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Mitotic checkpoint serine/threonine-protein kinase bub-1 (EC 2.7.11.1) (Budding uninhibited by benzimidazole 1)

 BUB1_CAEEL              Reviewed;         987 AA.
Q21776;
29-APR-2015, integrated into UniProtKB/Swiss-Prot.
01-NOV-1996, sequence version 1.
22-NOV-2017, entry version 148.
RecName: Full=Mitotic checkpoint serine/threonine-protein kinase bub-1 {ECO:0000250|UniProtKB:O43683};
EC=2.7.11.1 {ECO:0000269|PubMed:24567362};
AltName: Full=Budding uninhibited by benzimidazole 1 {ECO:0000303|PubMed:19526056};
Name=bub-1 {ECO:0000312|WormBase:R06C7.8};
ORFNames=R06C7.8 {ECO:0000312|WormBase:R06C7.8};
Caenorhabditis elegans.
Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
Rhabditoidea; Rhabditidae; Peloderinae; Caenorhabditis.
NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
[1] {ECO:0000312|Proteomes:UP000001940}
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
PubMed=9851916; DOI=10.1126/science.282.5396.2012;
The C. elegans sequencing consortium;
"Genome sequence of the nematode C. elegans: a platform for
investigating biology.";
Science 282:2012-2018(1998).
[2] {ECO:0000305}
SUBCELLULAR LOCATION.
PubMed=11402065; DOI=10.1083/jcb.153.6.1209;
Oegema K., Desai A., Rybina S., Kirkham M., Hyman A.A.;
"Functional analysis of kinetochore assembly in Caenorhabditis
elegans.";
J. Cell Biol. 153:1209-1226(2001).
[3]
SUBCELLULAR LOCATION.
PubMed=17339379; DOI=10.1083/jcb.200701065;
Maddox P.S., Hyndman F., Monen J., Oegema K., Desai A.;
"Functional genomics identifies a Myb domain-containing protein family
required for assembly of CENP-A chromatin.";
J. Cell Biol. 176:757-763(2007).
[4]
FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
PubMed=18765790; DOI=10.1101/gad.1687508;
Gassmann R., Essex A., Hu J.-S., Maddox P.S., Motegi F., Sugimoto A.,
O'Rourke S.M., Bowerman B., McLeod I., Yates J.R. III, Oegema K.,
Cheeseman I.M., Desai A.;
"A new mechanism controlling kinetochore-microtubule interactions
revealed by comparison of two dynein-targeting components: SPDL-1 and
the Rod/Zwilch/Zw10 complex.";
Genes Dev. 22:2385-2399(2008).
[5]
FUNCTION, AND SUBCELLULAR LOCATION.
PubMed=18936247; DOI=10.1083/jcb.200805185;
Yamamoto T.G., Watanabe S., Essex A., Kitagawa R.;
"SPDL-1 functions as a kinetochore receptor for MDF-1 in
Caenorhabditis elegans.";
J. Cell Biol. 183:187-194(2008).
[6]
FUNCTION.
PubMed=19109417; DOI=10.1091/mbc.E08-10-1047;
Essex A., Dammermann A., Lewellyn L., Oegema K., Desai A.;
"Systematic analysis in Caenorhabditis elegans reveals that the
spindle checkpoint is composed of two largely independent branches.";
Mol. Biol. Cell 20:1252-1267(2009).
[7]
FUNCTION, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
PubMed=19526056; DOI=10.1371/journal.pone.0005912;
Wang X., Liu M., Li W., Suh C.D., Zhu Z., Jin Y., Fan Q.;
"The function of a spindle checkpoint gene bub-1 in C. elegans
development.";
PLoS ONE 4:E5912-E5912(2009).
[8]
FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
PubMed=20729837; DOI=10.1038/ncb2093;
Dumont J., Oegema K., Desai A.;
"A kinetochore-independent mechanism drives anaphase chromosome
separation during acentrosomal meiosis.";
Nat. Cell Biol. 12:894-901(2010).
[9]
FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH MDF-1, INTERACTION WITH
BUB-3, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-718; LEU-777;
ASN-781; ASP-814 AND ASP-847.
PubMed=24567362; DOI=10.1083/jcb.201311015;
Moyle M.W., Kim T., Hattersley N., Espeut J., Cheerambathur D.K.,
Oegema K., Desai A.;
"A Bub1-Mad1 interaction targets the Mad1-Mad2 complex to unattached
kinetochores to initiate the spindle checkpoint.";
J. Cell Biol. 204:647-657(2014).
[10]
FUNCTION, INTERACTION WITH BUB-3, SUBCELLULAR LOCATION, AND DISRUPTION
PHENOTYPE.
