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protein coding gene - mad3 (SPCC1795.01c) - mitotic spindle checkpoint protein Mad3

Gene summary

Standard name
mad3
Systematic ID
SPCC1795.01c
Product
mitotic spindle checkpoint protein Mad3
Organism
Schizosaccharomyces pombe (fission yeast)
Synonyms
SPCC895.02
UniProt ID
O59767
ORFeome ID
13/13A10
Characterisation status
biological role published
Feature type
mRNA gene
Genomic location
chromosome III: 997416..998839 forward strand

Annotation

PBO:0000285 - Mad2-dependent checkpoint response

Comment

PBO:0109301 - codon-optimization increases the mRNA concentration

References:

PBO:0109300 - low codon stabilization coefficient

References:

Disease association

MONDO:0005575 - colorectal cancer

References:

MONDO:0859342 - microcephaly 30, primary, autosomal recessive

References:

MONDO:0009759 - mosaic variegated aneuploidy syndrome 1

References:

MONDO:0008304 - premature chromatid separation trait

References:

GO biological process

GO:0007094 - mitotic spindle assembly checkpoint signaling

References:

GO:0045841 - negative regulation of mitotic metaphase/anaphase transition

References:

GO cellular component

GO:0005829 - cytosol

References:

GO:0000776 - kinetochore

References:

GO:0033597 - mitotic checkpoint complex

References:

GO:0005634 - nucleus

References:

GO molecular function

GO:0010997 - anaphase-promoting complex binding

References:

GO:0140678 - molecular function inhibitor activity

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GO:0005515 - protein binding

References:

GO:1990948 - ubiquitin ligase inhibitor activity

References:

Modification

MOD:00046 - O-phospho-L-serine

References:

MOD:00047 - O-phospho-L-threonine

References:

Multi-locus phenotype

FYPO:0000168 - abnormal mitotic spindle assembly checkpoint

References:

Genotypes:

FYPO:0004318 - abolished mitotic spindle assembly checkpoint

References:

Genotypes:

FYPO:0005928 - abolished protein polyubiquitination during vegetative growth

References:

Genotypes:

FYPO:0003165 - cut with abnormal chromosome segregation

References:

Genotypes:

FYPO:0001407 - decreased cell population growth on glucose carbon source

References:

Genotypes:

FYPO:0005781 - decreased duration of mitotic spindle assembly checkpoint

References:

Genotypes:

FYPO:0005784 - decreased extent and duration of protein-protein interaction

References:

Genotypes:

FYPO:0005782 - decreased mitotic checkpoint complex level

References:

Genotypes:

FYPO:0005684 - increased duration of mitotic prometaphase

References:

Genotypes:

FYPO:0005683 - increased duration of mitotic prophase

References:

Genotypes:

FYPO:0001840 - increased minichromosome loss during vegetative growth

References:

Genotypes:

FYPO:0001489 - inviable vegetative cell

References:

Genotypes:

FYPO:0002061 - inviable vegetative cell population

References:

Genotypes:

FYPO:0004310 - normal duration of mitotic M phase

References:

Genotypes:

FYPO:0006646 - normal duration of mitotic prometaphase

References:

Genotypes:

FYPO:0006257 - normal duration of mitotic prophase

References:

Genotypes:

FYPO:0001164 - normal growth on glucose carbon source

References:

Genotypes:

FYPO:0003762 - normal mitotic spindle assembly checkpoint

References:

Genotypes:

FYPO:0006917 - normal onset of mitotic metaphase/anaphase transition

References:

Genotypes:

FYPO:0002966 - normal protein localization to mitotic spindle

References:

Genotypes:

FYPO:0001234 - slow vegetative cell population growth

References:

Genotypes:

FYPO:0002060 - viable vegetative cell population

References:

Genotypes:

Protein sequence feature

SO:0001807 - KEN_box

References:

Qualitative gene expression

PomGeneEx:0000011 - RNA level increased

References:

Quantitative gene expression

PBO:0006310 - protein level

References:

PBO:0011963 - RNA level

References:

Single locus phenotype

FYPO:0000168 - abnormal mitotic spindle assembly checkpoint

References:

Genotypes:

FYPO:0004318 - abolished mitotic spindle assembly checkpoint

References:

Genotypes:

FYPO:0000912 - abolished protein ubiquitination during vegetative growth

References:

