BUB1_HUMAN
ID BUB1_HUMAN Reviewed; 1085 AA.
AC O43683; E9PC26; F5GXI5; O43430; O43643; O60626; Q53QE4;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 204.
DE RecName: Full=Mitotic checkpoint serine/threonine-protein kinase BUB1;
DE Short=hBUB1;
DE EC=2.7.11.1;
DE AltName: Full=BUB1A;
GN Name=BUB1; Synonyms=BUB1L;
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), AND VARIANT TYR-492.
RX PubMed=9521327; DOI=10.1038/32688;
RA Cahill D.P., Lengauer C., Yu J., Riggins G.J., Willson J.K.V.,
RA Markowitz S.D., Kinzler K.W., Vogelstein B.;
RT "Mutations of mitotic checkpoint genes in human cancers.";
RL Nature 392:300-303(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9790499;
RA Ouyang B., Lan Z., Meadows J., Pan H., Fukasawa K., Li W., Dai W.;
RT "Human Bub1: a putative spindle checkpoint kinase closely linked to cell
RT proliferation.";
RL Cell Growth Differ. 9:877-885(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9660858; DOI=10.1083/jcb.142.1.1;
RA Taylor S.S., Ha E., McKeon F.;
RT "The human homologue of Bub3 is required for kinetochore localization of
RT Bub1 and a Mad3/Bub1-related protein kinase.";
RL J. Cell Biol. 142:1-11(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, PHOSPHORYLATION,
RP INTERACTION WITH BUB3 AND MAD1L1, AND MUTAGENESIS OF LYS-821.
RC TISSUE=Testis;
RX PubMed=10198256; DOI=10.1006/bbrc.1999.0514;
RA Seeley T.W., Wang L., Zhen J.Y.;
RT "Phosphorylation of human MAD1 by the BUB1 kinase in vitro.";
RL Biochem. Biophys. Res. Commun. 257:589-595(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), AND VARIANTS ASP-36 AND
RP ARG-648.
RX PubMed=10366450; DOI=10.1006/geno.1999.5831;
RA Cahill D.P., da Costa L.T., Carson-Walter E.B., Kinzler K.W.,
RA Vogelstein B., Lengauer C.;
RT "Characterization of MAD2B and other mitotic spindle checkpoint genes.";
RL Genomics 58:181-187(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [7]
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung;
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 [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 276-1085.
RX PubMed=9441741; DOI=10.1006/geno.1997.5068;
RA Pangilinan F., Li Q., Weaver T., Lewis B.C., Dang C.V., Spencer F.;
RT "Mammalian BUB1 protein kinases: map positions and in vivo expression.";
RL Genomics 46:379-388(1997).
RN [10]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15020684; DOI=10.1242/jcs.01006;
RA Johnson V.L., Scott M.I., Holt S.V., Hussein D., Taylor S.S.;
RT "Bub1 is required for kinetochore localization of BubR1, Cenp-E, Cenp-F and
RT Mad2, and chromosome congression.";
RL J. Cell Sci. 117:1577-1589(2004).
RN [11]
RP FUNCTION, PHOSPHORYLATION, AND INTERACTION WITH BUB3.
RX PubMed=15525512; DOI=10.1016/j.molcel.2004.09.031;
RA Tang Z., Shu H., Oncel D., Chen S., Yu H.;
RT "Phosphorylation of Cdc20 by Bub1 provides a catalytic mechanism for APC/C
RT inhibition by the spindle checkpoint.";
RL Mol. Cell 16:387-397(2004).
RN [12]
RP FUNCTION.
RX PubMed=15723797; DOI=10.1016/j.cub.2004.12.044;
RA Kitajima T.S., Hauf S., Ohsugi M., Yamamoto T., Watanabe Y.;
RT "Human Bub1 defines the persistent cohesion site along the mitotic
RT chromosome by affecting Shugoshin localization.";
RL Curr. Biol. 15:353-359(2005).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PLK1, PHOSPHORYLATION AT
RP THR-609, AND MUTAGENESIS OF THR-609.
RX PubMed=16760428; DOI=10.1091/mbc.e06-03-0240;
RA Qi W., Tang Z., Yu H.;
RT "Phosphorylation- and polo-box-dependent binding of Plk1 to Bub1 is
RT required for the kinetochore localization of Plk1.";
RL Mol. Biol. Cell 17:3705-3716(2006).
