JAK3_HUMAN
ID JAK3_HUMAN Reviewed; 1124 AA.
AC P52333; Q13259; Q13260; Q13611; Q8N1E8; Q99699; Q9Y6S2;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2004, sequence version 2.
DT 03-AUG-2022, entry version 228.
DE RecName: Full=Tyrosine-protein kinase JAK3 {ECO:0000305};
DE EC=2.7.10.2;
DE AltName: Full=Janus kinase 3;
DE Short=JAK-3;
DE AltName: Full=Leukocyte janus kinase;
DE Short=L-JAK;
GN Name=JAK3 {ECO:0000312|HGNC:HGNC:6193};
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 2).
RX PubMed=8022790; DOI=10.1073/pnas.91.14.6374;
RA Kawamura M., McVicar D.W., Johnston J.A., Blake T.B., Chen Y.-Q., Lal B.K.,
RA Lloyd A.R., Kelvin D.J., Staples J.E., Ortaldo J.R., O'Shea J.J.;
RT "Molecular cloning of L-JAK, a Janus family protein-tyrosine kinase
RT expressed in natural killer cells and activated leukocytes.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:6374-6378(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND ALTERNATIVE SPLICING (ISOFORM
RP 2).
RX PubMed=7559633; DOI=10.1074/jbc.270.42.25028;
RA Lai K.S., Jin Y., Graham D.K., Witthuhn B.A., Ihle J.N., Liu E.T.;
RT "A kinase-deficient splice variant of the human JAK3 is expressed in
RT hematopoietic and epithelial cancer cells.";
RL J. Biol. Chem. 270:25028-25036(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8921370; DOI=10.1006/geno.1996.0520;
RA Riedy M.C., Dutra A.S., Blake T.B., Modi W., Lal B.K., Davis J., Bosse A.,
RA O'Shea J.J., Johnston J.A.;
RT "Genomic sequence, organization, and chromosomal localization of human
RT JAK3.";
RL Genomics 37:57-61(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-132 AND ILE-722.
RG SeattleSNPs variation discovery resource;
RL Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Blood;
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 [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 36-191.
RX PubMed=8662778; DOI=10.1074/jbc.271.24.13976;
RA Verbsky J.W., Bach E.A., Fang Y.F., Yang L., Randolph D.A., Fields L.E.;
RT "Expression of Janus kinase 3 in human endothelial and other non-lymphoid
RT and non-myeloid cells.";
RL J. Biol. Chem. 271:13976-13980(1996).
RN [9]
RP FUNCTION IN IL2 SIGNALING PATHWAY.
RX PubMed=8022485; DOI=10.1038/370151a0;
RA Johnston J.A., Kawamura M., Kirken R.A., Chen Y.Q., Blake T.B., Shibuya K.,
RA Ortaldo J.R., McVicar D.W., O'Shea J.J.;
RT "Phosphorylation and activation of the Jak-3 Janus kinase in response to
RT interleukin-2.";
RL Nature 370:151-153(1994).
RN [10]
RP FUNCTION IN IL7 SIGNALING PATHWAY.
RX PubMed=7662955;
RA Sharfe N., Dadi H.K., Roifman C.M.;
RT "JAK3 protein tyrosine kinase mediates interleukin-7-induced activation of
RT phosphatidylinositol-3' kinase.";
RL Blood 86:2077-2085(1995).
RN [11]
RP TISSUE SPECIFICITY.
RX PubMed=7535338; DOI=10.1084/jem.181.4.1425;
RA Musso T., Johnston J.A., Linnekin D., Varesio L., Rowe T.K., O'Shea J.J.,
RA McVicar D.W.;
RT "Regulation of JAK3 expression in human monocytes: phosphorylation in
RT response to interleukins 2, 4, and 7.";
RL J. Exp. Med. 181:1425-1431(1995).
RN [12]
RP INTERACTION WITH STAM2.
RC TISSUE=Fetal brain;
RX PubMed=10899310; DOI=10.1016/s0014-5793(00)01760-9;
RA Endo K., Takeshita T., Kasai H., Sasaki Y., Tanaka N., Asao H., Kikuchi K.,
RA Yamada M., Chenb M., O'Shea J.J., Sugamura K.;
RT "STAM2, a new member of the STAM family, binding to the Janus kinases.";
RL FEBS Lett. 477:55-61(2000).
RN [13]
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 [14]
RP FUNCTION IN CYTOKINE SIGNALING, PHOSPHORYLATION, AND DEPHOSPHORYLATION AT
RP TYR-980 AND TYR-981 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 [15]
RP DOMAIN.
RX PubMed=12351625; DOI=10.1074/jbc.m205156200;
RA Saharinen P., Silvennoinen O.;
RT "The pseudokinase domain is required for suppression of basal activity of
RT Jak2 and Jak3 tyrosine kinases and for cytokine-inducible activation of
RT signal transduction.";
RL J. Biol. Chem. 277:47954-47963(2002).
RN [16]
RP PHOSPHORYLATION AT TYR-785, AND MUTAGENESIS OF TYR-785.
