ID LYST_HUMAN Reviewed; 3801 AA. AC Q99698; O43274; Q5T2U9; Q96TD7; Q96TD8; Q99709; Q9H133; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 27-SEP-2005, sequence version 3. DT 27-MAR-2024, entry version 208. DE RecName: Full=Lysosomal-trafficking regulator; DE AltName: Full=Beige homolog; GN Name=LYST; Synonyms=CHS, CHS1; 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 1). RX PubMed=8896560; DOI=10.1038/ng1196-307; RA Nagle D.L., Karim M.A., Woolf E.A., Holmgren L., Bork P., Misumi D.J., RA McGrail S.H., Dussault B.J., Perou C.M., Boissy R.E., Duyk G.M., RA Spritz R.A., Moore K.J.; RT "Identification and mutation analysis of the complete gene for Chediak- RT Higashi syndrome."; RL Nat. Genet. 14:307-311(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Liver; RX PubMed=8717042; DOI=10.1038/382262a0; RA Barbosa M.D.F.S., Nguyen Q.A., Tchernev V.T., Ashley J.A., Detter J.C., RA Blaydes S.M., Brandt S.J., Chotai D., Hodgman C., Solari R.C.E.S., RA Lovett M., Kingsmore S.F.; RT "Identification of the homologous beige and Chediak-Higashi syndrome RT genes."; RL Nature 382:262-265(1996). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND TISSUE SPECIFICITY. RX PubMed=9215680; DOI=10.1093/hmg/6.7.1091; RA Barbosa M.D.F.S., Barrat F.J., Tchernev V.T., Nguyen Q.A., Mishra V.S., RA Colman S.D., Pastural E., Dufourcq-Lagelouse R., Fischer A., Holcombe R.F., RA Wallace M.R., Brandt S.J., De Saint Basile G., Kingsmore S.F.; RT "Identification of mutations in two major mRNA isoforms of the Chediak- RT Higashi syndrome gene in human and mouse."; RL Hum. Mol. Genet. 6:1091-1098(1997). RN [4] 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 [5] RP FUNCTION, AND INTERACTION WITH CENPJ; LIP8 AND ZNF521. RX PubMed=11984006; DOI=10.1007/bf03402003; RA Tchernev V.T., Mansfield T.A., Giot L., Kumar A.M., Nandabalan K., Li Y., RA Mishra V.S., Detter J.C., Rothberg J.M., Wallace M.R., Southwick F.S., RA Kingsmore S.F.; RT "The Chediak-Higashi protein interacts with SNARE complex and signal RT transduction proteins."; RL Mol. Med. 8:56-64(2002). RN [6] RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S). RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8; RA Hillman R.T., Green R.E., Brenner S.E.; RT "An unappreciated role for RNA surveillance."; RL Genome Biol. 5:R8.1-R8.16(2004). RN [7] RP INVOLVEMENT IN CHS, AND VARIANTS CHS HIS-1563 AND ASP-1999. RX PubMed=11857544; DOI=10.1002/ajmg.10184.abs; RA Karim M.A., Suzuki K., Fukai K., Oh J., Nagle D.L., Moore K.J., Barbosa E., RA Falik-Borenstein T., Filipovich A., Ishida Y., Kivrikko S., Klein C., RA Kreuz F., Levin A., Miyajima H., Regueiro J., Russo C., Uyama E., RA Vierimaa O., Spritz R.A.; RT "Apparent genotype-phenotype correlation in childhood, adolescent, and RT adult Chediak-Higashi syndrome."; RL Am. J. Med. Genet. 108:16-22(2002). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2105, AND IDENTIFICATION BY RP 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 [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2105, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2124, AND IDENTIFICATION BY RP 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 [12] RP FUNCTION. RX PubMed=25216107; DOI=10.1111/tra.12227; RA Holland P., Torgersen M.L., Sandvig K., Simonsen A.; RT "LYST affects lysosome size and quantity, but not trafficking or RT degradation through autophagy or endocytosis."; RL Traffic 15:1390-1405(2014). RN [13] RP FUNCTION. RX PubMed=25425525; DOI=10.1111/tra.12244; RA Sepulveda F.E., Burgess A., Heiligenstein X., Goudin N., Menager M.M., RA Romao M., Cote M., Mahlaoui N., Fischer A., Raposo G., Menasche G., RA de Saint Basile G.; RT "LYST controls the biogenesis of the endosomal compartment required for RT secretory lysosome function."; RL Traffic 16:191-203(2015). RN [14] RP FUNCTION. RX PubMed=26478006; DOI=10.1016/j.jaci.2015.08.039; RA Gil-Krzewska A., Wood S.M., Murakami Y., Nguyen V., Chiang S.C.C., RA Cullinane A.R., Peruzzi G., Gahl W.A., Coligan J.E., Introne W.J., RA Bryceson Y.T., Krzewski K.; RT "Chediak-Higashi syndrome: Lysosomal trafficking regulator domains regulate RT exocytosis of lytic granules but not cytokine secretion by natural killer RT cells."; RL J. Allergy Clin. Immunol. 137:1165-1177(2016). RN [15] RP FUNCTION. RX PubMed=27881733; DOI=10.1084/jem.20141461; RA Westphal A., Cheng W., Yu J., Grassl G., Krautkraemer M., Holst O., RA Foeger N., Lee K.H.; RT "Lysosomal trafficking regulator Lyst links membrane trafficking to toll- RT like receptor-mediated inflammatory responses."; RL J. Exp. Med. 214:227-244(2017). RN [16] RP VARIANTS CHS 1208-GLN--GLY-3801 DEL AND 3668-GLU--GLY-3801 DEL. RX PubMed=20368792; DOI=10.1155/2010/967535; RA Morrone K., Wang Y., Huizing M., Sutton E., White J.G., Gahl W.A., RA Moody K.; RT "Two novel mutations identified in an african-american child with chediak- RT higashi syndrome."; RL Case Rep. Med. 2010:967535-967535(2010). RN [17] RP VARIANT CHS VAL-1397. RX PubMed=24521565; DOI=10.1136/jnnp-2013-306981; RA Shimazaki H., Honda J., Naoi T., Namekawa M., Nakano I., Yazaki M., RA Nakamura K., Yoshida K., Ikeda S., Ishiura H., Fukuda Y., Takahashi Y., RA Goto J., Tsuji S., Takiyama Y.; RT "Autosomal-recessive complicated spastic paraplegia with a novel lysosomal RT trafficking regulator gene mutation."; RL J. Neurol. Neurosurg. Psych. 85:1024-1028(2014). RN [18] RP VARIANT CHS VAL-1907. RX PubMed=31906877; DOI=10.1186/s12881-019-0922-8; RA Song Y., Dong Z., Luo S., Yang J., Lu Y., Gao B., Fan T.; RT "Identification of a compound heterozygote in LYST gene: a case report on RT Chediak-Higashi syndrome."; RL BMC Med. Genet. 21:4-4(2020). CC -!