PubMed=25987605; DOI=10.1083/jcb.201412035;
Kim T., Moyle M.W., Lara-Gonzalez P., De Groot C., Oegema K.,
Desai A.;
"Kinetochore-localized BUB-1/BUB-3 complex promotes anaphase onset in
C. elegans.";
J. Cell Biol. 209:507-517(2015).
-!- FUNCTION: Serine/threonine-protein kinase essential for spindle-
assembly checkpoint signaling. Plays a key role in the recruitment
of the checkpoint proteins bub-3, mdf-1 and mdf-2 to unattached
kinetochores (PubMed:18936247, PubMed:19109417, PubMed:24567362,
PubMed:25987605). mdf-1 recruitment is independent of bub-1 kinase
activity (PubMed:24567362). Has a role in the correct kinetochore
localization of the spindly-like protein spdl-1 (PubMed:18765790).
In addition, during meiotic anaphase I, controls the recruitment
of hcp-1/2 and klp-19 to the ring-shaped domain formed between
chromosomes (PubMed:20729837). Involved in chromosome alignment,
chromosome homolog segregation and spindle assembly
(PubMed:20729837, PubMed:25987605). In association with bub-3 at
the kinetochore region of chromosomes, promotes the onset on
anaphase independently from spindle checkpoint signaling and
promotes the formation of stable end-on bipolar attachments of
chromosomes (PubMed:25987605). Plays a role in nuclear envelope
breakdown (PubMed:19109417). Required maternally during
embryogenesis and in the zygote for the postembryonic development
of several tissues including ventral cord neurons, gonad,
intestine and seam cells (PubMed:19526056).
{ECO:0000269|PubMed:18765790, ECO:0000269|PubMed:19109417,
ECO:0000269|PubMed:19526056, ECO:0000269|PubMed:20729837,
ECO:0000269|PubMed:24567362, ECO:0000269|PubMed:25987605}.
-!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
{ECO:0000269|PubMed:24567362}.
-!- SUBUNIT: Interacts (via kinase domain) with mdf-1 (via coiled coil
domain); the interaction recruits mdf-1 to unattached kinetochores
during mitosis and between homologous chromosomes in early
anaphase of meiosis I (PubMed:24567362). May interact with bub-3;
for localization at the kinetochore and the onset of anaphase
(PubMed:24567362, PubMed:25987605). {ECO:0000269|PubMed:24567362,
ECO:0000269|PubMed:25987605, ECO:0000305|PubMed:24567362}.
-!- SUBCELLULAR LOCATION: Cytoplasm, cell cortex
{ECO:0000269|PubMed:20729837}. Nucleus
{ECO:0000269|PubMed:19526056}. Chromosome, centromere, kinetochore
{ECO:0000269|PubMed:17339379, ECO:0000269|PubMed:18765790,
ECO:0000269|PubMed:18936247, ECO:0000269|PubMed:20729837,
ECO:0000269|PubMed:24567362, ECO:0000269|PubMed:25987605}.
Note=Localizes to kinetochores during prophase and metaphase. In
metaphase, localizes also to a matrix-like structure around the
spindle (PubMed:11402065). In anaphase, localizes only to
unattached kinetochores which is kln-1-dependent (PubMed:11402065,
PubMed:24567362). Localizes also in a ring-shaped domain between
kinetochores, during anaphase of meiosis I which is air-2 and kln-
1-dependent and between sister chromatids during meiosis II, which
is kln-1-independent (PubMed:20729837). Localization to the
kinetochore is dependent on bub-3 and on knl-2 (PubMed:25987605,
PubMed:17339379). {ECO:0000269|PubMed:11402065,
ECO:0000269|PubMed:17339379, ECO:0000269|PubMed:20729837,
ECO:0000269|PubMed:24567362, ECO:0000269|PubMed:25987605}.
-!- DEVELOPMENTAL STAGE: Expressed throughout embryogenesis mainly in
dividing cells. {ECO:0000269|PubMed:19526056}.
-!- DISRUPTION PHENOTYPE: Embryonic lethal (PubMed:25987605). RNAi-
mediated knockdown in oocytes results in aberrant homologous
chromosome segregation during meiosis due to severe pre-anaphase
spindle defects characterized by disorganized microtubule bundles
(PubMed:20729837). Delays in the processes leading up to exit from
mitosis including delayed activation of separase, which results in
a delay in the separation of sister chromatids, delayed
cytokinesis onset and delayed chromosome decondensation
(PubMed:25987605). These culminate in a delay in the onset of
anaphase with a 50% increase in the interval between nuclear
envelope breakdown and the onset of anaphase during embryogenesis
(PubMed:25987605). Reduced bub-3 localization at the kinetochore
region of chromosomes in embryos, but without a reduction in bub-3
protein (PubMed:25987605). In addition there is reduced
localization of the spindly-like protein spdl-1 to kinetochores
(PubMed:18765790). {ECO:0000269|PubMed:18765790,
ECO:0000269|PubMed:20729837, ECO:0000269|PubMed:25987605}.
-!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr
protein kinase family. BUB1 subfamily. {ECO:0000305}.
-----------------------------------------------------------------------
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-----------------------------------------------------------------------
EMBL; BX284601; CAA95845.1; -; Genomic_DNA.
PIR; T23971; T23971.
RefSeq; NP_492051.1; NM_059650.4.
UniGene; Cel.17390; -.
ProteinModelPortal; Q21776; -.
SMR; Q21776; -.
DIP; DIP-27465N; -.
