PWP2B_HUMAN
ID PWP2B_HUMAN Reviewed; 590 AA.
AC Q6NUJ5; A6NM90; B5MDQ1; H9KV61; Q5SZI0; Q6ZQX5; Q96F43;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2007, sequence version 3.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=PWWP domain-containing protein 2B;
GN Name=PWWP2B; Synonyms=PWWP2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS CYS-89 AND
RP GLY-98.
RC TISSUE=Placenta;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 46-590 (ISOFORM 1), AND VARIANT
RP CYS-89.
RC TISSUE=Uterus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-84; SER-186; SER-206; SER-250
RP AND SER-447, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [5]
RP FUNCTION, INTERACTION WITH MTA1 AND HDAC1, ABSENCE OF INTERACTION WITH CHD4
RP AND MBD3, AND IDENTIFICATION IN A MTA1-SPECIFIC SUBCOMPLEX OF THE NURD
RP COMPLEX.
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 [6]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 475-590.
RG Structural genomics consortium (SGC);
RT "Crystal structure of PWWP domain of human PWWP domain-containing protein
RT 2b.";
RL Submitted (JUL-2013) to the PDB data bank.
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 Competes with CHD4 and MBD3 for interaction with MTA1 to form a NuRD
CC subcomplex, preventing the formation of full NuRD complex (containing
CC CHD4 and MBD3), leading to recruitment of HDACs to gene promoters
CC resulting in turn in the deacetylation of nearby H3K27 and H2A.Z
CC (PubMed:30228260). Plays a role in facilitating transcriptional
CC elongation through regulation of histone acetylation (By similarity).
CC Negatively regulates brown adipocyte thermogenesis by interacting with
CC and stabilizing HDAC1 at the UCP1 gene promoter, thereby promoting
CC histone deacetylation at the promoter leading to the repression of UCP1
CC expression (By similarity). {ECO:0000250|UniProtKB:Q69Z61,
CC ECO:0000269|PubMed:30228260}.
CC -!- SUBUNIT: Component of a MTA1-specific subcomplex of the NuRD complex
CC composed of PWWP2B, MTA1 and HDAC1 but does not contain CHD4 and MBD3
CC (PubMed:30228260). Interacts with MTA1 and HDAC1 (PubMed:30228260).
CC Interacts with MTA2, MTA3, HDAC2, RBBP4, RBBP7, BRCC3 and ZNF516 (By
CC similarity). Does not interact with CHD4 and MBD3 (PubMed:30228260).
CC {ECO:0000250|UniProtKB:Q69Z61, ECO:0000269|PubMed:30228260}.
CC -!- INTERACTION:
CC Q6NUJ5; Q9NYB9-2: ABI2; NbExp=3; IntAct=EBI-10251192, EBI-11096309;
CC Q6NUJ5; A6NEM1: GOLGA6L9; NbExp=3; IntAct=EBI-10251192, EBI-5916454;
CC Q6NUJ5; P25788: PSMA3; NbExp=3; IntAct=EBI-10251192, EBI-348380;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6NUJ5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6NUJ5-2; Sequence=VSP_054223, VSP_054224;
CC -!- PTM: Deubiquitinated by BRCC3; leading to its stabilization.
CC {ECO:0000250|UniProtKB:Q69Z61}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH68574.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AK128663; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AK128663; Type=Frameshift; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AL590105; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC011630; AAH11630.2; -; mRNA.
DR EMBL; BC068574; AAH68574.1; ALT_INIT; mRNA.
DR EMBL; AK128663; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS44497.1; -. [Q6NUJ5-2]
DR CCDS; CCDS7667.2; -. [Q6NUJ5-1]
DR RefSeq; NP_001092107.1; NM_001098637.1. [Q6NUJ5-2]
DR RefSeq; NP_612508.3; NM_138499.3. [Q6NUJ5-1]
DR RefSeq; XP_006717722.1; XM_006717659.3. [Q6NUJ5-1]
DR PDB; 4LD6; X-ray; 1.70 A; A=475-590.
DR PDBsum; 4LD6; -.
DR AlphaFoldDB; Q6NUJ5; -.
DR SMR; Q6NUJ5; -.
DR BioGRID; 128004; 15.
DR IntAct; Q6NUJ5; 7.
DR STRING; 9606.ENSP00000306324; -.
DR iPTMnet; Q6NUJ5; -.
DR PhosphoSitePlus; Q6NUJ5; -.
DR BioMuta; PWWP2B; -.
DR DMDM; 160140805; -.
DR EPD; Q6NUJ5; -.
DR jPOST; Q6NUJ5; -.
DR MassIVE; Q6NUJ5; -.
DR MaxQB; Q6NUJ5; -.
DR PaxDb; Q6NUJ5; -.
DR PeptideAtlas; Q6NUJ5; -.
DR PRIDE; Q6NUJ5; -.
DR ProteomicsDB; 46217; -.
DR ProteomicsDB; 66684; -. [Q6NUJ5-1]
DR Antibodypedia; 46422; 83 antibodies from 22 providers.
DR DNASU; 170394; -.
DR Ensembl; ENST00000305233.6; ENSP00000306324.5; ENSG00000171813.14. [Q6NUJ5-1]
DR Ensembl; ENST00000631148.2; ENSP00000486501.1; ENSG00000171813.14. [Q6NUJ5-2]
DR GeneID; 170394; -.
DR KEGG; hsa:170394; -.
DR MANE-Select; ENST00000305233.6; ENSP00000306324.5; NM_138499.4; NP_612508.3.
DR UCSC; uc001lll.5; human. [Q6NUJ5-1]
DR CTD; 170394; -.
DR DisGeNET; 170394; -.
DR GeneCards; PWWP2B; -.
