CUL4_SCHPO
ID CUL4_SCHPO Reviewed; 734 AA.
AC O14122; Q9USB6;
DT 20-JUN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Cullin-4;
DE Short=Cul-4;
GN Name=pcu4; Synonyms=cul4; ORFNames=SPAC3A11.08;
OS Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae;
OC Schizosaccharomyces.
OX NCBI_TaxID=284812;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=972 / ATCC 24843;
RX PubMed=9990507; DOI=10.1046/j.1365-2443.1998.00225.x;
RA Kominami K., Ochotorena I., Toda T.;
RT "Two F-box/WD-repeat proteins Pop1 and Pop2 form hetero- and homo-complexes
RT together with cullin-1 in fission yeast SCF (Skip-cullin-1-F-box) ubiquitin
RT ligase.";
RL Genes Cells 3:721-735(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=972 / ATCC 24843;
RX PubMed=11859360; DOI=10.1038/nature724;
RA Wood V., Gwilliam R., Rajandream M.A., Lyne M.H., Lyne R., Stewart A.,
RA Sgouros J.G., Peat N., Hayles J., Baker S.G., Basham D., Bowman S.,
RA Brooks K., Brown D., Brown S., Chillingworth T., Churcher C.M., Collins M.,
RA Connor R., Cronin A., Davis P., Feltwell T., Fraser A., Gentles S.,
RA Goble A., Hamlin N., Harris D.E., Hidalgo J., Hodgson G., Holroyd S.,
RA Hornsby T., Howarth S., Huckle E.J., Hunt S., Jagels K., James K.D.,
RA Jones L., Jones M., Leather S., McDonald S., McLean J., Mooney P.,
RA Moule S., Mungall K.L., Murphy L.D., Niblett D., Odell C., Oliver K.,
RA O'Neil S., Pearson D., Quail M.A., Rabbinowitsch E., Rutherford K.M.,
RA Rutter S., Saunders D., Seeger K., Sharp S., Skelton J., Simmonds M.N.,
RA Squares R., Squares S., Stevens K., Taylor K., Taylor R.G., Tivey A.,
RA Walsh S.V., Warren T., Whitehead S., Woodward J.R., Volckaert G., Aert R.,
RA Robben J., Grymonprez B., Weltjens I., Vanstreels E., Rieger M.,
RA Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Duesterhoeft A.,
RA Fritzc C., Holzer E., Moestl D., Hilbert H., Borzym K., Langer I., Beck A.,
RA Lehrach H., Reinhardt R., Pohl T.M., Eger P., Zimmermann W., Wedler H.,
RA Wambutt R., Purnelle B., Goffeau A., Cadieu E., Dreano S., Gloux S.,
RA Lelaure V., Mottier S., Galibert F., Aves S.J., Xiang Z., Hunt C.,
RA Moore K., Hurst S.M., Lucas M., Rochet M., Gaillardin C., Tallada V.A.,
RA Garzon A., Thode G., Daga R.R., Cruzado L., Jimenez J., Sanchez M.,
RA del Rey F., Benito J., Dominguez A., Revuelta J.L., Moreno S.,
RA Armstrong J., Forsburg S.L., Cerutti L., Lowe T., McCombie W.R.,
RA Paulsen I., Potashkin J., Shpakovski G.V., Ussery D., Barrell B.G.,
RA Nurse P.;
RT "The genome sequence of Schizosaccharomyces pombe.";
RL Nature 415:871-880(2002).
RN [3]
RP PARTIAL PROTEIN SEQUENCE, FUNCTION, IDENTIFICATION IN THE RIK1-ASSOCIATED
RP E3 UBIQUITIN LIGASE COMPLEX, AND MUTAGENESIS OF LYS-680.
RX PubMed=16024659; DOI=10.1101/gad.1328005;
RA Horn P.J., Bastie J.-N., Peterson C.L.;
RT "A Rik1-associated, cullin-dependent E3 ubiquitin ligase is essential for
RT heterochromatin formation.";
RL Genes Dev. 19:1705-1714(2005).
RN [4]
RP PROTEIN SEQUENCE OF 180-195; 223-241; 321-340 AND 591-601, FUNCTION, AND
RP INTERACTION WITH CLR4 AND RIK1.
