ID JAK1_HUMAN Reviewed; 1154 AA. AC P23458; Q59GQ2; Q9UD26; DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot. DT 25-NOV-2008, sequence version 2. DT 27-MAR-2024, entry version 238. DE RecName: Full=Tyrosine-protein kinase JAK1; DE EC=2.7.10.2 {ECO:0000269|PubMed:1848670, ECO:0000269|PubMed:7615558}; DE AltName: Full=Janus kinase 1; DE Short=JAK-1; GN Name=JAK1; Synonyms=JAK1A, JAK1B; 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], AND CATALYTIC ACTIVITY. RX PubMed=1848670; DOI=10.1128/mcb.11.4.2057-2065.1991; RA Wilks A.F., Harpur A.G., Kurban R.R., Ralph S.J., Zuercher G., RA Ziemiecki A.; RT "Two novel protein-tyrosine kinases, each with a second phosphotransferase- RT related catalytic domain, define a new class of protein kinase."; RL Mol. Cell. Biol. 11:2057-2065(1991). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [3] 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1005-1062. RX PubMed=8247543; RA Lee S.-T., Strunk K.M., Spritz R.A.; RT "A survey of protein tyrosine kinase mRNAs expressed in normal human RT melanocytes."; RL Oncogene 8:3403-3410(1993). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1008-1062, AND TISSUE SPECIFICITY. RC TISSUE=Colon tumor; RX PubMed=7896447; DOI=10.1002/ijc.2910600611; RA Craven R.J., Xu L.H., Weiner T.M., Fridell Y.-W., Dent G.A., Srivastava S., RA Varnum B., Liu E.T., Cance W.G.; RT "Receptor tyrosine kinases expressed in metastatic colon cancer."; RL Int. J. Cancer 60:791-797(1995). RN [8] RP FUNCTION, AND PHOSPHORYLATION. RX PubMed=8232552; DOI=10.1038/366129a0; RA Mueller M., Briscoe J., Laxton C., Guschin D., Ziemiecki A., RA Silvennoinen O., Harpur A.G., Barbieri G., Witthuhn B.A., Schindler C.; RT "The protein tyrosine kinase JAK1 complements defects in interferon- RT alpha/beta and -gamma signal transduction."; RL Nature 366:129-135(1993). RN [9] RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, INTERACTION WITH IFNGR1, AND RP PHOSPHORYLATION. RX PubMed=7615558; DOI=10.1074/jbc.270.29.17528; RA Sakatsume M., Igarashi K., Winestock K.D., Garotta G., Larner A.C., RA Finbloom D.S.; RT "The Jak kinases differentially associate with the alpha and beta RT (accessory factor) chains of the interferon gamma receptor to form a RT functional receptor unit capable of activating STAT transcription RT factors."; RL J. Biol. Chem. 270:17528-17534(1995). RN [10] RP FUNCTION. RX PubMed=7657660; DOI=10.1074/jbc.270.35.20775; RA Quelle F.W., Thierfelder W., Witthuhn B.A., Tang B., Cohen S., Ihle J.N.; RT "Phosphorylation and activation of the DNA binding activity of purified RT Stat1 by the Janus protein-tyrosine kinases and the epidermal growth factor RT receptor."; RL J. Biol. Chem. 270:20775-20780(1995). RN [11] RP FUNCTION. RX PubMed=7759950; DOI=10.1002/jlb.57.5.712; RA Novick D., Cohen B., Tal N., Rubinstein M.; RT "Soluble and membrane-anchored forms of the human IFN-alpha/beta RT receptor."; RL J. Leukoc. Biol. 57:712-718(1995). RN [12] RP INTERACTION WITH SHB. RX PubMed=12200137; DOI=10.1016/s0006-291x(02)02016-8; RA Lindholm C.K.; RT "IL-2 receptor signaling through the Shb adapter protein in T and NK RT cells."; RL Biochem. Biophys. Res. Commun. 296:929-936(2002). RN [13] RP FUNCTION IN CYTOKINE SIGNALING, PHOSPHORYLATION AT TYR-1034 AND TYR-1035, RP AND DEPHOSPHORYLATION AT TYR-1034 AND TYR-1035 BY PTPN2. RX PubMed=11909529; DOI=10.1016/s0960-9822(02)00697-8; RA Simoncic P.D., Lee-Loy A., Barber D.L., Tremblay M.L., McGlade C.J.; RT "The T cell protein tyrosine phosphatase is a negative regulator of janus RT family kinases 1 and 3."; RL Curr. Biol. 12:446-453(2002). RN [14] RP FUNCTION, AND INTERACTION WITH IL2RB AND IL10RA. RX PubMed=12133952; DOI=10.4049/jimmunol.169.3.1302; RA Usacheva A., Kotenko S., Witte M.M., Colamonici O.R.; RT "Two distinct domains within the N-terminal region of Janus kinase 1 RT interact with cytokine receptors."; RL J. Immunol. 