IntAct; Q21776; 4.
MINT; MINT-1057818; -.
STRING; 6239.R06C7.8; -.
EPD; Q21776; -.
PaxDb; Q21776; -.
PeptideAtlas; Q21776; -.
EnsemblMetazoa; R06C7.8; R06C7.8; WBGene00000275.
GeneID; 172468; -.
KEGG; cel:CELE_R06C7.8; -.
UCSC; R06C7.8; c. elegans.
CTD; 172468; -.
WormBase; R06C7.8; CE06251; WBGene00000275; bub-1.
eggNOG; KOG1166; Eukaryota.
eggNOG; ENOG410XQ67; LUCA.
GeneTree; ENSGT00520000055622; -.
HOGENOM; HOG000019104; -.
InParanoid; Q21776; -.
KO; K02178; -.
OMA; ADWCIMQ; -.
OrthoDB; EOG091G00MB; -.
Reactome; R-CEL-141430; Inactivation of APC/C via direct inhibition of the APC/C complex.
SignaLink; Q21776; -.
PRO; PR:Q21776; -.
Proteomes; UP000001940; Chromosome I.
Bgee; WBGene00000275; -.
GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
GO; GO:0000778; C:condensed nuclear chromosome kinetochore; IBA:GO_Central.
GO; GO:0000776; C:kinetochore; IDA:UniProtKB.
GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO; GO:0004672; F:protein kinase activity; IBA:GO_Central.
GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
GO; GO:0051316; P:attachment of spindle microtubules to kinetochore involved in meiotic chromosome segregation; IMP:UniProtKB.
GO; GO:0051301; P:cell division; IMP:UniProtKB.
GO; GO:0048598; P:embryonic morphogenesis; IMP:UniProtKB.
GO; GO:0008406; P:gonad development; IMP:UniProtKB.
GO; GO:0051307; P:meiotic chromosome separation; IMP:UniProtKB.
GO; GO:0051754; P:meiotic sister chromatid cohesion, centromeric; IBA:GO_Central.
GO; GO:0051257; P:meiotic spindle midzone assembly; IMP:UniProtKB.
GO; GO:0000212; P:meiotic spindle organization; IMP:UniProtKB.
GO; GO:0007094; P:mitotic spindle assembly checkpoint; IBA:GO_Central.
GO; GO:0048666; P:neuron development; IMP:UniProtKB.
GO; GO:0000280; P:nuclear division; IMP:UniProtKB.
GO; GO:1905342; P:positive regulation of protein localization to kinetochore; IMP:UniProtKB.
GO; GO:0034501; P:protein localization to kinetochore; IMP:UniProtKB.
GO; GO:1903394; P:protein localization to kinetochore involved in kinetochore assembly; IMP:UniProtKB.
InterPro; IPR015661; Bub1/Mad3.
InterPro; IPR011009; Kinase-like_dom_sf.
InterPro; IPR000719; Prot_kinase_dom.
InterPro; IPR017441; Protein_kinase_ATP_BS.
InterPro; IPR008271; Ser/Thr_kinase_AS.
PANTHER; PTHR14030; PTHR14030; 1.
Pfam; PF00069; Pkinase; 1.
SMART; SM00220; S_TKc; 1.
SUPFAM; SSF56112; SSF56112; 1.
PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
1: Evidence at protein level;
ATP-binding; Cell cycle; Cell division; Centromere; Chromosome;
Complete proteome; Cytoplasm; Developmental protein; Kinase;
Kinetochore; Meiosis; Mitosis; Nucleotide-binding; Nucleus;
Reference proteome; Serine/threonine-protein kinase; Transferase.
CHAIN 1 987 Mitotic checkpoint serine/threonine-
protein kinase bub-1.
/FTId=PRO_0000433016.
DOMAIN 690 987 Protein kinase. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
NP_BIND 696 704 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
ACT_SITE 814 814 Proton acceptor. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
BINDING 718 718 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
MUTAGEN 718 718 K->R: No effect on embryo viability,
severe loss of mdf-1 recruitment to
unattached kinetochores and probably loss
of kinase activity; when associated with
N-847. {ECO:0000269|PubMed:24567362}.
MUTAGEN 777 777 L->K: Loss of interaction with mdf-1 but
not with bub-3. No effect on embryo
viability and severe loss of mdf-1
recruitment to unattached kinetochores;
when associated with K-781.
{ECO:0000269|PubMed:24567362}.
MUTAGEN 781 781 N->K: Loss of interaction with mdf-1 but
not with bub-3. No effect on embryo
viability and severe loss of mdf-1
recruitment to unattached kinetochores;
when associated with K-777.
{ECO:0000269|PubMed:24567362}.
MUTAGEN 814 814 D->N: Loss of activity. No effect on
embryo viability and mdf-1 recruitment to
unattached kinetochores.
{ECO:0000269|PubMed:24567362}.
MUTAGEN 847 847 D->N: No effect on embryo viability,
severe loss of mdf-1 recruitment to
unattached kinetochores and probably loss
of kinase activity; when associated with
N-718. {ECO:0000269|PubMed:24567362}.
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


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