RN [14]
RP SUBCELLULAR LOCATION, INTERACTION WITH KNL1, AND MUTAGENESIS OF ALA-106 AND
RP LEU-122.
RX PubMed=17981135; DOI=10.1016/j.devcel.2007.09.005;
RA Kiyomitsu T., Obuse C., Yanagida M.;
RT "Human Blinkin/AF15q14 is required for chromosome alignment and the mitotic
RT checkpoint through direct interaction with Bub1 and BubR1.";
RL Dev. Cell 13:663-676(2007).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, UBIQUITINATION, DOMAIN KEN BOX, AND
RP MUTAGENESIS OF LYS-535; GLU-536; ASN-537; LYS-625; GLU-626 AND ASN-627.
RX PubMed=17158872; DOI=10.1074/jbc.m609376200;
RA Qi W., Yu H.;
RT "KEN-box-dependent degradation of the Bub1 spindle checkpoint kinase by the
RT anaphase-promoting complex/cyclosome.";
RL J. Biol. Chem. 282:3672-3679(2007).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-314, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-596 AND SER-655, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-593 AND SER-596, AND
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 [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [20]
RP INTERACTION WITH SV40 LARGE T ANTIGEN (MICROBIAL INFECTION).
RX PubMed=18922873; DOI=10.1128/jvi.01515-08;
RA Hein J., Boichuk S., Wu J., Cheng Y., Freire R., Jat P.S., Roberts T.M.,
RA Gjoerup O.V.;
RT "Simian virus 40 large T antigen disrupts genome integrity and activates a
RT DNA damage response via Bub1 binding.";
RL J. Virol. 83:117-127(2009).
RN [21]
RP FUNCTION, MUTAGENESIS OF ALA-130, AND CHARACTERIZATION OF VARIANTS CYS-259
RP AND ASN-265.
RX PubMed=19487456; DOI=10.1083/jcb.200902128;
RA Klebig C., Korinth D., Meraldi P.;
RT "Bub1 regulates chromosome segregation in a kinetochore-independent
RT manner.";
RL J. Cell Biol. 185:841-858(2009).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-314; SER-375; SER-563;
RP SER-596 AND SER-655, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-563; SER-593 AND SER-596, AND
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 [24]
RP FUNCTION.
RX PubMed=20739936; DOI=10.1038/nature09390;
RA Tsukahara T., Tanno Y., Watanabe Y.;
RT "Phosphorylation of the CPC by Cdk1 promotes chromosome bi-orientation.";
RL Nature 467:719-723(2010).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-593 AND SER-596, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [26]
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 [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-596, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-307; SER-331; SER-525;
RP SER-593; SER-596; SER-655; SER-661; SER-668 AND SER-672, AND IDENTIFICATION
RP BY 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 [29]
RP INTERACTION WITH HERPES VIRUS 8 PROTEIN LANA1 (MICROBIAL INFECTION).
RX PubMed=26223641; DOI=10.1128/jvi.01524-15;
RA Sun Z., Jha H.C., Robertson E.S.;
RT "Bub1 in Complex with LANA Recruits PCNA To Regulate Kaposi's Sarcoma-
RT Associated Herpesvirus Latent Replication and DNA Translesion Synthesis.";
RL J. Virol. 89:10206-10218(2015).
RN [30]
RP VARIANTS PANCREATIC CANCER CYS-259 AND ASN-265.
RX PubMed=12655561; DOI=10.1002/humu.9120;
RA Hempen P.M., Kurpad H., Calhoun E.S., Abraham S., Kern S.E.;
RT "A double missense variation of the BUB1 gene and a defective mitotic
RT spindle checkpoint in the pancreatic cancer cell line Hs766T.";
RL Hum. Mutat. 21:445-445(2003).
RN [31]
RP VARIANTS [LARGE SCALE ANALYSIS] ASP-20 AND ASP-534.
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: Serine/threonine-protein kinase that performs 2 crucial
CC functions during mitosis: it is essential for spindle-assembly
CC checkpoint signaling and for correct chromosome alignment. Has a key
CC role in the assembly of checkpoint proteins at the kinetochore, being
CC required for the subsequent localization of CENPF, BUB1B, CENPE and
CC MAD2L1. Required for the kinetochore localization of PLK1. Required for
CC centromeric enrichment of AUKRB in prometaphase. Plays an important
CC role in defining SGO1 localization and thereby affects sister chromatid
CC cohesion. Acts as a substrate for anaphase-promoting complex or
CC cyclosome (APC/C) in complex with its activator CDH1 (APC/C-Cdh1).
