PWP2A_MOUSE
ID PWP2A_MOUSE Reviewed; 730 AA.
AC Q69Z61; A2AJK9; A2AJL0; Q3TBG3; Q9CUT9;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2007, sequence version 2.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=PWWP domain-containing protein 2A;
GN Name=Pwwp2a; Synonyms=Kiaa1935;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Embryonic tail;
RX PubMed=15368895; DOI=10.1093/dnares/11.3.205;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H.,
RA Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: IV.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 11:205-218(2004).
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 173-730 (ISOFORM 2), AND
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 316-730 (ISOFORM 1).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Skin;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP FUNCTION.
RX PubMed=30228260; DOI=10.1038/s41467-018-06235-9;
RA Zhang T., Wei G., Millard C.J., Fischer R., Konietzny R., Kessler B.M.,
RA Schwabe J.W.R., Brockdorff N.;
RT "A variant NuRD complex containing PWWP2A/B excludes MBD2/3 to regulate
RT transcription at active genes.";
RL Nat. Commun. 9:3798-3798(2018).
RN [5]
RP FUNCTION.
RX PubMed=33235983; DOI=10.1016/j.isci.2020.101741;
RA Wei G., Brockdorff N., Zhang T.;
RT "The PWWP2A Histone Deacetylase Complex Represses Intragenic Spurious
RT Transcription Initiation in mESCs.";
RL IScience 23:101741-101741(2020).
CC -!- FUNCTION: Chromatin-binding protein that acts as an adapter between
CC distinct nucleosome components (H3K36me3 or H2A.Z) and chromatin-
CC modifying complexes, contributing to the regulation of the levels of
CC histone acetylation at actively transcribed genes (PubMed:30228260,
CC PubMed:33235983). Competes with CHD4 and MBD3 for interaction with MTA1
CC to form a NuRD subcomplex, preventing the formation of full NuRD
CC complex (containing CHD4 and MBD3), leading to recruitment of HDACs to
CC gene promoters resulting in turn in the deacetylation of nearby H3K27
CC and H2A.Z (By similarity). Plays a role in facilitating transcriptional
CC elongation and repression of spurious transcription initiation through
CC regulation of histone acetylation (PubMed:30228260, PubMed:33235983).
CC Essential for proper mitosis progression (By similarity).
CC {ECO:0000250|UniProtKB:Q96N64, ECO:0000269|PubMed:30228260,
CC ECO:0000269|PubMed:33235983}.
CC -!- SUBUNIT: Component of a MTA1-specific subcomplex of the NuRD complex
CC (M1HR), which is composed of PWWP2A, MTA1/2, HDAC1/2, and RBBP4/7 but
CC does not contain CHD4 and MBD3 (By similarity). Interacts with MTA1;
CC the interaction mediates the association of PWWP2A with the M1HR
CC complex (By similarity). Interacts with H2A.Z/H2AZ1 (By similarity).
CC Interacts (via PWWP domain) with histone H3 trimethylated at 'Lys-36'
CC (H3K36me3) (By similarity). Does not interact with CHD4 and MBD3 (By
CC similarity). {ECO:0000250|UniProtKB:Q96N64}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q96N64}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q69Z61-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q69Z61-2; Sequence=VSP_029549, VSP_029550, VSP_029551;
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB29417.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAD32583.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=CAM20715.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AK173305; BAD32583.1; ALT_INIT; mRNA.
DR EMBL; AL732633; CAM20714.1; -; Genomic_DNA.
DR EMBL; AL732633; CAM20715.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AK014534; BAB29417.1; ALT_FRAME; mRNA.
DR EMBL; AK171257; BAE42348.1; -; mRNA.
DR CCDS; CCDS48773.1; -. [Q69Z61-2]
DR CCDS; CCDS48774.1; -. [Q69Z61-1]
DR RefSeq; NP_001157703.1; NM_001164231.1. [Q69Z61-2]
DR RefSeq; NP_081833.1; NM_027557.1. [Q69Z61-1]
DR AlphaFoldDB; Q69Z61; -.
DR SMR; Q69Z61; -.
DR STRING; 10090.ENSMUSP00000091852; -.
DR iPTMnet; Q69Z61; -.
DR PhosphoSitePlus; Q69Z61; -.
DR EPD; Q69Z61; -.
DR MaxQB; Q69Z61; -.
DR PaxDb; Q69Z61; -.
DR PeptideAtlas; Q69Z61; -.
DR PRIDE; Q69Z61; -.
DR ProteomicsDB; 301851; -. [Q69Z61-1]
DR ProteomicsDB; 301852; -. [Q69Z61-2]
DR Antibodypedia; 28516; 34 antibodies from 15 providers.
DR Ensembl; ENSMUST00000061070; ENSMUSP00000054154; ENSMUSG00000044950. [Q69Z61-1]
DR Ensembl; ENSMUST00000094294; ENSMUSP00000091852; ENSMUSG00000044950. [Q69Z61-2]
DR GeneID; 70802; -.
DR KEGG; mmu:70802; -.
DR UCSC; uc007imu.2; mouse. [Q69Z61-1]
DR UCSC; uc007imv.2; mouse. [Q69Z61-2]
DR CTD; 114825; -.
DR MGI; MGI:1918052; Pwwp2a.
DR VEuPathDB; HostDB:ENSMUSG00000044950; -.
