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protein coding gene - mis4 (SPAC31A2.05c) - cohesin loading factor (adherin) Mis4/Scc2

Gene summary

Standard name
mis4
Systematic ID
SPAC31A2.05c
Product
cohesin loading factor (adherin) Mis4/Scc2
Organism
Schizosaccharomyces pombe (fission yeast)
Synonyms
scc2
UniProt ID
Q09725
ORFeome ID
31/31B01
Characterisation status
biological role published
Feature type
mRNA gene
Genomic location
chromosome I: 391628..396939 reverse strand

Annotation

Disease association

MONDO:0007387 - Cornelia de Lange syndrome 1

References:

GO biological process

GO:0140588 - chromatin looping

References:

GO:0034087 - establishment of mitotic sister chromatid cohesion

References:

GO:0007064 - mitotic sister chromatid cohesion

References:

GO:0000070 - mitotic sister chromatid segregation

References:

GO:1990414 - replication-born double-strand break repair via sister chromatid exchange

References:

GO cellular component

GO:0005829 - cytosol

References:

GO:1990342 - heterochromatin island

References:

GO:0000228 - nuclear chromosome

References:

GO:0005634 - nucleus

References:

GO:0090694 - Scc2-Scc4 cohesin loading complex

References:

GO:0032116 - SMC loading complex

References:

GO molecular function

GO:0001671 - ATPase activator activity

References:

GO:0003682 - chromatin binding

References:

GO:0061775 - cohesin loader activity

References:

GO:0003690 - double-stranded DNA binding

References:

GO:0005515 - protein binding

References:

GO:0003697 - single-stranded DNA binding

References:

Modification

MOD:00046 - O-phospho-L-serine

References:

MOD:00047 - O-phospho-L-threonine

References:

MOD:00048 - O4'-phospho-L-tyrosine

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MOD:00696 - phosphorylated residue

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Multi-locus phenotype

FYPO:0000620 - abnormal cell cycle arrest in mitotic metaphase

References:

Genotypes:

FYPO:0004308 - abnormal CENP-A containing chromatin organization

References:

Genotypes:

FYPO:0000141 - abnormal mitotic sister chromatid segregation

References:

Genotypes:

FYPO:0000046 - decreased cell population growth

References:

Genotypes:

FYPO:0000460 - decreased mitotic centromeric sister chromatid cohesion

References:

Genotypes:

FYPO:0007499 - increased chromatin binding at cohesin associated regions

References:

Genotypes:

FYPO:0005898 - increased protein localization to centromeric chromatin during mitotic G1 phase

References:

Genotypes:

FYPO:0005897 - increased protein localization to chromatin during mitotic G1 phase

References:

Genotypes:

FYPO:0000839 - inviable elongated mononucleate aseptate cell

References:

Genotypes:

FYPO:0002061 - inviable vegetative cell population

References:

Genotypes:

FYPO:0000228 - lagging mitotic chromosomes

References:

Genotypes:

FYPO:0006480 - normal cohesin loading

References:

Genotypes:

FYPO:0007198 - normal mitotic centromeric sister chromatid cohesion

References:

Genotypes:

FYPO:0005072 - normal protein localization to centromeric chromatin

References:

Genotypes:

FYPO:0005894 - normal protein localization to chromatin during mitotic G1 phase

References:

Genotypes:

FYPO:0000703 - normal protein-protein interaction

References:

Genotypes:

FYPO:0005342 - normal rate of mitotic spindle elongation during anaphase B

References:

Genotypes:

FYPO:0001234 - slow vegetative cell population growth

References:

Genotypes:

FYPO:0003241 - unequal mitotic sister chromatid segregation

References:

Genotypes:

FYPO:0002060 - viable vegetative cell population

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Genotypes:

Protein features

PBO:0111765 - HEAT repeat

Qualitative gene expression

PomGeneEx:0000018 - protein level increased

References:

PomGeneEx:0000011 - RNA level increased

References:

Quantitative gene expression

PBO:0006310 - protein level

References:

PBO:0011963 - RNA level

References:

Single locus phenotype

FYPO:0000619 - abnormal cell cycle arrest in mitotic anaphase

References:

Genotypes:

FYPO:0000620 - abnormal cell cycle arrest in mitotic metaphase

References:

Genotypes:

FYPO:0000611 - abnormal cell cycle arrest in mitotic S phase

References:

Genotypes:

FYPO:0001127 - abnormal cell size

References:

Genotypes:

FYPO:0004308 - abnormal CENP-A containing chromatin organization

References:

Genotypes:

FYPO:0000059 - abnormal mitotic cell cycle

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Genotypes:

FYPO:0005306 - abnormal protein localization to centromeric chromatin during vegetative growth

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Genotypes:

FYPO:0007543 - abolished double-stranded DNA binding

References:

Genotypes:

FYPO:0006174 - abolished mitotic spindle elongation during anaphase B

References:

Genotypes:

FYPO:0001269 - abolished protein localization to kinetochore during vegetative growth

References:

Genotypes:

FYPO:0004412 - abolished protein localization to mitotic spindle midzone during anaphase

References:

Genotypes:

FYPO:0004832 - abolished protein localization to mitotic spindle midzone during anaphase A

References:

Genotypes:

FYPO:0004562 - binucleate aseptate vegetative cell

References:

Genotypes:

FYPO:0003165 - cut with abnormal chromosome segregation

References:

Genotypes:

FYPO:0000082 - decreased cell population growth at high temperature

References:

Genotypes:

FYPO:0007498 - decreased chromatin binding at cohesin associated regions

References:

Genotypes:

FYPO:0005018 - decreased double-stranded DNA binding

References:

Genotypes:

FYPO:0005555 - decreased mitotic cohesin loading

References:

Genotypes:

FYPO:0002394 - decreased protein acetylation during vegetative growth

References:

Genotypes:

FYPO:0002797 - decreased protein degradation

References:

Genotypes:

FYPO:0002391 - decreased protein localization to chromatin at rDNA

References:

Genotypes:

FYPO:0005896 - decreased protein localization to chromatin during mitotic G1 phase

References:

Genotypes:

FYPO:0004833 - decreased protein localization to mitotic spindle midzone during anaphase B

References:

Genotypes:

FYPO:0002386 - decreased protein localization to pericentric heterochromatin at centromere outer repeat region

References:

Genotypes:

FYPO:0002387 - decreased protein localization to subtelomeric heterochromatin during vegetative growth

References:

Genotypes:

FYPO:0001838 - decreased protein phosphorylation during vegetative growth

References:

Genotypes:

FYPO:0001355 - decreased vegetative cell population growth

References:

Genotypes:

FYPO:0009007 - decreased vegetative cell population viability

References:

Genotypes:

FYPO:0000639 - delayed onset of septum assembly

References:

Genotypes:

FYPO:0008189 - equational sister chromatid segregation during achiasmatic meiosis I

References:

Genotypes:

FYPO:0002638 - increased activation of mitotic spindle assembly checkpoint

References:

Genotypes:

FYPO:0000274 - increased duration of mitotic M phase

References:

Genotypes:

FYPO:0001707 - increased mitotic DNA damage checkpoint activation

References:

Genotypes:

FYPO:0003307 - increased mitotic index

References:

Genotypes:

FYPO:0004710 - increased number of Rad52 foci during G0 to G1 transition

References:

Genotypes:

FYPO:0000786 - increased plasmid loss

References:

Genotypes:

FYPO:0005735 - increased protein localization to kinetochore during mitotic M phase

References:

Genotypes:

FYPO:0000839 - inviable elongated mononucleate aseptate cell

References:

Genotypes:

FYPO:0001490 - inviable elongated vegetative cell

References:

Genotypes:

FYPO:0002150 - inviable spore population

References:

Genotypes:

FYPO:0002061 - inviable vegetative cell population

References:

Genotypes:

FYPO:0001511 - inviable vegetative cell, abnormal cell shape, normal cell size

References:

Genotypes:

FYPO:0002090 - lagging chromosomes

References:

Genotypes:

FYPO:0000228 - lagging mitotic chromosomes

References:

Genotypes:

FYPO:0004307 - long mitotic spindle during metaphase

References:

Genotypes:

FYPO:0001387 - loss of viability at high temperature

References:

Genotypes:

FYPO:0006518 - loss of viability in G0

References:

Genotypes:

FYPO:0005345 - mitotic sister chromatid separation during interphase

References:

Genotypes:

FYPO:0007914 - mitotic sister chromatid separation during metaphase

References:

Genotypes:

FYPO:0003166 - monoseptate vegetative cell with binucleate and anucleate compartments

References:

Genotypes:

FYPO:0000674 - normal cell population growth at high temperature

References:

Genotypes:

FYPO:0002141 - normal cell population growth at low temperature

References:

Genotypes:

FYPO:0007544 - normal cohesin complex binding

References:

Genotypes:

FYPO:0006480 - normal cohesin loading

References:

Genotypes:

FYPO:0007542 - normal double-stranded DNA binding

References:

Genotypes:

FYPO:0001532 - normal duration of mitotic S phase

References:

Genotypes:

FYPO:0003176 - normal meiotic chromosome segregation

References:

Genotypes:

FYPO:0006482 - normal mitotic cohesin ssDNA (lagging strand) loading

References:

Genotypes:

FYPO:0002102 - normal mitotic DNA damage checkpoint during cellular response to UV

References:

Genotypes:

FYPO:0002390 - normal mitotic sister chromatid cohesion

References:

Genotypes:

FYPO:0005894 - normal protein localization to chromatin during mitotic G1 phase

References:

Genotypes:

FYPO:0001357 - normal vegetative cell population growth

References:

Genotypes:

FYPO:0000088 - sensitive to hydroxyurea

References:

Genotypes:

FYPO:0000091 - sensitive to thiabendazole

References:

Genotypes:

FYPO:0000268 - sensitive to UV during vegetative growth

References:

Genotypes:

FYPO:0007304 - short bipolar mitotic spindle during anaphase

References:

Genotypes:

FYPO:0003241 - unequal mitotic sister chromatid segregation

References:

Genotypes:

FYPO:0005069 - unequal mitotic sister chromatid segregation following normal mitosis

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)

Warnings

PBO:0000070 - gene structure updated

References:

Protein features

IDNameInterPro nameDB name
PF12765Cohesin_HEATCohesin_HEATPFAM
PF12830Nipped-B_CNipped-B_CPFAM
cd23958SCC2CDD
SSF48371ARM repeatARM-type_foldSUPERFAMILY
G3DSA:1.25.10.10ARM-likeGENE3D
PTHR21704NIPPED-B-LIKE PROTEIN DELANGIN SCC2-RELATEDScc2/Nipped-BPANTHER
mobidb-lite-Disorderdisorder_predictionMOBIDB-Disorder
mobidb-lite-Low-complexitydisorder_predictionMOBIDB-Low-complexity
mobidb-lite-Polardisorder_predictionMOBIDB-Polar