CC Necessary for ensuring proper chromosome segregation and binding to
CC BUB3 is essential for this function. Can regulate chromosome
CC segregation in a kinetochore-independent manner. Can phosphorylate
CC BUB3. The BUB1-BUB3 complex plays a role in the inhibition of APC/C
CC when spindle-assembly checkpoint is activated and inhibits the
CC ubiquitin ligase activity of APC/C by phosphorylating its activator
CC CDC20. This complex can also phosphorylate MAD1L1. Kinase activity is
CC essential for inhibition of APC/CCDC20 and for chromosome alignment but
CC does not play a major role in the spindle-assembly checkpoint activity.
CC Mediates cell death in response to chromosome missegregation and acts
CC to suppress spontaneous tumorigenesis. {ECO:0000269|PubMed:10198256,
CC ECO:0000269|PubMed:15020684, ECO:0000269|PubMed:15525512,
CC ECO:0000269|PubMed:15723797, ECO:0000269|PubMed:16760428,
CC ECO:0000269|PubMed:17158872, ECO:0000269|PubMed:19487456,
CC ECO:0000269|PubMed:20739936}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- ACTIVITY REGULATION: Autophosphorylated when the cells enters mitosis.
CC -!- SUBUNIT: Interacts with BUB3 and KNL1. Interacts (when phosphorylated)
CC with PLK1. The BUB1-BUB3 complex interacts with MAD1L1.
CC {ECO:0000305|PubMed:10198256, ECO:0000305|PubMed:15525512,
CC ECO:0000305|PubMed:16760428, ECO:0000305|PubMed:17981135}.
CC -!- SUBUNIT: (Microbial infection) Interacts with SV40 Large T antigen;
CC this interaction induces activation of a DNA damage response and
CC promotes p53/TP53 stabilization and phosphorylation.
CC {ECO:0000269|PubMed:18922873}.
CC -!- SUBUNIT: (Microbial infection) Interacts with herpes virus 8 protein
CC LANA1. {ECO:0000269|PubMed:26223641}.
CC -!- INTERACTION:
CC O43683; O95376: ARIH2; NbExp=5; IntAct=EBI-748936, EBI-711158;
CC O43683; O60566: BUB1B; NbExp=3; IntAct=EBI-748936, EBI-1001438;
CC O43683; O43684: BUB3; NbExp=5; IntAct=EBI-748936, EBI-1050987;
CC O43683; P46108: CRK; NbExp=2; IntAct=EBI-748936, EBI-886;
CC O43683; Q8NG31: KNL1; NbExp=2; IntAct=EBI-748936, EBI-1001161;
CC O43683; Q8NG31-2: KNL1; NbExp=3; IntAct=EBI-748936, EBI-10973816;
CC O43683; P03070; Xeno; NbExp=2; IntAct=EBI-748936, EBI-617698;
CC -!- SUBCELLULAR LOCATION: Nucleus. Chromosome, centromere, kinetochore.
CC Note=Nuclear in interphase cells. Accumulates gradually during G1 and S
CC phase of the cell cycle, peaks at G2/M, and drops dramatically after
CC mitosis. Localizes to the outer kinetochore. Kinetochore localization
CC is required for normal mitotic timing and checkpoint response to
CC spindle damage and occurs very early in prophase. AURKB, KNL1 and
CC INCENP are required for kinetochore localization (By similarity).
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O43683-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O43683-2; Sequence=VSP_054761;
CC Name=3;
CC IsoId=O43683-3; Sequence=VSP_054760;
CC -!- TISSUE SPECIFICITY: High expression in testis and thymus, less in
CC colon, spleen, lung and small intestine. Expressed in fetal thymus,
CC bone marrow, heart, liver, spleen and thymus. Expression is associated
CC with cells/tissues with a high mitotic index.
CC -!- INDUCTION: Inhibited by phorbol 12-myristate 13-acetate (PMA).
CC -!- DOMAIN: The KEN box is required for its ubiquitination and degradation.
