PWP3A_HUMAN
ID PWP3A_HUMAN Reviewed; 710 AA.
AC Q2TAK8; A1L489; B5ME02; B7ZLY8; J3KQD6; Q13109; Q5XKB9; Q8N2I4; Q96A67;
DT 10-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 22-SEP-2009, sequence version 3.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=PWWP domain-containing DNA repair factor 3A {ECO:0000305};
DE Short=PWWP3A {ECO:0000305};
DE AltName: Full=Mutated melanoma-associated antigen 1;
DE Short=MUM-1;
DE AltName: Full=PWWP domain-containing protein MUM1;
DE AltName: Full=Protein expandere;
GN Name=PWWP3A {ECO:0000312|HGNC:HGNC:29641};
GN Synonyms=EXPAND1 {ECO:0000303|PubMed:20347427},
GN MUM1 {ECO:0000303|PubMed:20347427};
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=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), AND VARIANT
RP ARG-219.
RC TISSUE=Brain, and PNS;
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 [MRNA] OF 1-411, AND VARIANT ARG-219.
RC TISSUE=Melanoma;
RX PubMed=7644523; DOI=10.1073/pnas.92.17.7976;
RA Coulie P.G., Lehmann F., Lethe B., Herman J., Lurquin C., Andrawiss M.,
RA Boon T.;
RT "A mutated intron sequence codes for an antigenic peptide recognized by
RT cytolytic T lymphocytes on a human melanoma.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:7976-7980(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 421-710 (ISOFORMS 1/2).
RC TISSUE=Placenta, and Thyroid;
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [6]
RP FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION, DOMAIN
RP PWWP, AND INTERACTION WITH TP53BP1 AND NUCLEOSOMES.
RX PubMed=20347427; DOI=10.1016/j.molcel.2009.12.040;
RA Huen M.S., Huang J., Leung J.W., Sy S.M., Leung K.M., Ching Y.P.,
RA Tsao S.W., Chen J.;
RT "Regulation of chromatin architecture by the PWWP domain-containing DNA
RT damage-responsive factor EXPAND1/MUM1.";
RL Mol. Cell 37:854-864(2010).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.82 ANGSTROMS) OF 405-538, AND INTERACTION WITH
RP TRIMETHYLATED HISTONE H3.
RX PubMed=21720545; DOI=10.1371/journal.pone.0018919;
RA Wu H., Zeng H., Lam R., Tempel W., Amaya M.F., Xu C., Dombrovski L.,
RA Qiu W., Wang Y., Min J.;
RT "Structural and histone binding ability characterizations of human PWWP
RT domains.";
RL PLoS ONE 6:E18919-E18919(2011).
CC -!- FUNCTION: Involved in the DNA damage response pathway by contributing
CC to the maintenance of chromatin architecture. Recruited to the vicinity
CC of DNA breaks by TP53BP1 and plays an accessory role to facilitate
CC damage-induced chromatin changes and promoting chromatin relaxation.
CC Required for efficient DNA repair and cell survival following DNA
CC damage. {ECO:0000269|PubMed:20347427}.
CC -!- SUBUNIT: Interacts with TP53BP1 (via BRCT domain); the interaction is
CC not dependent on its phosphorylation status. Binds nucleosomes.
CC Interacts with trimethylated 'Lys-36' of histone H3 (H3K36me3) (in
CC vitro). {ECO:0000269|PubMed:20347427, ECO:0000269|PubMed:21720545}.
CC -!- INTERACTION:
CC Q2TAK8-2; Q53EZ4: CEP55; NbExp=3; IntAct=EBI-10239402, EBI-747776;
CC Q2TAK8-2; Q9HD26: GOPC; NbExp=3; IntAct=EBI-10239402, EBI-349832;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20347427}.
CC Note=Recruited to DNA damage sites via its interaction with the BRCT
CC domain of TP53BP1.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q2TAK8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q2TAK8-2; Sequence=VSP_026684, VSP_026685;
CC Name=3;
CC IsoId=Q2TAK8-3; Sequence=VSP_053986;
CC -!- DOMAIN: The PWWP domain mediates the interaction with nucleosomes.
CC {ECO:0000269|PubMed:20347427}.
CC -!- MISCELLANEOUS: Acts as an antigenic peptide recognized by cytolytic T-
CC lymphocytes in a melanoma. {ECO:0000305|PubMed:7644523}.
