
FT /evidence="ECO:0000269|PubMed:10982191,
FT ECO:0000269|PubMed:11159935"
FT /id="VAR_009626"
FT VARIANT 566
FT /note="M -> T (in dbSNP:rs55892037)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041468"
FT VARIANT 572
FT /note="I -> S (in CIPA)"
FT /evidence="ECO:0000269|PubMed:18077166"
FT /id="VAR_077474"
FT VARIANT 577
FT /note="G -> R (in CIPA; loss of function; processed as
FT wild-type but shows significantly diminished
FT autophosphorylation in both neuronal and non-neuronal
FT cells; dbSNP:rs121964866)"
FT /evidence="ECO:0000269|PubMed:10567924,
FT ECO:0000269|PubMed:10982191, ECO:0000269|PubMed:11159935,
FT ECO:0000269|PubMed:8696348"
FT /id="VAR_004103"
FT VARIANT 587
FT /note="M -> V (in CIPA; dbSNP:rs121964870)"
FT /evidence="ECO:0000269|PubMed:10233776"
FT /id="VAR_009627"
FT VARIANT 596
FT /note="D -> N (in CIPA; abolishes autophosphorylation)"
FT /evidence="ECO:0000269|PubMed:28177573"
FT /id="VAR_079404"
FT VARIANT 604
FT /note="H -> Y (in dbSNP:rs6336)"
FT /evidence="ECO:0000269|PubMed:10330344,
FT ECO:0000269|PubMed:10391209, ECO:0000269|PubMed:10443680,
FT ECO:0000269|PubMed:11159935, ECO:0000269|PubMed:11310631,
FT ECO:0000269|PubMed:17344846"
FT /id="VAR_009628"
FT VARIANT 613
FT /note="G -> V (in dbSNP:rs6339)"
FT /evidence="ECO:0000269|PubMed:10330344,
FT ECO:0000269|PubMed:10391209, ECO:0000269|PubMed:10443680,
FT ECO:0000269|PubMed:10861667, ECO:0000269|PubMed:11159935,
FT ECO:0000269|PubMed:11310631, ECO:0000269|PubMed:17344846"
FT /id="VAR_009629"
FT VARIANT 649
FT /note="R -> Q (in CIPA; dbSNP:rs786205449)"
FT /evidence="ECO:0000269|PubMed:28328124"
FT /id="VAR_079405"
FT VARIANT 649
FT /note="R -> W (in CIPA; processed as wild-type but shows
FT significantly diminished autophosphorylation in both
FT neuronal and non-neuronal cells; dbSNP:rs369353892)"
FT /evidence="ECO:0000269|PubMed:10330344,
FT ECO:0000269|PubMed:11159935"
FT /id="VAR_009630"
FT VARIANT 654
FT /note="R -> C (in CIPA; processed as wild-type but shows
FT significantly diminished autophosphorylation in both
FT neuronal and non-neuronal cells; dbSNP:rs764992664)"
FT /evidence="ECO:0000269|PubMed:10982191,
FT ECO:0000269|PubMed:11159935, ECO:0000269|PubMed:22302274"
FT /id="VAR_009631"
FT VARIANT 657
FT /note="L -> P (in CIPA; following transfection in
FT neuroblastoma cells and NGF treatment, loss of
FT differentiation into neuronal phenotype; partially
FT decreased N-glycosylation; reduced expression at the plasma
FT membrane; reduced basal autophosphorylation and complete
FT loss of NGF-induced autophosphorylation; loss of NGF-
FT stimulated calcium flux)"
FT /evidence="ECO:0000269|PubMed:27676246"
FT /id="VAR_077475"
FT VARIANT 674
FT /note="D -> Y (in CIPA; might impair the function of the
FT enzyme without compromising autophosphorylation;
FT dbSNP:rs80356677)"
FT /evidence="ECO:0000269|PubMed:10982191,
FT ECO:0000269|PubMed:11159935, ECO:0000269|PubMed:28177573"
FT /id="VAR_009632"
FT VARIANT 695
FT /note="P -> L (in CIPA; dbSNP:rs121964868)"
FT /evidence="ECO:0000269|PubMed:10861667"
FT /id="VAR_009633"
FT VARIANT 699
FT /note="I -> T (in CIPA; partially decreased N-
FT glycosylation; reduced expression at the plasma membrane;
FT reduced basal autophosphorylation and complete loss of NGF-