CC {ECO:0000269|PubMed:17158872}.
CC -!- DOMAIN: BUB1 N-terminal domain directs kinetochore localization and
CC binding to BUB3. {ECO:0000269|PubMed:17158872}.
CC -!- PTM: Upon spindle-assembly checkpoint activation it is
CC hyperphosphorylated and its kinase activity toward CDC20 is stimulated.
CC Phosphorylation at Thr-609 is required for interaction with PLK1,
CC phosphorylation at this site probably creates a binding site for the
CC POLO-box domain of PLK1, thus enhancing the PLK1-BUB1 interaction.
CC {ECO:0000269|PubMed:10198256, ECO:0000269|PubMed:15525512,
CC ECO:0000269|PubMed:16760428}.
CC -!- PTM: Ubiquitinated and degraded during mitotic exit by APC/C-Cdh1.
CC {ECO:0000269|PubMed:17158872}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. BUB1 subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/BUB1ID853ch2q13.html";
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DR EMBL; AF046078; AAC12729.1; -; mRNA.
DR EMBL; AF043294; AAB97855.2; -; mRNA.
DR EMBL; AF053305; AAC06259.1; -; mRNA.
DR EMBL; AF047471; AAC03122.1; -; mRNA.
DR EMBL; AF139363; AAD43675.1; -; Genomic_DNA.
DR EMBL; AF139349; AAD43675.1; JOINED; Genomic_DNA.
DR EMBL; AF139350; AAD43675.1; JOINED; Genomic_DNA.
DR EMBL; AF139351; AAD43675.1; JOINED; Genomic_DNA.
DR EMBL; AF139352; AAD43675.1; JOINED; Genomic_DNA.
DR EMBL; AF139353; AAD43675.1; JOINED; Genomic_DNA.
DR EMBL; AF139354; AAD43675.1; JOINED; Genomic_DNA.
DR EMBL; AF139355; AAD43675.1; JOINED; Genomic_DNA.
DR EMBL; AF139356; AAD43675.1; JOINED; Genomic_DNA.
DR EMBL; AF139357; AAD43675.1; JOINED; Genomic_DNA.
DR EMBL; AF139358; AAD43675.1; JOINED; Genomic_DNA.
DR EMBL; AF139359; AAD43675.1; JOINED; Genomic_DNA.
DR EMBL; AF139360; AAD43675.1; JOINED; Genomic_DNA.
DR EMBL; AF139361; AAD43675.1; JOINED; Genomic_DNA.
DR EMBL; AF139362; AAD43675.1; JOINED; Genomic_DNA.
DR EMBL; AC114776; AAY14706.1; -; Genomic_DNA.
DR EMBL; AC226101; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471237; EAW50355.1; -; Genomic_DNA.
DR EMBL; BC028201; AAH28201.1; -; mRNA.
DR EMBL; AF011387; AAC39546.1; -; mRNA.
DR CCDS; CCDS33273.1; -. [O43683-1]
DR CCDS; CCDS62984.1; -. [O43683-3]
DR CCDS; CCDS62985.1; -. [O43683-2]
DR RefSeq; NP_001265546.1; NM_001278617.1. [O43683-2]
DR RefSeq; NP_004327.1; NM_004336.4. [O43683-1]
DR PDB; 2LAH; NMR; -; A=1-150.
DR PDB; 4A1G; X-ray; 2.60 A; A/B/C/D=1-150.
DR PDB; 4QPM; X-ray; 2.20 A; A/B=740-1085.
DR PDB; 4R8Q; X-ray; 2.31 A; A=724-1085.
DR PDB; 5DMZ; X-ray; 2.40 A; A/B=726-1085.
DR PDB; 6F7B; X-ray; 2.00 A; A=726-1085.
DR PDB; 7B1F; X-ray; 1.75 A; C/D=455-479.
DR PDB; 7B1H; X-ray; 2.40 A; C/D/G/H=455-479.
DR PDB; 7B1J; X-ray; 2.90 A; C/D=455-479.
DR PDBsum; 2LAH; -.
DR PDBsum; 4A1G; -.
DR PDBsum; 4QPM; -.
DR PDBsum; 4R8Q; -.
DR PDBsum; 5DMZ; -.
DR PDBsum; 6F7B; -.
DR PDBsum; 7B1F; -.
