BUB1_CAEEL
ID BUB1_CAEEL Reviewed; 987 AA.
AC Q21776;
DT 29-APR-2015, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Mitotic checkpoint serine/threonine-protein kinase bub-1 {ECO:0000250|UniProtKB:O43683};
DE EC=2.7.11.1 {ECO:0000269|PubMed:24567362};
DE AltName: Full=Budding uninhibited by benzimidazole 1 {ECO:0000303|PubMed:19526056};
GN Name=bub-1 {ECO:0000312|WormBase:R06C7.8};
GN ORFNames=R06C7.8 {ECO:0000312|WormBase:R06C7.8};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP SUBCELLULAR LOCATION.
RX PubMed=11402065; DOI=10.1083/jcb.153.6.1209;
RA Oegema K., Desai A., Rybina S., Kirkham M., Hyman A.A.;
RT "Functional analysis of kinetochore assembly in Caenorhabditis elegans.";
RL J. Cell Biol. 153:1209-1226(2001).
RN [3]
RP SUBCELLULAR LOCATION.
RX PubMed=17339379; DOI=10.1083/jcb.200701065;
RA Maddox P.S., Hyndman F., Monen J., Oegema K., Desai A.;
RT "Functional genomics identifies a Myb domain-containing protein family
RT required for assembly of CENP-A chromatin.";
RL J. Cell Biol. 176:757-763(2007).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=18765790; DOI=10.1101/gad.1687508;
RA Gassmann R., Essex A., Hu J.-S., Maddox P.S., Motegi F., Sugimoto A.,
RA O'Rourke S.M., Bowerman B., McLeod I., Yates J.R. III, Oegema K.,
RA Cheeseman I.M., Desai A.;
RT "A new mechanism controlling kinetochore-microtubule interactions revealed
RT by comparison of two dynein-targeting components: SPDL-1 and the
RT Rod/Zwilch/Zw10 complex.";
RL Genes Dev. 22:2385-2399(2008).
RN [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18936247; DOI=10.1083/jcb.200805185;
RA Yamamoto T.G., Watanabe S., Essex A., Kitagawa R.;
RT "SPDL-1 functions as a kinetochore receptor for MDF-1 in Caenorhabditis
RT elegans.";
RL J. Cell Biol. 183:187-194(2008).
RN [6]
RP FUNCTION.
RX PubMed=19109417; DOI=10.1091/mbc.e08-10-1047;
RA Essex A., Dammermann A., Lewellyn L., Oegema K., Desai A.;
RT "Systematic analysis in Caenorhabditis elegans reveals that the spindle
RT checkpoint is composed of two largely independent branches.";
RL Mol. Biol. Cell 20:1252-1267(2009).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=19526056; DOI=10.1371/journal.pone.0005912;
RA Wang X., Liu M., Li W., Suh C.D., Zhu Z., Jin Y., Fan Q.;
RT "The function of a spindle checkpoint gene bub-1 in C. elegans
RT development.";
RL PLoS ONE 4:E5912-E5912(2009).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=20729837; DOI=10.1038/ncb2093;
RA Dumont J., Oegema K., Desai A.;
RT "A kinetochore-independent mechanism drives anaphase chromosome separation
RT during acentrosomal meiosis.";
RL Nat. Cell Biol. 12:894-901(2010).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH MDF-1, INTERACTION WITH
RP BUB-3, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-718; LEU-777; ASN-781;
RP ASP-814 AND ASP-847.
RX PubMed=24567362; DOI=10.1083/jcb.201311015;
RA Moyle M.W., Kim T., Hattersley N., Espeut J., Cheerambathur D.K.,
RA Oegema K., Desai A.;
RT "A Bub1-Mad1 interaction targets the Mad1-Mad2 complex to unattached
RT kinetochores to initiate the spindle checkpoint.";
RL J. Cell Biol. 204:647-657(2014).
RN [10]
RP FUNCTION, INTERACTION WITH BUB-3, SUBCELLULAR LOCATION, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=25987605; DOI=10.1083/jcb.201412035;
RA Kim T., Moyle M.W., Lara-Gonzalez P., De Groot C., Oegema K., Desai A.;
RT "Kinetochore-localized BUB-1/BUB-3 complex promotes anaphase onset in C.
RT elegans.";
RL J. Cell Biol. 209:507-517(2015).