RX PubMed=16127433; DOI=10.1038/ncb1300;
RA Jia S., Kobayashi R., Grewal S.I.S.;
RT "Ubiquitin ligase component Cul4 associates with Clr4 histone
RT methyltransferase to assemble heterochromatin.";
RL Nat. Cell Biol. 7:1007-1013(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] OF 186-412, AND SUBCELLULAR
RP LOCATION.
RC STRAIN=ATCC 38364 / 968;
RX PubMed=10759889; DOI=10.1046/j.1365-2443.2000.00317.x;
RA Ding D.-Q., Tomita Y., Yamamoto A., Chikashige Y., Haraguchi T.,
RA Hiraoka Y.;
RT "Large-scale screening of intracellular protein localization in living
RT fission yeast cells by the use of a GFP-fusion genomic DNA library.";
RL Genes Cells 5:169-190(2000).
RN [6]
RP FUNCTION.
RX PubMed=12695334; DOI=10.1101/gad.1090803;
RA Liu C., Powell K.A., Mundt K., Wu L., Carr A.M., Caspari T.;
RT "Cop9/signalosome subunits and Pcu4 regulate ribonucleotide reductase by
RT both checkpoint-dependent and -independent mechanisms.";
RL Genes Dev. 17:1130-1140(2003).
RN [7]
RP INTERACTION WITH RAF2.
RX PubMed=16157682; DOI=10.1534/genetics.105.048298;
RA Thon G., Hansen K.R., Altes S.P., Sidhu D., Singh G., Verhein-Hansen J.,
RA Bonaduce M.J., Klar A.J.;
RT "The Clr7 and Clr8 directionality factors and the Pcu4 cullin mediate
RT heterochromatin formation in the fission yeast Schizosaccharomyces pombe.";
RL Genetics 171:1583-1595(2005).
RN [8]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=16823372; DOI=10.1038/nbt1222;
RA Matsuyama A., Arai R., Yashiroda Y., Shirai A., Kamata A., Sekido S.,
RA Kobayashi Y., Hashimoto A., Hamamoto M., Hiraoka Y., Horinouchi S.,
RA Yoshida M.;
RT "ORFeome cloning and global analysis of protein localization in the fission
RT yeast Schizosaccharomyces pombe.";
RL Nat. Biotechnol. 24:841-847(2006).
RN [9]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18345014; DOI=10.1038/nsmb.1406;
RA Zhang K., Mosch K., Fischle W., Grewal S.I.;
RT "Roles of the Clr4 methyltransferase complex in nucleation, spreading and
RT maintenance of heterochromatin.";
RL Nat. Struct. Mol. Biol. 15:381-388(2008).
RN [10]
RP FUNCTION.
RX PubMed=31468675; DOI=10.15252/embr.201948111;
RA Oya E., Nakagawa R., Yoshimura Y., Tanaka M., Nishibuchi G., Machida S.,
RA Shirai A., Ekwall K., Kurumizaka H., Tagami H., Nakayama J.I.;
RT "H3K14 ubiquitylation promotes H3K9 methylation for heterochromatin
RT assembly.";
RL EMBO Rep. 20:E48111-E48111(2019).
CC -!- FUNCTION: Required, indirectly, for activation of ribonucleotide
CC reductase through the degradation of the protein spd1, thereby
CC supplying deoxyribonucleotides for DNA replication and repair. Also has
CC a role as a scaffold for assembling ubiquitin ligases
CC (PubMed:12695334). Component of the Clr4 methyltransferase complex
CC (ClrC) which contributes to the establishment of heterochromatin by
CC specifically methylating histone H3 to form H3K9me (PubMed:16024659,
CC PubMed:16127433, PubMed:18345014). ClrC preferentially ubiquitylates
CC H3K14 and ClrC-mediated H3 ubiquitination promotes clr4
CC methyltransferase activity for the methylation of H3K9
CC (PubMed:31468675). H3K9me represents a specific tag for epigenetic
CC transcriptional repression by recruiting swi6/HP1 to methylated
CC histones which leads to transcriptional silencing within centromeric
CC heterochromatin, telomeric regions and at the silent mating-type loci
CC (PubMed:16024659). {ECO:0000269|PubMed:12695334,
CC ECO:0000269|PubMed:16024659, ECO:0000269|PubMed:16127433,
CC ECO:0000269|PubMed:18345014, ECO:0000269|PubMed:31468675}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Component of the Clr4 methyltransferase complex (ClrC)
CC composed of at least clr4, rik1, pcu4, rbx1, raf1 and raf2. The cullin
CC pcu4, rik1, raf1, raf2 and the ring-box protein rbx1 are components of
CC an E3 ubiquitin ligase, whose activity is essential for heterochromatin
CC assembly. {ECO:0000269|PubMed:16024659, ECO:0000269|PubMed:16127433}.