Genotypes:

FYPO:0000705 - abolished protein-protein interaction

References:

Genotypes:

FYPO:0000251 - decreased cell population growth on galactose carbon source

References:

Genotypes:

FYPO:0005781 - decreased duration of mitotic spindle assembly checkpoint

References:

Genotypes:

FYPO:0005785 - decreased duration of protein-protein interaction

References:

Genotypes:

FYPO:0005784 - decreased extent and duration of protein-protein interaction

References:

Genotypes:

FYPO:0001382 - decreased protein kinase activity

References:

Genotypes:

FYPO:0001324 - decreased protein level during vegetative growth

References:

Genotypes:

FYPO:0008165 - decreased protein localization to kinetochore during mitotic prometaphase

References:

Genotypes:

FYPO:0001645 - decreased protein-protein interaction

References:

Genotypes:

FYPO:0007385 - increased duration of protein-protein interaction

References:

Genotypes:

FYPO:0000786 - increased plasmid loss

References:

Genotypes:

FYPO:0001571 - increased protein-protein interaction

References:

Genotypes:

FYPO:0002972 - increased ubiquitin ligase activity

References:

Genotypes:

FYPO:0006518 - loss of viability in G0

References:

Genotypes:

FYPO:0004310 - normal duration of mitotic M phase

References:

Genotypes:

FYPO:0007553 - normal G1 to G0 transition

References:

Genotypes:

FYPO:0001687 - normal growth on benomyl

References:

Genotypes:

FYPO:0005783 - normal mitotic checkpoint complex assembly

References:

Genotypes:

FYPO:0003762 - normal mitotic spindle assembly checkpoint

References:

Genotypes:

FYPO:0005779 - normal protein localization to kinetochore during mitosis

References:

Genotypes:

FYPO:0000703 - normal protein-protein interaction

References:

Genotypes:

FYPO:0002693 - resistance to diamide

References:

Genotypes:

FYPO:0009043 - resistance to potassium chloride and sodium dodecyl sulfate

References:

Genotypes:

FYPO:0003383 - resistance to tert-butyl hydroperoxide

References:

Genotypes:

FYPO:0000069 - resistance to thiabendazole

References:

Genotypes:

FYPO:0000094 - sensitive to benomyl

References:

Genotypes:

FYPO:0000096 - sensitive to cadmium

References:

Genotypes:

FYPO:0000091 - sensitive to thiabendazole

References:

Genotypes:

FYPO:0001491 - viable vegetative cell

References:

Genotypes:

FYPO:0002060 - viable vegetative cell population

References:

Genotypes:

FYPO:0002177 - viable vegetative cell with normal cell morphology

References:

Genotypes:

Taxonomic conservation

PBO:0011065 - conserved in eukaryotes

PBO:0011071 - conserved in eukaryotes only

PBO:0011064 - conserved in fungi

PBO:0011069 - conserved in metazoa

PBO:0011070 - conserved in vertebrates

PBO:0006222 - predominantly single copy (one to one)

Protein features

IDNameInterPro nameDB name
PF08311Mad3_BUB1_IMad3/Bub1_IPfam
PS51489BUB1_NMad3/Bub1_IPROSITE profiles
SM00777Mad3_BUB1_IMad3/Bub1_ISMART
G3DSA:1.25.40.430:FF:000004CATH-FunFam
G3DSA:1.25.40.430CATH-Gene3D
SSF48452TPR-like_helical_dom_sfSUPERFAMILY
PTHR14030Bub1/Mad3PANTHER
CoilCOILS
mobidb-lite-Disorderdisorder_predictionMobiDB-Disorder
mobidb-lite-Polyampholytedisorder_predictionMobiDB-Polyampholyte