DR eggNOG; ENOG502QU6V; Eukaryota.
DR GeneTree; ENSGT00940000157692; -.
DR HOGENOM; CLU_020678_0_0_1; -.
DR InParanoid; Q69Z61; -.
DR OMA; PPCWSPK; -.
DR OrthoDB; 326248at2759; -.
DR PhylomeDB; Q69Z61; -.
DR TreeFam; TF331271; -.
DR BioGRID-ORCS; 70802; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Pwwp2a; mouse.
DR PRO; PR:Q69Z61; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q69Z61; protein.
DR Bgee; ENSMUSG00000044950; Expressed in manus and 229 other tissues.
DR ExpressionAtlas; Q69Z61; baseline and differential.
DR Genevisible; Q69Z61; MM.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0042393; F:histone binding; ISO:MGI.
DR GO; GO:0035064; F:methylated histone binding; ISS:UniProtKB.
DR GO; GO:0120325; F:NuRD complex binding; ISS:UniProtKB.
DR GO; GO:0035067; P:negative regulation of histone acetylation; IMP:UniProtKB.
DR GO; GO:1901675; P:negative regulation of histone H3-K27 acetylation; IMP:UniProtKB.
DR GO; GO:2000616; P:negative regulation of histone H3-K9 acetylation; IMP:UniProtKB.
DR GO; GO:0032968; P:positive regulation of transcription elongation from RNA polymerase II promoter; IMP:UniProtKB.
DR GO; GO:2000142; P:regulation of DNA-templated transcription, initiation; IMP:UniProtKB.
DR InterPro; IPR000313; PWWP_dom.
DR Pfam; PF00855; PWWP; 1.
DR SMART; SM00293; PWWP; 1.
DR PROSITE; PS50812; PWWP; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Isopeptide bond; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation;
KW Ubl conjugation.
FT CHAIN 1..730
FT /note="PWWP domain-containing protein 2A"
FT /id="PRO_0000311364"
FT DOMAIN 630..690
FT /note="PWWP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00162"
FT REGION 1..134
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 128..346
FT /note="Interaction with HDAC1 and MTA1"
FT /evidence="ECO:0000250|UniProtKB:Q96N64"
FT REGION 257..276
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 311..355
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 396..547
FT /note="Interaction with the H2A.Z/H2AZ1"
FT /evidence="ECO:0000250|UniProtKB:Q96N64"
FT REGION 409..531
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 63..79
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 93..125
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 311..350
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 450..467
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 478..493
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 508..530
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 82
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96N64"
FT MOD_RES 99
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96N64"
FT CROSSLNK 188
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q96N64"
FT VAR_SEQ 491..529
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_029549"
FT VAR_SEQ 530..572
FT /note="KKGSKSSISVYLTLNQETSDSSSASVCSIDSMDDLKSSNSECS -> LNKWQ
FT LLHQTVTSPAAPLQCLTDHCGFRLGALKLTVKRAAQRH (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_029550"
FT VAR_SEQ 573..730
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_029551"
FT CONFLICT 173
FT /note="S -> A (in Ref. 3; BAE42348)"
FT /evidence="ECO:0000305"
FT CONFLICT 335
FT /note="N -> K (in Ref. 3; BAE42348)"
FT /evidence="ECO:0000305"
FT CONFLICT 521
FT /note="E -> D (in Ref. 3; BAB29417)"
FT /evidence="ECO:0000305"
FT CONFLICT Q69Z61-2:510
FT /note="C -> Y (in Ref. 3; BAE42348)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 730 AA; 79388 MW; EC3F67CC6CCC1D6D CRC64;
MAAVAAEAAA TAASPGEGGA GEAEPELEPI PGSEAGTPLP VTATEAAVPD GEADGRQSAP
QADEQPLPPP PPPPPPGELA DSSEAEEAKP PEPAAVPVSP PEQPPAAPEQ PEDAPRPPPA
PALVPPAGGD SAVSHLIPGS EVRVTLDHII EDALVVSFRL GEKLFSGVLM DLSKRFGPHG
IPVTVFPKRE YKDKPDAMQL QSTTFQEGIE VKQEVNGAVP DDLSPVPPPE RLWASKPPPL
FHEGAPYPPP LFIRDTYNQS IPQPPPRKIK RPKRKMYREE PTSIMNAIKL RPRQVLCDKC
KNSVVAEKKE IRKGSSDSSR YEDKKRRNDS VATVNKKLKT DHKVDGKNQN ESQRRNTVVR
VSSIAHSRGR VVKVSAQANT SKAQLNTKKV LQSKNMDHAK AREVLKIAKE KAQKKQSETS
TSKTAHAKVH FTRRYQSPSS GSLPPRVRLK PQRYRNEEND SSLKTGLEKI RSGKLAPKPQ
SRCTSTRSAG EAPSEKPSPS EGPEESAGEV QDTSRVRVPG EQEELRMLGK KGSKSSISVY
LTLNQETSDS SSASVCSIDS MDDLKSSNSE CSSSESFVFP PGCMHAPSAS STSTSFSSKE
ENSLRNSLKM KIFSKNVSKC ITPDGRTICV GDIVWAKIYG FPWWPARILT ITVSRKDNGL
LARQEARISW FASPTTSSLA LSQLSPFLEN FQLRFNKKRK GLYRRAITEA AKAAKQLTPE
VRALLTQFET
