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 27-MAR-2024, entry version 272. 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}, TRKA GN {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; P08238: HSP90AB1; NbExp=3; IntAct=EBI-1028226, EBI-352572; 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; Q16288: NTRK3; NbExp=2; IntAct=EBI-1028226, EBI-3936704; CC P04629; P27986: PIK3R1; NbExp=4; IntAct=EBI-1028226, EBI-79464; CC P04629; P19174: PLCG1; NbExp=4; IntAct=EBI-1028226, EBI-79387; 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 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 PDB; 7N3T; X-ray; 1.84 A; A/B=36-382. DR PDB; 7VKM; X-ray; 2.55 A; A=502-796. DR PDB; 7VKN; X-ray; 2.70 A; A=502-796. DR PDB; 7VKO; X-ray; 2.90 A; A=502-796. DR PDB; 7XAF; X-ray; 3.00 A; A=498-796. DR PDB; 7XBI; X-ray; 2.16 A; A=485-795. DR PDB; 8J5W; X-ray; 2.28 A; A=484-796. DR PDB; 8J5X; X-ray; 2.09 A; A=498-796. DR PDB; 8J61; X-ray; 3.05 A; A=498-796. DR PDB; 8J63; X-ray; 3.00 A; A=498-796. 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 PDBsum; 7N3T; -. DR PDBsum; 7VKM; -. DR PDBsum; 7VKN; -. DR PDBsum; 7VKO; -. DR PDBsum; 7XAF; -. DR PDBsum; 7XBI; -. DR PDBsum; 8J5W; -. DR PDBsum; 8J5X; -. DR PDBsum; 8J61; -. DR PDBsum; 8J63; -. DR AlphaFoldDB; P04629; -. DR BMRB; P04629; -. DR SMR; P04629; -. DR BioGRID; 110969; 2050. DR CORUM; P04629; -. DR DIP; DIP-5714N; -. DR ELM; P04629; -. DR IntAct; P04629; 213. 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 GlyCosmos; P04629; 13 sites, No reported glycans. DR GlyGen; P04629; 13 sites. DR iPTMnet; P04629; -. DR PhosphoSitePlus; P04629; -. DR BioMuta; NTRK1; -. DR DMDM; 94730402; -. DR CPTAC; CPTAC-3047; -. DR CPTAC; CPTAC-3048; -. DR MassIVE; P04629; -. DR PaxDb; 9606-ENSP00000431418; -. DR PeptideAtlas; P04629; -. DR ProteomicsDB; 51723; -. [P04629-1] DR ProteomicsDB; 51724; -. [P04629-2] DR ProteomicsDB; 51725; -. [P04629-3] DR ProteomicsDB; 51726; -. [P04629-4] DR Pumba; P04629; -. DR ABCD; P04629; 33 sequenced antibodies. DR Antibodypedia; 3896; 1895 antibodies from 45 providers. DR DNASU; 4914; -. DR Ensembl; ENST00000368196.7; ENSP00000357179.3; ENSG00000198400.14. [P04629-2] DR Ensembl; ENST00000524377.7; ENSP00000431418.1; ENSG00000198400.14. [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 AGR; HGNC:8031; -. DR CTD; 4914; -. DR DisGeNET; 4914; -. DR GeneCards; NTRK1; -. DR GeneReviews; NTRK1; -. DR HGNC; HGNC:8031; NTRK1. DR HPA; ENSG00000198400; Tissue enhanced (adrenal). 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; LTCHISA; -. DR OrthoDB; 1614410at2759; -. 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; 16 hits in 1198 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 96 other cell types or tissues. DR ExpressionAtlas; P04629; baseline and differential. 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: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: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: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:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; 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 phosphatidylinositol 3-kinase/protein kinase B signal transduction; 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: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 CDD; cd04972; Ig_TrkABC_d4; 1. DR CDD; cd04971; IgI_TrKABC_d5; 1. DR CDD; cd05092; PTKc_TrkA; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 2. DR Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 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 PANTHER; PTHR24416:SF370; HIGH AFFINITY NERVE GROWTH FACTOR RECEPTOR; 1. DR PANTHER; PTHR24416; TYROSINE-PROTEIN KINASE RECEPTOR; 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; SM00082; LRRCT; 1. DR SMART; SM00219; TyrKc; 1. DR SUPFAM; SSF48726; Immunoglobulin; 2. DR SUPFAM; SSF52058; L domain-like; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 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. DR Genevisible; P04629; HS. 