ID PHC2_MOUSE Reviewed; 850 AA.
AC Q9QWH1; B1AS98; B1ASA4; O88463; Q8K5D9;
DT 10-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 27-MAR-2024, entry version 180.
DE RecName: Full=Polyhomeotic-like protein 2;
DE Short=mPH2;
DE AltName: Full=Early development regulatory protein 2;
DE AltName: Full=p36;
GN Name=Phc2; Synonyms=Edr2, Ph2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), DOMAIN HD1 MOTIF, AND TISSUE
RP SPECIFICITY.
RX PubMed=12034499; DOI=10.1016/s0378-1119(02)00458-4;
RA Yamaki M., Isono K., Takada Y., Abe K., Akasaka T., Tanzawa H., Koseki H.;
RT "The mouse Edr2 (Mph2) gene has two forms of mRNA encoding 90- and 36-kDa
RT polypeptides.";
RL Gene 288:103-110(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=NIH Swiss;
RA Howard T.L., Ingermann A.R., Hollenberg S.M.;
RT "The basic helix-loop-helix protein Th1 interacts with polycomb-group
RT proteins.";
RL Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Brain, and Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 419-850 (ISOFORM 1), AND INTERACTION WITH
RP BMI1 AND RNF2.
RX PubMed=9627119; DOI=10.1038/sj.onc.1202042;
RA Hemenway C.S., Halligan B.W., Levy L.S.;
RT "The Bmi-1 oncoprotein interacts with dinG and MPh2: the role of RING
RT finger domains.";
RL Oncogene 16:2541-2547(1998).
RN [6]
RP DEVELOPMENTAL STAGE.
RX PubMed=15580621; DOI=10.1002/dvdy.20213;
RA Kim M.H., Gunnersen J.M., Tan S.S.;
RT "Mph2 expression in germinal zones of the mouse brain.";
RL Dev. Dyn. 232:209-215(2005).
RN [7]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INTERACTION WITH PCGF2; PHC1 AND RNF2.
RX PubMed=16024804; DOI=10.1128/mcb.25.15.6694-6706.2005;
RA Isono K., Fujimura Y., Shinga J., Yamaki M., O-Wang J., Takihara Y.,
RA Murahashi Y., Takada Y., Mizutani-Koseki Y., Koseki H.;
RT "Mammalian polyhomeotic homologues Phc2 and Phc1 act in synergy to mediate
RT polycomb repression of Hox genes.";
RL Mol. Cell. Biol. 25:6694-6706(2005).
RN [8]
RP INTERACTION WITH CHTOP.
RX PubMed=22872859; DOI=10.1074/mcp.m112.017194;
RA Fanis P., Gillemans N., Aghajanirefah A., Pourfarzad F., Demmers J.,
RA Esteghamat F., Vadlamudi R.K., Grosveld F., Philipsen S., van Dijk T.B.;
RT "Five friends of methylated chromatin target of protein-arginine-
RT methyltransferase[prmt]-1 (chtop), a complex linking arginine methylation
RT to desumoylation.";
RL Mol. Cell. Proteomics 11:1263-1273(2012).
RN [9] {ECO:0007744|PDB:2NA1}
RP STRUCTURE BY NMR OF 557-590 IN COMPLEX WITH BMI1.
RX PubMed=27827373; DOI=10.1038/ncomms13343;
RA Gray F., Cho H.J., Shukla S., He S., Harris A., Boytsov B., Jaremko L.,
RA Jaremko M., Demeler B., Lawlor E.R., Grembecka J., Cierpicki T.;
RT "BMI1 regulates PRC1 architecture and activity through homo- and hetero-
RT oligomerization.";
RL Nat. Commun. 7:13343-13343(2016).
CC -!- FUNCTION: Component of a Polycomb group (PcG) multiprotein PRC1-like
CC complex, a complex class required to maintain the transcriptionally
CC repressive state of many genes, including Hox genes, throughout
CC development. PcG PRC1 complex acts via chromatin remodeling and
CC modification of histones; it mediates monoubiquitination of histone H2A
CC 'Lys-119', rendering chromatin heritably changed in its expressibility.
CC {ECO:0000269|PubMed:16024804}.