169:1302-1308(2002). RN [15] RP INTERACTION WITH IL31RA. RX PubMed=15194700; DOI=10.1074/jbc.m401122200; RA Dreuw A., Radtke S., Pflanz S., Lippok B.E., Heinrich P.C., Hermanns H.M.; RT "Characterization of the signaling capacities of the novel gp130-like RT cytokine receptor."; RL J. Biol. Chem. 279:36112-36120(2004). RN [16] RP INTERACTION WITH JAKMIP1. RX PubMed=15277531; DOI=10.1074/jbc.m401915200; RA Steindler C., Li Z., Algarte M., Alcover A., Libri V., Ragimbeau J., RA Pellegrini S.; RT "Jamip1 (marlin-1) defines a family of proteins interacting with Janus RT kinases and microtubules."; RL J. Biol. Chem. 279:43168-43177(2004). RN [17] RP FUNCTION, DOMAIN, AND MUTAGENESIS OF VAL-658. RX PubMed=16239216; DOI=10.1074/jbc.c500358200; RA Staerk J., Kallin A., Demoulin J.B., Vainchenker W., Constantinescu S.N.; RT "JAK1 and Tyk2 activation by the homologous polycythemia vera JAK2 V617F RT mutation: cross-talk with IGF1 receptor."; RL J. Biol. Chem. 280:41893-41899(2005). RN [18] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE RP ANALYSIS] AT TYR-3 AND SER-228, AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [19] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [21] RP UBIQUITINATION. RX PubMed=26027934; DOI=10.1016/j.celrep.2015.04.049; RA Kim H., Frederick D.T., Levesque M.P., Cooper Z.A., Feng Y., Krepler C., RA Brill L., Samuels Y., Hayward N.K., Perlina A., Piris A., Zhang T., RA Halaban R., Herlyn M.M., Brown K.M., Wargo J.A., Dummer R., Flaherty K.T., RA Ronai Z.A.; RT "Downregulation of the ubiquitin ligase RNF125 underlies resistance of RT melanoma cells to BRAF inhibitors via JAK1 deregulation."; RL Cell Rep. 11:1458-1473(2015). RN [22] RP INVOLVEMENT IN AIIDE, VARIANT AIIDE ASP-634, CHARACTERIZATION OF VARIANT RP AIIDE ASP-634, AND FUNCTION. RX PubMed=28111307; DOI=10.1016/j.jaci.2016.12.957; RA Del Bel K.L., Ragotte R.J., Saferali A., Lee S., Vercauteren S.M., RA Mostafavi S.A., Schreiber R.A., Prendiville J.S., Phang M.S., Halparin J., RA Au N., Dean J.M., Priatel J.J., Jewels E., Junker A.K., Rogers P.C., RA Seear M., McKinnon M.L., Turvey S.E.; RT "JAK1 gain-of-function causes an autosomal dominant immune dysregulatory RT and hypereosinophilic syndrome."; RL J. Allergy Clin. Immunol. 139:e52016-e52020(2017). RN [23] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 865-1154 IN COMPLEXES WITH RP SYNTHETIC INHIBITORS CMP6 AND CP-690,550. RX PubMed=19361440; DOI=10.1016/j.jmb.2009.01.041; RA Williams N.K., Bamert R.S., Patel O., Wang C., Walden P.M., Wilks A.F., RA Fantino E., Rossjohn J., Lucet I.S.; RT "Dissecting specificity in the Janus kinases: the structures of JAK- RT specific inhibitors complexed to the JAK1 and JAK2 protein tyrosine kinase RT domains."; RL J. Mol. Biol. 387:219-232(2009). RN [24] RP VARIANT [LARGE SCALE ANALYSIS] LYS-973. 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 [25] RP VARIANT AIIDE ILE-703, CHARACTERIZATION OF VARIANT AIIDE ILE-703, FUNCTION, RP MUTAGENESIS OF LYS-908, AND ATP-BINDING. RX PubMed=32750333; DOI=10.1016/j.immuni.2020.07.006; RA Gruber C.N., Calis J.J.A., Buta S., Evrony G., Martin J.C., Uhl S.A., RA Caron R., Jarchin L., Dunkin D., Phelps R., Webb B.D., Saland J.M., RA Merad M., Orange J.S., Mace E.M., Rosenberg B.R., Gelb B.D., Bogunovic D.; RT "Complex Autoinflammatory Syndrome Unveils Fundamental Principles of JAK1 RT Kinase Transcriptional and Biochemical Function."; RL Immunity 53:e11672-e11684(2020). CC -!- FUNCTION: Tyrosine kinase of the non-receptor type, involved in the CC IFN-alpha/beta/gamma signal pathway (PubMed:8232552, PubMed:7615558, CC PubMed:28111307, PubMed:32750333, PubMed:16239216). Kinase partner for CC the interleukin (IL)-2 receptor (PubMed:11909529) as well as CC interleukin (IL)-10 receptor (PubMed:12133952). Kinase partner for the CC type I interferon receptor IFNAR2 (PubMed:8232552, PubMed:7615558, CC PubMed:28111307, PubMed:32750333, PubMed:16239216). In response to CC interferon-binding to IFNAR1-IFNAR2 heterodimer, phosphorylates and CC activates its binding partner IFNAR2, creating docking sites for STAT CC proteins (PubMed:7759950). Directly phosphorylates STAT proteins but CC also activates STAT signaling through the transactivation of other JAK CC kinases associated with signaling receptors (PubMed:8232552, CC PubMed:16239216, PubMed:32750333). {ECO:0000269|PubMed:11909529, CC ECO:0000269|PubMed:12133952, ECO:0000269|PubMed:16239216, CC ECO:0000269|PubMed:28111307, ECO:0000269|PubMed:32750333, CC ECO:0000269|PubMed:7615558, ECO:0000269|PubMed:7657660, CC ECO:0000269|PubMed:8232552}. 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=2.7.10.2; CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028, CC ECO:0000269|PubMed:1848670, ECO:0000269|PubMed:7615558}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000305|PubMed:7615558}; CC Note=Mn(2+) was used in the in vitro kinase assay but Mg(2+) is likely CC to be the in vivo cofactor. {ECO:0000305|PubMed:7615558}; CC -!