CC -!- FUNCTION: Serine/threonine-protein kinase essential for spindle-
CC assembly checkpoint signaling. Plays a key role in the recruitment of
CC the checkpoint proteins bub-3, mdf-1 and mdf-2 to unattached
CC kinetochores (PubMed:18936247, PubMed:19109417, PubMed:24567362,
CC PubMed:25987605). mdf-1 recruitment is independent of bub-1 kinase
CC activity (PubMed:24567362). Has a role in the correct kinetochore
CC localization of the spindly-like protein spdl-1 (PubMed:18765790). In
CC addition, during meiotic anaphase I, controls the recruitment of hcp-
CC 1/2 and klp-19 to the ring-shaped domain formed between chromosomes
CC (PubMed:20729837). Involved in chromosome alignment, chromosome homolog
CC segregation and spindle assembly (PubMed:20729837, PubMed:25987605). In
CC association with bub-3 at the kinetochore region of chromosomes,
CC promotes the onset on anaphase independently from spindle checkpoint
CC signaling and promotes the formation of stable end-on bipolar
CC attachments of chromosomes (PubMed:25987605). Plays a role in nuclear
CC envelope breakdown (PubMed:19109417). Required maternally during
CC embryogenesis and in the zygote for the postembryonic development of
CC several tissues including ventral cord neurons, gonad, intestine and
CC seam cells (PubMed:19526056). {ECO:0000269|PubMed:18765790,
CC ECO:0000269|PubMed:19109417, ECO:0000269|PubMed:19526056,
CC ECO:0000269|PubMed:20729837, ECO:0000269|PubMed:24567362,
CC ECO:0000269|PubMed:25987605}.
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 Evidence={ECO:0000269|PubMed:24567362};
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; Evidence={ECO:0000269|PubMed:24567362};
CC -!- SUBUNIT: Interacts (via kinase domain) with mdf-1 (via coiled coil
CC domain); the interaction recruits mdf-1 to unattached kinetochores
CC during mitosis and between homologous chromosomes in early anaphase of
CC meiosis I (PubMed:24567362). May interact with bub-3; for localization
CC at the kinetochore and the onset of anaphase (PubMed:24567362,
CC PubMed:25987605). {ECO:0000269|PubMed:24567362,
CC ECO:0000269|PubMed:25987605, ECO:0000305|PubMed:24567362}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cell cortex
CC {ECO:0000269|PubMed:20729837}. Nucleus {ECO:0000269|PubMed:19526056}.
CC Chromosome, centromere, kinetochore {ECO:0000269|PubMed:17339379,
CC ECO:0000269|PubMed:18765790, ECO:0000269|PubMed:18936247,
CC ECO:0000269|PubMed:20729837, ECO:0000269|PubMed:24567362,
CC ECO:0000269|PubMed:25987605}. Note=Localizes to kinetochores during
CC prophase and metaphase. In metaphase, localizes also to a matrix-like
CC structure around the spindle (PubMed:11402065). In anaphase, localizes
CC only to unattached kinetochores which is kln-1-dependent
CC (PubMed:11402065, PubMed:24567362). Localizes also in a ring-shaped
CC domain between kinetochores, during anaphase of meiosis I which is air-
CC 2 and kln-1-dependent and between sister chromatids during meiosis II,
CC which is kln-1-independent (PubMed:20729837). Localization to the
CC kinetochore is dependent on bub-3 and on knl-2 (PubMed:25987605,
CC PubMed:17339379). {ECO:0000269|PubMed:11402065,
CC ECO:0000269|PubMed:17339379, ECO:0000269|PubMed:20729837,
CC ECO:0000269|PubMed:24567362, ECO:0000269|PubMed:25987605}.
CC -!- DEVELOPMENTAL STAGE: Expressed throughout embryogenesis mainly in
CC dividing cells. {ECO:0000269|PubMed:19526056}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethal (PubMed:25987605). RNAi-mediated
CC knockdown in oocytes results in aberrant homologous chromosome
CC segregation during meiosis due to severe pre-anaphase spindle defects
CC characterized by disorganized microtubule bundles (PubMed:20729837).