- FUNCTION: Adapter protein that regulates and/or fission of CC intracellular vesicles such as lysosomes (PubMed:11984006, CC PubMed:25216107). Might regulate trafficking of effectors involved in CC exocytosis (PubMed:25425525). In cytotoxic T-cells and natural killer CC (NK) cells, has role in the regulation of size, number and exocytosis CC of lytic granules (PubMed:26478006). In macrophages and dendritic CC cells, regulates phagosome maturation by controlling the conversion of CC early phagosomal compartments into late phagosomes (By similarity). In CC macrophages and dendritic cells, specifically involved in TLR3- and CC TLR4-induced production of pro-inflammatory cytokines by regulating the CC endosomal TLR3- TICAM1/TRIF and TLR4- TICAM1/TRIF signaling pathways CC (PubMed:27881733). {ECO:0000250|UniProtKB:P97412, CC ECO:0000269|PubMed:11984006, ECO:0000269|PubMed:25216107, CC ECO:0000269|PubMed:25425525, ECO:0000269|PubMed:26478006, CC ECO:0000269|PubMed:27881733}. CC -!- SUBUNIT: Interacts with CENPJ, LIP8 and ZNF521. CC {ECO:0000269|PubMed:11984006}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Comment=Additional isoforms seem to exist.; CC Name=1; CC IsoId=Q99698-1; Sequence=Displayed; CC Name=2; CC IsoId=Q99698-2; Sequence=VSP_006781, VSP_006782; CC Name=3; CC IsoId=Q99698-3; Sequence=VSP_006779, VSP_006780; CC -!- TISSUE SPECIFICITY: Abundantly expressed in adult and fetal thymus, CC peripheral blood leukocytes, bone marrow and several regions of the CC adult brain. {ECO:0000269|PubMed:9215680}. CC -!- DISEASE: Chediak-Higashi syndrome (CHS) [MIM:214500]: A rare autosomal CC recessive disorder characterized by hypopigmentation, severe CC immunologic deficiency, a bleeding tendency, neurologic abnormalities, CC abnormal intracellular transport to and from the lysosome, and giant CC inclusion bodies in a variety of cell types. Most patients die at an CC early age unless they receive an allogeneic hematopoietic stem cell CC transplant (SCT). {ECO:0000269|PubMed:11857544, CC ECO:0000269|PubMed:20368792, ECO:0000269|PubMed:24521565, CC ECO:0000269|PubMed:31906877}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform 1]: May be produced at very low levels due to a CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA CC decay. CC -!- WEB RESOURCE: Name=LYSTbase; Note=LYST mutation db; CC URL="http://structure.bmc.lu.se/idbase/LYSTbase/"; CC -!- WEB RESOURCE: Name=Mutations of the LYST gene; Note=Retina CC International's Scientific Newsletter; CC URL="https://www.retina-international.org/files/sci-news/chsmut.htm"; CC -!- WEB RESOURCE: Name=Albinism database (ADB); Note=LYST mutations; CC URL="http://www.ifpcs.org/albinism/chs1mut.html"; 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; U84744; AAB87737.1; -; mRNA. DR EMBL; U67615; AAB41309.1; -; mRNA. DR EMBL; U72192; AAB39697.1; -; mRNA. DR EMBL; L77889; AAB51608.1; -; mRNA. DR EMBL; U70064; AAB41533.1; -; mRNA. DR EMBL; AL121997; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL390765; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS31062.1; -. [Q99698-1] DR RefSeq; NP_000072.2; NM_000081.3. [Q99698-1] DR RefSeq; NP_001288294.1; NM_001301365.1. [Q99698-1] DR SMR; Q99698; -. DR BioGRID; 107552; 53. DR IntAct; Q99698; 31. DR MINT; Q99698; -. DR STRING; 9606.ENSP00000374443; -. DR GlyCosmos; Q99698; 2 sites, 1 glycan. DR GlyGen; Q99698; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; Q99698; -. DR PhosphoSitePlus; Q99698; -. DR