DR PDBsum; 7B1H; -.
DR PDBsum; 7B1J; -.
DR AlphaFoldDB; O43683; -.
DR BMRB; O43683; -.
DR SMR; O43683; -.
DR BioGRID; 107164; 116.
DR CORUM; O43683; -.
DR DIP; DIP-24206N; -.
DR ELM; O43683; -.
DR IntAct; O43683; 95.
DR MINT; O43683; -.
DR STRING; 9606.ENSP00000302530; -.
DR BindingDB; O43683; -.
DR ChEMBL; CHEMBL1772932; -.
DR GuidetoPHARMACOLOGY; 1949; -.
DR GlyGen; O43683; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O43683; -.
DR PhosphoSitePlus; O43683; -.
DR BioMuta; BUB1; -.
DR EPD; O43683; -.
DR jPOST; O43683; -.
DR MassIVE; O43683; -.
DR MaxQB; O43683; -.
DR PaxDb; O43683; -.
DR PeptideAtlas; O43683; -.
DR PRIDE; O43683; -.
DR ProteomicsDB; 19348; -.
DR ProteomicsDB; 24432; -.
DR ProteomicsDB; 49112; -. [O43683-1]
DR Antibodypedia; 1133; 555 antibodies from 41 providers.
DR DNASU; 699; -.
DR Ensembl; ENST00000302759.11; ENSP00000302530.6; ENSG00000169679.15. [O43683-1]
DR Ensembl; ENST00000409311.5; ENSP00000386701.1; ENSG00000169679.15. [O43683-2]
DR Ensembl; ENST00000535254.6; ENSP00000441013.1; ENSG00000169679.15. [O43683-3]
DR GeneID; 699; -.
DR KEGG; hsa:699; -.
DR MANE-Select; ENST00000302759.11; ENSP00000302530.6; NM_004336.5; NP_004327.1.
DR UCSC; uc002tgc.5; human. [O43683-1]
DR CTD; 699; -.
DR DisGeNET; 699; -.
DR GeneCards; BUB1; -.
DR HGNC; HGNC:1148; BUB1.
DR HPA; ENSG00000169679; Group enriched (bone marrow, lymphoid tissue, testis).
DR MalaCards; BUB1; -.
DR MIM; 602452; gene.
DR neXtProt; NX_O43683; -.
DR OpenTargets; ENSG00000169679; -.
DR Orphanet; 1052; Mosaic variegated aneuploidy syndrome.
DR PharmGKB; PA81; -.
DR VEuPathDB; HostDB:ENSG00000169679; -.
DR eggNOG; KOG1166; Eukaryota.
DR GeneTree; ENSGT00940000157865; -.
DR HOGENOM; CLU_296458_0_0_1; -.
DR InParanoid; O43683; -.
DR OMA; RSWSYET; -.
DR OrthoDB; 1411806at2759; -.
DR PhylomeDB; O43683; -.
DR TreeFam; TF105455; -.
DR BRENDA; 2.7.11.1; 2681.
DR PathwayCommons; O43683; -.
DR Reactome; R-HSA-141444; Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal.
DR Reactome; R-HSA-2467813; Separation of Sister Chromatids.
DR Reactome; R-HSA-2500257; Resolution of Sister Chromatid Cohesion.
DR Reactome; R-HSA-5663220; RHO GTPases Activate Formins.
DR Reactome; R-HSA-68877; Mitotic Prometaphase.
DR Reactome; R-HSA-9648025; EML4 and NUDC in mitotic spindle formation.
DR SignaLink; O43683; -.
DR SIGNOR; O43683; -.
DR BioGRID-ORCS; 699; 560 hits in 1129 CRISPR screens.
DR ChiTaRS; BUB1; human.
DR EvolutionaryTrace; O43683; -.
DR GeneWiki; BUB1; -.
DR GenomeRNAi; 699; -.
DR Pharos; O43683; Tchem.
DR PRO; PR:O43683; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; O43683; protein.
DR Bgee; ENSG00000169679; Expressed in ventricular zone and 111 other tissues.
DR ExpressionAtlas; O43683; baseline and differential.
DR Genevisible; O43683; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0000776; C:kinetochore; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; IBA:GO_Central.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl.
DR GO; GO:0051754; P:meiotic sister chromatid cohesion, centromeric; IBA:GO_Central.