Orthologs

References / Literature

PMID:15930132 - Spindle checkpoint signaling requires the mis6 kinetochore subcomplex, which interacts with mad2 and mitotic spindles.
Saitoh S et al. Mol Biol Cell 2005 Aug;16(8):3666-77
PMID:18562692 - Latrunculin A delays anaphase onset in fission yeast by disrupting an Ase1-independent pathway controlling mitotic spindle stability.
Meadows JC et al. Mol Biol Cell 2008 Sep;19(9):3713-23
PMID:16823372 - ORFeome cloning and global analysis of protein localization in the fission yeast Schizosaccharomyces pombe.
Matsuyama A et al. Nat Biotechnol 2006 Jul;24(7):841-7
PMID:23697806 - A genome-wide resource of cell cycle and cell shape genes of fission yeast.
Hayles J et al. Open Biol 2013 May 22;3(5):130053
PMID:23166349 - Csi1 links centromeres to the nuclear envelope for centromere clustering.
Hou H et al. J Cell Biol 2012 Nov 26;199(5):735-44
PMID:19680287 - Bub1 and Bub3 promote the conversion from monopolar to bipolar chromosome attachment independently of shugoshin.
Windecker H et al. EMBO Rep 2009 Sep;10(9):1022-8
PMID:24763107 - Absolute proteome and phosphoproteome dynamics during the cell cycle of Schizosaccharomyces pombe (Fission Yeast).
Carpy A et al. Mol Cell Proteomics 2014 Aug;13(8):1925-36
PMID:27984725 - CDK Substrate Phosphorylation and Ordering the Cell Cycle.
Swaffer MP et al. Cell 2016 Dec 15;167(7):1750-1761.e16
PB_REF:0000006 - Disease associations from Monarch via human-pombe orthologs
PMID:15509783 - Kinetochore targeting of fission yeast Mad and Bub proteins is essential for spindle checkpoint function but not for all chromosome segregation roles of Bub1p.
Vanoosthuyse V et al. Mol Cell Biol 2004 Nov;24(22):9786-801
PMID:16394105 - The V260I mutation in fission yeast alpha-tubulin Atb2 affects microtubule dynamics and EB1-Mal3 localization and activates the Bub1 branch of the spindle checkpoint.
Asakawa K et al. Mol Biol Cell 2006 Mar;17(3):1421-35
PMID:21664573 - Spindle checkpoint silencing requires association of PP1 to both Spc7 and kinesin-8 motors.
Meadows JC et al. Dev Cell 2011 Jun 14;20(6):739-50
PMID:17277378 - Novel mad2 alleles isolated in a Schizosaccharomyces pombe gamma-tubulin mutant are defective in metaphase arrest activity, but remain functional for chromosome stability in unperturbed mitosis.
Tange Y et al. Genetics 2007 Apr;175(4):1571-84
PMID:22521786 - Phosphodependent recruitment of Bub1 and Bub3 to Spc7/KNL1 by Mph1 kinase maintains the spindle checkpoint.
Shepperd LA et al. Curr Biol 2012 May 22;22(10):891-9
PMID:22681890 - Hierarchical modularity and the evolution of genetic interactomes across species.
Ryan CJ et al. Mol Cell 2012 Jun 08;46(5):691-704
PMID:30726745 - Fission Yeast NDR/LATS Kinase Orb6 Regulates Exocytosis via Phosphorylation of the Exocyst Complex.
Tay YD et al. Cell Rep 2019 Feb 05;26(6):1654-1667.e7
PMID:22437499 - Structure of the mitotic checkpoint complex.
Chao WC et al. Nature 2012 Mar 21;484(7393):208-13
PMID:24161933 - Determinants of robustness in spindle assembly checkpoint signalling.
Heinrich S et al. Nat Cell Biol 2013 Nov;15(11):1328-39
PMID:24583014 - Slow checkpoint activation kinetics as a safety device in anaphase.
Kamenz J et al. Curr Biol 2014 Mar 17;24(6):646-51
PMID:19592249 - A novel protein phosphatase 1-dependent spindle checkpoint silencing mechanism.
Vanoosthuyse V et al. Curr Biol 2009 Jul 28;19(14):1176-81
PMID:26771498 - A Proteome-wide Fission Yeast Interactome Reveals Network Evolution Principles from Yeasts to Human.
Vo TV et al. Cell 2016 Jan 14;164(1-2):310-323
PMID:26258632 - Mad1 promotes chromosome congression by anchoring a kinesin motor to the kinetochore.