Orthologs

References / Literature

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:19443688 - Diverse roles of HP1 proteins in heterochromatin assembly and functions in fission yeast.
Fischer T et al. Proc Natl Acad Sci U S A 2009 Jun 02;106(22):8998-9003
PMID:26687354 - DNA Entry into and Exit out of the Cohesin Ring by an Interlocking Gate Mechanism.
Murayama Y et al. Cell 2015 Dec 17;163(7):1628-40
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: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:29735656 - Suppressor mutation analysis combined with 3D modeling explains cohesin's capacity to hold and release DNA.
Xu X et al. Proc Natl Acad Sci U S A 2018 May 22;115(21):E4833-E4842
GO_REF:0000033 - Annotation inferences using phylogenetic trees
PMID:11882285 - Requirement of chromatid cohesion proteins rad21/scc1 and mis4/scc2 for normal spindle-kinetochore interaction in fission yeast.
Toyoda Y et al. Curr Biol 2002 Mar 05;12(5):347-58
PMID:23050226 - A genetic screen to discover pathways affecting cohesin function in Schizosaccharomyces pombe identifies chromatin effectors.
Chen Z et al. G3 (Bethesda) 2012 Oct;2(10):1161-8
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:39705284 - Proteomic and phosphoproteomic analyses reveal that TORC1 is reactivated by pheromone signaling during sexual reproduction in fission yeast.
Bérard M et al. PLoS Biol 2024 Dec 20;22(12):e3002963
PMID:11598020 - Establishment and maintenance of sister chromatid cohesion in fission yeast by a unique mechanism.
Tanaka K et al. EMBO J 2001 Oct 15;20(20):5779-90
PMID:39367033 - Quantitative proteomics and phosphoproteomics profiling of meiotic divisions in the fission yeast Schizosaccharomyces pombe.
Sivakova B et al. Sci Rep 2024 Oct 04;14(1):23105
PMID:11554922 - Bir1/Cut17 moving from chromosome to spindle upon the loss of cohesion is required for condensation, spindle elongation and repair.
Morishita J et al. Genes Cells 2001 Sep;6(9):743-63
PMID:15507118 - An interactive gene network for securin-separase, condensin, cohesin, Dis1/Mtc1 and histones constructed by mass transformation.
Yuasa T et al. Genes Cells 2004 Nov;9(11):1069-82
PMID:38830897 - Sororin is an evolutionary conserved antagonist of WAPL.
Prusén Mota I et al. Nat Commun 2024 Jun 03;15(1):4729
PMID:21511999 - Comparative functional genomics of the fission yeasts.
Rhind N et al. Science 2011 May 20;332(6032):930-6
PMID:26583750 - The ATPases of cohesin interface with regulators to modulate cohesin-mediated DNA tethering.
Çamdere G et al. Elife 2015 Nov 19;4
PMID:9808627 - Faithful anaphase is ensured by Mis4, a sister chromatid cohesion molecule required in S phase and not destroyed in G1 phase.
Furuya K et al. Genes Dev 1998 Nov 01;12(21):3408-18
PB_REF:0000006 - Disease associations from Monarch via human-pombe orthologs
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:11069892 - Characterization of fission yeast cohesin: essential anaphase proteolysis of Rad21 phosphorylated in the S phase.
Tomonaga T et al. Genes Dev 2000 Nov 01;14(21):2757-70
PMID:40015273 - A comprehensive Schizosaccharomyces pombe atlas of physical transcription factor interactions with proteins and chromatin.
Skribbe M et al. Mol Cell 2025 Feb 19;
PMID:11861765 - Fission yeast Pds5 is required for accurate chromosome segregation and for survival after DNA damage or metaphase arrest.
Wang SW et al. J Cell Sci 2002 Feb 01;115(Pt 3):587-98
PMID:10779336 - Fission yeast Eso1p is required for establishing sister chromatid cohesion during S phase.
Tanaka K et al. Mol Cell Biol 2000 May;20(10):3459-69
PMID:34309513 - A Brownian ratchet model for DNA loop extrusion by the cohesin complex.
Higashi TL et al. Elife 2021 Jul 26;10
PMID:31072933 - Suppressor screening reveals common kleisin-hinge interaction in condensin and cohesin, but different modes of regulation.
Xu X et al. Proc Natl Acad Sci U S A 2019 May 28;116(22):10889-10898
PMID:19366728 - Genetic control of cellular quiescence in S. pombe.
Sajiki K et al. J Cell Sci 2009 May 01;122(Pt 9):1418-29
PMID:7865880 - Fission yeast minichromosome loss mutants mis cause lethal aneuploidy and replication abnormality.
Takahashi K et al. Mol Biol Cell 1994 Oct;5(10):1145-58