FT induced autophosphorylation; loss of NGF-stimulated calcium
FT flux)"
FT /evidence="ECO:0000269|PubMed:27676246"
FT /id="VAR_077476"
FT VARIANT 700
FT /note="L -> P (in CIPA)"
FT /evidence="ECO:0000269|PubMed:28328124"
FT /id="VAR_079406"
FT VARIANT 714
FT /note="G -> S (in CIPA; processed as wild-type but shows
FT significantly diminished autophosphorylation in both
FT neuronal and non-neuronal cells; dbSNP:rs770727871)"
FT /evidence="ECO:0000269|PubMed:10330344,
FT ECO:0000269|PubMed:11159935"
FT /id="VAR_009634"
FT VARIANT 717
FT /note="L -> R (in CIPA)"
FT /evidence="ECO:0000269|PubMed:18077166"
FT /id="VAR_077477"
FT VARIANT 752
FT /note="C -> S (in CIPA; unknown pathological significance;
FT following transfection in neuroblastoma cells and NGF
FT treatment, no effect on neurite outgrowth, nor neurite
FT length; no effect on N-glycosylation, subcellular location,
FT basal and NGF-induced autophosphorylation, nor on NGF-
FT stimulated calcium flux)"
FT /evidence="ECO:0000269|PubMed:27676246"
FT /id="VAR_077478"
FT VARIANT 763
FT /note="C -> S (in CIPA; following transfection in
FT neuroblastoma cells and NGF treatment, decreased percentage
FT of cells differentiated into neuronal phenotype and reduced
FT neurite length compared with wild-type; slightly decreased
FT N-glycosylation; reduced expression at the plasma membrane;
FT reduced basal and NGF-induced autophosphorylation; small
FT reduction in NGF-stimulated calcium flux)"
FT /evidence="ECO:0000269|PubMed:27676246"
FT /id="VAR_077479"
FT VARIANT 771
FT /note="R -> C (in CIPA; partially decreased N-
FT glycosylation; reduced expression at the plasma membrane;
FT reduced basal autophosphorylation and complete loss of NGF-
FT induced autophosphorylation; loss of NGF-stimulated calcium
FT flux; dbSNP:rs1324983370)"
FT /evidence="ECO:0000269|PubMed:27676246"
FT /id="VAR_077480"
FT VARIANT 780
FT /note="R -> P (in CIPA; loss of function;
FT dbSNP:rs35669708)"
FT /evidence="ECO:0000269|PubMed:10090906"
FT /id="VAR_009635"
FT VARIANT 780
FT /note="R -> Q (in dbSNP:rs35669708)"
FT /evidence="ECO:0000269|PubMed:10443680,
FT ECO:0000269|PubMed:17344846"
FT /id="VAR_009636"
FT VARIANT 790
FT /note="V -> I (in dbSNP:rs55948542)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041469"
FT MUTAGEN 496
FT /note="Y->F: Loss of interaction with SHC1 and altered
FT phosphorylation of SHC1. Altered neurite outgrowth and
FT altered activation of the MAPK pathway; when associated
FT with F-791."
FT /evidence="ECO:0000269|PubMed:8155326"
FT MUTAGEN 540..541
FT /note="LV->AA: Abolishes interaction with GGA3."
FT /evidence="ECO:0000269|PubMed:26446845"
FT MUTAGEN 544
FT /note="K->A: No effect on interaction with GGA3."
FT /evidence="ECO:0000269|PubMed:26446845"
FT MUTAGEN 544
FT /note="K->N: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:1281417,
FT ECO:0000269|PubMed:8155326"
FT MUTAGEN 610..611
FT /note="LL->AA: No effect on interaction with GGA3."
FT /evidence="ECO:0000269|PubMed:26446845"
FT MUTAGEN 791
FT /note="Y->F: Loss of interaction with PLCG1 and altered
FT phosphorylation of PLCG1. Altered neurite outgrowth and
FT altered activation of the MAPK pathway; when associated
FT with F-496."