CC Delays in the processes leading up to exit from mitosis including
CC delayed activation of separase, which results in a delay in the
CC separation of sister chromatids, delayed cytokinesis onset and delayed
CC chromosome decondensation (PubMed:25987605). These culminate in a delay
CC in the onset of anaphase with a 50% increase in the interval between
CC nuclear envelope breakdown and the onset of anaphase during
CC embryogenesis (PubMed:25987605). Reduced bub-3 localization at the
CC kinetochore region of chromosomes in embryos, but without a reduction
CC in bub-3 protein (PubMed:25987605). In addition there is reduced
CC localization of the spindly-like protein spdl-1 to kinetochores
CC (PubMed:18765790). {ECO:0000269|PubMed:18765790,
CC ECO:0000269|PubMed:20729837, ECO:0000269|PubMed:25987605}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. BUB1 subfamily. {ECO:0000305}.
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DR EMBL; BX284601; CAA95845.1; -; Genomic_DNA.
DR PIR; T23971; T23971.
DR RefSeq; NP_492051.1; NM_059650.4.
DR AlphaFoldDB; Q21776; -.
DR SMR; Q21776; -.
DR ComplexPortal; CPX-400; Bub-1-Bub-3 complex.
DR ComplexPortal; CPX-401; Mitotic checkpoint complex, Mad-1-Mad-2-Bub-1-Bub-3 subcomplex.
DR DIP; DIP-27465N; -.
DR IntAct; Q21776; 4.
DR STRING; 6239.R06C7.8; -.
DR EPD; Q21776; -.
DR PaxDb; Q21776; -.
DR PeptideAtlas; Q21776; -.
DR EnsemblMetazoa; R06C7.8.1; R06C7.8.1; WBGene00000275.
DR GeneID; 172468; -.
DR KEGG; cel:CELE_R06C7.8; -.
DR UCSC; R06C7.8; c. elegans.
DR CTD; 172468; -.
DR WormBase; R06C7.8; CE06251; WBGene00000275; bub-1.
DR eggNOG; KOG1166; Eukaryota.
DR GeneTree; ENSGT00940000167713; -.
DR HOGENOM; CLU_012854_0_0_1; -.
DR InParanoid; Q21776; -.
DR OMA; YNDMKAM; -.
DR OrthoDB; 441269at2759; -.
DR Reactome; R-CEL-141430; Inactivation of APC/C via direct inhibition of the APC/C complex.
DR PRO; PR:Q21776; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00000275; Expressed in embryo and 4 other tissues.
DR GO; GO:1990298; C:bub1-bub3 complex; IPI:ComplexPortal.
DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR GO; GO:0000776; C:kinetochore; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0043515; F:kinetochore binding; IDA:UniProtKB.
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:0051316; P:attachment of spindle microtubules to kinetochore involved in meiotic chromosome segregation; IMP:UniProtKB.
DR GO; GO:1990299; P:Bub1-Bub3 complex localization to kinetochore; IDA:ComplexPortal.
DR GO; GO:0051301; P:cell division; IMP:UniProtKB.
DR GO; GO:0048598; P:embryonic morphogenesis; IMP:UniProtKB.
DR GO; GO:0008406; P:gonad development; IMP:UniProtKB.
DR GO; GO:0051307; P:meiotic chromosome separation; IMP:UniProtKB.
DR GO; GO:0051754; P:meiotic sister chromatid cohesion, centromeric; IBA:GO_Central.
DR GO; GO:0051257; P:meiotic spindle midzone assembly; IMP:UniProtKB.
DR GO; GO:0000212; P:meiotic spindle organization; IMP:UniProtKB.
DR GO; GO:0007094; P:mitotic spindle assembly checkpoint signaling; IDA:ComplexPortal.
DR GO; GO:0048666; P:neuron development; IMP:UniProtKB.
DR GO; GO:0000280; P:nuclear division; IMP:UniProtKB.
DR GO; GO:0110039; P:positive regulation of nematode male tail tip morphogenesis; IMP:UniProtKB.
DR GO; GO:1905342; P:positive regulation of protein localization to kinetochore; IMP:UniProtKB.
DR GO; GO:0034501; P:protein localization to kinetochore; IMP:UniProtKB.
DR GO; GO:1903394; P:protein localization to kinetochore involved in kinetochore assembly; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR InterPro; IPR015661; Bub1/Mad3.
DR InterPro; IPR011009; Kinase-like_dom_sf.
