ZCPW1_MOUSE
ID ZCPW1_MOUSE Reviewed; 630 AA.
AC Q6IR42; Q2YFS4;
DT 31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Zinc finger CW-type PWWP domain protein 1;
GN Name=Zcwpw1; Synonyms=Gm1053;
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 [GENOMIC DNA].
RC STRAIN=129/Sv;
RX PubMed=16926269; DOI=10.1152/physiolgenomics.00284.2005;
RA Wilson M.D., Cheung J., Martindale D.W., Scherer S.W., Koop B.F.;
RT "Comparative analysis of the paired immunoglobulin-like receptor (PILR)
RT locus in six mammalian genomes: duplication, conversion, and the birth of
RT new genes.";
RL Physiol. Genomics 27:201-218(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryonic germ cell;
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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-619, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND TISSUE
RP SPECIFICITY.
RX PubMed=31453335; DOI=10.1126/sciadv.aax1101;
RA Li M., Huang T., Li M.J., Zhang C.X., Yu X.C., Yin Y.Y., Liu C., Wang X.,
RA Feng H.W., Zhang T., Liu M.F., Han C.S., Lu G., Li W., Ma J.L., Chen Z.J.,
RA Liu H.B., Liu K.;
RT "The histone modification reader ZCWPW1 is required for meiosis prophase I
RT in male but not in female mice.";
RL Sci. Adv. 5:eaax1101-eaax1101(2019).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY,
RP AND MUTAGENESIS OF TRP-247; GLU-292 AND TRP-294.
RX PubMed=32374261; DOI=10.7554/elife.53459;
RA Huang T., Yuan S., Gao L., Li M., Yu X., Zhang J., Yin Y., Liu C.,
RA Zhang C., Lu G., Li W., Liu J., Chen Z.J., Liu H.;
RT "The histone modification reader ZCWPW1 links histone methylation to PRDM9-
RT induced double-strand break repair.";
RL Elife 9:0-0(2020).
RN [6]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=32352380; DOI=10.7554/elife.53360;
RA Mahgoub M., Paiano J., Bruno M., Wu W., Pathuri S., Zhang X., Ralls S.,
RA Cheng X., Nussenzweig A., Macfarlan T.S.;
RT "Dual histone methyl reader ZCWPW1 facilitates repair of meiotic double
RT strand breaks in male mice.";
RL Elife 9:0-0(2020).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND TISSUE
RP SPECIFICITY.
RX PubMed=32744506; DOI=10.7554/elife.53392;
RA Wells D., Bitoun E., Moralli D., Zhang G., Hinch A., Jankowska J.,
RA Donnelly P., Green C., Myers S.R.;
RT "ZCWPW1 is recruited to recombination hotspots by PRDM9, and is essential
RT for meiotic double strand break repair.";
RL Elife 9:0-0(2020).
CC -!- FUNCTION: Dual histone methylation reader specific for PRDM9-catalyzed
CC histone marks (H3K4me3 and H3K36me3) that facilitates the repair of
CC PRDM9-induced meiotic double-strand breaks (DSBs) (PubMed:32374261,
CC PubMed:32352380, PubMed:32744506). Essential for male fertility and
CC spermatogenesis (PubMed:31453335, PubMed:32374261, PubMed:32352380,
CC PubMed:32744506). Required for meiosis prophase I progression in male
CC but not in female germ cells (PubMed:31453335).
CC {ECO:0000269|PubMed:31453335, ECO:0000269|PubMed:32352380,
CC ECO:0000269|PubMed:32374261, ECO:0000269|PubMed:32744506}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:31453335,
CC ECO:0000269|PubMed:32374261, ECO:0000269|PubMed:32744506}. Chromosome
CC {ECO:0000269|PubMed:31453335, ECO:0000269|PubMed:32744506}.
CC -!- TISSUE SPECIFICITY: Testis (at protein level) (PubMed:31453335,
CC PubMed:32352380, PubMed:32374261, PubMed:32744506). Expressed in
CC thymus, brain, lung, ovary, oviduct and uterus (PubMed:31453335).
