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protein coding gene - cul4 (SPAC3A11.08) - CLRC complex subunit, cullin 4

Gene summary

Standard name
cul4
Systematic ID
SPAC3A11.08
Product
CLRC complex subunit, cullin 4
Organism
Schizosaccharomyces pombe (fission yeast)
Synonyms
pcu4, Cul-4
UniProt ID
O14122
ORFeome ID
37/37H12
Characterisation status
biological role published
Feature type
mRNA gene
Genomic location
chromosome I: 3452945..3455747 forward strand

Annotation

Disease association

MONDO:0010306 - X-linked intellectual disability, Cabezas type

References:

GO biological process

GO:0033621 - nuclear mRNA surveillance of meiosis-specific transcripts

References:

GO:0031508 - pericentric heterochromatin formation

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GO:0043161 - proteasome-mediated ubiquitin-dependent protein catabolic process

References:

GO:0030466 - silent mating-type cassette heterochromatin formation

References:

GO:0140727 - siRNA-mediated pericentric heterochromatin formation

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GO:0031509 - subtelomeric heterochromatin formation

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GO:0006283 - transcription-coupled nucleotide-excision repair

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GO cellular component

GO:0043494 - CLRC complex

References:

GO:0080008 - Cul4-RING E3 ubiquitin ligase complex

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GO:0005737 - cytoplasm

References:

GO:0005829 - cytosol

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GO:0031934 - mating-type region heterochromatin

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GO:0005634 - nucleus

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GO:0005721 - pericentric heterochromatin

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GO:0140720 - subtelomeric heterochromatin

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GO molecular function

GO:0160072 - ubiquitin ligase complex scaffold activity

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GO:0031625 - ubiquitin protein ligase binding

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Modification

MOD:00046 - O-phospho-L-serine

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Multi-locus phenotype

FYPO:0007334 - abolished chromatin silencing at centromere outer repeat

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Genotypes:

FYPO:0004745 - abolished histone H3-K9 dimethylation at centromere outer repeat during vegetative growth

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Genotypes:

FYPO:0005850 - abolished protein localization to heterochromatin at centromere outer repeat

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Genotypes:

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

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Genotypes:

FYPO:0002768 - decreased protein ubiquitination during vegetative growth

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Genotypes:

FYPO:0001355 - decreased vegetative cell population growth

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Genotypes:

FYPO:0002331 - increased histone H3-K4 dimethylation at centromere outer repeat during vegetative growth

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Genotypes:

FYPO:0007226 - normal chromatin silencing at heterochromatin island

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Genotypes:

FYPO:0007281 - normal level of meiotic gene mRNA during vegetative growth

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Genotypes:

FYPO:0000833 - normal protein level during vegetative growth

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Genotypes:

FYPO:0000085 - sensitive to camptothecin

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Genotypes:

FYPO:0000089 - sensitive to methyl methanesulfonate

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Genotypes:

Quantitative gene expression

PBO:0006310 - protein level

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PBO:0011963 - RNA level

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Single locus phenotype

FYPO:0000159 - abnormal chromosome condensation

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Genotypes:

FYPO:0000468 - abnormal mating type switching

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Genotypes:

FYPO:0000059 - abnormal mitotic cell cycle

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Genotypes:

FYPO:0000216 - abnormal negative regulation of mitotic DNA replication initiation

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Genotypes:

FYPO:0007334 - abolished chromatin silencing at centromere outer repeat

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Genotypes:

FYPO:0007336 - abolished chromatin silencing at silent mating-type cassette

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Genotypes:

FYPO:0006112 - abolished histone H3-K9 dimethylation at silent mating-type cassette during vegetative growth

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Genotypes:

FYPO:0008208 - abolished protein neddylation during vegetative growth

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Genotypes:

FYPO:0009078 - decreased cell population growth on ethanol carbon source

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Genotypes:

FYPO:0009053 - decreased cell population growth on glutamate nitrogen source

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Genotypes:

FYPO:0009100 - decreased cell population growth on glycerol and galactose carbon source

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Genotypes:

FYPO:0000684 - decreased cell population growth on glycerol carbon source

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Genotypes:

FYPO:0009091 - decreased cell population growth on lysine and proline nitrogen source

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Genotypes:

FYPO:0002924 - decreased cell population growth on maltose carbon source

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Genotypes:

FYPO:0009099 - decreased cell population growth on mannitol carbon source

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Genotypes:

FYPO:0001176 - decreased cell population growth on sucrose carbon source

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Genotypes:

FYPO:0002834 - decreased chromatin silencing at centromere

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Genotypes:

FYPO:0006993 - decreased chromatin silencing at centromere otr1R

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Genotypes:

FYPO:0003412 - decreased chromatin silencing at centromere outer repeat

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Genotypes:

FYPO:0002827 - decreased chromatin silencing at silent mating-type cassette

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Genotypes:

FYPO:0004604 - decreased chromatin silencing at subtelomere

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Genotypes:

FYPO:0000888 - decreased histone H3-K9 dimethylation at centromere outer repeat during vegetative growth

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Genotypes:

FYPO:0002355 - decreased histone H3-K9 dimethylation at silent mating-type cassette during vegetative growth

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Genotypes:

FYPO:0004137 - decreased histone H3-K9 dimethylation at subtelomeric heterochromatin during vegetative growth

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Genotypes:

FYPO:0003573 - decreased protein localization to heterochromatin at silent mating-type cassette

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Genotypes:

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

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Genotypes:

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

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Genotypes:

FYPO:0004085 - decreased vegetative cell growth

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Genotypes:

FYPO:0001355 - decreased vegetative cell population growth

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Genotypes:

FYPO:0001122 - elongated vegetative cell

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Genotypes:

FYPO:0005261 - increased cell population growth on galactose carbon source

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Genotypes:

FYPO:0009028 - increased cell population growth on proline nitrogen source

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Genotypes:

FYPO:0002836 - increased centromeric outer repeat transcript-derived siRNA level

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Genotypes:

FYPO:0002331 - increased histone H3-K4 dimethylation at centromere outer repeat during vegetative growth

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Genotypes:

FYPO:0005063 - increased histone H3-K4 methylation at mating type locus during vegetative growth

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Genotypes:

FYPO:0001861 - increased minichromosome loss upon segregation during vegetative growth

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Genotypes:

FYPO:0003152 - increased protein level during cellular response to heat

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Genotypes:

FYPO:0001327 - increased protein level during vegetative growth

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Genotypes:

FYPO:0004237 - increased protein localization to heterochromatin at centromere outer repeat region

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Genotypes:

FYPO:0004377 - increased protein localization to heterochromatin at silent mating-type cassette

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Genotypes:

FYPO:0003529 - inviable after spore germination, multiple cell divisions, cell cycle arrest in mitotic interphase, elongated cells

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Genotypes:

FYPO:0002113 - inviable curved vegetative cell

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Genotypes:

FYPO:0002061 - inviable vegetative cell population

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Genotypes:

FYPO:0000228 - lagging mitotic chromosomes

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Genotypes:

FYPO:0000245 - loss of viability in stationary phase

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Genotypes:

FYPO:0002800 - normal protein degradation during vegetative growth

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Genotypes:

FYPO:0000833 - normal protein level during vegetative growth

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Genotypes:

FYPO:0002389 - normal protein localization to heterochromatin at centromere outer repeat

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Genotypes:

FYPO:0000703 - normal protein-protein interaction

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Genotypes:

FYPO:0001357 - normal vegetative cell population growth

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Genotypes:

FYPO:0009079 - resistance to calcofluor and sodium dodecyl sulfate

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Genotypes:

FYPO:0009085 - resistance to lithium chloride and sodium dodecyl sulfate

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Genotypes:

FYPO:0000077 - resistance to rapamycin

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Genotypes:

FYPO:0005968 - resistance to sodium chloride

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Genotypes:

FYPO:0007933 - sensitive to 2,2′-dipyridyl

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Genotypes:

FYPO:0001501 - sensitive to brefeldin A

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Genotypes:

FYPO:0000097 - sensitive to caffeine during vegetative growth

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Genotypes:

FYPO:0000085 - sensitive to camptothecin

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Genotypes:

FYPO:0000104 - sensitive to cycloheximide

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Genotypes:

FYPO:0000799 - sensitive to diamide

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Genotypes:

FYPO:0007931 - sensitive to egtazic acid

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Genotypes:

FYPO:0000842 - sensitive to ethanol during vegetative growth

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Genotypes:

FYPO:0007928 - sensitive to ethylenediaminetetraacetic acid

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Genotypes:

FYPO:0003858 - sensitive to etoposide

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Genotypes:

FYPO:0000785 - sensitive to formamide

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Genotypes:

FYPO:0000087 - sensitive to hydrogen peroxide

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Genotypes:

FYPO:0000088 - sensitive to hydroxyurea

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Genotypes:

FYPO:0009071 - sensitive to itraconazole

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Genotypes:

FYPO:0001719 - sensitive to lithium

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Genotypes:

FYPO:0009086 - sensitive to lithium chloride and sodium dodecyl sulfate

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Genotypes:

FYPO:0006836 - sensitive to magnesium chloride

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Genotypes:

FYPO:0009088 - sensitive to magnesium chloride and sodium dodecyl sulfate

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Genotypes:

FYPO:0000089 - sensitive to methyl methanesulfonate

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Genotypes:

FYPO:0001214 - sensitive to potassium chloride

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Genotypes:

FYPO:0009082 - sensitive to potassium chloride and methyl methanesulfonate

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Genotypes:

FYPO:0007924 - sensitive to potassium chloride and sodium dodecyl sulfate

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Genotypes:

FYPO:0000797 - sensitive to tert-butyl hydroperoxide

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Genotypes:

FYPO:0002701 - sensitive to torin1

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Genotypes:

FYPO:0000115 - sensitive to valproic acid

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Genotypes:

FYPO:0003656 - sensitive to vanadate

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Genotypes:

FYPO:0009064 - sensitive to X-rays and rapamycin during vegetative growth.

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Genotypes:

FYPO:0001491 - viable vegetative cell

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Genotypes:

FYPO:0002060 - viable vegetative cell population

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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:0000055 - no apparent S. cerevisiae ortholog

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

Protein features

IDNameInterPro nameDB name
PF00888CullinCullin_NPfam
PF10557Cullin_Nedd8Cullin_neddylation_domainPfam
PF26557Cullin_ABCullin-like_ABPfam
PS01256CULLIN_1Cullin_CSPROSITE patterns
PS50069CULLIN_2Cullin_homologyPROSITE profiles
SM00182CULLINCullin_homologySMART
SM00884Cullin_Nedd8Cullin_neddylation_domainSMART
G3DSA:1.10.10.10:FF:000014CATH-FunFam
G3DSA:1.20.1310.10:FF:000055CATH-FunFam
G3DSA:1.10.10.10WH-like_DNA-bd_sfCATH-Gene3D
G3DSA:1.20.1310.10CATH-Gene3D
G3DSA:3.30.230.130CATH-Gene3D
SSF46785WH_DNA-bd_sfSUPERFAMILY
SSF74788Cullin_repeat-like_dom_sfSUPERFAMILY
SSF75632Cullin_homology_sfSUPERFAMILY
PTHR11932CullinPANTHER