CC -!- SUBUNIT: Component of a PRC1-like complex. Interacts with CBX4 (By
CC similarity). Interacts with BMI1, PCGF2, PHC1 and RNF2 (PubMed:9627119,
CC PubMed:16024804, PubMed:27827373). Interacts with CHTOP
CC (PubMed:22872859). Interacts with the N-terminal region of the SP1
CC transcription factor and with MAPKAPK2 (By similarity).
CC {ECO:0000250|UniProtKB:Q8IXK0, ECO:0000269|PubMed:16024804,
CC ECO:0000269|PubMed:22872859, ECO:0000269|PubMed:27827373,
CC ECO:0000269|PubMed:9627119}.
CC -!- INTERACTION:
CC Q9QWH1; P25916: Bmi1; NbExp=3; IntAct=EBI-642357, EBI-927401;
CC Q9QWH1; P49138: Mapkapk2; NbExp=5; IntAct=EBI-642357, EBI-298776;
CC Q9QWH1; P23798: Pcgf2; NbExp=5; IntAct=EBI-642357, EBI-926857;
CC Q9QWH1; Q64028: Phc1; NbExp=2; IntAct=EBI-642357, EBI-927346;
CC Q9QWH1; O35730: Ring1; NbExp=2; IntAct=EBI-642357, EBI-929310;
CC Q9QWH1; Q9CQJ4: Rnf2; NbExp=7; IntAct=EBI-642357, EBI-927321;
CC Q9QWH1; P49137: MAPKAPK2; Xeno; NbExp=2; IntAct=EBI-642357, EBI-993299;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q8IXK0}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9QWH1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9QWH1-2; Sequence=VSP_016919;
CC -!- TISSUE SPECIFICITY: Isoform 2 is ubiquitously expressed in embryos and
CC adult tissues at much higher level than isoform 1.
CC {ECO:0000269|PubMed:12034499}.
CC -!- DEVELOPMENTAL STAGE: Detected at 11.5 dpc in the developing brain, in
CC the ventricular zones of the cortex and ganglionic eminences as well as
CC in adult, in mature structures such as the granule cell layer of the
CC dentate gyrus and cerebellum. {ECO:0000269|PubMed:15580621}.
CC -!- DOMAIN: HD1 motif interacts with SAM domain of PHC1.
CC {ECO:0000269|PubMed:12034499}.
CC -!- DISRUPTION PHENOTYPE: Mice are viable and fertile but show posterior
CC transformations of the axial skeleton and premature senescence of mouse
CC embryonic fibroblast associated with derepression of Hox cluster genes
CC and Cdkn2a genes, respectively. Mice lacking Phc2 and Phc1 die at an
CC early gestational stage. Mice mutant for Phc1 and/or Phc2 demonstrate
CC that Phc1 and Phc2 mutations affect synergistically the survival of
CC embryos in a gene dosage-dependent manner and thus show functional
CC redundancy of Phc1 and Phc2. {ECO:0000269|PubMed:16024804}.
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DR EMBL; AB062362; BAB93527.1; -; mRNA.
DR EMBL; U81491; AAD00519.1; -; mRNA.
DR EMBL; AL611969; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL611983; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC057571; AAH57571.1; -; mRNA.
DR EMBL; BC071246; AAH71246.1; -; mRNA.
DR EMBL; AF060076; AAC23570.1; -; mRNA.
DR CCDS; CCDS18674.1; -. [Q9QWH1-1]
DR CCDS; CCDS57297.1; -. [Q9QWH1-2]
DR RefSeq; NP_001182012.1; NM_001195083.1. [Q9QWH1-2]
DR RefSeq; NP_001182059.1; NM_001195130.1. [Q9QWH1-1]
DR RefSeq; NP_061244.1; NM_018774.4. [Q9QWH1-1]
DR RefSeq; XP_006503300.1; XM_006503237.3.
DR RefSeq; XP_006503301.1; XM_006503238.1. [Q9QWH1-2]
DR RefSeq; XP_017175809.1; XM_017320320.1. [Q9QWH1-1]
DR PDB; 2NA1; NMR; -; A=557-590.
DR PDBsum; 2NA1; -.
DR AlphaFoldDB; Q9QWH1; -.
DR SMR; Q9QWH1; -.