CC -!- INTERACTION:
CC O14122; O60016: clr4; NbExp=3; IntAct=EBI-904890, EBI-354657;
CC O14122; Q10426: rik1; NbExp=3; IntAct=EBI-904890, EBI-1111936;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16823372}. Nucleus
CC {ECO:0000269|PubMed:16823372, ECO:0000269|PubMed:18345014}. Chromosome
CC {ECO:0000269|PubMed:18345014}.
CC -!- PTM: Neddylated; enhancing the ubiquitin-ligase activity.
CC {ECO:0000250|UniProtKB:P47050}.
CC -!- SIMILARITY: Belongs to the cullin family. {ECO:0000255|PROSITE-
CC ProRule:PRU00330}.
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DR EMBL; CU329670; CAB16383.1; -; Genomic_DNA.
DR EMBL; AB017029; BAA32520.1; -; Genomic_DNA.
DR EMBL; AB027893; BAA87197.1; -; Genomic_DNA.
DR PIR; T43408; T43408.
DR RefSeq; NP_594195.1; NM_001019619.2.
DR AlphaFoldDB; O14122; -.
DR SMR; O14122; -.
DR BioGRID; 279548; 15.
DR IntAct; O14122; 7.
DR STRING; 4896.SPAC3A11.08.1; -.
DR iPTMnet; O14122; -.
DR MaxQB; O14122; -.
DR PaxDb; O14122; -.
DR PRIDE; O14122; -.
DR EnsemblFungi; SPAC3A11.08.1; SPAC3A11.08.1:pep; SPAC3A11.08.
DR GeneID; 2543116; -.
DR KEGG; spo:SPAC3A11.08; -.
DR PomBase; SPAC3A11.08; pcu4.
DR VEuPathDB; FungiDB:SPAC3A11.08; -.
DR eggNOG; KOG2167; Eukaryota.
DR HOGENOM; CLU_004747_7_0_1; -.
DR InParanoid; O14122; -.
DR OMA; WPTYPVM; -.
DR PhylomeDB; O14122; -.
DR Reactome; R-SPO-110314; Recognition of DNA damage by PCNA-containing replication complex.
DR Reactome; R-SPO-5696395; Formation of Incision Complex in GG-NER.
DR Reactome; R-SPO-5696400; Dual Incision in GG-NER.
DR Reactome; R-SPO-6781823; Formation of TC-NER Pre-Incision Complex.
DR Reactome; R-SPO-6782135; Dual incision in TC-NER.
DR Reactome; R-SPO-6782210; Gap-filling DNA repair synthesis and ligation in TC-NER.
DR Reactome; R-SPO-8951664; Neddylation.
DR UniPathway; UPA00143; -.
DR PRO; PR:O14122; -.
DR Proteomes; UP000002485; Chromosome I.
DR GO; GO:0000781; C:chromosome, telomeric region; IEA:GOC.
DR GO; GO:0043494; C:CLRC complex; IDA:PomBase.
DR GO; GO:0080008; C:Cul4-RING E3 ubiquitin ligase complex; EXP:PomBase.
DR GO; GO:0031461; C:cullin-RING ubiquitin ligase complex; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; HDA:PomBase.
DR GO; GO:0005634; C:nucleus; HDA:PomBase.
DR GO; GO:0005721; C:pericentric heterochromatin; TAS:PomBase.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IBA:GO_Central.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IBA:GO_Central.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IBA:GO_Central.