CC -!- SIMILARITY: Belongs to the PWWP3A family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC50240.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAH08098.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAI10875.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAI44139.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB55357.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC11493.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; U20897; AAC50240.1; ALT_FRAME; mRNA.
DR EMBL; AC004258; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC004623; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC005329; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC005330; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC008098; AAH08098.1; ALT_INIT; mRNA.
DR EMBL; BC082987; AAH82987.1; -; mRNA.
DR EMBL; BC110874; AAI10875.1; ALT_INIT; mRNA.
DR EMBL; BC130443; AAI30444.1; -; mRNA.
DR EMBL; BC144138; AAI44139.1; ALT_INIT; mRNA.
DR EMBL; AK027774; BAB55357.1; ALT_INIT; mRNA.
DR EMBL; AK075241; BAC11493.1; ALT_INIT; mRNA.
DR CCDS; CCDS12062.1; -. [Q2TAK8-1]
DR PIR; I38945; I38946.
DR RefSeq; NP_116242.2; NM_032853.3. [Q2TAK8-1]
DR RefSeq; XP_011526687.1; XM_011528385.2.
DR PDB; 3PMI; X-ray; 2.82 A; A/B/C/D=405-538.
DR PDBsum; 3PMI; -.
DR AlphaFoldDB; Q2TAK8; -.
DR SMR; Q2TAK8; -.
DR BioGRID; 124373; 31.
DR IntAct; Q2TAK8; 7.
DR STRING; 9606.ENSP00000467083; -.
DR iPTMnet; Q2TAK8; -.
DR PhosphoSitePlus; Q2TAK8; -.
DR BioMuta; MUM1; -.
DR DMDM; 259016340; -.
DR EPD; Q2TAK8; -.
DR jPOST; Q2TAK8; -.
DR MassIVE; Q2TAK8; -.
DR MaxQB; Q2TAK8; -.
DR PaxDb; Q2TAK8; -.
DR PeptideAtlas; Q2TAK8; -.
DR PRIDE; Q2TAK8; -.
DR ProteomicsDB; 61463; -. [Q2TAK8-1]
DR ProteomicsDB; 61464; -. [Q2TAK8-2]
DR Antibodypedia; 10456; 243 antibodies from 35 providers.
DR DNASU; 84939; -.
DR Ensembl; ENST00000415183.7; ENSP00000394925.3; ENSG00000160953.17. [Q2TAK8-3]
DR Ensembl; ENST00000591337.7; ENSP00000467287.4; ENSG00000160953.17. [Q2TAK8-1]
DR Ensembl; ENST00000591806.6; ENSP00000467083.2; ENSG00000160953.17. [Q2TAK8-1]
DR GeneID; 84939; -.
DR KEGG; hsa:84939; -.
DR MANE-Select; ENST00000591337.7; ENSP00000467287.4; NM_001369789.1; NP_001356718.1.
DR UCSC; uc060qzk.1; human. [Q2TAK8-1]
DR CTD; 84939; -.
DR DisGeNET; 84939; -.
DR GeneCards; PWWP3A; -.
DR HGNC; HGNC:29641; PWWP3A.
DR HPA; ENSG00000160953; Low tissue specificity.
DR neXtProt; NX_Q2TAK8; -.
DR OpenTargets; ENSG00000160953; -.
DR PharmGKB; PA164742142; -.
DR VEuPathDB; HostDB:ENSG00000160953; -.
DR eggNOG; ENOG502QPRU; Eukaryota.
DR GeneTree; ENSGT00390000001700; -.
DR InParanoid; Q2TAK8; -.
DR OMA; AGMLVWC; -.
DR OrthoDB; 339225at2759; -.
DR PhylomeDB; Q2TAK8; -.
DR PathwayCommons; Q2TAK8; -.
DR SignaLink; Q2TAK8; -.
DR BioGRID-ORCS; 84939; 17 hits in 1080 CRISPR screens.
DR ChiTaRS; MUM1; human.
DR EvolutionaryTrace; Q2TAK8; -.
DR GenomeRNAi; 84939; -.
DR Pharos; Q2TAK8; Tbio.
DR PRO; PR:Q2TAK8; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q2TAK8; protein.
DR Bgee; ENSG00000160953; Expressed in right hemisphere of cerebellum and 183 other tissues.
DR ExpressionAtlas; Q2TAK8; baseline and differential.
DR Genevisible; Q2TAK8; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0031491; F:nucleosome binding; IDA:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; IMP:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IMP:UniProtKB.
DR CDD; cd06080; MUM1_like; 1.