Orthologs

References / Literature

PMID:31468675 - H3K14 ubiquitylation promotes H3K9 methylation for heterochromatin assembly.
Oya E et al. EMBO Rep 2019 Oct 04;20(10):e48111
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:34250083 - Barcode sequencing and a high-throughput assay for chronological lifespan uncover ageing-associated genes in fission yeast.
Romila CA et al. Microb Cell 2021 Jul 05;8(7):146-160
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: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:24449894 - CRL4-like Clr4 complex in Schizosaccharomyces pombe depends on an exposed surface of Dos1 for heterochromatin silencing.
Kuscu C et al. Proc Natl Acad Sci U S A 2014 Feb 04;111(5):1795-800
PMID:28228545 - Ablation of RNA interference and retrotransposons accompany acquisition and evolution of transposases to heterochromatin protein CENPB.
Upadhyay U et al. Mol Biol Cell 2017 Apr 15;28(8):1132-1146
PMID:10880460 - Covalent modifier NEDD8 is essential for SCF ubiquitin-ligase in fission yeast.
Osaka F et al. EMBO J 2000 Jul 03;19(13):3475-84
PMID:10759889 - Large-scale screening of intracellular protein localization in living fission yeast cells by the use of a GFP-fusion genomic DNA library.
Ding DQ et al. Genes Cells 2000 Mar;5(3):169-90
PB_REF:0000006 - Disease associations from Monarch via human-pombe orthologs
PMID:18957202 - Lid2 is required for coordinating H3K4 and H3K9 methylation of heterochromatin and euchromatin.
Li F et al. Cell 2008 Oct 17;135(2):272-83
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:21511999 - Comparative functional genomics of the fission yeasts.
Rhind N et al. Science 2011 May 20;332(6032):930-6
PMID:18794354 - Schizosaccharomyces pombe Ddb1 recruits substrate-specific adaptor proteins through a novel protein motif, the DDB-box.
Fukumoto Y et al. Mol Cell Biol 2008 Nov;28(22):6746-56
PMID:16252005 - Transactivation of Schizosaccharomyces pombe cdt2+ stimulates a Pcu4-Ddb1-CSN ubiquitin ligase.
Liu C et al. EMBO J 2005 Nov 16;24(22):3940-51
PMID:21183410 - Schizosaccharomyces pombe Mms1 channels repair of perturbed replication into Rhp51 independent homologous recombination.
Vejrup-Hansen R et al. DNA Repair (Amst) 2011 Mar 07;10(3):283-95
PMID:17114925 - A cullin E3 ubiquitin ligase complex associates with Rik1 and the Clr4 histone H3-K9 methyltransferase and is required for RNAi-mediated heterochromatin formation.
Hong EJ et al. RNA Biol 2005;2(3):106-11
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:33574613 - TOR targets an RNA processing network to regulate facultative heterochromatin, developmental gene expression and cell proliferation.
Wei Y et al. Nat Cell Biol 2021 Mar;23(3):243-256
PMID:15769255 - Nep1, a Schizosaccharomyces pombe deneddylating enzyme.
Zhou L et al. Biochem J 2005 Jul 15;389(Pt 2):307-14
PMID:25090107 - The RFTS domain of Raf2 is required for Cul4 interaction and heterochromatin integrity in fission yeast.
White SA et al. PLoS One 2014;9(8):e104161
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:27168121 - Discovery of genes involved in mitosis, cell division, cell wall integrity and chromosome segregation through construction of Schizosaccharomyces pombe deletion strains.
Chen JS et al. Yeast 2016 Sep;33(9):507-17
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:38181050 - The Cross-Regulation Between Set1, Clr4, and Lsd1/2 in Schizosaccharomyces pombe.
Liu H et al. PLoS Genet 2024 Jan 05;20(1):e1011107
PMID:15805471 - Ddb1 controls genome stability and meiosis in fission yeast.
Holmberg C et al. Genes Dev 2005 Apr 01;19(7):853-62
PMID:24713849 - Post-transcriptional regulation of meiotic genes by a nuclear RNA silencing complex.
Egan ED et al. RNA 2014 Jun;20(6):867-81
PMID:16157682 - The Clr7 and Clr8 directionality factors and the Pcu4 cullin mediate heterochromatin formation in the fission yeast Schizosaccharomyces pombe.
Thon G et al. Genetics 2005 Dec;171(4):1583-95
PMID:18345014 - Roles of the Clr4 methyltransferase complex in nucleation, spreading and maintenance of heterochromatin.
Zhang K et al. Nat Struct Mol Biol 2008 Apr;15(4):381-8
PMID:16127433 - Ubiquitin ligase component Cul4 associates with Clr4 histone methyltransferase to assemble heterochromatin.
Jia S et al. Nat Cell Biol 2005 Oct;7(10):1007-13
GO_REF:0000033 - Annotation inferences using phylogenetic trees
PMID:20211136 - Stc1: a critical link between RNAi and chromatin modification required for heterochromatin integrity.
Bayne EH et al. Cell 2010 Mar 05;140(5):666-77
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:16024659 - A Rik1-associated, cullin-dependent E3 ubiquitin ligase is essential for heterochromatin formation.
Horn PJ et al. Genes Dev 2005 Jul 15;19(14):1705-14
PMID:21060862 - Continuous requirement for the Clr4 complex but not RNAi for centromeric heterochromatin assembly in fission yeast harboring a disrupted RITS complex.
Shanker S et al. PLoS Genet 2010 Oct 28;6(10):e1001174
PMID:26988418 - The proper connection between shelterin components is required for telomeric heterochromatin assembly.
Wang J et al. Genes Dev 2016 Apr 01;30(7):827-39
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:21340088 - Microarray-based target identification using drug hypersensitive fission yeast expressing ORFeome.
Arita Y et al. Mol Biosyst 2011 May;7(5):1463-72
PMID:27098497 - CRL4(Wdr70) regulates H2B monoubiquitination and facilitates Exo1-dependent resection.
Zeng M et al. Nat Commun 2016 Apr 21;7:11364
PMID:27538348 - Set3 contributes to heterochromatin integrity by promoting transcription of subunits of Clr4-Rik1-Cul4 histone methyltransferase complex in fission yeast.
Yu Y et al. Sci Rep 2016 Aug 19;6:31752