DR GO; GO:0007094; P:mitotic spindle assembly checkpoint signaling; IBA:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0051983; P:regulation of chromosome segregation; IMP:UniProtKB.
DR GO; GO:0007063; P:regulation of sister chromatid cohesion; IDA:UniProtKB.
DR IDEAL; IID00406; -.
DR InterPro; IPR015661; Bub1/Mad3.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR013212; Mad3/Bub1_I.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR14030; PTHR14030; 1.
DR Pfam; PF08311; Mad3_BUB1_I; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00777; Mad3_BUB1_I; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51489; BUB1_N; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; ATP-binding; Cell cycle;
KW Cell division; Centromere; Chromosome; Chromosome partition;
KW Host-virus interaction; Kinase; Kinetochore; Mitosis; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Ubl conjugation.
FT CHAIN 1..1085
FT /note="Mitotic checkpoint serine/threonine-protein kinase
FT BUB1"
FT /id="PRO_0000085671"
FT DOMAIN 11..182
FT /note="BUB1 N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00822"
FT DOMAIN 787..1085
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..146
FT /note="Necessary for kinetochore localization"
FT REGION 99..132
FT /note="Necessary for interaction with KNL1"
FT /evidence="ECO:0000269|PubMed:17981135"
FT REGION 229..256
FT /note="Necessary for interaction with BUB3"
FT REGION 305..333
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 458..476
FT /note="Essential for loading of BUBR1, MAD1L1 and MAD2L1 to
FT kinetochores"
FT REGION 538..570
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 58..65
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOTIF 535..537
FT /note="KEN box 1"
FT MOTIF 625..627
FT /note="KEN box 2"
FT ACT_SITE 917
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 793..801
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 821
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 307
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 314
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 331
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 375
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 525
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 563
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 593
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 596
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 609
FT /note="Phosphothreonine; by CDK1"
FT /evidence="ECO:0000269|PubMed:16760428"
FT MOD_RES 655
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163"
FT MOD_RES 661
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 668
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 672
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 10..29
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_054760"
FT VAR_SEQ 876..932
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_054761"
FT VARIANT 20
FT /note="G -> D (in dbSNP:rs35890336)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040400"
FT VARIANT 36
FT /note="E -> D (in colorectal cancer; dbSNP:rs1801328)"
FT /evidence="ECO:0000269|PubMed:10366450"
FT /id="VAR_008849"
FT VARIANT 259
FT /note="Y -> C (in pancreatic cancer; associated with N-265;
FT failure to rescue the spindle-assembly checkpoint activity
FT as a result of a deficient recruitment of MAD2L1 and BUBR1
FT to kinetochores; efficient restoration of chromosome
FT congression; reduced binding to BUB3; rescue of the ability
FT of kinetochores to bind SGO1 and CENPF but not MCAK)"
FT /evidence="ECO:0000269|PubMed:12655561,
FT ECO:0000269|PubMed:19487456"
FT /id="VAR_015687"
FT VARIANT 265
FT /note="H -> N (in pancreatic cancer; associated with C-259;
FT complete rescue of the spindle-assembly checkpoint
FT activity; increased rate of chromosome congression errors)"
FT /evidence="ECO:0000269|PubMed:12655561,
FT ECO:0000269|PubMed:19487456"
FT /id="VAR_015688"
FT VARIANT 492
FT /note="S -> Y (in colorectal cancer; dbSNP:rs121909055)"
FT /evidence="ECO:0000269|PubMed:9521327"
FT /id="VAR_008850"
FT VARIANT 534
FT /note="N -> D (in dbSNP:rs36109304)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040401"
FT VARIANT 648
FT /note="P -> R (in colorectal cancer; dbSNP:rs376649190)"
FT /evidence="ECO:0000269|PubMed:10366450"
FT /id="VAR_008851"
FT MUTAGEN 106
FT /note="A->D,W: Loss of interaction with KNL1."
FT /evidence="ECO:0000269|PubMed:17981135"
FT MUTAGEN 122
FT /note="L->G: Loss of interaction with KNL1."
FT /evidence="ECO:0000269|PubMed:17981135"
FT MUTAGEN 130
FT /note="A->S: Partial rescue of the spindle-assembly
FT checkpoint activity. Increased rate of chromosome
FT congression errors. Impaired localization to kinetochores
FT and loss of kinetochore binding of CENPF, SGO1 and BUBR1
FT but not of MCAK, MAD1L1 or MAD2L1."