SwissPalm; Q99698; -. DR BioMuta; LYST; -. DR DMDM; 76803797; -. DR EPD; Q99698; -. DR jPOST; Q99698; -. DR MassIVE; Q99698; -. DR MaxQB; Q99698; -. DR PaxDb; 9606-ENSP00000374443; -. DR PeptideAtlas; Q99698; -. DR ProteomicsDB; 78406; -. [Q99698-1] DR ProteomicsDB; 78407; -. [Q99698-2] DR ProteomicsDB; 78408; -. [Q99698-3] DR Pumba; Q99698; -. DR Antibodypedia; 34697; 25 antibodies from 13 providers. DR DNASU; 1130; -. DR Ensembl; ENST00000389793.7; ENSP00000374443.2; ENSG00000143669.16. [Q99698-1] DR Ensembl; ENST00000489585.5; ENSP00000513166.1; ENSG00000143669.16. [Q99698-2] DR GeneID; 1130; -. DR KEGG; hsa:1130; -. DR MANE-Select; ENST00000389793.7; ENSP00000374443.2; NM_000081.4; NP_000072.2. DR UCSC; uc001hxj.4; human. [Q99698-1] DR AGR; HGNC:1968; -. DR CTD; 1130; -. DR DisGeNET; 1130; -. DR GeneCards; LYST; -. DR GeneReviews; LYST; -. DR HGNC; HGNC:1968; LYST. DR HPA; ENSG00000143669; Tissue enhanced (bone). DR MalaCards; LYST; -. DR MIM; 214500; phenotype. DR MIM; 606897; gene. DR neXtProt; NX_Q99698; -. DR OpenTargets; ENSG00000143669; -. DR Orphanet; 352723; Attenuated Chediak-Higashi syndrome. DR Orphanet; 167; Chediak-Higashi syndrome. DR PharmGKB; PA26500; -. DR VEuPathDB; HostDB:ENSG00000143669; -. DR eggNOG; KOG1786; Eukaryota. DR GeneTree; ENSGT00940000156359; -. DR HOGENOM; CLU_000213_1_0_1; -. DR InParanoid; Q99698; -. DR OMA; MGAPPEF; -. DR OrthoDB; 47483at2759; -. DR PhylomeDB; Q99698; -. DR TreeFam; TF313658; -. DR PathwayCommons; Q99698; -. DR SignaLink; Q99698; -. DR SIGNOR; Q99698; -. DR BioGRID-ORCS; 1130; 18 hits in 1147 CRISPR screens. DR ChiTaRS; LYST; human. DR GenomeRNAi; 1130; -. DR Pharos; Q99698; Tbio. DR PRO; PR:Q99698; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q99698; Protein. DR Bgee; ENSG00000143669; Expressed in monocyte and 193 other cell types or tissues. DR ExpressionAtlas; Q99698; baseline and differential. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0016020; C:membrane; IBA:GO_Central. DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; IBA:GO_Central. DR GO; GO:0042742; P:defense response to bacterium; ISS:UniProtKB. DR GO; GO:0042832; P:defense response to protozoan; ISS:UniProtKB. DR GO; GO:0051607; P:defense response to virus; ISS:UniProtKB. DR GO; GO:0032510; P:endosome to lysosome transport via multivesicular body sorting pathway; IMP:UniProtKB. DR GO; GO:0030595; P:leukocyte chemotaxis; ISS:UniProtKB. DR GO; GO:0033364; P:mast cell secretory granule organization; ISS:UniProtKB. DR GO; GO:0032438; P:melanosome organization; ISS:UniProtKB. DR GO; GO:0042267; P:natural killer cell mediated cytotoxicity; IMP:UniProtKB. DR GO; GO:0006909; P:phagocytosis; IEA:UniProtKB-KW. DR GO; GO:0043473; P:pigmentation; IMP:UniProtKB. DR GO; GO:0008104; P:protein localization; IBA:GO_Central. DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW. DR CDD; cd06071; Beach; 1. DR CDD; cd01201; PH_BEACH; 1. DR Gene3D; 1.10.1540.10; BEACH domain; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 2. DR InterPro; IPR016024; ARM-type_fold. DR