RX PubMed=15121872; DOI=10.1128/mcb.24.10.4557-4570.2004;
RA Kurzer J.H., Argetsinger L.S., Zhou Y.J., Kouadio J.L., O'Shea J.J.,
RA Carter-Su C.;
RT "Tyrosine 813 is a site of JAK2 autophosphorylation critical for activation
RT of JAK2 by SH2-B beta.";
RL Mol. Cell. Biol. 24:4557-4570(2004).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [18]
RP PHOSPHORYLATION AT TYR-904 AND TYR-939, AND MUTAGENESIS OF LYS-855; TYR-904
RP AND TYR-939.
RX PubMed=18250158; DOI=10.1128/mcb.01789-07;
RA Cheng H., Ross J.A., Frost J.A., Kirken R.A.;
RT "Phosphorylation of human Jak3 at tyrosines 904 and 939 positively
RT regulates its activity.";
RL Mol. Cell. Biol. 28:2271-2282(2008).
RN [19]
RP REVIEW ON FUNCTION.
RX PubMed=19290934; DOI=10.1111/j.1600-065x.2008.00754.x;
RA Ghoreschi K., Laurence A., O'Shea J.J.;
RT "Janus kinases in immune cell signaling.";
RL Immunol. Rev. 228:273-287(2009).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [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 [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [22]
RP FUNCTION IN IL15 SIGNALING PATHWAY.
RX PubMed=20440074; DOI=10.1172/jci41344;
RA Malamut G., El Machhour R., Montcuquet N., Martin-Lanneree S.,
RA Dusanter-Fourt I., Verkarre V., Mention J.J., Rahmi G., Kiyono H.,
RA Butz E.A., Brousse N., Cellier C., Cerf-Bensussan N., Meresse B.;
RT "IL-15 triggers an antiapoptotic pathway in human intraepithelial
RT lymphocytes that is a potential new target in celiac disease-associated
RT inflammation and lymphomagenesis.";
RL J. Clin. Invest. 120:2131-2143(2010).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 814-1103 IN COMPLEX WITH
RP STAUROSPORINE ANALOG AFN941, AND PHOSPHORYLATION AT TYR-980 AND TYR-981.
RX PubMed=15831699; DOI=10.1182/blood-2005-02-0707;
RA Boggon T.J., Li Y., Manley P.W., Eck M.J.;
RT "Crystal structure of the Jak3 kinase domain in complex with a
RT staurosporine analog.";
RL Blood 106:996-1002(2005).
RN [24]
RP VARIANT T(-)B(+)NK(-) SCID CYS-100.
RX PubMed=7659163; DOI=10.1038/377065a0;
RA Macchi P., Villa A., Giliani S., Sacco M.G., Frattini A., Porta F.,
RA Ugazio A.G., Johnston J.A., Candotti F., O'Shea J.J., Vezzoni P.,
RA Notarangelo L.D.;
RT "Mutations of Jak-3 gene in patients with autosomal severe combined immune
RT deficiency (SCID).";
RL Nature 377:65-68(1995).
RN [25]
RP VARIANTS T(-)B(+)NK(-) SCID GLY-481; 586-LEU--MET-592 DEL AND ARG-759.
RX PubMed=9354668;
RA Candotti F., Oakes S.A., Johnston J.A., Giliani S., Schumacher R.F.,
RA Mella P., Fiorini M., Ugazio A.G., Badolato R., Notarangelo L.D., Bozzi F.,
RA Macchi P., Strina D., Vezzoni P., Blaese R.M., O'Shea J.J., Villa A.;
RT "Structural and functional basis for JAK3-deficient severe combined
RT immunodeficiency.";
RL Blood 90:3996-4003(1997).
RN [26]
RP VARIANT T(-)B(+)NK(-) SCID TRP-582.
RX PubMed=9753072; DOI=10.1111/j.1365-2141.1998.tb08990.x;
RA Bozzi F., Lefranc G., Villa A., Badolato R., Schumacher R.F., Khalil G.,
RA Loiselet J., Bresciani S., O'Shea J.J., Vezzoni P., Notarangelo L.D.,
RA Candotti F.;
RT "Molecular and biochemical characterization of JAK3 deficiency in a patient
RT with severe combined immunodeficiency over 20 years after bone marrow
RT transplantation: implications for treatment.";
RL Br. J. Haematol. 102:1363-1366(1998).
RN [27]
RP VARIANTS T(-)B(+)NK(-) SCID ARG-151 AND SER-910, AND VARIANT ILE-722.
RX PubMed=10982185; DOI=10.1007/s004390051012;
RA Schumacher R.F., Mella P., Badolato R., Fiorini M., Savoldi G., Giliani S.,
RA Villa A., Candotti F., Tampalini A., O'Shea J.J., Notarangelo L.D.;
RT "Complete genomic organization of the human JAK3 gene and mutation analysis
RT in severe combined immunodeficiency by single-strand conformation
RT polymorphism.";
RL Hum. Genet. 106:73-79(2000).
RN [28]
RP VARIANTS T(-)B(+)NK(-) SCID ALA-58 DEL; GLU-169 AND SER-589, AND VARIANT
RP ILE-722.
RX PubMed=14615376; DOI=10.1182/blood-2003-06-2104;
RA Roberts J.L., Lengi A., Brown S.M., Chen M., Zhou Y.-J., O'Shea J.J.,
RA Buckley R.H.;
RT "Janus kinase 3 (JAK3) deficiency: clinical, immunologic, and molecular
RT analyses of 10 patients and outcomes of stem cell transplantation.";
RL Blood 103:2009-2018(2004).