FT /evidence="ECO:0000269|PubMed:19487456"
FT MUTAGEN 535
FT /note="K->A: Loss of ubiquitination and CDH1-dependent
FT degradation; when associated with A-536 and A-537."
FT /evidence="ECO:0000269|PubMed:17158872"
FT MUTAGEN 536
FT /note="E->A: Loss of ubiquitination and CDH1-dependent
FT degradation; when associated with A-535 and A-537."
FT /evidence="ECO:0000269|PubMed:17158872"
FT MUTAGEN 537
FT /note="N->A: Loss of ubiquitination and CDH1-dependent
FT degradation; when associated with A-535 and A-536."
FT /evidence="ECO:0000269|PubMed:17158872"
FT MUTAGEN 609
FT /note="T->A: Diminished interaction with PLK1."
FT /evidence="ECO:0000269|PubMed:16760428"
FT MUTAGEN 625
FT /note="K->A: Loss of ubiquitination and CDH1-dependent
FT degradation; when associated with A-626 and A-627."
FT /evidence="ECO:0000269|PubMed:17158872"
FT MUTAGEN 626
FT /note="E->A: Loss of ubiquitination and CDH1-dependent
FT degradation; when associated with A-625 and A-627."
FT /evidence="ECO:0000269|PubMed:17158872"
FT MUTAGEN 627
FT /note="N->A: Loss of ubiquitination and CDH1-dependent
FT degradation; when associated with A-625 and A-626."
FT /evidence="ECO:0000269|PubMed:17158872"
FT MUTAGEN 821
FT /note="K->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:10198256"
FT CONFLICT 70
FT /note="S -> T (in Ref. 5; AAC06259)"
FT /evidence="ECO:0000305"
FT CONFLICT 276..279
FT /note="MKRK -> IRHE (in Ref. 9; AAC39546)"
FT /evidence="ECO:0000305"
FT HELIX 3..14
FT /evidence="ECO:0007829|PDB:4A1G"
FT HELIX 23..35
FT /evidence="ECO:0007829|PDB:4A1G"
FT HELIX 43..56
FT /evidence="ECO:0007829|PDB:4A1G"
FT HELIX 60..62
FT /evidence="ECO:0007829|PDB:4A1G"
FT HELIX 66..76
FT /evidence="ECO:0007829|PDB:4A1G"
FT HELIX 82..90
FT /evidence="ECO:0007829|PDB:4A1G"
FT TURN 91..97
FT /evidence="ECO:0007829|PDB:4A1G"
FT HELIX 99..111
FT /evidence="ECO:0007829|PDB:4A1G"
FT HELIX 115..127
FT /evidence="ECO:0007829|PDB:4A1G"
FT HELIX 133..145
FT /evidence="ECO:0007829|PDB:4A1G"
FT HELIX 462..471
FT /evidence="ECO:0007829|PDB:7B1F"
FT HELIX 472..475
FT /evidence="ECO:0007829|PDB:7B1F"
FT STRAND 736..739
FT /evidence="ECO:0007829|PDB:6F7B"
FT HELIX 744..752
FT /evidence="ECO:0007829|PDB:6F7B"
FT HELIX 758..760
FT /evidence="ECO:0007829|PDB:6F7B"
FT STRAND 764..766
FT /evidence="ECO:0007829|PDB:6F7B"
FT STRAND 779..782
FT /evidence="ECO:0007829|PDB:6F7B"
FT STRAND 785..796
FT /evidence="ECO:0007829|PDB:6F7B"
FT STRAND 799..805
FT /evidence="ECO:0007829|PDB:6F7B"
FT STRAND 817..825