InterPro; IPR000409; BEACH_dom. DR InterPro; IPR036372; BEACH_dom_sf. DR InterPro; IPR023362; PH-BEACH_dom. DR InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf. DR InterPro; IPR019775; WD40_repeat_CS. DR InterPro; IPR036322; WD40_repeat_dom_sf. DR InterPro; IPR001680; WD40_rpt. DR PANTHER; PTHR13743; BEIGE/BEACH-RELATED; 1. DR PANTHER; PTHR13743:SF163; LYSOSOMAL-TRAFFICKING REGULATOR; 1. DR Pfam; PF02138; Beach; 1. DR Pfam; PF14844; PH_BEACH; 1. DR Pfam; PF00400; WD40; 2. DR SMART; SM01026; Beach; 1. DR SMART; SM00320; WD40; 4. DR SUPFAM; SSF48371; ARM repeat; 1. DR SUPFAM; SSF81837; BEACH domain; 1. DR SUPFAM; SSF50729; PH domain-like; 1. DR SUPFAM; SSF50978; WD40 repeat-like; 1. DR PROSITE; PS50197; BEACH; 1. DR PROSITE; PS51783; PH_BEACH; 1. DR PROSITE; PS00678; WD_REPEATS_1; 1. DR PROSITE; PS50082; WD_REPEATS_2; 1. DR PROSITE; PS50294; WD_REPEATS_REGION; 1. DR Genevisible; Q99698; HS. PE 1: Evidence at protein level; KW Alternative splicing; Cytoplasm; Disease variant; Phagocytosis; KW Phosphoprotein; Protein transport; Reference proteome; Repeat; Transport; KW WD repeat. FT CHAIN 1..3801 FT /note="Lysosomal-trafficking regulator" FT /id="PRO_0000051071" FT REPEAT 662..700 FT /note="WD 1" FT REPEAT 1582..1626 FT /note="WD 2" FT DOMAIN 3009..3115 FT /note="BEACH-type PH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01119" FT DOMAIN 3120..3422 FT /note="BEACH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00026" FT REPEAT 3563..3602 FT /note="WD 3" FT REPEAT 3614..3653 FT /note="WD 4" FT REPEAT 3656..3699 FT /note="WD 5" FT REPEAT 3700..3744 FT /note="WD 6" FT REPEAT 3749..3788 FT /note="WD 7" FT REGION 148..173 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1181..1203 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1221..1256 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2205..2224 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 159..173 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1188..1202 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 164 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P97412" FT MOD_RES 165 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P97412" FT MOD_RES 166 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P97412" FT MOD_RES 1509 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P97412" FT MOD_RES 1510 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P97412" FT MOD_RES 2105 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19369195, FT ECO:0007744|PubMed:23186163" FT MOD_RES 2124 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 2213 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P97412" FT MOD_RES 2217 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P97412" FT MOD_RES 2264 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P97412" FT VAR_SEQ 1515..1531 FT /note="ESDRPEGAEYINPGERL -> GMMTGLSDLYTKIVFRL (in isoform FT 3)" FT /evidence="ECO:0000303|PubMed:9215680" FT /id="VSP_006779" FT VAR_SEQ 1532..3801 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:9215680" FT /id="VSP_006780" FT VAR_SEQ 1988..2001 FT /note="VCRSFVKIIAEVLG -> MARSFRRKCGQSCT (in isoform 2)" FT /evidence="ECO:0000303|PubMed:8717042" FT /id="VSP_006781" FT VAR_SEQ 2002..3801 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:8717042" FT /id="VSP_006782" FT VARIANT 123 FT /note="H -> R (in dbSNP:rs3768067)" FT /id="VAR_022029" FT VARIANT 192 FT /note="L -> V (in dbSNP:rs7524261)" FT /id="VAR_024699" FT VARIANT 702 FT /note="E -> G (in dbSNP:rs1063129)" FT /id="VAR_053404" FT VARIANT 1017 FT /note="S -> N (in dbSNP:rs10465613)" FT /id="VAR_053405" FT VARIANT 1208..3801 FT /note="Missing (in CHS; dbSNP:rs797044535)" FT /evidence="ECO:0000269|PubMed:20368792" FT /id="VAR_083515" FT VARIANT 1397 FT /note="F -> V (in CHS)" FT /evidence="ECO:0000269|PubMed:24521565" FT /id="VAR_071512" FT VARIANT 1563 FT /note="R -> H (in CHS; dbSNP:rs80338657)" FT /evidence="ECO:0000269|PubMed:11857544" FT /id="VAR_013556" FT VARIANT 1907 FT /note="I -> V (in CHS; loss of protein expression; FT dbSNP:rs370441301)" FT /evidence="ECO:0000269|PubMed:31906877" FT /id="VAR_083516" FT VARIANT 1949 FT /note="Q -> H (in dbSNP:rs6665568)" FT /id="VAR_053406" FT VARIANT 1999 FT /note="V -> D (in CHS; dbSNP:rs28942077)" FT /evidence="ECO:0000269|PubMed:11857544" FT /id="VAR_013557" FT VARIANT 2116 FT /note="T -> M (in dbSNP:rs7541041)" FT /id="VAR_060040" FT VARIANT 2598 FT /note="F -> Y (in dbSNP:rs34642241)" FT /id="VAR_053407" FT VARIANT 2804 FT /note="G -> D (in dbSNP:rs35333195)" FT /id="VAR_053408" FT VARIANT 2936 FT /note="V -> I (in dbSNP:rs2753327)" FT /id="VAR_053409" FT VARIANT 3668..3801 FT /note="Missing (in CHS; dbSNP:rs1444318368)" FT /evidence="ECO:0000269|PubMed:20368792" FT /id="VAR_083517" FT CONFLICT 1929..1930 FT /note="QG -> AC (in Ref. 4)" FT /evidence="ECO:0000305" FT CONFLICT 3514 FT /note="L -> V (in Ref. 1)" FT /evidence="ECO:0000305" SQ SEQUENCE 3801 AA; 429139 MW; E11BAB6357059D17 CRC64; MSTDSNSLAR EFLTDVNRLC NAVVQRVEAR EEEEEETHMA TLGQYLVHGR GFLLLTKLNS IIDQALTCRE ELLTLLLSLL PLVWKIPVQE EKATDFNLPL SADIILTKEK NSSSQRSTQE KLHLEGSALS SQVSAKVNVF RKSRRQRKIT HRYSVRDARK TQLSTSDSEA NSDEKGIAMN KHRRPHLLHH FLTSFPKQDH PKAKLDRLAT KEQTPPDAMA LENSREIIPR QGSNTDILSE PAALSVISNM NNSPFDLCHV LLSLLEKVCK FDVTLNHNSP LAASVVPTLT EFLAGFGDCC SLSDNLESRV VSAGWTEEPV ALIQRMLFRT VLHLLSVDVS TAEMMPENLR KNLTELLRAA LKIRICLEKQ PDPFAPRQKK TLQEVQEDFV FSKYRHRALL LPELLEGVLQ ILICCLQSAA SNPFYFSQAM DLVQEFIQHH GFNLFETAVL QMEWLVLRDG VPPEASEHLK ALINSVMKIM STVKKVKSEQ LHHSMCTRKR HRRCEYSHFM HHHRDLSGLL VSAFKNQVSK NPFEETADGD VYYPERCCCI AVCAHQCLRL LQQASLSSTC VQILSGVHNI GICCCMDPKS VIIPLLHAFK LPALKNFQQH ILNILNKLIL DQLGGAEISP KIKKAACNIC TVDSDQLAQL EETLQGNLCD AELSSSLSSP SYRFQGILPS SGSEDLLWKW DALKAYQNFV FEEDRLHSIQ IANHICNLIQ KGNIVVQWKL YNYIFNPVLQ RGVELAHHCQ HLSVTSAQSH VCSHHNQCLP QDVLQIYVKT LPILLKSRVI RDLFLSCNGV SQIIELNCLN GIRSHSLKAF ETLIISLGEQ QKDASVPDID GIDIEQKELS SVHVGTSFHH QQAYSDSPQS LSKFYAGLKE AYPKRRKTVN QDVHINTINL FLCVAFLCVS KEAESDRESA NDSEDTSGYD STASEPLSHM LPCISLESLV LPSPEHMHQA ADIWSMCRWI YMLSSVFQKQ FYRLGGFRVC HKLIFMIIQK LFRSHKEEQG KKEGDTSVNE NQDLNRISQP