DR BioGRID; 207636; 17.
DR IntAct; Q9QWH1; 8.
DR MINT; Q9QWH1; -.
DR STRING; 10090.ENSMUSP00000030588; -.
DR iPTMnet; Q9QWH1; -.
DR PhosphoSitePlus; Q9QWH1; -.
DR EPD; Q9QWH1; -.
DR MaxQB; Q9QWH1; -.
DR PaxDb; 10090-ENSMUSP00000101690; -.
DR PeptideAtlas; Q9QWH1; -.
DR ProteomicsDB; 289489; -. [Q9QWH1-1]
DR ProteomicsDB; 289490; -. [Q9QWH1-2]
DR Pumba; Q9QWH1; -.
DR Antibodypedia; 31416; 138 antibodies from 22 providers.
DR DNASU; 54383; -.
DR Ensembl; ENSMUST00000030588.13; ENSMUSP00000030588.7; ENSMUSG00000028796.18. [Q9QWH1-1]
DR Ensembl; ENSMUST00000106079.10; ENSMUSP00000101689.4; ENSMUSG00000028796.18. [Q9QWH1-2]
DR Ensembl; ENSMUST00000106080.8; ENSMUSP00000101690.2; ENSMUSG00000028796.18. [Q9QWH1-1]
DR GeneID; 54383; -.
DR KEGG; mmu:54383; -.
DR UCSC; uc008uvh.2; mouse. [Q9QWH1-1]
DR UCSC; uc008uvk.2; mouse. [Q9QWH1-2]
DR AGR; MGI:1860454; -.
DR CTD; 1912; -.
DR MGI; MGI:1860454; Phc2.
DR VEuPathDB; HostDB:ENSMUSG00000028796; -.
DR eggNOG; ENOG502QS5Q; Eukaryota.
DR GeneTree; ENSGT00940000160840; -.
DR HOGENOM; CLU_012048_0_0_1; -.
DR InParanoid; Q9QWH1; -.
DR OMA; HSPAHET; -.
DR OrthoDB; 5399754at2759; -.
DR PhylomeDB; Q9QWH1; -.
DR TreeFam; TF331299; -.
DR Reactome; R-MMU-3108214; SUMOylation of DNA damage response and repair proteins.
DR Reactome; R-MMU-3899300; SUMOylation of transcription cofactors.
DR Reactome; R-MMU-4551638; SUMOylation of chromatin organization proteins.
DR Reactome; R-MMU-4570464; SUMOylation of RNA binding proteins.
DR Reactome; R-MMU-8939243; RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known.
DR Reactome; R-MMU-8943724; Regulation of PTEN gene transcription.
DR BioGRID-ORCS; 54383; 1 hit in 76 CRISPR screens.
DR ChiTaRS; Phc2; mouse.
DR PRO; PR:Q9QWH1; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q9QWH1; Protein.
DR Bgee; ENSMUSG00000028796; Expressed in rostral migratory stream and 267 other cell types or tissues.
DR ExpressionAtlas; Q9QWH1; baseline and differential.
DR Genevisible; Q9QWH1; MM.
DR GO; GO:0000792; C:heterochromatin; IDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0031519; C:PcG protein complex; ISO:MGI.
DR GO; GO:0035102; C:PRC1 complex; IDA:MGI.
DR GO; GO:0003682; F:chromatin binding; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0042393; F:histone binding; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IBA:GO_Central.
DR GO; GO:0007283; P:spermatogenesis; IGI:MGI.
DR CDD; cd09577; SAM_Ph1_2_3; 1.
DR DisProt; DP01315; -.
DR Gene3D; 3.30.60.160; -; 1.
DR Gene3D; 1.10.150.50; Transcription Factor, Ets-1; 1.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed_sf.
DR InterPro; IPR012313; Znf_FCS.
DR InterPro; IPR038603; Znf_FCS_sf.
DR PANTHER; PTHR12247; POLYCOMB GROUP PROTEIN; 1.
DR PANTHER; PTHR12247:SF86; POLYHOMEOTIC-LIKE PROTEIN 2; 1.
DR Pfam; PF16616; PHC2_SAM_assoc; 1.
DR Pfam; PF00536; SAM_1; 1.
DR Pfam; PF21319; zf-FCS_1; 1.