DR HGNC; HGNC:25150; PWWP2B.
DR HPA; ENSG00000171813; Low tissue specificity.
DR neXtProt; NX_Q6NUJ5; -.
DR OpenTargets; ENSG00000171813; -.
DR PharmGKB; PA162400513; -.
DR VEuPathDB; HostDB:ENSG00000171813; -.
DR eggNOG; ENOG502QQ5Q; Eukaryota.
DR GeneTree; ENSGT00940000160735; -.
DR HOGENOM; CLU_020678_0_0_1; -.
DR InParanoid; Q6NUJ5; -.
DR OMA; TSPEMCD; -.
DR OrthoDB; 326248at2759; -.
DR PhylomeDB; Q6NUJ5; -.
DR TreeFam; TF331271; -.
DR PathwayCommons; Q6NUJ5; -.
DR SignaLink; Q6NUJ5; -.
DR BioGRID-ORCS; 170394; 9 hits in 1077 CRISPR screens.
DR ChiTaRS; PWWP2B; human.
DR GenomeRNAi; 170394; -.
DR Pharos; Q6NUJ5; Tdark.
DR PRO; PR:Q6NUJ5; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q6NUJ5; protein.
DR Bgee; ENSG00000171813; Expressed in pancreatic ductal cell and 181 other tissues.
DR Genevisible; Q6NUJ5; HS.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0120325; F:NuRD complex binding; IDA:UniProtKB.
DR GO; GO:0035067; P:negative regulation of histone acetylation; ISS:UniProtKB.
DR GO; GO:1901675; P:negative regulation of histone H3-K27 acetylation; ISS:UniProtKB.
DR GO; GO:2000616; P:negative regulation of histone H3-K9 acetylation; ISS:UniProtKB.
DR GO; GO:0032968; P:positive regulation of transcription elongation from RNA polymerase II promoter; ISS:UniProtKB.
DR GO; GO:0120161; P:regulation of cold-induced thermogenesis; ISS:UniProtKB.
DR InterPro; IPR000313; PWWP_dom.
DR Pfam; PF00855; PWWP; 1.
DR SMART; SM00293; PWWP; 1.
DR PROSITE; PS50812; PWWP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation.
FT CHAIN 1..590
FT /note="PWWP domain-containing protein 2B"
FT /id="PRO_0000240878"
FT DOMAIN 490..550
FT /note="PWWP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00162"
FT REGION 52..110
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 182..347
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 360..398
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 426..467
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 87..110
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 203..220
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 228..245
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 332..347
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 426..441
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 84
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 186
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 206
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 250
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 447
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 497..499
FT /note="KIH -> HRR (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_054223"
FT VAR_SEQ 500..590
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_054224"
FT VARIANT 89
FT /note="R -> C (in dbSNP:rs11146363)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_037233"
FT VARIANT 98
FT /note="R -> G (in dbSNP:rs10747057)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_037234"
FT STRAND 475..481
FT /evidence="ECO:0007829|PDB:4LD6"
FT STRAND 487..489
FT /evidence="ECO:0007829|PDB:4LD6"
FT STRAND 493..496
FT /evidence="ECO:0007829|PDB:4LD6"
FT STRAND 504..513
FT /evidence="ECO:0007829|PDB:4LD6"
FT STRAND 518..520
FT /evidence="ECO:0007829|PDB:4LD6"
FT STRAND 524..530
FT /evidence="ECO:0007829|PDB:4LD6"
FT STRAND 536..540
FT /evidence="ECO:0007829|PDB:4LD6"
FT HELIX 541..543
FT /evidence="ECO:0007829|PDB:4LD6"
FT STRAND 544..546
FT /evidence="ECO:0007829|PDB:4LD6"
FT TURN 547..550
FT /evidence="ECO:0007829|PDB:4LD6"
FT HELIX 551..554
FT /evidence="ECO:0007829|PDB:4LD6"
FT HELIX 562..573
FT /evidence="ECO:0007829|PDB:4LD6"
FT TURN 574..577
FT /evidence="ECO:0007829|PDB:4LD6"
FT HELIX 579..588
FT /evidence="ECO:0007829|PDB:4LD6"
SQ SEQUENCE 590 AA; 63967 MW; 67C9124B40258EC4 CRC64;
MEPRAGCRLP VRVEQVVNGA LVVTVSCGER SFAGILLDCT KKSGLFGLPP LAPLPQVDES
PVNDSHGRAP EEGDAEVMQL GSSSPPPARG VQPPETTRPE PPPPLVPPLP AGSLPPYPPY
FEGAPFPHPL WLRDTYKLWV PQPPPRTIKR TRRRLSRNRD PGRLILSTIR LRPRQVLCEK
CKSTLSPPEA SPGPPAAPRA RRRLGSGPDR ELRKPEEPEN GEPTAAATAR RSKRERREED
RAPAEQVPRS PVIKISYSTP QGKGEVVKIP SRVHGSLEPF RPQQAPQDDG SQDPEVLDRE
SRDRPSCAPS ASIPKLKLTR PVPAGADLPP PKIRLKPHRL GDSEHEPVYR AELVGELNGY
LRDSSPAPCA DGPAGGLADL SSGSSGEDDD FKSCPQGPQG REGLAFLVSC PEGRADCASE
SACSSDSLDE ARSSGSEGTP ADTGDLSPGH GASAPSVSRE ARQTVPPLTV RLHTQSVSEC
ITEDGRTVAV GDIVWGKIHG FPWWPARVLD ISLGQKEDGE PSWREAKVSW FGSPTTSFLS
ISKLSPFSEF FKLRFNRKKK GMYRKAITEA ANAARHVAPE IRELLTQFET