RN [29]
RP VARIANTS [LARGE SCALE ANALYSIS] LEU-12; HIS-40; THR-132; ARG-151; VAL-521;
RP PRO-527; PHE-688 AND ILE-722.
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).
CC -!- FUNCTION: Non-receptor tyrosine kinase involved in various processes
CC such as cell growth, development, or differentiation. Mediates
CC essential signaling events in both innate and adaptive immunity and
CC plays a crucial role in hematopoiesis during T-cells development. In
CC the cytoplasm, plays a pivotal role in signal transduction via its
CC association with type I receptors sharing the common subunit gamma such
CC as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. Following ligand binding to
CC cell surface receptors, phosphorylates specific tyrosine residues on
CC the cytoplasmic tails of the receptor, creating docking sites for STATs
CC proteins. Subsequently, phosphorylates the STATs proteins once they are
CC recruited to the receptor. Phosphorylated STATs then form homodimer or
CC heterodimers and translocate to the nucleus to activate gene
CC transcription. For example, upon IL2R activation by IL2, JAK1 and JAK3
CC molecules bind to IL2R beta (IL2RB) and gamma chain (IL2RG) subunits
CC inducing the tyrosine phosphorylation of both receptor subunits on
CC their cytoplasmic domain. Then, STAT5A AND STAT5B are recruited,
CC phosphorylated and activated by JAK1 and JAK3. Once activated,
CC dimerized STAT5 translocates to the nucleus and promotes the
CC transcription of specific target genes in a cytokine-specific fashion.
CC {ECO:0000269|PubMed:11909529, ECO:0000269|PubMed:20440074,
CC ECO:0000269|PubMed:7662955, ECO:0000269|PubMed:8022485}.
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 -!- SUBUNIT: Interacts with STAM2 and MYO18A (By similarity). Interacts
CC with SHB. {ECO:0000250, ECO:0000269|PubMed:10899310,
CC ECO:0000269|PubMed:12200137, ECO:0000269|PubMed:15831699}.
CC -!- INTERACTION:
CC P52333; Q07666: KHDRBS1; NbExp=2; IntAct=EBI-518246, EBI-1364;
CC P52333; Q9UNF1: MAGED2; NbExp=4; IntAct=EBI-518246, EBI-725832;
CC P52333; P55209: NAP1L1; NbExp=4; IntAct=EBI-518246, EBI-356392;
CC -!- SUBCELLULAR LOCATION: Endomembrane system {ECO:0000250}; Peripheral
CC membrane protein {ECO:0000250}. Cytoplasm {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=2; Synonyms=JAK3S, Spleen-JAK3;
CC IsoId=P52333-1; Sequence=Displayed;
CC Name=1; Synonyms=JAK3B, Breast-JAK3;
CC IsoId=P52333-2; Sequence=VSP_004989;
CC Name=3;
CC IsoId=P52333-4; Sequence=VSP_054165, VSP_054166;
CC -!- TISSUE SPECIFICITY: In NK cells and an NK-like cell line but not in
CC resting T-cells or in other tissues. The S-form is more commonly seen
CC in hematopoietic lines, whereas the B-form is detected in cells both of
CC hematopoietic and epithelial origins. {ECO:0000269|PubMed:7535338}.
CC -!- DOMAIN: Possesses two phosphotransferase domains. The second one
CC probably contains the catalytic domain (By similarity), while the
CC presence of slight differences suggest a different role for domain 1.
CC {ECO:0000250, ECO:0000269|PubMed:12351625}.
CC -!- PTM: Tyrosine phosphorylated in response to IL-2 and IL-4.
CC Dephosphorylation of Tyr-980 and Tyr-981 by PTPN2 negatively regulates
CC cytokine-mediated signaling (Probable). {ECO:0000305|PubMed:11909529,
CC ECO:0000305|PubMed:15121872, ECO:0000305|PubMed:15831699,
CC ECO:0000305|PubMed:18250158}.
CC -!- DISEASE: Severe combined immunodeficiency autosomal recessive T-cell-
CC negative/B-cell-positive/NK-cell-negative (T(-)B(+)NK(-) SCID)
CC [MIM:600802]: A form of severe combined immunodeficiency (SCID), a
CC genetically and clinically heterogeneous group of rare congenital
CC disorders characterized by impairment of both humoral and cell-mediated
CC immunity, leukopenia, and low or absent antibody levels. Patients
CC present in infancy recurrent, persistent infections by opportunistic
CC organisms. The common characteristic of all types of SCID is absence of
CC T-cell-mediated cellular immunity due to a defect in T-cell
CC development. {ECO:0000269|PubMed:10982185, ECO:0000269|PubMed:14615376,
CC ECO:0000269|PubMed:7659163, ECO:0000269|PubMed:9354668,
CC ECO:0000269|PubMed:9753072}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 1]: May be inactive as it lacks some part of
CC the kinase domain. {ECO:0000305}.
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=AAC50227.1; Type=Miscellaneous discrepancy; Note=Wrong choice of CDS. Was erroneously described as an isoform JAK3M while it is a fragmentary mRNA of INSL3.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/JAK3ID41032ch19p13.html";
CC -!- WEB RESOURCE: Name=JAK3base; Note=JAK3 mutation db;
CC URL="http://structure.bmc.lu.se/idbase/JAK3base/";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/jak3/";
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DR EMBL; U09607; AAA19626.1; -; mRNA.
