LYST_HUMAN
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 03-AUG-2022, entry version 199.
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 AND 3668-GLU--GLY-3801.
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";
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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; 42.
DR IntAct; Q99698; 24.
DR MINT; Q99698; -.
DR STRING; 9606.ENSP00000374443; -.
DR GlyGen; Q99698; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; Q99698; -.
DR PhosphoSitePlus; Q99698; -.
DR BioMuta; LYST; -.
DR DMDM; 76803797; -.
DR EPD; Q99698; -.
DR jPOST; Q99698; -.
DR MassIVE; Q99698; -.
DR MaxQB; Q99698; -.
DR PaxDb; Q99698; -.
DR PeptideAtlas; Q99698; -.
DR PRIDE; Q99698; -.
DR ProteomicsDB; 78406; -. [Q99698-1]
DR ProteomicsDB; 78407; -. [Q99698-2]
DR ProteomicsDB; 78408; -. [Q99698-3]
DR Antibodypedia; 34697; 22 antibodies from 11 providers.
DR DNASU; 1130; -.
DR Ensembl; ENST00000389793.7; ENSP00000374443.2; ENSG00000143669.15. [Q99698-1]
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 CTD; 1130; -.
DR DisGeNET; 1130; -.
DR GeneCards; LYST; -.
DR GeneReviews; LYST; -.
DR HGNC; HGNC:1968; LYST.
DR HPA; ENSG00000143669; Tissue enhanced (bone marrow, retina).
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; CVCKPYS; -.
DR OrthoDB; 101142at2759; -.
DR PhylomeDB; Q99698; -.
DR TreeFam; TF313658; -.
DR PathwayCommons; Q99698; -.
DR SignaLink; Q99698; -.
DR SIGNOR; Q99698; -.
DR BioGRID-ORCS; 1130; 16 hits in 1069 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 192 other tissues.
DR ExpressionAtlas; Q99698; baseline and differential.
DR Genevisible; Q99698; HS.
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:0007040; P:lysosome organization; IEA:InterPro.
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; -; 1.
DR Gene3D; 2.130.10.10; -; 2.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR000409; BEACH_dom.
DR InterPro; IPR036372; BEACH_dom_sf.
DR InterPro; IPR030464; LYST.
DR InterPro; IPR023362; PH-BEACH_dom.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR PANTHER; PTHR13743:SF86; PTHR13743:SF86; 1.
DR Pfam; PF02138; Beach; 1.
DR Pfam; PF14844; PH_BEACH; 1.
DR Pfam; PF00400; WD40; 1.
DR SMART; SM01026; Beach; 1.
DR SMART; SM00320; WD40; 4.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF50978; SSF50978; 1.
DR SUPFAM; SSF81837; SSF81837; 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.
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