DR InterPro; IPR033368; MUM1.
DR InterPro; IPR035504; MUM1-like_PWWP.
DR InterPro; IPR040263; PWP3A/B.
DR PANTHER; PTHR31333; PTHR31333; 1.
DR PANTHER; PTHR31333:SF4; PTHR31333:SF4; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; DNA damage; DNA repair; Nucleus;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..710
FT /note="PWWP domain-containing DNA repair factor 3A"
FT /id="PRO_0000295046"
FT DOMAIN 411..472
FT /note="PWWP"
FT REGION 106..160
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 177..204
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 230..398
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 128..142
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 161
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:B1H224"
FT MOD_RES 374
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6DID5"
FT MOD_RES 375
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6DID5"
FT VAR_SEQ 1..68
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_026684"
FT VAR_SEQ 69..71
FT /note="SSL -> MVS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_026685"
FT VAR_SEQ 663..710
FT /note="AIICAISAVDEVDYKTAEEKYIKGPSLSYREKEIFDNQLLEERNRRRR ->
FT CWEMRVRALDPVRRRSRLLDPCAEMELLRSCQHQGVRTPSLLRAHRCFPASVGHHLCDL
FT CGGRGGLQDG (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_053986"
FT VARIANT 219
FT /note="G -> R (in dbSNP:rs3826942)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:7644523"
FT /id="VAR_033195"
FT VARIANT 551
FT /note="G -> A (in dbSNP:rs34502536)"
FT /id="VAR_033196"
FT CONFLICT 532
FT /note="K -> R (in Ref. 4; BAB55357)"
FT /evidence="ECO:0000305"
FT STRAND 414..417
FT /evidence="ECO:0007829|PDB:3PMI"
FT STRAND 425..433
FT /evidence="ECO:0007829|PDB:3PMI"
FT HELIX 434..436
FT /evidence="ECO:0007829|PDB:3PMI"
FT STRAND 438..443
FT /evidence="ECO:0007829|PDB:3PMI"
FT STRAND 455..458
FT /evidence="ECO:0007829|PDB:3PMI"
FT HELIX 459..461
FT /evidence="ECO:0007829|PDB:3PMI"
FT HELIX 470..477
FT /evidence="ECO:0007829|PDB:3PMI"
FT TURN 478..480
FT /evidence="ECO:0007829|PDB:3PMI"
FT HELIX 482..500
FT /evidence="ECO:0007829|PDB:3PMI"
FT HELIX 508..513
FT /evidence="ECO:0007829|PDB:3PMI"
FT HELIX 518..527
FT /evidence="ECO:0007829|PDB:3PMI"
SQ SEQUENCE 710 AA; 78636 MW; 96D8A77FE814F6F8 CRC64;
MADAKYVLCR WEKRLWPAKV LARTATSTKN KRRKEYFLAV QILSLEEKIK VKSTEVEILE
KSQIEAIASS LASQNEVPAA PLEELAYRRS LRVALDVLSE GSIWSQESSA GTGRADRSLR
GKPMEHVSSP CDSNSSSLPR GDVLGSSRPH RRRPCVQQSL SSSFTCEKDP ECKVDHKKGL
RKSENPRGPL VLPAGGGAQD ESGSRIHHKN WTLASKRGGN SAQKASLCLN GSSLSEDDTE
RDMGSKGGSW AAPSLPSGVR EDDPCANAEG HDPGLPLGSL TAPPAPEPSA CSEPGECPAK
KRPRLDGSQR PPAVQLEPMA AGAAPSPGPG PGPRESVTPR STARLGPPPS HASADATRCL
PCPDSQKLEK ECQSSEESMG SNSMRSILEE DEEDEEPPRV LLYHEPRSFE VGMLVWHKHK
KYPFWPAVVK SVRQRDKKAS VLYIEGHMNP KMKGFTVSLK SLKHFDCKEK QTLLNQARED
FNQDIGWCVS LITDYRVRLG CGSFAGSFLE YYAADISYPV RKSIQQDVLG TKLPQLSKGS
PEEPVVGCPL GQRQPCRKML PDRSRAARDR ANQKLVEYIV KAKGAESHLR AILKSRKPSR
WLQTFLSSSQ YVTCVETYLE DEGQLDLVVK YLQGVYQEVG AKVLQRTNGD RIRFILDVLL
PEAIICAISA VDEVDYKTAE EKYIKGPSLS YREKEIFDNQ LLEERNRRRR