- SUBUNIT: Interacts with IL31RA (PubMed:15194700). Interacts with IFNGR1 CC (PubMed:7615558). Interacts with JAKMIP1 (PubMed:15277531). Interacts CC with SHB (PubMed:12200137). Interacts (via N-terminus) with IL2RB and CC IL10RA (via its cytoplasmic domain) (PubMed:12133952). Interacts with CC FER (By similarity). {ECO:0000250|UniProtKB:P52332, CC ECO:0000269|PubMed:12133952, ECO:0000269|PubMed:12200137, CC ECO:0000269|PubMed:15194700, ECO:0000269|PubMed:15277531, CC ECO:0000269|PubMed:7615558, ECO:0000269|PubMed:7759950}. CC -!- INTERACTION: CC P23458; P04626: ERBB2; NbExp=2; IntAct=EBI-1383438, EBI-641062; CC P23458; P48551: IFNAR2; NbExp=3; IntAct=EBI-1383438, EBI-958408; CC P23458; P40189-1: IL6ST; NbExp=3; IntAct=EBI-1383438, EBI-15742214; CC P23458; O60674: JAK2; NbExp=4; IntAct=EBI-1383438, EBI-518647; CC P23458; P42224: STAT1; NbExp=6; IntAct=EBI-1383438, EBI-1057697; CC P23458; P40763: STAT3; NbExp=2; IntAct=EBI-1383438, EBI-518675; CC -!- SUBCELLULAR LOCATION: Endomembrane system; Peripheral membrane protein. CC Note=Wholly intracellular, possibly membrane associated. CC -!- TISSUE SPECIFICITY: Expressed at higher levels in primary colon tumors CC than in normal colon tissue. The expression level in metastatic colon CC tumors is comparable to the expression level in normal colon tissue. CC {ECO:0000269|PubMed:7896447}. CC -!- DOMAIN: The protein kinase 1 domain is also called the pseudokinase CC domain and has a regulatory role through the transactivation of other CC JAK kinases associated with signaling receptors. CC {ECO:0000269|PubMed:16239216, ECO:0000269|PubMed:32750333}. CC -!- DOMAIN: The protein kinase 2 domain is the catalytically active domain. CC {ECO:0000269|PubMed:32750333}. CC -!- DOMAIN: The FERM domain mediates interaction with JAKMIP1. CC -!- PTM: Autophosphorylated (PubMed:7615558). Phosphorylated by TYK2 on CC tyrosine residues in response to type-I interferon signaling, leading CC to its activation (PubMed:8232552). Phosphorylated on tyrosine residues CC in response to interferon gamma signaling (PubMed:7615558). CC Dephosphorylation of Tyr-1034 and Tyr-1035 by PTPN2 negatively CC regulates cytokine-mediated signaling (PubMed:11909529). CC {ECO:0000269|PubMed:11909529, ECO:0000269|PubMed:7615558, CC ECO:0000305|PubMed:8232552}. CC -!- PTM: Ubiquitinated by RNF125; leading to its degradation by the CC proteasome. {ECO:0000269|PubMed:26027934}. CC -!- DISEASE: Autoinflammation, immune dysregulation, and eosinophilia CC (AIIDE) [MIM:618999]: An autosomal dominant disorder characterized by CC immune dysregulation, severe atopic dermatitis, and chronic CC gastrointestinal inflammation. Additional features include asthma, food CC or environmental allergies, as well as poor overall growth with short CC stature. {ECO:0000269|PubMed:28111307, ECO:0000269|PubMed:32750333}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. JAK subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA36527.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAA36527.1; Type=Frameshift; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/41031/JAK1"; 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; M64174; AAA36527.1; ALT_SEQ; mRNA. DR EMBL; AB209057; BAD92294.1; -; mRNA. DR EMBL; AC093427; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471059; EAX06547.1; -; Genomic_DNA. DR EMBL; BC132729; AAI32730.1; -; mRNA. DR CCDS; CCDS41346.1; -. DR PIR; A39577; A39577. DR RefSeq; NP_001307852.1; NM_001320923.1. DR RefSeq; NP_001308781.1; NM_001321852.1. DR RefSeq; NP_001308782.1; NM_001321853.1. DR RefSeq; NP_001308783.1; NM_001321854.1. DR RefSeq; NP_001308784.1; NM_001321855.1. DR RefSeq; NP_001308785.1; NM_001321856.1. DR RefSeq; NP_002218.2; NM_002227.3. DR PDB; 3EYG; X-ray; 1.90 A; A=865-1154. DR PDB; 3EYH; X-ray; 2.00 A; A=865-1154. DR PDB; 4E4L; X-ray; 2.00 A; A/B/D/E=854-1154. DR PDB; 4E4N; X-ray; 1.90 A; A/B=854-1154. DR PDB; 4E5W; X-ray; 1.86 A; A/B=854-1154. DR PDB; 4EHZ; X-ray; 2.17 A; A/B/C/D=854-1154. DR PDB; 4EI4; X-ray; 2.22 A; A/B=854-1154. DR PDB; 4FK6; X-ray; 2.20 A; A/B=854-1154. DR PDB; 4GS0; X-ray; 1.80 A; C=1033-1036. DR PDB; 4I5C; X-ray; 2.10 A; A/B=854-1154. DR PDB; 4IVB; X-ray; 1.90 A; A/B=854-1154. DR PDB; 4IVC; X-ray; 2.35 A; A/B=854-1154. DR PDB; 4IVD; X-ray; 1.93 A; A/B=854-1154. DR PDB; 4K6Z; X-ray; 2.73 A; A=854-1154. DR PDB; 4K77; X-ray; 2.40 A; A/B=854-1154. DR PDB; 4L00; X-ray; 1.80 A; A/B=561-860. DR PDB; 4L01; X-ray; 1.90 A; A/B=561-860. DR PDB; 5E1E; X-ray; 2.30 A; A/B=865-1154. DR PDB; 5HX8; X-ray; 2.20 A; A/B=854-1154. DR PDB; 5IXD; X-ray; 2.85 A; A=35-559. DR PDB; 5IXI; X-ray; 2.57 A; A=35-559. DR PDB; 5KHW; X-ray; 2.47 A; A/B=841-1154. DR PDB; 5KHX; X-ray; 2.40 A; A=841-1154. DR PDB; 5L04; X-ray; 2.10 A; A=31-577. DR