FT /evidence="ECO:0007829|PDB:6F7B"
FT HELIX 828..840
FT /evidence="ECO:0007829|PDB:6F7B"
FT HELIX 843..848
FT /evidence="ECO:0007829|PDB:6F7B"
FT STRAND 852..857
FT /evidence="ECO:0007829|PDB:6F7B"
FT STRAND 862..866
FT /evidence="ECO:0007829|PDB:6F7B"
FT HELIX 874..881
FT /evidence="ECO:0007829|PDB:6F7B"
FT STRAND 884..886
FT /evidence="ECO:0007829|PDB:5DMZ"
FT HELIX 891..910
FT /evidence="ECO:0007829|PDB:6F7B"
FT HELIX 920..922
FT /evidence="ECO:0007829|PDB:6F7B"
FT STRAND 923..925
FT /evidence="ECO:0007829|PDB:6F7B"
FT HELIX 927..931
FT /evidence="ECO:0007829|PDB:6F7B"
FT STRAND 940..944
FT /evidence="ECO:0007829|PDB:6F7B"
FT HELIX 953..955
FT /evidence="ECO:0007829|PDB:6F7B"
FT STRAND 960..962
FT /evidence="ECO:0007829|PDB:6F7B"
FT STRAND 967..971
FT /evidence="ECO:0007829|PDB:4QPM"
FT HELIX 974..977
FT /evidence="ECO:0007829|PDB:6F7B"
FT HELIX 985..1000
FT /evidence="ECO:0007829|PDB:6F7B"
FT STRAND 1006..1008
FT /evidence="ECO:0007829|PDB:6F7B"
FT STRAND 1013..1016
FT /evidence="ECO:0007829|PDB:6F7B"
FT HELIX 1025..1036
FT /evidence="ECO:0007829|PDB:6F7B"
FT HELIX 1047..1061
FT /evidence="ECO:0007829|PDB:6F7B"
FT TURN 1062..1065
FT /evidence="ECO:0007829|PDB:6F7B"
FT HELIX 1066..1081
FT /evidence="ECO:0007829|PDB:6F7B"
SQ SEQUENCE 1085 AA; 122375 MW; 38AE5E1F88C53BDC CRC64;
MDTPENVLQM LEAHMQSYKG NDPLGEWERY IQWVEENFPE NKEYLITLLE HLMKEFLDKK
KYHNDPRFIS YCLKFAEYNS DLHQFFEFLY NHGIGTLSSP LYIAWAGHLE AQGELQHASA
VLQRGIQNQA EPREFLQQQY RLFQTRLTET HLPAQARTSE PLHNVQVLNQ MITSKSNPGN
NMACISKNQG SELSGVISSA CDKESNMERR VITISKSEYS VHSSLASKVD VEQVVMYCKE
KLIRGESEFS FEELRAQKYN QRRKHEQWVN EDRHYMKRKE ANAFEEQLLK QKMDELHKKL
HQVVETSHED LPASQERSEV NPARMGPSVG SQQELRAPCL PVTYQQTPVN MEKNPREAPP
VVPPLANAIS AALVSPATSQ SIAPPVPLKA QTVTDSMFAV ASKDAGCVNK STHEFKPQSG
AEIKEGCETH KVANTSSFHT TPNTSLGMVQ ATPSKVQPSP TVHTKEALGF IMNMFQAPTL
PDISDDKDEW QSLDQNEDAF EAQFQKNVRS SGAWGVNKII SSLSSAFHVF EDGNKENYGL
PQPKNKPTGA RTFGERSVSR LPSKPKEEVP HAEEFLDDST VWGIRCNKTL APSPKSPGDF
TSAAQLASTP FHKLPVESVH ILEDKENVVA KQCTQATLDS CEENMVVPSR DGKFSPIQEK
SPKQALSSHM YSASLLRLSQ PAAGGVLTCE AELGVEACRL TDTDAAIAED PPDAIAGLQA
EWMQMSSLGT VDAPNFIVGN PWDDKLIFKL LSGLSKPVSS YPNTFEWQCK LPAIKPKTEF
QLGSKLVYVH HLLGEGAFAQ VYEATQGDLN DAKNKQKFVL KVQKPANPWE FYIGTQLMER
LKPSMQHMFM KFYSAHLFQN GSVLVGELYS YGTLLNAINL YKNTPEKVMP QGLVISFAMR
MLYMIEQVHD CEIIHGDIKP DNFILGNGFL EQDDEDDLSA GLALIDLGQS IDMKLFPKGT
IFTAKCETSG FQCVEMLSNK PWNYQIDYFG VAATVYCMLF GTYMKVKNEG GECKPEGLFR
RLPHLDMWNE FFHVMLNIPD CHHLPSLDLL RQKLKKVFQQ HYTNKIRALR NRLIVLLLEC
KRSRK