DR EMBL; U31601; AAC50226.1; -; mRNA.
DR EMBL; U31602; AAC50227.1; ALT_SEQ; mRNA.
DR EMBL; U70065; AAC50950.1; -; Genomic_DNA.
DR EMBL; AF513860; AAM44860.1; -; Genomic_DNA.
DR EMBL; AC007201; AAD22741.1; -; Genomic_DNA.
DR EMBL; CH471106; EAW84639.1; -; Genomic_DNA.
DR EMBL; BC028068; AAH28068.1; -; mRNA.
DR EMBL; U57096; AAC50542.1; -; mRNA.
DR CCDS; CCDS12366.1; -. [P52333-1]
DR PIR; A55747; A55747.
DR RefSeq; NP_000206.2; NM_000215.3. [P52333-1]
DR PDB; 1YVJ; X-ray; 2.55 A; A=814-1103.
DR PDB; 3LXK; X-ray; 2.00 A; A=806-1124.
DR PDB; 3LXL; X-ray; 1.74 A; A=806-1124.
DR PDB; 3PJC; X-ray; 2.20 A; A=812-1124.
DR PDB; 3ZC6; X-ray; 2.42 A; A/B/C/D=813-1100.
DR PDB; 3ZEP; X-ray; 2.35 A; A/B/C/D=813-1047, A/B/C/D=813-1100.
DR PDB; 4HVD; X-ray; 1.85 A; A=811-1124.
DR PDB; 4HVG; X-ray; 2.75 A; A=811-1124.
DR PDB; 4HVH; X-ray; 2.30 A; A=811-1124.
DR PDB; 4HVI; X-ray; 2.40 A; A=811-1124.
DR PDB; 4I6Q; X-ray; 1.85 A; A=811-1124.
DR PDB; 4QPS; X-ray; 1.80 A; A/C=811-1103.
DR PDB; 4QT1; X-ray; 2.40 A; A=811-1124.
DR PDB; 4RIO; X-ray; 2.69 A; A=810-1100.
DR PDB; 4V0G; X-ray; 3.00 A; A/B=816-1098.
DR PDB; 4Z16; X-ray; 2.90 A; A/B/C/D=811-1124.
DR PDB; 5LWM; X-ray; 1.55 A; A=812-1103.
DR PDB; 5LWN; X-ray; 1.60 A; A=812-1103.
DR PDB; 5TOZ; X-ray; 1.98 A; A=812-1124.
DR PDB; 5TTS; X-ray; 2.34 A; A=812-1124.
DR PDB; 5TTU; X-ray; 1.72 A; A=812-1124.
DR PDB; 5TTV; X-ray; 1.93 A; A=812-1124.
DR PDB; 5VO6; X-ray; 2.65 A; A=812-1100.
DR PDB; 5W86; X-ray; 2.61 A; A/B/C/D=814-1100.
DR PDB; 5WFJ; X-ray; 2.48 A; A=810-1100.
DR PDB; 6AAK; X-ray; 2.67 A; A/B/C/D=814-1100.
DR PDB; 6DA4; X-ray; 2.90 A; A=812-1124.
DR PDB; 6DB3; X-ray; 1.97 A; A=812-1124.
DR PDB; 6DB4; X-ray; 1.66 A; A=812-1124.
DR PDB; 6DUD; X-ray; 1.66 A; A=812-1124.
DR PDB; 6GL9; X-ray; 1.70 A; A/B=812-1103.
DR PDB; 6GLA; X-ray; 1.92 A; A/B=812-1103.
DR PDB; 6GLB; X-ray; 2.00 A; A/B=812-1103.
DR PDB; 6HZV; X-ray; 2.46 A; A/B/C/D=815-1099.
DR PDB; 6NY4; X-ray; 2.33 A; A=810-1100.
DR PDB; 7APF; X-ray; 1.95 A; A/B=812-1103.
DR PDB; 7APG; X-ray; 2.40 A; A/B/C/D=812-1103.
DR PDB; 7C3N; X-ray; 1.98 A; A=812-1124.
DR PDB; 7Q6H; X-ray; 1.75 A; AAA=806-1124.
DR PDBsum; 1YVJ; -.
DR PDBsum; 3LXK; -.
DR PDBsum; 3LXL; -.
DR PDBsum; 3PJC; -.
DR PDBsum; 3ZC6; -.
DR PDBsum; 3ZEP; -.
DR PDBsum; 4HVD; -.
DR PDBsum; 4HVG; -.
DR PDBsum; 4HVH; -.
DR PDBsum; 4HVI; -.
DR PDBsum; 4I6Q; -.
DR PDBsum; 4QPS; -.
DR PDBsum; 4QT1; -.
DR PDBsum; 4RIO; -.
DR PDBsum; 4V0G; -.
DR PDBsum; 4Z16; -.
DR PDBsum; 5LWM; -.
DR PDBsum; 5LWN; -.
DR PDBsum; 5TOZ; -.
DR PDBsum; 5TTS; -.
DR PDBsum; 5TTU; -.
DR PDBsum; 5TTV; -.
DR PDBsum; 5VO6; -.
DR PDBsum; 5W86; -.
DR PDBsum; 5WFJ; -.
DR PDBsum; 6AAK; -.
DR PDBsum; 6DA4; -.
DR PDBsum; 6DB3; -.
DR PDBsum; 6DB4; -.
