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   27-MAR-2024, entry version 137.
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}, MUM1
GN   {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; CCDS12062.2; -. [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; 34.
DR   IntAct; Q2TAK8; 7.
DR   STRING; 9606.ENSP00000498656; -.
DR   GlyGen; Q2TAK8; 1 site, 1 O-linked glycan (1 site).
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; 9606-ENSP00000467083; -.
DR   PeptideAtlas; Q2TAK8; -.
DR   ProteomicsDB; 61463; -. [Q2TAK8-1]
DR   ProteomicsDB; 61464; -. [Q2TAK8-2]
DR   Pumba; Q2TAK8; -.
DR   Antibodypedia; 10456; 279 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   AGR; HGNC:29641; -.
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; PPWAHRC; -.
DR   OrthoDB; 5403864at2759; -.
DR   PhylomeDB; Q2TAK8; -.
DR   PathwayCommons; Q2TAK8; -.
DR   SignaLink; Q2TAK8; -.
DR   BioGRID-ORCS; 84939; 19 hits in 1153 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 185 other cell types or tissues.
DR   ExpressionAtlas; Q2TAK8; baseline and differential.
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; PWWP_MUM1-like; 1.
DR   Gene3D; 2.30.30.140; -; 1.
DR   Gene3D; 6.10.300.20; -; 1.
DR   InterPro; IPR035504; MUM1-like_PWWP.
DR   InterPro; IPR040263; PWP3A_3B_4.
DR   InterPro; IPR048795; PWP3A_3B_4_C.
DR   InterPro; IPR048765; PWP3A_3B_4_N.
DR   PANTHER; PTHR31333; PWWP DOMAIN-CONTAINING DNA REPAIR FACTOR 3 FAMILY MEMBER; 1.
DR   PANTHER; PTHR31333:SF4; PWWP DOMAIN-CONTAINING DNA REPAIR FACTOR 3A; 1.
DR   Pfam; PF20884; MUM1-like_PWWP; 1.
DR   Pfam; PF20886; PWP3A-B_C; 1.
DR   Pfam; PF20887; PWP3A-B_N; 1.
DR   SUPFAM; SSF63748; Tudor/PWWP/MBT; 1.
DR   Genevisible; Q2TAK8; HS.
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
//