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; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 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 ATP-binding; Cell cycle; Cell division; Centromere; Chromosome; Cytoplasm;
KW Developmental protein; Kinase; Kinetochore; Meiosis; Mitosis;
KW Nucleotide-binding; Nucleus; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..987
FT /note="Mitotic checkpoint serine/threonine-protein kinase
FT bub-1"
FT /id="PRO_0000433016"
FT DOMAIN 690..987
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 278..385
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 574..599
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 278..302
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 363..384
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 574..588
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 814
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 696..704
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 718
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MUTAGEN 718
FT /note="K->R: No effect on embryo viability, severe loss of
FT mdf-1 recruitment to unattached kinetochores and probably
FT loss of kinase activity; when associated with N-847."
FT /evidence="ECO:0000269|PubMed:24567362"
FT MUTAGEN 777
FT /note="L->K: Loss of interaction with mdf-1 but not with
FT bub-3. No effect on embryo viability and severe loss of
FT mdf-1 recruitment to unattached kinetochores; when
FT associated with K-781."
FT /evidence="ECO:0000269|PubMed:24567362"
FT MUTAGEN 781
FT /note="N->K: Loss of interaction with mdf-1 but not with
FT bub-3. No effect on embryo viability and severe loss of
FT mdf-1 recruitment to unattached kinetochores; when
FT associated with K-777."
FT /evidence="ECO:0000269|PubMed:24567362"
FT MUTAGEN 814
FT /note="D->N: Loss of activity. No effect on embryo
FT viability and mdf-1 recruitment to unattached
FT kinetochores."
FT /evidence="ECO:0000269|PubMed:24567362"
FT MUTAGEN 847
FT /note="D->N: No effect on embryo viability, severe loss of
FT mdf-1 recruitment to unattached kinetochores and probably
FT loss of kinase activity; when associated with N-718."
FT /evidence="ECO:0000269|PubMed:24567362"
SQ SEQUENCE 987 AA; 112034 MW; 48E7915551AE2194 CRC64;
MSHIRVAFAP LDTNPSTCGL ETFATQIETL SQMMTAEEMK AELYDCVRRI LREQKFDQIR
ENEAMLRLYK VMGRSSTNLK GRGIYEQLFK KDHFTGSLKF YLQWAEECGK DQMLEEFKDV
LKLARDRLSE RIEMTAIESG FRDLVDEYFN GESGDMFTRP DETMDLFRFN AGSKKKRRSS
VCFLQHNVPI NNSGKAAFGP KTKTDLRQAC IDRPNYHGIS IEEFRFAKWK DTFGEDVDDD
YRKRKDSGVV FVKHQVIDTD RQAREEVENR FNANLNPRRR HLSPVSEKTV DDEEEKRSRI
YSPLVATKDA HRPALRSKIE NPPATVTLSS DTKSASEKDV SDSDDADDDE RLKIMTAGRK
DGNPPDRSTS ISSNYSTASA RTSKSGAGLD LMAENKCLEA HAMFSDTVHL ASEKTMVLGD
DSVFVPERSL ATTQIVTDFS VLCDPDPTMT ITQERPKKVS NGLNVVYDEA AEPEESQKVE
ESEVQPEIVL VSPVTQTSPA TMFNDIYDDE IEFGFFKPSR GNFVTSTPAQ GVHLVNIDEY
FGNKEEESTH EQEAPVFVAP TSSTFSKLTR RKSLAANQAV QPSVTESSKP ERSDPKDSSI
DCLTANLGRR LSIGADEIPN LTENNESEIT GCKIRRRSEI IKQGDINPWD ETLRKKLMCL
VRPPQNMHEF QERAPKIQAL RDCEVSGEKL HIQTLIGQGG YAKVYRAVTD DQRTVAVKYE
VPSCSWEVYI CDQMRNRLKD RGLELMAKCC IMEVMDAYVY STASLLVNQY HEYGTLLEYA
NNMKDPNWHI TCFLITQMAR VVKEVHASKI IHGDIKPDNF MITRKIDDKW GKDALMSNDS
FVIKIIDWGR AIDMMPLKNQ RFKGRAGTEA FDCPEMVDGR SWTYQADYFG FAATMAVVVA
GKYAQLTGAS VGDYSLNVDI KRRNILRDAC YDVINRFLNI PSCDSLPDWN ILIKSFSEIW
NEKFEASGWR QAVSKFNEAC DLAANQK