DR PDBsum; 6DUD; -.
DR PDBsum; 6GL9; -.
DR PDBsum; 6GLA; -.
DR PDBsum; 6GLB; -.
DR PDBsum; 6HZV; -.
DR PDBsum; 6NY4; -.
DR PDBsum; 7APF; -.
DR PDBsum; 7APG; -.
DR PDBsum; 7C3N; -.
DR PDBsum; 7Q6H; -.
DR AlphaFoldDB; P52333; -.
DR SMR; P52333; -.
DR BioGRID; 109921; 86.
DR DIP; DIP-274N; -.
DR IntAct; P52333; 85.
DR MINT; P52333; -.
DR STRING; 9606.ENSP00000391676; -.
DR BindingDB; P52333; -.
DR ChEMBL; CHEMBL2148; -.
DR DrugBank; DB04716; 2-tert-butyl-9-fluoro-1,6-dihydrobenzo[h]imidazo[4,5-f]isoquinolin-7-one.
DR DrugBank; DB11817; Baricitinib.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB06321; R-348.
DR DrugBank; DB08877; Ruxolitinib.
DR DrugBank; DB08895; Tofacitinib.
DR DrugBank; DB15035; Zanubrutinib.
DR DrugCentral; P52333; -.
DR GuidetoPHARMACOLOGY; 2049; -.
DR iPTMnet; P52333; -.
DR PhosphoSitePlus; P52333; -.
DR BioMuta; JAK3; -.
DR DMDM; 50403745; -.
DR jPOST; P52333; -.
DR MassIVE; P52333; -.
DR MaxQB; P52333; -.
DR PaxDb; P52333; -.
DR PeptideAtlas; P52333; -.
DR PRIDE; P52333; -.
DR ProteomicsDB; 56482; -. [P52333-1]
DR ProteomicsDB; 56483; -. [P52333-2]
DR ProteomicsDB; 71591; -.
DR Antibodypedia; 35352; 487 antibodies from 36 providers.
DR DNASU; 3718; -.
DR Ensembl; ENST00000458235.7; ENSP00000391676.1; ENSG00000105639.20. [P52333-1]
DR Ensembl; ENST00000527670.5; ENSP00000432511.1; ENSG00000105639.20. [P52333-1]
DR Ensembl; ENST00000534444.1; ENSP00000436421.1; ENSG00000105639.20. [P52333-2]
DR GeneID; 3718; -.
DR KEGG; hsa:3718; -.
DR MANE-Select; ENST00000458235.7; ENSP00000391676.1; NM_000215.4; NP_000206.2.
DR UCSC; uc002nhn.5; human. [P52333-1]
DR CTD; 3718; -.
DR DisGeNET; 3718; -.
DR GeneCards; JAK3; -.
DR HGNC; HGNC:6193; JAK3.
DR HPA; ENSG00000105639; Tissue enhanced (lymphoid).
DR MalaCards; JAK3; -.
DR MIM; 600173; gene.
DR MIM; 600802; phenotype.
DR neXtProt; NX_P52333; -.
DR OpenTargets; ENSG00000105639; -.
DR Orphanet; 35078; T-B+ severe combined immunodeficiency due to JAK3 deficiency.
DR PharmGKB; PA29990; -.
DR VEuPathDB; HostDB:ENSG00000105639; -.
DR eggNOG; KOG0197; Eukaryota.
DR GeneTree; ENSGT00940000161827; -.
DR HOGENOM; CLU_008155_1_0_1; -.
DR InParanoid; P52333; -.
DR OMA; TEDLKCW; -.
DR OrthoDB; 58906at2759; -.
DR PhylomeDB; P52333; -.
DR TreeFam; TF327041; -.
DR BRENDA; 2.7.10.2; 2681.
DR PathwayCommons; P52333; -.
DR Reactome; R-HSA-1266695; Interleukin-7 signaling.
DR Reactome; R-HSA-201556; Signaling by ALK.
DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling.
DR Reactome; R-HSA-8854691; Interleukin-20 family signaling.
DR Reactome; R-HSA-8983432; Interleukin-15 signaling.
DR Reactome; R-HSA-8985947; Interleukin-9 signaling.
DR Reactome; R-HSA-9020558; Interleukin-2 signaling.
DR Reactome; R-HSA-9020958; Interleukin-21 signaling.
DR Reactome; R-HSA-912526; Interleukin receptor SHC signaling.
DR Reactome; R-HSA-9679191; Potential therapeutics for SARS.
DR SignaLink; P52333; -.
DR SIGNOR; P52333; -.
DR BioGRID-ORCS; 3718; 14 hits in 1108 CRISPR screens.
DR EvolutionaryTrace; P52333; -.
DR GeneWiki; Janus_kinase_3; -.
DR GenomeRNAi; 3718; -.
DR Pharos; P52333; Tclin.
DR PRO; PR:P52333; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P52333; protein.
DR Bgee; ENSG00000105639; Expressed in granulocyte and 148 other tissues.
DR ExpressionAtlas; P52333; baseline and differential.
DR Genevisible; P52333; HS.
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:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005126; F:cytokine receptor binding; IBA:GO_Central.
DR GO; GO:0005131; F:growth hormone receptor binding; IBA:GO_Central.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0019903; F:protein phosphatase binding; IPI:UniProtKB.