KRTMKEDLLS LAIKSDPIPS ELGSLKKSAD SLGKLELQHI SSINVEEVSA TEAAPEEAKL FTSQESETSL QSIRLLEALL AICLHGARTS QQKMELELPN QNLSVESILF EMRDHLSQSK VIETQLAKPL FDALLRVALG NYSADFEHND AMTEKSHQSA EELSSQPGDF SEEAEDSQCC SFKLLVEEEG YEADSESNPE DGETQDDGVD LKSETEGFSA SSSPNDLLEN LTQGEIIYPE ICMLELNLLS ASKAKLDVLA HVFESFLKII RQKEKNVFLL MQQGTVKNLL GGFLSILTQD DSDFQACQRV LVDLLVSLMS SRTCSEELTL LLRIFLEKSP CTKILLLGIL KIIESDTTMS PSQYLTFPLL HAPNLSNGVS SQKYPGILNS KAMGLLRRAR VSRSKKEADR ESFPHRLLSS WHIAPVHLPL LGQNCWPHLS EGFSVSLWFN VECIHEAEST TEKGKKIKKR NKSLILPDSS FDGTESDRPE GAEYINPGER LIEEGCIHII SLGSKALMIQ VWADPHNATL IFRVCMDSND DMKAVLLAQV ESQENIFLPS KWQHLVLTYL QQPQGKRRIH GKISIWVSGQ RKPDVTLDFM LPRKTSLSSD SNKTFCMIGH CLSSQEEFLQ LAGKWDLGNL LLFNGAKVGS QEAFYLYACG PNHTSVMPCK YGKPVNDYSK YINKEILRCE QIRELFMTKK DVDIGLLIES LSVVYTTYCP AQYTIYEPVI RLKGQMKTQL SQRPFSSKEV QSILLEPHHL KNLQPTEYKT IQGILHEIGG TGIFVFLFAR VVELSSCEET QALALRVILS LIKYNQQRVH ELENCNGLSM IHQVLIKQKC IVGFYILKTL LEGCCGEDII YMNENGEFKL DVDSNAIIQD VKLLEELLLD WKIWSKAEQG VWETLLAALE VLIRADHHQQ MFNIKQLLKA QVVHHFLLTC QVLQEYKEGQ LTPMPREVCR SFVKIIAEVL GSPPDLELLT IIFNFLLAVH PPTNTYVCHN PTNFYFSLHI DGKIFQEKVR SIMYLRHSSS GGRSLMSPGF MVISPSGFTA SPYEGENSSN IIPQQMAAHM LRSRSLPAFP TSSLLTQSQK LTGSLGCSID RLQNIADTYV ATQSKKQNSL GSSDTLKKGK EDAFISSCES AKTVCEMEAV LSAQVSVSDV PKGVLGFPVV KADHKQLGAE PRSEDDSPGD ESCPRRPDYL KGLASFQRSH STIASLGLAF PSQNGSAAVG RWPSLVDRNT DDWENFAYSL GYEPNYNRTA SAHSVTEDCL VPICCGLYEL LSGVLLILPD VLLEDVMDKL IQADTLLVLV NHPSPAIQQG VIKLLDAYFA RASKEQKDKF LKNRGFSLLA NQLYLHRGTQ ELLECFIEMF FGRHIGLDEE FDLEDVRNMG LFQKWSVIPI LGLIETSLYD NILLHNALLL LLQILNSCSK VADMLLDNGL LYVLCNTVAA LNGLEKNIPM SEYKLLACDI QQLFIAVTIH ACSSSGSQYF RVIEDLIVML GYLQNSKNKR TQNMAVALQL RVLQAAMEFI RTTANHDSEN LTDSLQSPSA PHHAVVQKRK SIAGPRKFPL AQTESLLMKM RSVANDELHV MMQRRMSQEN PSQATETELA QRLQRLTVLA VNRIIYQEFN SDIIDILRTP ENVTQSKTSV FQTEISEENI HHEQSSVFNP FQKEIFTYLV EGFKVSIGSS KASGSKQQWT KILWSCKETF RMQLGRLLVH ILSPAHAAQE RKQIFEIVHE PNHQEILRDC LSPSLQHGAK LVLYLSELIH NHQGELTEEE LGTAELLMNA LKLCGHKCIP PSASTKADLI KMIKEEQKKY ETEEGVNKAA WQKTVNNNQQ SLFQRLDSKS KDISKIAADI TQAVSLSQGN ERKKVIQHIR GMYKVDLSAS RHWQELIQQL THDRAVWYDP IYYPTSWQLD PTEGPNRERR RLQRCYLTIP NKYLLRDRQK SEDVVKPPLS YLFEDKTHSS FSSTVKDKAA SESIRVNRRC ISVAPSRETA GELLLGKCGM YFVEDNASDT VESSSLQGEL EPASFSWTYE EIKEVHKRWW QLRDNAVEIF LTNGRTLLLA FDNTKVRDDV YHNILTNNLP NLLEYGNITA LTNLWYTGQI TNFEYLTHLN KHAGRSFNDL MQYPVFPFIL ADYVSETLDL NDLLIYRNLS KPIAVQYKEK EDRYVDTYKY LEEEYRKGAR EDDPMPPVQP YHYGSHYSNS GTVLHFLVRM PPFTKMFLAY QDQSFDIPDR TFHSTNTTWR LSSFESMTDV KELIPEFFYL PEFLVNREGF DFGVRQNGER VNHVNLPPWA RNDPRLFILI HRQALESDYV SQNICQWIDL VFGYKQKGKA SVQAINVFHP ATYFGMDVSA VEDPVQRRAL ETMIKTYGQT PRQLFHMAHV SRPGAKLNIE GELPAAVGLL VQFAFRETRE QVKEITYPSP LSWIKGLKWG EYVGSPSAPV PVVCFSQPHG ERFGSLQALP TRAICGLSRN FCLLMTYSKE QGVRSMNSTD IQWSAILSWG YADNILRLKS KQSEPPVNFI QSSQQYQVTS CAWVPDSCQL FTGSKCGVIT AYTNRFTSST PSEIEMETQI HLYGHTEEIT SLFVCKPYSI LISVSRDGTC IIWDLNRLCY VQSLAGHKSP VTAVSASETS GDIATVCDSA GGGSDLRLWT VNGDLVGHVH CREIICSVAF SNQPEGVSIN VIAGGLENGI VRLWSTWDLK PVREITFPKS NKPIISLTFS CDGHHLYTAN SDGTVIAWCR KDQQRLKQPM FYSFLSSYAA G //