FT /evidence="ECO:0000269|PubMed:7510697,
FT ECO:0000269|PubMed:8155326"
FT CONFLICT 263
FT /note="V -> L (in Ref. 1; AAA36770)"
FT /evidence="ECO:0000305"
FT CONFLICT 300
FT /note="C -> S (in Ref. 1; AAA36770)"
FT /evidence="ECO:0000305"
FT CONFLICT 529
FT /note="C -> S (in Ref. 10; CAA59936)"
FT /evidence="ECO:0000305"
FT STRAND 38..40
FT /evidence="ECO:0007829|PDB:2IFG"
FT STRAND 43..46
FT /evidence="ECO:0007829|PDB:2IFG"
FT TURN 57..61
FT /evidence="ECO:0007829|PDB:2IFG"
FT STRAND 69..72
FT /evidence="ECO:0007829|PDB:2IFG"
FT HELIX 84..86
FT /evidence="ECO:0007829|PDB:2IFG"
FT STRAND 94..97
FT /evidence="ECO:0007829|PDB:2IFG"
FT HELIX 110..112
FT /evidence="ECO:0007829|PDB:2IFG"
FT STRAND 119..121
FT /evidence="ECO:0007829|PDB:2IFG"
FT TURN 133..135
FT /evidence="ECO:0007829|PDB:2IFG"
FT STRAND 142..144
FT /evidence="ECO:0007829|PDB:2IFG"
FT HELIX 154..156
FT /evidence="ECO:0007829|PDB:2IFG"
FT HELIX 157..164
FT /evidence="ECO:0007829|PDB:2IFG"
FT HELIX 171..173
FT /evidence="ECO:0007829|PDB:2IFG"
FT STRAND 178..181
FT /evidence="ECO:0007829|PDB:2IFG"
FT STRAND 195..199
FT /evidence="ECO:0007829|PDB:2IFG"
FT STRAND 211..218
FT /evidence="ECO:0007829|PDB:2IFG"
FT STRAND 227..230
FT /evidence="ECO:0007829|PDB:2IFG"
FT STRAND 234..238
FT /evidence="ECO:0007829|PDB:2IFG"
FT STRAND 244..253
FT /evidence="ECO:0007829|PDB:2IFG"
FT TURN 257..260
FT /evidence="ECO:0007829|PDB:2IFG"
FT STRAND 263..265
FT /evidence="ECO:0007829|PDB:2IFG"
FT STRAND 276..278
FT /evidence="ECO:0007829|PDB:2IFG"
FT STRAND 284..290
FT /evidence="ECO:0007829|PDB:1WWW"
FT STRAND 298..305
FT /evidence="ECO:0007829|PDB:1HE7"
FT STRAND 312..317
FT /evidence="ECO:0007829|PDB:1HE7"
FT STRAND 326..333
FT /evidence="ECO:0007829|PDB:1HE7"
FT STRAND 342..350
FT /evidence="ECO:0007829|PDB:1HE7"
FT HELIX 353..355
FT /evidence="ECO:0007829|PDB:1HE7"
FT STRAND 357..365
FT /evidence="ECO:0007829|PDB:1HE7"
FT STRAND 368..376
FT /evidence="ECO:0007829|PDB:1HE7"
FT HELIX 418..441
FT /evidence="ECO:0007829|PDB:2N90"
FT STRAND 476..478
FT /evidence="ECO:0007829|PDB:5KML"
FT HELIX 490..492
FT /evidence="ECO:0007829|PDB:5KMI"
FT TURN 494..496
FT /evidence="ECO:0007829|PDB:1SHC"
FT HELIX 507..509
FT /evidence="ECO:0007829|PDB:5JFW"
FT STRAND 510..517
FT /evidence="ECO:0007829|PDB:5JFW"
FT STRAND 520..522
FT /evidence="ECO:0007829|PDB:5JFW"
FT STRAND 524..533
FT /evidence="ECO:0007829|PDB:5JFW"
FT TURN 534..536
FT /evidence="ECO:0007829|PDB:5KMI"
FT STRAND 537..545
FT /evidence="ECO:0007829|PDB:5JFW"
FT HELIX 552..566