PDB; 5WO4; X-ray; 1.84 A; A/B=854-1154. DR PDB; 6AAH; X-ray; 1.83 A; A/B=865-1154. DR PDB; 6BBU; X-ray; 2.08 A; A=841-1154. DR PDB; 6C7Y; X-ray; 2.50 A; A=869-1153. DR PDB; 6DBN; X-ray; 2.48 A; A=841-1154. DR PDB; 6ELR; X-ray; 1.80 A; A/B=854-1154. DR PDB; 6GGH; X-ray; 1.70 A; A/B=863-1154. DR PDB; 6HZU; X-ray; 2.20 A; A/B=854-1154. DR PDB; 6N77; X-ray; 1.64 A; A/B=854-1154. DR PDB; 6N78; X-ray; 1.83 A; A=854-1154. DR PDB; 6N79; X-ray; 2.27 A; A=854-1154. DR PDB; 6N7A; X-ray; 1.33 A; A/B=854-1154. DR PDB; 6N7B; X-ray; 1.81 A; A=854-1154. DR PDB; 6N7C; X-ray; 1.69 A; A/B=854-1154. DR PDB; 6N7D; X-ray; 1.78 A; A=854-1154. DR PDB; 6RSB; X-ray; 1.80 A; A/B=854-1154. DR PDB; 6RSC; X-ray; 1.85 A; A/B=854-1154. DR PDB; 6RSD; X-ray; 1.76 A; A/B=854-1154. DR PDB; 6RSE; X-ray; 1.80 A; A/B=854-1154. DR PDB; 6RSH; X-ray; 1.71 A; A/B=854-1154. DR PDB; 6SM8; X-ray; 1.85 A; A/B=854-1154. DR PDB; 6SMB; X-ray; 2.04 A; A/B=854-1154. DR PDB; 6TPE; X-ray; 2.87 A; A/B=864-1154. DR PDB; 6TPF; X-ray; 2.31 A; A/B=864-1154. DR PDB; 6W8L; X-ray; 2.11 A; A=841-1154. DR PDB; 8EXJ; X-ray; 2.30 A; D=1027-1042. DR PDBsum; 3EYG; -. DR PDBsum; 3EYH; -. DR PDBsum; 4E4L; -. DR PDBsum; 4E4N; -. DR PDBsum; 4E5W; -. DR PDBsum; 4EHZ; -. DR PDBsum; 4EI4; -. DR PDBsum; 4FK6; -. DR PDBsum; 4GS0; -. DR PDBsum; 4I5C; -. DR PDBsum; 4IVB; -. DR PDBsum; 4IVC; -. DR PDBsum; 4IVD; -. DR PDBsum; 4K6Z; -. DR PDBsum; 4K77; -. DR PDBsum; 4L00; -. DR PDBsum; 4L01; -. DR PDBsum; 5E1E; -. DR PDBsum; 5HX8; -. DR PDBsum; 5IXD; -. DR PDBsum; 5IXI; -. DR PDBsum; 5KHW; -. DR PDBsum; 5KHX; -. DR PDBsum; 5L04; -. DR PDBsum; 5WO4; -. DR PDBsum; 6AAH; -. DR PDBsum; 6BBU; -. DR PDBsum; 6C7Y; -. DR PDBsum; 6DBN; -. DR PDBsum; 6ELR; -. DR PDBsum; 6GGH; -. DR PDBsum; 6HZU; -. DR PDBsum; 6N77; -. DR PDBsum; 6N78; -. DR PDBsum; 6N79; -. DR PDBsum; 6N7A; -. DR PDBsum; 6N7B; -. DR PDBsum; 6N7C; -. DR PDBsum; 6N7D; -. DR PDBsum; 6RSB; -. DR PDBsum; 6RSC; -. DR PDBsum; 6RSD; -. DR PDBsum; 6RSE; -. DR PDBsum; 6RSH; -. DR PDBsum; 6SM8; -. DR PDBsum; 6SMB; -. DR PDBsum; 6TPE; -. DR PDBsum; 6TPF; -. DR PDBsum; 6W8L; -. DR PDBsum; 8EXJ; -. DR AlphaFoldDB; P23458; -. DR SMR; P23458; -. DR BioGRID; 109919; 254. DR ComplexPortal; CPX-5995; Interferon alpha receptor-ligand complex, IFNA2 variant. DR ComplexPortal; CPX-5996; Interferon alpha receptor-ligand complex, IFNA1 variant. DR ComplexPortal; CPX-5997; Interferon alpha receptor-ligand complex, IFNA7 variant. DR ComplexPortal; CPX-5998; Interferon alpha receptor-ligand complex, IFNA4 variant. DR ComplexPortal; CPX-5999; Interferon alpha receptor-ligand complex, IFNA5 variant. DR ComplexPortal; CPX-6000; Interferon alpha receptor-ligand complex, IFNA6 variant. DR ComplexPortal; CPX-6001; Interferon alpha receptor-ligand complex, IFNA8 variant. DR ComplexPortal; CPX-6002; Interferon alpha receptor-ligand complex, IFNA10 variant. DR ComplexPortal; CPX-6003; Interferon alpha receptor-ligand complex, IFNA14 variant. DR ComplexPortal; CPX-6004; Interferon alpha receptor-ligand complex, IFNA16 variant. DR ComplexPortal; CPX-6005; Interferon alpha receptor-ligand complex, IFNA17 variant. DR ComplexPortal; CPX-6006; Interferon alpha receptor-ligand complex, IFNA21 variant. DR ComplexPortal; CPX-6007; Interferon beta receptor-ligand complex. DR ComplexPortal; CPX-6008; Interferon epsilon receptor-ligand complex. DR ComplexPortal; CPX-6009; Interferon kappa receptor-ligand complex. DR ComplexPortal; CPX-6010; Interferon omega receptor-ligand complex. DR ComplexPortal; CPX-6011; Interferon lambda receptor-ligand complex, IFNL1 variant. DR ComplexPortal; CPX-6012; Interferon lambda receptor-ligand complex, IFNL2 variant. DR ComplexPortal; CPX-6013; Interferon lambda receptor-ligand complex, IFNL3 variant. DR ComplexPortal; CPX-6014; Interferon lambda receptor-ligand complex, IFNL4 variant. DR ComplexPortal; CPX-6015; Interferon gamma receptor-ligand complex. DR CORUM; P23458; -. DR DIP; DIP-133N; -. DR IntAct; P23458; 88. DR MINT; P23458; -. DR STRING; 9606.ENSP00000499900; -. DR BindingDB; P23458; -. DR ChEMBL; CHEMBL2835; -. DR DrugBank; DB04716; 2-tert-butyl-9-fluoro-1,6-dihydrobenzo[h]imidazo[4,5-f]isoquinolin-7-one. DR DrugBank; DB14973; Abrocitinib. DR DrugBank; DB11817; Baricitinib. DR DrugBank; DB12500; Fedratinib. DR DrugBank; DB14845; Filgotinib. DR DrugBank; DB12010; Fostamatinib. DR DrugBank; DB16756; Ivarmacitinib. DR DrugBank; DB02375; Myricetin. DR DrugBank; DB15822; Pralsetinib. DR DrugBank; DB08877; Ruxolitinib. DR DrugBank; DB08895; Tofacitinib. DR DrugBank; DB15091; Upadacitinib. DR