Akera T et al. Nat Cell Biol 2015 Sep;17(9):1124-33
PMID: - Unknown title
PMID:22660415 - MPS1/Mph1 phosphorylates the kinetochore protein KNL1/Spc7 to recruit SAC components.
Yamagishi Y et al. Nat Cell Biol 2012 Jun 03;14(7):746-52
PMID:21965289 - Nsk1 ensures accurate chromosome segregation by promoting association of kinetochores to spindle poles during anaphase B.
Buttrick GJ et al. Mol Biol Cell 2011 Dec;22(23):4486-502
PMID:23101633 - Quantitative analysis of fission yeast transcriptomes and proteomes in proliferating and quiescent cells.
Marguerat S et al. Cell 2012 Oct 26;151(3):671-83
PMID:24477934 - Mad1 contribution to spindle assembly checkpoint signalling goes beyond presenting Mad2 at kinetochores.
Heinrich S et al. EMBO Rep 2014 Mar;15(3):291-8
PMID:28017606 - Generation of a Spindle Checkpoint Arrest from Synthetic Signaling Assemblies.
Yuan I et al. Curr Biol 2017 Jan 09;27(1):137-143
PMID:33823663 - A TOR (target of rapamycin) and nutritional phosphoproteome of fission yeast reveals novel targets in networks conserved in humans.
Halova L et al. Open Biol 2021 Apr;11(4):200405
PMID:39476757 - Characterization of Ksg1 protein kinase-dependent phosphoproteome in the fission yeast S. pombe.
Cipak L et al. Biochem Biophys Res Commun 2024 Oct 25;736:150895
PMID:22375062 - Plo1 phosphorylates Dam1 to promote chromosome bi-orientation in fission yeast.
Buttrick GJ et al. J Cell Sci 2012 Apr 01;125(Pt 7):1645-51
PMID:16179942 - Mal3, the fission yeast EB1 homologue, cooperates with Bub1 spindle checkpoint to prevent monopolar attachment.
Asakawa K et al. EMBO Rep 2005 Dec;6(12):1194-200
PMID:12676091 - S. pombe aurora kinase/survivin is required for chromosome condensation and the spindle checkpoint attachment response.
Petersen J et al. Curr Biol 2003 Apr 01;13(7):590-7
PMID:18556659 - The spindle checkpoint functions of Mad3 and Mad2 depend on a Mad3 KEN box-mediated interaction with Cdc20-anaphase-promoting complex (APC/C).
Sczaniecka M et al. J Biol Chem 2008 Aug 22;283(34):23039-47
PMID:27618268 - Bub3-Bub1 Binding to Spc7/KNL1 Toggles the Spindle Checkpoint Switch by Licensing the Interaction of Bub1 with Mad1-Mad2.
Mora-Santos MD et al. Curr Biol 2016 Oct 10;26(19):2642-2650
PMID:21511999 - Comparative functional genomics of the fission yeasts.
Rhind N et al. Science 2011 May 20;332(6032):930-6
PMID:28281664 - Genetic interactions and functional analyses of the fission yeast gsk3 and amk2 single and double mutants defective in TORC1-dependent processes.
Rallis C et al. Sci Rep 2017 Mar 10;7:44257
PMID:36108046 - Recovery from spindle checkpoint-mediated arrest requires a novel Dnt1-dependent APC/C activation mechanism.
Bai S et al. PLoS Genet 2022 Sep;18(9):e1010397
PMID:28366744 - Fission Yeast Apc15 Stabilizes MCC-Cdc20-APC/C Complexes, Ensuring Efficient Cdc20 Ubiquitination and Checkpoint Arrest.
May KM et al. Curr Biol 2017 Apr 24;27(8):1221-1228
PMID:37787768 - Broad functional profiling of fission yeast proteins using phenomics and machine learning.
Rodríguez-López M et al. Elife 2023 Oct 03;12
PMID:35811551 - Mitotic checkpoint gene expression is tuned by codon usage bias.
Esposito E et al. EMBO J 2022 Aug 01;41(15):e107896
PMID:33260998 - High-Throughput Flow Cytometry Combined with Genetic Analysis Brings New Insights into the Understanding of Chromatin Regulation of Cellular Quiescence.
Zahedi Y et al. Int J Mol Sci 2020 Nov 27;21(23)
PMID:28178520 - Identification of a Sgo2-Dependent but Mad2-Independent Pathway Controlling Anaphase Onset in Fission Yeast.
Meadows JC et al. Cell Rep 2017 Feb 07;18(6):1422-1433