FT /evidence="ECO:0007829|PDB:5JFW"
FT STRAND 575..579
FT /evidence="ECO:0007829|PDB:5JFW"
FT STRAND 581..584
FT /evidence="ECO:0007829|PDB:5JFW"
FT STRAND 586..590
FT /evidence="ECO:0007829|PDB:5JFW"
FT HELIX 597..603
FT /evidence="ECO:0007829|PDB:5JFW"
FT STRAND 605..607
FT /evidence="ECO:0007829|PDB:4F0I"
FT HELIX 608..611
FT /evidence="ECO:0007829|PDB:4PMP"
FT STRAND 615..617
FT /evidence="ECO:0007829|PDB:6NSS"
FT STRAND 619..621
FT /evidence="ECO:0007829|PDB:5KMI"
FT HELIX 624..643
FT /evidence="ECO:0007829|PDB:5JFW"
FT STRAND 646..648
FT /evidence="ECO:0007829|PDB:5KML"
FT HELIX 653..655
FT /evidence="ECO:0007829|PDB:5JFW"
FT STRAND 656..659
FT /evidence="ECO:0007829|PDB:5JFW"
FT HELIX 660..662
FT /evidence="ECO:0007829|PDB:5JFW"
FT STRAND 663..666
FT /evidence="ECO:0007829|PDB:5JFW"
FT HELIX 672..675
FT /evidence="ECO:0007829|PDB:5KMI"
FT HELIX 677..679
FT /evidence="ECO:0007829|PDB:4PMP"
FT STRAND 680..683
FT /evidence="ECO:0007829|PDB:5KMI"
FT TURN 684..686
FT /evidence="ECO:0007829|PDB:5KMI"
FT STRAND 687..689
FT /evidence="ECO:0007829|PDB:5KMI"
FT HELIX 691..693
FT /evidence="ECO:0007829|PDB:5JFW"
FT HELIX 696..701
FT /evidence="ECO:0007829|PDB:5JFW"
FT HELIX 706..721
FT /evidence="ECO:0007829|PDB:5JFW"
FT TURN 722..724
FT /evidence="ECO:0007829|PDB:5JFV"
FT TURN 727..730
FT /evidence="ECO:0007829|PDB:5JFW"
FT HELIX 733..742
FT /evidence="ECO:0007829|PDB:5JFW"
FT HELIX 754..763
FT /evidence="ECO:0007829|PDB:5JFW"
FT HELIX 768..770
FT /evidence="ECO:0007829|PDB:5JFW"
FT HELIX 774..786
FT /evidence="ECO:0007829|PDB:5JFW"
FT HELIX 789..793
FT /evidence="ECO:0007829|PDB:5KMI"
SQ SEQUENCE 796 AA; 87497 MW; 6C15C721E336B601 CRC64;
MLRGGRRGQL GWHSWAAGPG SLLAWLILAS AGAAPCPDAC CPHGSSGLRC TRDGALDSLH
HLPGAENLTE LYIENQQHLQ HLELRDLRGL GELRNLTIVK SGLRFVAPDA FHFTPRLSRL
NLSFNALESL SWKTVQGLSL QELVLSGNPL HCSCALRWLQ RWEEEGLGGV PEQKLQCHGQ
GPLAHMPNAS CGVPTLKVQV PNASVDVGDD VLLRCQVEGR GLEQAGWILT ELEQSATVMK
SGGLPSLGLT LANVTSDLNR KNVTCWAEND VGRAEVSVQV NVSFPASVQL HTAVEMHHWC
IPFSVDGQPA PSLRWLFNGS VLNETSFIFT EFLEPAANET VRHGCLRLNQ PTHVNNGNYT
LLAANPFGQA SASIMAAFMD NPFEFNPEDP IPVSFSPVDT NSTSGDPVEK KDETPFGVSV
AVGLAVFACL FLSTLLLVLN KCGRRNKFGI NRPAVLAPED GLAMSLHFMT LGGSSLSPTE
GKGSGLQGHI IENPQYFSDA CVHHIKRRDI VLKWELGEGA FGKVFLAECH NLLPEQDKML
VAVKALKEAS ESARQDFQRE AELLTMLQHQ HIVRFFGVCT EGRPLLMVFE YMRHGDLNRF
LRSHGPDAKL LAGGEDVAPG PLGLGQLLAV ASQVAAGMVY LAGLHFVHRD LATRNCLVGQ
GLVVKIGDFG MSRDIYSTDY YRVGGRTMLP IRWMPPESIL YRKFTTESDV WSFGVVLWEI
FTYGKQPWYQ LSNTEAIDCI TQGRELERPR ACPPEVYAIM RGCWQREPQQ RHSIKDVHAR
LQALAQAPPV YLDVLG