DrugCentral; P23458; -. DR GuidetoPHARMACOLOGY; 2047; -. DR CarbonylDB; P23458; -. DR GlyConnect; 1869; 2 N-Linked glycans (1 site). DR GlyCosmos; P23458; 1 site, 2 glycans. DR GlyGen; P23458; 1 site, 2 N-linked glycans (1 site). DR iPTMnet; P23458; -. DR PhosphoSitePlus; P23458; -. DR SwissPalm; P23458; -. DR BioMuta; JAK1; -. DR DMDM; 215274013; -. DR CPTAC; CPTAC-1251; -. DR CPTAC; CPTAC-3185; -. DR CPTAC; CPTAC-3186; -. DR EPD; P23458; -. DR jPOST; P23458; -. DR MassIVE; P23458; -. DR MaxQB; P23458; -. DR PaxDb; 9606-ENSP00000343204; -. DR PeptideAtlas; P23458; -. DR ProteomicsDB; 54097; -. DR Pumba; P23458; -. DR Antibodypedia; 3400; 787 antibodies from 43 providers. DR CPTC; P23458; 1 antibody. DR DNASU; 3716; -. DR Ensembl; ENST00000342505.5; ENSP00000343204.4; ENSG00000162434.14. DR Ensembl; ENST00000671929.2; ENSP00000500485.1; ENSG00000162434.14. DR Ensembl; ENST00000671954.2; ENSP00000500841.1; ENSG00000162434.14. DR Ensembl; ENST00000672179.2; ENSP00000500296.1; ENSG00000162434.14. DR Ensembl; ENST00000672247.2; ENSP00000499884.1; ENSG00000162434.14. DR Ensembl; ENST00000672434.2; ENSP00000499900.1; ENSG00000162434.14. DR Ensembl; ENST00000672751.2; ENSP00000500745.2; ENSG00000162434.14. DR Ensembl; ENST00000699262.1; ENSP00000514243.1; ENSG00000162434.14. DR Ensembl; ENST00000699312.1; ENSP00000514291.1; ENSG00000162434.14. DR GeneID; 3716; -. DR KEGG; hsa:3716; -. DR MANE-Select; ENST00000342505.5; ENSP00000343204.4; NM_002227.4; NP_002218.2. DR UCSC; uc001dbu.2; human. DR AGR; HGNC:6190; -. DR CTD; 3716; -. DR DisGeNET; 3716; -. DR GeneCards; JAK1; -. DR HGNC; HGNC:6190; JAK1. DR HPA; ENSG00000162434; Low tissue specificity. DR MalaCards; JAK1; -. DR MIM; 147795; gene. DR MIM; 618999; phenotype. DR neXtProt; NX_P23458; -. DR OpenTargets; ENSG00000162434; -. DR Orphanet; 574957; Autosomal recessive mendelian susceptibility to mycobacterial diseases due to partial JAK1 deficiency. DR PharmGKB; PA29988; -. DR VEuPathDB; HostDB:ENSG00000162434; -. DR eggNOG; KOG0197; Eukaryota. DR GeneTree; ENSGT00940000157092; -. DR HOGENOM; CLU_008155_1_0_1; -. DR InParanoid; P23458; -. DR OMA; KDIMQGE; -. DR OrthoDB; 1614410at2759; -. DR PhylomeDB; P23458; -. DR TreeFam; TF327041; -. DR BRENDA; 2.7.10.2; 2681. DR PathwayCommons; P23458; -. DR Reactome; R-HSA-1059683; Interleukin-6 signaling. DR Reactome; R-HSA-110056; MAPK3 (ERK1) activation. DR Reactome; R-HSA-112411; MAPK1 (ERK2) activation. DR Reactome; R-HSA-1169408; ISG15 antiviral mechanism. DR Reactome; R-HSA-1266695; Interleukin-7 signaling. DR Reactome; R-HSA-449836; Other interleukin signaling. DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade. DR Reactome; R-HSA-6783783; Interleukin-10 signaling. DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling. DR Reactome; R-HSA-6788467; IL-6-type cytokine receptor ligand interactions. DR Reactome; R-HSA-877300; Interferon gamma signaling. DR Reactome; R-HSA-877312; Regulation of IFNG signaling. DR Reactome; R-HSA-8854691; Interleukin-20 family signaling. DR Reactome; R-HSA-8983432; Interleukin-15 signaling. DR Reactome; R-HSA-8984722; Interleukin-35 Signalling. DR Reactome; R-HSA-8985947; Interleukin-9 signaling. DR Reactome; R-HSA-9020558; Interleukin-2 signaling. DR Reactome; R-HSA-9020591; Interleukin-12 signaling. DR Reactome; R-HSA-9020956; Interleukin-27 signaling. DR Reactome; R-HSA-9020958; Interleukin-21 signaling. DR Reactome; R-HSA-909733; Interferon alpha/beta signaling. DR Reactome; R-HSA-912526; Interleukin receptor SHC signaling. DR Reactome; R-HSA-912694; Regulation of IFNA/IFNB signaling. DR Reactome; R-HSA-9674555; Signaling by CSF3 (G-CSF). DR Reactome; R-HSA-9679191; Potential therapeutics for SARS. DR Reactome; R-HSA-9705462; Inactivation of CSF3 (G-CSF) signaling. DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses. DR Reactome; R-HSA-9732724; IFNG signaling activates MAPKs. DR SignaLink; P23458; -. DR SIGNOR; P23458; -. DR BioGRID-ORCS; 3716; 49 hits in 1224 CRISPR screens. DR ChiTaRS; JAK1; human. DR EvolutionaryTrace; P23458; -. DR GeneWiki; Janus_kinase_1; -. DR GenomeRNAi; 3716; -. DR Pharos; P23458; Tclin. DR PRO; PR:P23458; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; P23458; Protein. DR Bgee; ENSG00000162434; Expressed in type B pancreatic cell and 205 other cell types or tissues. DR ExpressionAtlas; P23458; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL. DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IDA:UniProt. DR GO; GO:0005856; C:cytoskeleton; IEA:InterPro. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0005768; C:endosome; TAS:Reactome. DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IDA:UniProt. DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL. DR GO; GO:0005886; C:plasma membrane; TAS:UniProt. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0031730; F:CCR5 chemokine receptor binding; IEA:Ensembl. DR GO; GO:0005131; F:growth hormone receptor binding; ISS:BHF-UCL. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IDA:UniProtKB. DR GO; GO:0019903; F:protein phosphatase binding; IPI:UniProtKB. DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProt. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB. DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central. DR GO; GO:0098586; P:cellular response to virus; NAS:ComplexPortal. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central. DR GO; GO:0060397; P:growth hormone receptor signaling pathway via JAK-STAT; IBA:GO_Central. DR GO; GO:0038154; P:interleukin-11-mediated signaling pathway; IDA:UniProt. DR GO; GO:0035723; P:interleukin-15-mediated signaling pathway; IDA:UniProt. DR GO; GO:0038110; P:interleukin-2-mediated signaling pathway; IDA:UniProtKB. DR GO; GO:0035771; P:interleukin-4-mediated signaling pathway; IDA:UniProt. DR GO; GO:0070102; P:interleukin-6-mediated signaling pathway; IDA:UniProt. DR GO; GO:0038113; P:interleukin-9-mediated signaling pathway; IDA:UniProt. DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central. DR GO; GO:0034112; P:positive regulation of homotypic cell-cell adhesion; IMP:ARUK-UCL. DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; IDA:UniProt. DR GO; GO:1903672; P:positive regulation of sprouting angiogenesis; IGI:BHF-UCL. DR GO; GO:0150105; P:protein localization to cell-cell junction; IMP:ARUK-UCL. DR GO; GO:0006468; P:protein phosphorylation; IMP:UniProtKB. DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; IDA:UniProtKB. DR GO; GO:0046677; P:response to antibiotic; IDA:MGI. DR GO; GO:0072540; P:T-helper 17 cell lineage commitment; TAS:UniProt. DR GO; GO:0060337; P:type I interferon-mediated signaling pathway; IDA:UniProtKB. DR GO; GO:0060333; P:type II interferon-mediated signaling pathway; IDA:UniProtKB. DR GO; GO:0038196; P:type III interferon-mediated signaling pathway; NAS:ComplexPortal. DR CDD; cd14473; FERM_B-lobe; 1. DR CDD; cd13332; FERM_C_JAK1; 1. DR CDD; cd05077; PTK_Jak1_rpt1; 1. DR CDD; cd05079; PTKc_Jak1_rpt2; 1. DR Gene3D; 3.30.505.10; SH2 domain; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 2. DR InterPro; IPR019749; Band_41_domain. DR InterPro; IPR035963; FERM_2. DR InterPro; IPR019748; FERM_central. DR InterPro; IPR000299; FERM_domain. DR InterPro; IPR041155; FERM_F1. DR InterPro; IPR041046; FERM_F2. DR InterPro; IPR041381; JAK1-3/TYK2_PHL_dom. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom. DR InterPro; IPR000980; SH2. DR InterPro; IPR036860; SH2_dom_sf. DR InterPro; IPR008266; Tyr_kinase_AS. DR InterPro; IPR020635; Tyr_kinase_cat_dom. DR InterPro; IPR016251; Tyr_kinase_non-rcpt_Jak/Tyk2. DR InterPro; IPR020776; Tyr_kinase_non-rcpt_Jak1. DR PANTHER; PTHR45807; TYROSINE-PROTEIN KINASE HOPSCOTCH; 1. DR PANTHER; PTHR45807:SF5; TYROSINE-PROTEIN KINASE JAK1; 1. DR Pfam; PF18379; FERM_F1; 1. DR Pfam; PF18377; FERM_F2; 1. DR Pfam; PF17887; Jak1_Phl; 1. DR Pfam; PF07714; PK_Tyr_Ser-Thr; 2. DR PIRSF; PIRSF000636; TyrPK_Jak; 1. DR PRINTS; PR01823; JANUSKINASE. DR PRINTS; PR01824; JANUSKINASE1. DR PRINTS; PR00109; TYRKINASE. DR SMART; SM00295; B41; 1. DR SMART; SM00252; SH2; 1. DR SMART; SM00219; TyrKc; 2. DR SUPFAM; SSF50729; PH domain-like; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 2. DR SUPFAM; SSF47031; Second domain of FERM; 1. DR SUPFAM; SSF55550; SH2 domain; 1. DR PROSITE; PS50057; FERM_3; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 2. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. DR PROSITE; PS50001; SH2; 1. DR Genevisible; P23458; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; ATP-binding; Disease variant; Kinase; Magnesium; KW Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein; KW Reference proteome; Repeat; SH2 domain; Transferase; KW Tyrosine-protein kinase; Ubl conjugation. FT CHAIN 1..1154 FT /note="Tyrosine-protein kinase JAK1" FT /id="PRO_0000088108" FT DOMAIN 34..420 FT /note="FERM" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00084" FT DOMAIN 439..544 FT /note="SH2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191" FT DOMAIN 583..855 FT /note="Protein kinase 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT DOMAIN 875..1153 FT /note="Protein kinase 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT ACT_SITE 1003 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10028" FT BINDING 881..889 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 908 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000305|PubMed:32750333" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:19369195" FT MOD_RES 3 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:19369195" FT MOD_RES 228 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19369195" FT MOD_RES 1034 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:11909529" FT MOD_RES 1035 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:11909529" FT VARIANT 634 FT /note="A -> D (in AIIDE; constitutive gain of function FT resulting in increased receptor signaling pathway via FT JAK-STAT; no effect on protein abundance)" FT /evidence="ECO:0000269|PubMed:28111307" FT /id="VAR_084991" FT VARIANT 703 FT /note="S -> I (in AIIDE; increased activation of protein FT kinase activity; constitutive gain of function through the FT transactivation of associated JAK kinases; increased FT receptor signaling pathway via JAK-STAT)" FT /evidence="ECO:0000269|PubMed:32750333" FT /id="VAR_084992" FT VARIANT 973 FT /note="N -> K (in dbSNP:rs34680086)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041715" FT MUTAGEN 658 FT /note="V->F: Constitutively active. Increased receptor FT signaling pathway via JAK-STAT." FT /evidence="ECO:0000269|PubMed:16239216" FT MUTAGEN 908 FT /note="K->A: Loss of protein tyrosine kinase activity." FT /evidence="ECO:0000269|PubMed:32750333" FT CONFLICT 350 FT /note="H -> D (in Ref. 1; AAA36527)" FT /evidence="ECO:0000305" FT CONFLICT 368 FT /note="Y -> F (in Ref. 1; AAA36527)" FT /evidence="ECO:0000305" FT CONFLICT 898 FT /note="Missing (in Ref. 1; AAA36527)" FT /evidence="ECO:0000305" FT STRAND 36..39 FT /evidence="ECO:0007829|PDB:5L04" FT STRAND 43..45 FT /evidence="ECO:0007829|PDB:5IXI" FT STRAND 48..50 FT /evidence="ECO:0007829|PDB:5L04" FT STRAND 52..56 FT /evidence="ECO:0007829|PDB:5L04" FT HELIX 57..67 FT /evidence="ECO:0007829|PDB:5L04" FT TURN 72..74 FT /evidence="ECO:0007829|PDB:5L04" FT HELIX 75..77 FT /evidence="ECO:0007829|PDB:5L04" FT STRAND 78..82 FT /evidence="ECO:0007829|PDB:5L04" FT TURN 83..86 FT /evidence="ECO:0007829|PDB:5L04" FT STRAND 94..97 FT /evidence="ECO:0007829|PDB:5L04" FT STRAND 103..109 FT /evidence="ECO:0007829|PDB:5L04" FT TURN 114..117 FT /evidence="ECO:0007829|PDB:5L04" FT STRAND 121..123 FT /evidence="ECO:0007829|PDB:5IXI" FT STRAND 149..151 FT /evidence="ECO:0007829|PDB:5L04" FT HELIX 152..167 FT /evidence="ECO:0007829|PDB:5L04" FT HELIX 179..204 FT /evidence="ECO:0007829|PDB:5L04" FT TURN 208..210 FT /evidence="ECO:0007829|PDB:5IXD" FT HELIX 217..220 FT /evidence="ECO:0007829|PDB:5L04" FT HELIX 223..230 FT /evidence="ECO:0007829|PDB:5L04" FT HELIX 234..252 FT /evidence="ECO:0007829|PDB:5L04" FT HELIX 254..259 FT /evidence="ECO:0007829|PDB:5L04" FT HELIX 263..277 FT /evidence="ECO:0007829|PDB:5L04" FT STRAND 278..280 FT /evidence="ECO:0007829|PDB:5L04" FT STRAND 284..289 FT /evidence="ECO:0007829|PDB:5L04" FT STRAND 291..293 FT /evidence="ECO:0007829|PDB:5L04" FT STRAND 299..304 FT /evidence="ECO:0007829|PDB:5IXI" FT STRAND 313..318 FT /evidence="ECO:0007829|PDB:5L04" FT TURN 319..321 FT /evidence="ECO:0007829|PDB:5L04" FT STRAND 322..327 FT /evidence="ECO:0007829|PDB:5L04" FT STRAND 364..367 FT /evidence="ECO:0007829|PDB:5L04" FT HELIX 369..371 FT /evidence="ECO:0007829|PDB:5L04" FT STRAND 372..378 FT /evidence="ECO:0007829|PDB:5L04" FT STRAND 381..386 FT /evidence="ECO:0007829|PDB:5L04" FT STRAND 391..395 FT /evidence="ECO:0007829|PDB:5L04" FT HELIX 399..416 FT /evidence="ECO:0007829|PDB:5L04" FT HELIX 425..427 FT /evidence="ECO:0007829|PDB:5L04" FT HELIX 430..437 FT /evidence="ECO:0007829|PDB:5L04" FT HELIX 446..456 FT /evidence="ECO:0007829|PDB:5L04" FT STRAND 463..467 FT /evidence="ECO:0007829|PDB:5L04" FT STRAND 472..482 FT /evidence="ECO:0007829|PDB:5L04" FT STRAND 493..503 FT /evidence="ECO:0007829|PDB:5L04" FT STRAND 506..509 FT /evidence="ECO:0007829|PDB:5L04" FT STRAND 516..518 FT /evidence="ECO:0007829|PDB:5L04" FT HELIX 519..527 FT /evidence="ECO:0007829|PDB:5L04" FT STRAND 529..533 FT /evidence="ECO:0007829|PDB:5L04" FT STRAND 536..538 FT /evidence="ECO:0007829|PDB:5L04" FT STRAND 555..557 FT /evidence="ECO:0007829|PDB:5L04" FT HELIX 559..562 FT /evidence="ECO:0007829|PDB:5L04" FT HELIX 569..572 FT /evidence="ECO:0007829|PDB:4L00" FT STRAND 575..578 