CC {ECO:0000269|PubMed:31453335, ECO:0000269|PubMed:32352380,
CC ECO:0000269|PubMed:32374261, ECO:0000269|PubMed:32744506}.
CC -!- DOMAIN: The CW-TYPE zinc finger mediates its binding to trimethylated
CC histone H3K4me3. {ECO:0000250|UniProtKB:Q9H0M4}.
CC -!- DISRUPTION PHENOTYPE: Male mice are sterile with complete azoospermia
CC and reduced testis size, show impaired spermatogenesis, spermatocytes
CC display meiotic arrest at around the zygotene to pachytene stage with
CC incomplete homologous synapsis which is accompanied by defective DNA
CC double-strand breaks repair (PubMed:31453335, PubMed:32374261,
CC PubMed:32352380, PubMed:32744506). Fertility of females is normal up to
CC mid-adulthood (5 to 6 months of age), at 3 and 6 months, ovaries
CC exhibit healthy ovarian morphologies, however ovaries are devoid of
CC follicles at around 8 months of age, and accordingly female mice become
CC infertile (PubMed:31453335, PubMed:32744506). Female germ cells exhibit
CC a successful but delayed meiosis prophase I progression
CC (PubMed:31453335). {ECO:0000269|PubMed:31453335,
CC ECO:0000269|PubMed:32352380, ECO:0000269|PubMed:32374261,
CC ECO:0000269|PubMed:32744506}.
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DR EMBL; AY823670; AAX39493.1; -; Genomic_DNA.
DR EMBL; BC071186; AAH71186.1; -; mRNA.
DR CCDS; CCDS19779.1; -.
DR RefSeq; NP_001005426.2; NM_001005426.2.
DR RefSeq; XP_006504647.1; XM_006504584.3.
DR AlphaFoldDB; Q6IR42; -.
DR SMR; Q6IR42; -.
DR STRING; 10090.ENSMUSP00000048730; -.
DR iPTMnet; Q6IR42; -.
DR PhosphoSitePlus; Q6IR42; -.
DR EPD; Q6IR42; -.
DR MaxQB; Q6IR42; -.
DR PaxDb; Q6IR42; -.
DR PRIDE; Q6IR42; -.
DR ProteomicsDB; 275060; -.
DR Antibodypedia; 8914; 70 antibodies from 16 providers.
DR Ensembl; ENSMUST00000035852; ENSMUSP00000048730; ENSMUSG00000037108.
DR GeneID; 381678; -.
DR KEGG; mmu:381678; -.
DR UCSC; uc009adz.2; mouse.
DR CTD; 55063; -.
DR MGI; MGI:2685899; Zcwpw1.
DR VEuPathDB; HostDB:ENSMUSG00000037108; -.
DR eggNOG; ENOG502QSQZ; Eukaryota.
DR GeneTree; ENSGT00560000077278; -.
DR HOGENOM; CLU_029321_1_0_1; -.
DR InParanoid; Q6IR42; -.
DR OMA; TQKLHSM; -.
DR OrthoDB; 1159953at2759; -.
DR PhylomeDB; Q6IR42; -.
DR TreeFam; TF336904; -.
DR BioGRID-ORCS; 381678; 1 hit in 75 CRISPR screens.
DR ChiTaRS; Zcwpw1; mouse.
DR PRO; PR:Q6IR42; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q6IR42; protein.
DR Bgee; ENSMUSG00000037108; Expressed in epiblast (generic) and 64 other tissues.
DR ExpressionAtlas; Q6IR42; baseline and differential.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0001741; C:XY body; IDA:UniProtKB.
DR GO; GO:0008327; F:methyl-CpG binding; ISO:MGI.
DR GO; GO:0035064; F:methylated histone binding; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0007129; P:homologous chromosome pairing at meiosis; IMP:UniProtKB.
DR GO; GO:0007127; P:meiosis I; IMP:ARUK-UCL.
DR GO; GO:0045911; P:positive regulation of DNA recombination; IMP:ARUK-UCL.
DR GO; GO:2000781; P:positive regulation of double-strand break repair; IMP:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; IMP:ARUK-UCL.