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: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:28438891 - A second Wpl1 anti-cohesion pathway requires dephosphorylation of fission yeast kleisin Rad21 by PP4.
Birot A et al. EMBO J 2017 May 15;36(10):1364-1378
PMID:32755595 - A Structure-Based Mechanism for DNA Entry into the Cohesin Ring.
Higashi TL et al. Mol Cell 2020 Sep 17;79(6):917-933.e9
PMID:18257517 - Phosphoproteome analysis of fission yeast.
Wilson-Grady JT et al. J Proteome Res 2008 Mar;7(3):1088-97
PMID:21189291 - Role for cohesin in the formation of a heterochromatic domain at fission yeast subtelomeres.
Dheur S et al. Mol Cell Biol 2011 Mar;31(5):1088-97
PMID:32277274 - Conserved roles of chromatin remodellers in cohesin loading onto chromatin.
Muñoz S et al. Curr Genet 2020 Oct;66(5):951-956
PMID:19454013 - Conserved features of cohesin binding along fission yeast chromosomes.
Schmidt CK et al. Genome Biol 2009;10(5):R52
PMID:39916665 - In quiescent G0 phase, Schizosaccharomyces pombe Mis4 ensures full nuclear separation during the subsequent M phase.
Suma M et al. J Cell Sci 2025 Feb 07;
PMID:21300781 - Psm3 acetylation on conserved lysine residues is dispensable for viability in fission yeast but contributes to Eso1-mediated sister chromatid cohesion by antagonizing Wpl1.
Feytout A et al. Mol Cell Biol 2011 Apr;31(8):1771-86
PMID:23163955 - Analysis of stress-induced duplex destabilization (SIDD) properties of replication origins, genes and intergenes in the fission yeast, Schizosaccharomyces pombe.
Yadav MP et al. BMC Res Notes 2012 Nov 19;5:643
PMID:24291789 - Biochemical reconstitution of topological DNA binding by the cohesin ring.
Murayama Y et al. Nature 2014 Jan 16;505(7483):367-71
PMID:27984725 - CDK Substrate Phosphorylation and Ordering the Cell Cycle.
Swaffer MP et al. Cell 2016 Dec 15;167(7):1750-1761.e16
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:16537923 - Sterol regulatory element binding protein is a principal regulator of anaerobic gene expression in fission yeast.
Todd BL et al. Mol Cell Biol 2006 Apr;26(7):2817-31
PMID:22144463 - RNA elimination machinery targeting meiotic mRNAs promotes facultative heterochromatin formation.
Zofall M et al. Science 2012 Jan 06;335(6064):96-100
PMID:33176147 - DNA Binding by the Mis4 Scc2 Loader Promotes Topological DNA Entrapment by the Cohesin Ring.
Kurokawa Y et al. Cell Rep 2020 Nov 10;33(6):108357
PMID:27298342 - Identification of S-phase DNA damage-response targets in fission yeast reveals conservation of damage-response networks.
Willis NA et al. Proc Natl Acad Sci U S A 2016 Jun 28;113(26):E3676-85
PMID:31895039 - The CDK Pef1 and protein phosphatase 4 oppose each other for regulating cohesin binding to fission yeast chromosomes.
Birot A et al. Elife 2020 Jan 02;9
PMID:18414064 - Schizosaccharomyces pombe Orc5 plays multiple roles in the maintenance of genome stability throughout the cell cycle.
Kato H et al. Cell Cycle 2008 Apr 15;7(8):1085-96
PMID:10398680 - Proper metaphase spindle length is determined by centromere proteins Mis12 and Mis6 required for faithful chromosome segregation.
Goshima G et al. Genes Dev 1999 Jul 01;13(13):1664-77
PMID:18079700 - Cell-cycle regulation of cohesin stability along fission yeast chromosomes.
Bernard P et al. EMBO J 2008 Jan 09;27(1):111-21
PMID:29358048 - Establishment of DNA-DNA Interactions by the Cohesin Ring.
Murayama Y et al. Cell 2018 Jan 25;172(3):465-477.e15
PMID:18354085 - Diminishing HDACs by drugs or mutations promotes normal or abnormal sister chromatid separation by affecting APC/C and adherin.
Kimata Y et al. J Cell Sci 2008 Apr 01;121(Pt 7):1107-18
PMID:38448160 - Phosphorylation of Rec8 cohesin complexes regulates mono-orientation of kinetochores in meiosis I.
Liu Y et al. Life Sci Alliance 2024 May;7(5)
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:16682348 - A screen for cohesion mutants uncovers Ssl3, the fission yeast counterpart of the cohesin loading factor Scc4.
Bernard P et al. Curr Biol 2006 May 09;16(9):875-81
PMID:40193710 - An enzymatic-independent function of palmitoyl hydrolase in cohesin loading onto chromosome.
Wang YT et al. Nucleic Acids Res 2025 Mar 20;53(6)
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