FT /evidence="ECO:0007829|PDB:4L00" FT HELIX 580..582 FT /evidence="ECO:0007829|PDB:4L00" FT STRAND 583..592 FT /evidence="ECO:0007829|PDB:4L00" FT STRAND 595..603 FT /evidence="ECO:0007829|PDB:4L00" FT STRAND 616..624 FT /evidence="ECO:0007829|PDB:4L00" FT HELIX 629..644 FT /evidence="ECO:0007829|PDB:4L00" FT STRAND 653..659 FT /evidence="ECO:0007829|PDB:4L00" FT STRAND 662..668 FT /evidence="ECO:0007829|PDB:4L00" FT HELIX 675..682 FT /evidence="ECO:0007829|PDB:4L00" FT TURN 683..685 FT /evidence="ECO:0007829|PDB:4L00" FT HELIX 688..707 FT /evidence="ECO:0007829|PDB:4L00" FT HELIX 717..719 FT /evidence="ECO:0007829|PDB:4L00" FT STRAND 720..724 FT /evidence="ECO:0007829|PDB:4L00" FT STRAND 727..731 FT /evidence="ECO:0007829|PDB:4L00" FT STRAND 734..737 FT /evidence="ECO:0007829|PDB:4L00" FT HELIX 744..746 FT /evidence="ECO:0007829|PDB:4L00" FT HELIX 749..754 FT /evidence="ECO:0007829|PDB:4L00" FT TURN 755..758 FT /evidence="ECO:0007829|PDB:4L00" FT HELIX 761..765 FT /evidence="ECO:0007829|PDB:4L00" FT HELIX 767..769 FT /evidence="ECO:0007829|PDB:4L00" FT HELIX 774..787 FT /evidence="ECO:0007829|PDB:4L00" FT TURN 788..790 FT /evidence="ECO:0007829|PDB:4L00" FT TURN 793..796 FT /evidence="ECO:0007829|PDB:4L00" FT HELIX 799..807 FT /evidence="ECO:0007829|PDB:4L00" FT HELIX 818..827 FT /evidence="ECO:0007829|PDB:4L00" FT HELIX 832..834 FT /evidence="ECO:0007829|PDB:4L00" FT HELIX 838..848 FT /evidence="ECO:0007829|PDB:4L00" FT HELIX 872..874 FT /evidence="ECO:0007829|PDB:6N7A" FT STRAND 875..883 FT /evidence="ECO:0007829|PDB:6N7A" FT STRAND 885..894 FT /evidence="ECO:0007829|PDB:6N7A" FT STRAND 898..900 FT /evidence="ECO:0007829|PDB:6N7A" FT STRAND 902..910 FT /evidence="ECO:0007829|PDB:6N7A" FT TURN 915..917 FT /evidence="ECO:0007829|PDB:6RSE" FT HELIX 919..930 FT /evidence="ECO:0007829|PDB:6N7A" FT STRAND 940..944 FT /evidence="ECO:0007829|PDB:6N7A" FT STRAND 947..949 FT /evidence="ECO:0007829|PDB:6HZU" FT STRAND 953..957 FT /evidence="ECO:0007829|PDB:6N7A" FT HELIX 964..970 FT /evidence="ECO:0007829|PDB:6N7A" FT TURN 972..974 FT /evidence="ECO:0007829|PDB:6N7A" FT HELIX 977..996 FT /evidence="ECO:0007829|PDB:6N7A" FT STRAND 998..1000 FT /evidence="ECO:0007829|PDB:4K6Z" FT HELIX 1006..1008 FT /evidence="ECO:0007829|PDB:6N7A" FT STRAND 1009..1013 FT /evidence="ECO:0007829|PDB:6N7A" FT STRAND 1016..1019 FT /evidence="ECO:0007829|PDB:6N7A" FT STRAND 1033..1036 FT /evidence="ECO:0007829|PDB:6N7A" FT STRAND 1039..1041 FT /evidence="ECO:0007829|PDB:5KHX" FT HELIX 1045..1047 FT /evidence="ECO:0007829|PDB:6N7A" FT HELIX 1050..1055 FT /evidence="ECO:0007829|PDB:6N7A" FT STRAND 1057..1059 FT /evidence="ECO:0007829|PDB:6N7A" FT HELIX 1060..1075 FT /evidence="ECO:0007829|PDB:6N7A" FT TURN 1076..1078 FT /evidence="ECO:0007829|PDB:6N7A" FT HELIX 1080..1082 FT /evidence="ECO:0007829|PDB:6N7A" FT HELIX 1084..1092 FT /evidence="ECO:0007829|PDB:6N7A" FT TURN 1097..1099 FT /evidence="ECO:0007829|PDB:6N7A" FT HELIX 1100..1109 FT /evidence="ECO:0007829|PDB:6N7A" FT HELIX 1122..1129 FT /evidence="ECO:0007829|PDB:6N7A" FT HELIX 1130..1132 FT /evidence="ECO:0007829|PDB:6N7A" FT HELIX 1136..1138 FT /evidence="ECO:0007829|PDB:6N7A" FT HELIX 1142..1153 FT /evidence="ECO:0007829|PDB:6N7A" SQ SEQUENCE 1154 AA; 133277 MW; A2C4BE27851ACABB CRC64; MQYLNIKEDC NAMAFCAKMR SSKKTEVNLE APEPGVEVIF YLSDREPLRL GSGEYTAEEL CIRAAQACRI SPLCHNLFAL YDENTKLWYA PNRTITVDDK MSLRLHYRMR FYFTNWHGTN DNEQSVWRHS PKKQKNGYEK KKIPDATPLL DASSLEYLFA QGQYDLVKCL APIRDPKTEQ DGHDIENECL GMAVLAISHY AMMKKMQLPE LPKDISYKRY IPETLNKSIR QRNLLTRMRI NNVFKDFLKE FNNKTICDSS VSTHDLKVKY LATLETLTKH YGAEIFETSM LLISSENEMN WFHSNDGGNV LYYEVMVTGN LGIQWRHKPN VVSVEKEKNK LKRKKLENKH KKDEEKNKIR EEWNNFSYFP EITHIVIKES VVSINKQDNK KMELKLSSHE EALSFVSLVD GYFRLTADAH HYLCTDVAPP LIVHNIQNGC HGPICTEYAI NKLRQEGSEE GMYVLRWSCT DFDNILMTVT CFEKSEQVQG AQKQFKNFQI EVQKGRYSLH GSDRSFPSLG DLMSHLKKQI LRTDNISFML KRCCQPKPRE ISNLLVATKK AQEWQPVYPM SQLSFDRILK KDLVQGEHLG RGTRTHIYSG TLMDYKDDEG TSEEKKIKVI LKVLDPSHRD ISLAFFEAAS MMRQVSHKHI VYLYGVCVRD VENIMVEEFV EGGPLDLFMH RKSDVLTTPW KFKVAKQLAS ALSYLEDKDL VHGNVCTKNL LLAREGIDSE CGPFIKLSDP GIPITVLSRQ ECIERIPWIA PECVEDSKNL SVAADKWSFG TTLWEICYNG EIPLKDKTLI EKERFYESRC RPVTPSCKEL ADLMTRCMNY DPNQRPFFRA IMRDINKLEE QNPDIVSEKK PATEVDPTHF EKRFLKRIRD LGEGHFGKVE LCRYDPEGDN TGEQVAVKSL KPESGGNHIA DLKKEIEILR NLYHENIVKY KGICTEDGGN GIKLIMEFLP SGSLKEYLPK NKNKINLKQQ LKYAVQICKG MDYLGSRQYV HRDLAARNVL VESEHQVKIG DFGLTKAIET DKEYYTVKDD RDSPVFWYAP ECLMQSKFYI ASDVWSFGVT LHELLTYCDS DSSPMALFLK MIGPTHGQMT VTRLVNTLKE GKRLPCPPNC PDEVYQLMRK CWEFQPSNRT SFQNLIEGFE ALLK //