DR InterPro; IPR000313; PWWP_dom.
DR InterPro; IPR042778; ZCWPW1/ZCWPW2.
DR InterPro; IPR011124; Znf_CW.
DR PANTHER; PTHR15999; PTHR15999; 1.
DR Pfam; PF00855; PWWP; 1.
DR Pfam; PF07496; zf-CW; 1.
DR SMART; SM00293; PWWP; 1.
DR PROSITE; PS50812; PWWP; 1.
DR PROSITE; PS51050; ZF_CW; 1.
PE 1: Evidence at protein level;
KW Chromosome; Coiled coil; Differentiation; Metal-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Spermatogenesis; Zinc; Zinc-finger.
FT CHAIN 1..630
FT /note="Zinc finger CW-type PWWP domain protein 1"
FT /id="PRO_0000066568"
FT DOMAIN 308..374
FT /note="PWWP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00162"
FT ZN_FING 241..295
FT /note="CW-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00454"
FT REGION 1..99
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 130..184
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 430..595
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 435..465
FT /evidence="ECO:0000255"
FT COMPBIAS 37..51
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 54..98
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 130..152
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 162..180
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 518..553
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 250
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00454"
FT BINDING 255
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00454"
FT BINDING 276
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00454"
FT BINDING 287
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00454"
FT MOD_RES 619
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MUTAGEN 247
FT /note="W->I: Knockin mice show impaired spermatogenesis,
FT loss of histone H3K4me3 binding, severe disruption of
FT chromosomal synapsis and DNA double-strand breaks repair in
FT spermatocytes; when associated with R-292 and P-294."
FT /evidence="ECO:0000269|PubMed:32374261"
FT MUTAGEN 292
FT /note="E->R: Knockin mice show impaired spermatogenesis,
FT loss of histone H3K4me3 binding, severe disruption of
FT chromosomal synapsis and DNA double-strand breaks repair in
FT spermatocytes; when associated with I-247 and P-294."
FT /evidence="ECO:0000269|PubMed:32374261"
FT MUTAGEN 294
FT /note="W->P: Knockin mice show impaired spermatogenesis,
FT loss of histone H3K4me3 binding, severe disruption of
FT chromosomal synapsis and DNA double-strand breaks repair in
FT spermatocytes; when associated with I-247 and R-292."
FT /evidence="ECO:0000269|PubMed:32374261"
FT CONFLICT 387
FT /note="S -> P (in Ref. 2; AAH71186)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 630 AA; 70569 MW; FB415590A6FA7243 CRC64;
MMAALQTHKE YEKGTKKTFA PPTQKLHSEK PQPSSWKEDA PGTSSPEAET KPSLLKASLK
KEQKPTTEHG PNRGQERKLK AQDQPAKKKG KERTLTSAEF EEIFQIVLQK SLQECLETSS
CVQHIRPTKL DEEPGIVPPA TDKKDADPEK VITPDTPKIA SSLEEEVNSE MGTSKLGQPV
TEPSKKKFNR LSLSKQKKKA EDEKMEKIQD GRECSLKEKQ KIVIQDQSQI RGPQKEEESG
FGHCVIWVQC SSPKCEKWRQ LRGNIDPSVL PDDWSCDQNP DPNYNRCDIP EESWAGCESD
VAYASYVPGS IIWAKQYGYP WWPGMIEADP DLGEYFLFAS HLDSLPSKYH VTFFGETVSR
AWIPVRMLKN FQELSLELVK KCKNKNSNQK LEAAIAMAHR AEQTSIQERV NLFGFWSRYN
GADISEEGED LTLCESNNPE SCLEKEEKDL EEEKEEEEEK KDPTLPRPKP AKMQTKKPKS
RGPAGGPDGT PKKKTAKKSL VSESTVPPVP TLGGKEEQGN SDLDHPVPKK KFKAPENKTS
ATNLSEEKEI KIVSKCPTPS AQHGACPLGK EGLVPHMPPT QEAASFPPDD DCSSDLDLEQ
LMEDIGEPEE RGEMQQRGSS EEFLAALFEE