DR GO; GO:0004713; F:protein tyrosine kinase activity; ISS:BHF-UCL.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0030183; P:B cell differentiation; ISS:BHF-UCL.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0007167; P:enzyme-linked receptor protein signaling pathway; ISS:BHF-UCL.
DR GO; GO:0030218; P:erythrocyte differentiation; IBA:GO_Central.
DR GO; GO:0060397; P:growth hormone receptor signaling pathway via JAK-STAT; IBA:GO_Central.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0038110; P:interleukin-2-mediated signaling pathway; TAS:Reactome.
DR GO; GO:0035771; P:interleukin-4-mediated signaling pathway; IDA:BHF-UCL.
DR GO; GO:0035556; P:intracellular signal transduction; ISS:BHF-UCL.
DR GO; GO:0002731; P:negative regulation of dendritic cell cytokine production; ISS:BHF-UCL.
DR GO; GO:0045221; P:negative regulation of FasL production; ISS:BHF-UCL.
DR GO; GO:0032693; P:negative regulation of interleukin-10 production; ISS:BHF-UCL.
DR GO; GO:0032695; P:negative regulation of interleukin-12 production; ISS:BHF-UCL.
DR GO; GO:0050868; P:negative regulation of T cell activation; ISS:BHF-UCL.
DR GO; GO:0045626; P:negative regulation of T-helper 1 cell differentiation; ISS:BHF-UCL.
DR GO; GO:0070244; P:negative regulation of thymocyte apoptotic process; ISS:BHF-UCL.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISS:BHF-UCL.
DR GO; GO:0042104; P:positive regulation of activated T cell proliferation; IEA:Ensembl.
DR GO; GO:0051928; P:positive regulation of calcium ion transport; IEA:Ensembl.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IEA:Ensembl.
DR GO; GO:0051770; P:positive regulation of nitric-oxide synthase biosynthetic process; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc.
DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; IBA:GO_Central.
DR GO; GO:0042981; P:regulation of apoptotic process; IBA:GO_Central.
DR GO; GO:0046425; P:regulation of receptor signaling pathway via JAK-STAT; TAS:UniProtKB.
DR GO; GO:0070232; P:regulation of T cell apoptotic process; ISS:BHF-UCL.
DR GO; GO:0070672; P:response to interleukin-15; TAS:BHF-UCL.
DR GO; GO:0070669; P:response to interleukin-2; TAS:BHF-UCL.
DR GO; GO:0070670; P:response to interleukin-4; IDA:BHF-UCL.
DR GO; GO:0071104; P:response to interleukin-9; TAS:BHF-UCL.
DR GO; GO:0043029; P:T cell homeostasis; ISS:BHF-UCL.
DR GO; GO:0007260; P:tyrosine phosphorylation of STAT protein; IBA:GO_Central.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR019749; Band_41_domain.
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; IPR011993; PH-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; IPR020775; Tyr_kinase_non-rcpt_Jak3.
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; PR01826; JANUSKINASE3.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00295; B41; 1.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00219; TyrKc; 2.
DR SUPFAM; SSF55550; SSF55550; 1.
DR SUPFAM; SSF56112; SSF56112; 2.
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.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Alternative splicing; ATP-binding;
KW Cytoplasm; Disease variant; Immunity; Innate immunity; Kinase; Membrane;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat; SCID;
KW SH2 domain; Transferase; Tyrosine-protein kinase.
FT CHAIN 1..1124
FT /note="Tyrosine-protein kinase JAK3"
FT /id="PRO_0000088115"
FT DOMAIN 24..356
FT /note="FERM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00084"
FT DOMAIN 375..475
FT /note="SH2; atypical"
FT DOMAIN 521..781
FT /note="Protein kinase 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 822..1111
FT /note="Protein kinase 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..223
FT /note="Interaction with cytokine/interferon/growth hormone
FT receptors"
FT /evidence="ECO:0000250"
FT ACT_SITE 949
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 828..836
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 855