DR SMART; SM00454; SAM; 1.
DR SUPFAM; SSF47769; SAM/Pointed domain; 1.
DR PROSITE; PS50105; SAM_DOMAIN; 1.
DR PROSITE; PS51024; ZF_FCS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Developmental protein; DNA-binding;
KW Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..850
FT /note="Polyhomeotic-like protein 2"
FT /id="PRO_0000076287"
FT DOMAIN 786..850
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT ZN_FING 625..659
FT /note="FCS-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00367"
FT REGION 1..79
FT /note="Disordered"
FT /evidence="ECO:0000269|PubMed:27827373"
FT REGION 33..56
FT /note="Interaction with BMI1"
FT /evidence="ECO:0000269|PubMed:27827373"
FT REGION 233..314
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 335..386
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 402..436
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 528..553
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 597..624
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 676..712
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 725..764
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 550..579
FT /note="HD1"
FT COMPBIAS 1..38
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 338..362
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 363..379
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 528..549
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 610..624
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 689..712
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 725..754
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 634
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00367"
FT BINDING 637
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00367"
FT BINDING 653
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00367"
FT BINDING 657
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00367"
FT MOD_RES 611
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8IXK0"
FT MOD_RES 613
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8IXK0"
FT MOD_RES 743
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8IXK0"
FT CROSSLNK 590
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q8IXK0"
FT CROSSLNK 592
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q8IXK0"
FT CROSSLNK 624
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q8IXK0"
FT CROSSLNK 694
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q8IXK0"
FT CROSSLNK 839
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q8IXK0"
FT VAR_SEQ 1..527
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12034499,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_016919"
FT STRAND 560..565
FT /evidence="ECO:0007829|PDB:2NA1"
FT STRAND 568..573
FT /evidence="ECO:0007829|PDB:2NA1"
FT TURN 578..580
FT /evidence="ECO:0007829|PDB:2NA1"
FT HELIX 583..586
FT /evidence="ECO:0007829|PDB:2NA1"
SQ SEQUENCE 850 AA; 89799 MW; 87746AFD7808DC7B CRC64;
MENELPVPHT SNRASVTTNT SGTNSSSGCI SSSGGGGGSG GRPTAPQISV YSGIPDRQTV
QVIQQALHRQ PSTAAQYLQQ MYAAQQQHLM LQTAALQQQH LSSAQLQSLA AVQQASLVAN
RQGSTPGSSV SSQAPAQSSS LNLAASPAAA QLINRAQSVN SAAASGLAQQ AVLLGNTSSP
ALTASQAQMY LRAQMLIFTP TATVATVQPE LCTGSPARPP TPAQVQNLTL RTQQTPAAAA
SGPPPTQPVL PSLALKPTPS SSQPLPAPPQ GRTMAQGSPA GAKPSGTDNA PETLKAGDGN
CNMEGRPGPG RAVPAVATHP LIAPAYAHLQ SHQLLPQPPA KHPQPQFVAQ QQPQPPRPAP
QVQSQPQLAS VSPSLALQSS PEDHALPLGS VTQALPLQCS TTHVHKPGNS QQCHLPTLDT
GSQNGHPEGG SHPPQRRFQH TSAVILQVQP ASPVTPQQCA PDDWKEVVPA EKSVPVARPG
PSPHQQAIIP AIPGGLPGPK SPNIQQCPAH ETGQGIVHAL TDLSSPGMTS GNGNSASSIA
GTAPQNGENK PPQAIVKPQI LTHVIEGFVI QEGAEPFPVG RSSLLVGNLK KKYAQGFLPE
KPPQQDHTTT TDSEMEEPYL QESKEEGTPL KLKCELCGRV DFAYKFKRSK RFCSMACAKR
YNVGCTKRVG LFHSDRSKLQ KAGTTTHNRR RASKASLPTL TKDTKKQPSG TVPLSVTAAL
QLAHSQEDSS RCSDNSSYEE PLSPISASSS TSRRRQGQRD LDLPDMHMRD LVGVGHHFLP
SEPTKWNVED VYEFIRSLPG CQEIAEEFRA QEIDGQALLL LKEDHLMSAM NIKLGPALKI
YARISMLKDS
//