PMID:18082611 - Structural organization of the anaphase-promoting complex bound to the mitotic activator Slp1.
Ohi MD et al. Mol Cell 2007 Dec 14;28(5):871-85
PMID:22825872 - Mph1 kinetochore localization is crucial and upstream in the hierarchy of spindle assembly checkpoint protein recruitment to kinetochores.
Heinrich S et al. J Cell Sci 2012 Oct 15;125(Pt 20):4720-7
PMID:27984744 - Survival in Quiescence Requires the Euchromatic Deployment of Clr4/SUV39H by Argonaute-Associated Small RNAs.
Joh RI et al. Mol Cell 2016 Dec 15;64(6):1088-1101
PMID:20473289 - Analysis of a genome-wide set of gene deletions in the fission yeast Schizosaccharomyces pombe.
Kim DU et al. Nat Biotechnol 2010 Jun;28(6):617-623
PMID:22281223 - Kinase activity of fission yeast Mph1 is required for Mad2 and Mad3 to stably bind the anaphase promoting complex.
Zich J et al. Curr Biol 2012 Feb 21;22(4):296-301
PMID:15483052 - BAF53/Arp4 homolog Alp5 in fission yeast is required for histone H4 acetylation, kinetochore-spindle attachment, and gene silencing at centromere.
Minoda A et al. Mol Biol Cell 2005 Jan;16(1):316-27
PMID:19523829 - Phosphorylation state defines discrete roles for monopolin in chromosome attachment and spindle elongation.
Choi SH et al. Curr Biol 2009 Jun 23;19(12):985-95
PMID:25720772 - Quantitative phosphoproteomics reveals pathways for coordination of cell growth and division by the conserved fission yeast kinase pom1.
Kettenbach AN et al. Mol Cell Proteomics 2015 May;14(5):1275-87
PMID:29996109 - Quantitative Phosphoproteomics Reveals the Signaling Dynamics of Cell-Cycle Kinases in the Fission Yeast Schizosaccharomyces pombe.
Swaffer MP et al. Cell Rep 2018 Jul 10;24(2):503-514
PMID:12951601 - Deletion of Mia1/Alp7 activates Mad2-dependent spindle assembly checkpoint in fission yeast.
Sato M et al. Nat Cell Biol 2003 Sep;5(9):764-6; author reply 766
PMID:26900649 - The hairpin region of Ndc80 is important for the kinetochore recruitment of Mph1/MPS1 in fission yeast.
Chmielewska AE et al. Cell Cycle 2016;15(5):740-7
PMID:21712547 - Mitotic substrates of the kinase aurora with roles in chromatin regulation identified through quantitative phosphoproteomics of fission yeast.
Koch A et al. Sci Signal 2011 Jun 28;4(179):rs6
PMID:23695164 - Cross-species protein interactome mapping reveals species-specific wiring of stress response pathways.
Das J et al. Sci Signal 2013 May 21;6(276):ra38
PMID:15347659 - DNA replication checkpoint control mediated by the spindle checkpoint protein Mad2p in fission yeast.
Sugimoto I et al. J Biol Chem 2004 Nov 05;279(45):47372-8
PMID:22184248 - Centromere-tethered Mps1 pombe homolog (Mph1) kinase is a sufficient marker for recruitment of the spindle checkpoint protein Bub1, but not Mad1.
Ito D et al. Proc Natl Acad Sci U S A 2012 Jan 03;109(1):209-14
PMID:28366743 - Different Functionality of Cdc20 Binding Sites within the Mitotic Checkpoint Complex.
Sewart K et al. Curr Biol 2017 Apr 24;27(8):1213-1220
PMID:26882497 - Mps1Mph1 Kinase Phosphorylates Mad3 to Inhibit Cdc20Slp1-APC/C and Maintain Spindle Checkpoint Arrests.
Zich J et al. PLoS Genet 2016 Feb;12(2):e1005834
PMID:31257143 - The Bub1-TPR Domain Interacts Directly with Mad3 to Generate Robust Spindle Checkpoint Arrest.
Leontiou I et al. Curr Biol 2019 Jul 22;29(14):2407-2414.e7
PMID:16360688 - Control of Shugoshin function during fission-yeast meiosis.
Vaur S et al. Curr Biol 2005 Dec 20;15(24):2263-70
PMID:11909965 - Fission yeast Mad3p is required for Mad2p to inhibit the anaphase-promoting complex and localizes to kinetochores in a Bub1p-, Bub3p-, and Mph1p-dependent manner.
Millband DN et al. Mol Cell Biol 2002 Apr;22(8):2728-42