DR GO; GO:0031048; P:heterochromatin assembly by small RNA; IMP:PomBase.
DR GO; GO:0033621; P:nuclear-transcribed mRNA catabolic process, meiosis-specific transcripts; IGI:PomBase.
DR GO; GO:0031508; P:pericentric heterochromatin assembly; IMP:PomBase.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0030466; P:silent mating-type cassette heterochromatin assembly; IMP:PomBase.
DR GO; GO:0031509; P:subtelomeric heterochromatin assembly; IMP:PomBase.
DR GO; GO:0006283; P:transcription-coupled nucleotide-excision repair; IMP:PomBase.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR033044; CUL4B.
DR InterPro; IPR045093; Cullin.
DR InterPro; IPR016157; Cullin_CS.
DR InterPro; IPR016158; Cullin_homology.
DR InterPro; IPR036317; Cullin_homology_sf.
DR InterPro; IPR001373; Cullin_N.
DR InterPro; IPR019559; Cullin_neddylation_domain.
DR InterPro; IPR016159; Cullin_repeat-like_dom_sf.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR PANTHER; PTHR11932; PTHR11932; 1.
DR PANTHER; PTHR11932:SF66; PTHR11932:SF66; 1.
DR Pfam; PF00888; Cullin; 1.
DR Pfam; PF10557; Cullin_Nedd8; 1.
DR SMART; SM00182; CULLIN; 1.
DR SMART; SM00884; Cullin_Nedd8; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF74788; SSF74788; 1.
DR SUPFAM; SSF75632; SSF75632; 1.
DR PROSITE; PS01256; CULLIN_1; 1.
DR PROSITE; PS50069; CULLIN_2; 1.
PE 1: Evidence at protein level;
KW Chromatin regulator; Chromosome; Cytoplasm; Direct protein sequencing;
KW Isopeptide bond; Nucleus; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..734
FT /note="Cullin-4"
FT /id="PRO_0000119810"
FT CROSSLNK 680
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in NEDD8)"
FT /evidence="ECO:0000250|UniProtKB:Q13616"
FT MUTAGEN 680
FT /note="K->R: Increase in H3-K4 methylation within
FT heterochromatin."
FT /evidence="ECO:0000269|PubMed:16024659"
SQ SEQUENCE 734 AA; 85330 MW; E90FFFE06D071C3E CRC64;
MPPEAKRIVV KGFDPRKSRQ RQETYYVTMI DRLNMALQVV MAGLGLKTGY QELYSGVENL
TRADQASRCF NILQHHMSSG IQLLKDSAES FIQLEGTETD TNACTVVVGC WNKWLERVEI
VQNIFYYMDK TFLSHHPDYP TIEELSLSLF REKLMAVKNI QIPFLNSLLQ SFENLHSSKS
TDHAYLQDAM LMLHRTEMYS SVFVPMYLVM LSRFYDTESS QKIQELPLEE YLEYAMSSLE
REDAYVEKFD IVRDKKSIRE TVQRCLITSH LDTLTKGISQ FIEKRDAHSC KLLYALLQFN
HETEYLIQPW SDCLVDVGFK LVNDESKDDT LVQELLSFHK FLQVVVDESF LHDETLSYAM
RKAFETFING AKGSQREAPA RLIAKYIDYL LRVGEQASGG KPLKEVFSEI LDLFRYIASK
DIFEAYYKLD IAKRLLLNKS ASAQNELMLL DMLKKTCGSQ FTHSLEGMFR DVNISKEFTS
SFRHSKAAHN LHRDLYVNVL SQAYWPSYPE SHIRLPDDMQ QDLDCFEKFY LSKQVGKKIS
WYASLGHCIV KARFPLGNKE LSISLFQACV LLQFNNCLGG EGISYQDLKK STELSDIDLT
RTLQSLSCAR IRPLVMVPKS KKPSPDTMFY VNEKFTDKLY RVKINQIYLK EERQENSDVQ
EQVVRDRQFE LQASIVRVMK QKEKMKHDDL VQYVINNVKD RGIPLVSDVK TAIEKLLEKE
YLEREDNDIY TYVT