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 FT N-glycosylation, subcellular location, nor on basal and FT NGF-induced autophosphorylation; loss of NGF-stimulated FT calcium 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 FT NGF-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 FT N-glycosylation; reduced expression at the plasma membrane; FT reduced basal autophosphorylation and complete loss of FT NGF-induced autophosphorylation; loss of NGF-stimulated FT calcium 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; uncertain significance; following FT transfection in neuroblastoma cells and NGF treatment, no FT effect on neurite outgrowth, nor neurite length; no effect FT on N-glycosylation, subcellular location, basal and FT NGF-induced autophosphorylation, nor on NGF-stimulated FT 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 FT N-glycosylation; reduced expression at the plasma membrane; FT reduced basal autophosphorylation and complete loss of FT NGF-induced autophosphorylation; loss of NGF-stimulated FT calcium 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 37..43 FT /evidence="ECO:0007829|PDB:7N3T" FT TURN 44..46 FT /evidence="ECO:0007829|PDB:7N3T" FT STRAND 47..50 FT /evidence="ECO:0007829|PDB:7N3T" FT HELIX 55..59 FT /evidence="ECO:0007829|PDB:7N3T" FT HELIX 65..67 FT /evidence="ECO:0007829|PDB:7N3T" FT STRAND 70..74 FT /evidence="ECO:0007829|PDB:7N3T" FT STRAND 80..82 FT /evidence="ECO:0007829|PDB:7N3T" FT HELIX 84..87 FT /evidence="ECO:0007829|PDB:7N3T" FT STRAND 95..101 FT /evidence="ECO:0007829|PDB:7N3T" FT TURN 108..113 FT /evidence="ECO:0007829|PDB:7N3T" FT STRAND 119..121 FT /evidence="ECO:0007829|PDB:7N3T" FT HELIX 132..135 FT /evidence="ECO:0007829|PDB:7N3T" FT STRAND 141..144 FT /evidence="ECO:0007829|PDB:7N3T" FT HELIX 154..156 FT /evidence="ECO:0007829|PDB:7N3T" FT HELIX 157..165 FT /evidence="ECO:0007829|PDB:7N3T" FT HELIX 170..173 FT /evidence="ECO:0007829|PDB:7N3T" FT STRAND 180..182 FT /evidence="ECO:0007829|PDB:7N3T" FT HELIX 183..185 FT /evidence="ECO:0007829|PDB:7N3T" FT STRAND 195..199 FT /evidence="ECO:0007829|PDB:7N3T" FT STRAND 211..218 FT /evidence="ECO:0007829|PDB:7N3T" FT STRAND 224..229 FT /evidence="ECO:0007829|PDB:7N3T" FT STRAND 234..243 FT /evidence="ECO:0007829|PDB:7N3T" FT STRAND 246..253 FT /evidence="ECO:0007829|PDB:7N3T" FT HELIX 256..258 FT /evidence="ECO:0007829|PDB:7N3T" FT STRAND 263..268 FT /evidence="ECO:0007829|PDB:7N3T" FT STRAND 273..278 FT /evidence="ECO:0007829|PDB:7N3T" FT STRAND 282..290 FT /evidence="ECO:0007829|PDB:7N3T" FT STRAND 294..309 FT /evidence="ECO:0007829|PDB:7N3T" FT STRAND 312..317 FT /evidence="ECO:0007829|PDB:7N3T" FT STRAND 326..332 FT /evidence="ECO:0007829|PDB:7N3T" FT STRAND 342..350 FT /evidence="ECO:0007829|PDB:7N3T" FT HELIX 353..355 FT /evidence="ECO:0007829|PDB:7N3T" FT STRAND 357..365 FT /evidence="ECO:0007829|PDB:7N3T" FT STRAND 368..376 FT /evidence="ECO:0007829|PDB:7N3T" 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 498..501 FT /evidence="ECO:0007829|PDB:7XBI" 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 TURN 749..751 FT /evidence="ECO:0007829|PDB:8J63" 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 //