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 17
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62137"
FT MOD_RES 785
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15121872"
FT MOD_RES 904
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:18250158"
FT MOD_RES 939
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:18250158"
FT MOD_RES 980
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15831699"
FT MOD_RES 981
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15831699"
FT VAR_SEQ 597..619
FT /note="TMVQEFVHLGAIDMYLRKRGHLV -> ESPPPTHPTPASPKSRLFFPPLF
FT (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_054165"
FT VAR_SEQ 620..1124
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_054166"
FT VAR_SEQ 1071..1124
FT /note="HELMKLCWAPSPQDRPSFSALGPQLDMLWSGSRGCETHAFTAHPEGKHHSLS
FT FS -> SAAGLASVSQSVDWAGVSGKPAGA (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:7559633"
FT /id="VSP_004989"
FT VARIANT 12
FT /note="P -> L (in dbSNP:rs56061056)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041722"
FT VARIANT 40
FT /note="R -> H (in dbSNP:rs56384680)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041723"
FT VARIANT 58
FT /note="Missing (in T(-)B(+)NK(-) SCID)"
FT /evidence="ECO:0000269|PubMed:14615376"
FT /id="VAR_019337"
FT VARIANT 100
FT /note="Y -> C (in T(-)B(+)NK(-) SCID; dbSNP:rs137852624)"
FT /evidence="ECO:0000269|PubMed:7659163"
FT /id="VAR_006284"
FT VARIANT 132
FT /note="P -> T (in dbSNP:rs3212723)"
FT /evidence="ECO:0000269|PubMed:17344846, ECO:0000269|Ref.4"
FT /id="VAR_019336"
FT VARIANT 151
FT /note="P -> R (in T(-)B(+)NK(-) SCID; likely benign
FT variant; dbSNP:rs55778349)"
FT /evidence="ECO:0000269|PubMed:10982185,
FT ECO:0000269|PubMed:17344846"
FT /id="VAR_010492"
FT VARIANT 169
FT /note="D -> E (in T(-)B(+)NK(-) SCID; dbSNP:rs147181709)"
FT /evidence="ECO:0000269|PubMed:14615376"
FT /id="VAR_019338"
FT VARIANT 481
FT /note="E -> G (in T(-)B(+)NK(-) SCID)"
FT /evidence="ECO:0000269|PubMed:9354668"
FT /id="VAR_010493"
FT VARIANT 521
FT /note="L -> V (in dbSNP:rs55666418)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041724"
FT VARIANT 527
FT /note="L -> P (in a gastric adenocarcinoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041725"
FT VARIANT 582
FT /note="R -> W (in T(-)B(+)NK(-) SCID; dbSNP:rs193922361)"
FT /evidence="ECO:0000269|PubMed:9753072"
FT /id="VAR_010494"
FT VARIANT 586..592
FT /note="Missing (in T(-)B(+)NK(-) SCID; lack of
FT phosphorylation in response to cytokine stimulation)"
FT /evidence="ECO:0000269|PubMed:9354668"
FT /id="VAR_010495"
FT VARIANT 589
FT /note="G -> S (in T(-)B(+)NK(-) SCID; dbSNP:rs886039394)"
FT /evidence="ECO:0000269|PubMed:14615376"
FT /id="VAR_019339"
FT VARIANT 688
FT /note="I -> F (in dbSNP:rs35785705)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041726"
FT VARIANT 722
FT /note="V -> I (in dbSNP:rs3213409)"
FT /evidence="ECO:0000269|PubMed:10982185,
FT ECO:0000269|PubMed:14615376, ECO:0000269|PubMed:17344846,
FT ECO:0000269|Ref.4"
FT /id="VAR_010496"
FT VARIANT 759
FT /note="C -> R (in T(-)B(+)NK(-) SCID; constitutive
FT phosphorylation)"
FT /evidence="ECO:0000269|PubMed:9354668"
FT /id="VAR_010497"
FT VARIANT 910
FT /note="L -> S (in T(-)B(+)NK(-) SCID)"
FT /evidence="ECO:0000269|PubMed:10982185"
FT /id="VAR_010498"
FT MUTAGEN 785
FT /note="Y->F: Strong decrease of JAK3 phosphorylation."
FT /evidence="ECO:0000269|PubMed:15121872"
FT MUTAGEN 855
FT /note="K->A: More than 90% loss of STAT5a activation."
FT /evidence="ECO:0000269|PubMed:18250158"
FT MUTAGEN 904
FT /note="Y->F: About 40% loss of STAT5a activation."
FT /evidence="ECO:0000269|PubMed:18250158"
FT MUTAGEN 939
FT /note="Y->F: About 80% loss of STAT5a activation."
FT /evidence="ECO:0000269|PubMed:18250158"
FT CONFLICT 34
FT /note="G -> A (in Ref. 1; AAA19626)"
FT /evidence="ECO:0000305"
FT CONFLICT 45
FT /note="F -> S (in Ref. 3; AAC50950)"
FT /evidence="ECO:0000305"
FT CONFLICT 103
FT /note="R -> RS (in Ref. 3; AAC50950)"
FT /evidence="ECO:0000305"
FT CONFLICT 147
FT /note="Missing (in Ref. 8; AAC50542)"
FT /evidence="ECO:0000305"
FT CONFLICT 187
FT /note="T -> A (in Ref. 8; AAC50542)"
FT /evidence="ECO:0000305"
FT CONFLICT 212
FT /note="R -> A (in Ref. 1; AAA19626 and 3; AAC50950)"
FT /evidence="ECO:0000305"
FT CONFLICT 222
FT /note="R -> P (in Ref. 1; AAA19626 and 3; AAC50950)"
FT /evidence="ECO:0000305"
FT CONFLICT 271
FT /note="L -> F (in Ref. 3; AAC50950)"
FT /evidence="ECO:0000305"
FT CONFLICT 287
FT /note="Missing (in Ref. 3; AAC50950)"
FT /evidence="ECO:0000305"
FT CONFLICT 610
FT /note="M -> I (in Ref. 2; AAC50226)"
FT /evidence="ECO:0000305"
FT CONFLICT 845..846
FT /note="GD -> AH (in Ref. 1; AAA19626)"
FT /evidence="ECO:0000305"
FT CONFLICT 895..897
FT /note="RQS -> EPE (in Ref. 3; AAC50950)"
FT /evidence="ECO:0000305"
FT CONFLICT 896..897
FT /note="QS -> PE (in Ref. 1; AAA19626)"
FT /evidence="ECO:0000305"
FT STRAND 816..818
FT /evidence="ECO:0007829|PDB:5LWM"
FT HELIX 819..821
FT /evidence="ECO:0007829|PDB:5LWM"
FT STRAND 822..830
FT /evidence="ECO:0007829|PDB:5LWM"
FT STRAND 832..841
FT /evidence="ECO:0007829|PDB:5LWM"
FT STRAND 845..847
FT /evidence="ECO:0007829|PDB:5LWM"
FT STRAND 849..859
FT /evidence="ECO:0007829|PDB:5LWM"
FT HELIX 862..877
FT /evidence="ECO:0007829|PDB:5LWM"
FT STRAND 886..891
FT /evidence="ECO:0007829|PDB:5LWM"
FT STRAND 893..896
FT /evidence="ECO:0007829|PDB:5LWM"
FT STRAND 898..903
FT /evidence="ECO:0007829|PDB:5LWM"
FT HELIX 910..917
FT /evidence="ECO:0007829|PDB:5LWM"
FT HELIX 918..920
FT /evidence="ECO:0007829|PDB:5LWM"
FT HELIX 923..942
FT /evidence="ECO:0007829|PDB:5LWM"
FT HELIX 952..954
FT /evidence="ECO:0007829|PDB:5LWM"
FT STRAND 955..959
FT /evidence="ECO:0007829|PDB:5LWM"
FT STRAND 962..965
FT /evidence="ECO:0007829|PDB:5LWM"
FT HELIX 968..970
FT /evidence="ECO:0007829|PDB:3LXL"
FT STRAND 979..982
FT /evidence="ECO:0007829|PDB:5LWM"
FT HELIX 991..993
FT /evidence="ECO:0007829|PDB:5LWM"
FT HELIX 996..1001
FT /evidence="ECO:0007829|PDB:5LWM"
FT STRAND 1003..1005
FT /evidence="ECO:0007829|PDB:5LWM"
FT HELIX 1006..1021
FT /evidence="ECO:0007829|PDB:5LWM"
FT TURN 1022..1024
FT /evidence="ECO:0007829|PDB:5LWM"
FT HELIX 1026..1028
FT /evidence="ECO:0007829|PDB:5LWM"
FT HELIX 1030..1037
FT /evidence="ECO:0007829|PDB:5LWM"
FT STRAND 1042..1044
FT /evidence="ECO:0007829|PDB:4QPS"
FT HELIX 1046..1055
FT /evidence="ECO:0007829|PDB:5LWM"
FT HELIX 1068..1077
FT /evidence="ECO:0007829|PDB:5LWM"
FT HELIX 1082..1084
FT /evidence="ECO:0007829|PDB:5LWM"
FT HELIX 1088..1102
FT /evidence="ECO:0007829|PDB:5LWM"
SQ SEQUENCE 1124 AA; 125099 MW; 895D8563439B2B7C CRC64;
MAPPSEETPL IPQRSCSLLS TEAGALHVLL PARGPGPPQR LSFSFGDHLA EDLCVQAAKA
SGILPVYHSL FALATEDLSC WFPPSHIFSV EDASTQVLLY RIRFYFPNWF GLEKCHRFGL
RKDLASAILD LPVLEHLFAQ HRSDLVSGRL PVGLSLKEQG ECLSLAVLDL ARMAREQAQR
PGELLKTVSY KACLPPSLRD LIQGLSFVTR RRIRRTVRRA LRRVAACQAD RHSLMAKYIM
DLERLDPAGA AETFHVGLPG ALGGHDGLGL LRVAGDGGIA WTQGEQEVLQ PFCDFPEIVD
ISIKQAPRVG PAGEHRLVTV TRTDNQILEA EFPGLPEALS FVALVDGYFR LTTDSQHFFC
KEVAPPRLLE EVAEQCHGPI TLDFAINKLK TGGSRPGSYV LRRSPQDFDS FLLTVCVQNP
LGPDYKGCLI RRSPTGTFLL VGLSRPHSSL RELLATCWDG GLHVDGVAVT LTSCCIPRPK
EKSNLIVVQR GHSPPTSSLV QPQSQYQLSQ MTFHKIPADS LEWHENLGHG SFTKIYRGCR
HEVVDGEARK TEVLLKVMDA KHKNCMESFL EAASLMSQVS YRHLVLLHGV CMAGDSTMVQ
EFVHLGAIDM YLRKRGHLVP ASWKLQVVKQ LAYALNYLED KGLPHGNVSA RKVLLAREGA
DGSPPFIKLS DPGVSPAVLS LEMLTDRIPW VAPECLREAQ TLSLEADKWG FGATVWEVFS
GVTMPISALD PAKKLQFYED RQQLPAPKWT ELALLIQQCM AYEPVQRPSF RAVIRDLNSL
ISSDYELLSD PTPGALAPRD GLWNGAQLYA CQDPTIFEER HLKYISQLGK GNFGSVELCR
YDPLGDNTGA LVAVKQLQHS GPDQQRDFQR EIQILKALHS DFIVKYRGVS YGPGRQSLRL
VMEYLPSGCL RDFLQRHRAR LDASRLLLYS SQICKGMEYL GSRRCVHRDL AARNILVESE
AHVKIADFGL AKLLPLDKDY YVVREPGQSP IFWYAPESLS DNIFSRQSDV WSFGVVLYEL
FTYCDKSCSP SAEFLRMMGC ERDVPALCRL LELLEEGQRL PAPPACPAEV HELMKLCWAP
SPQDRPSFSA LGPQLDMLWS GSRGCETHAF TAHPEGKHHS LSFS
