Full text data of MMS19
MMS19
(MMS19L)
[Confidence: low (only semi-automatic identification from reviews)]
MMS19 nucleotide excision repair protein homolog; hMMS19 (MET18 homolog; MMS19-like protein)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
MMS19 nucleotide excision repair protein homolog; hMMS19 (MET18 homolog; MMS19-like protein)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q96T76
ID MMS19_HUMAN Reviewed; 1030 AA.
AC Q96T76; B0QZ75; B3KPE5; B4DQX2; B4E2I3; D3DR55; F8W9Y2; Q17RZ8;
read moreAC Q5T455; Q66K82; Q7L4W8; Q969Z1; Q96DF1; Q96MR1; Q96RK5; Q96SK1;
AC Q9BUE2; Q9BYS9;
DT 13-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 26-JUN-2007, sequence version 2.
DT 22-JAN-2014, entry version 110.
DE RecName: Full=MMS19 nucleotide excision repair protein homolog;
DE Short=hMMS19;
DE AltName: Full=MET18 homolog;
DE AltName: Full=MMS19-like protein;
GN Name=MMS19; Synonyms=MMS19L;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT GLY-68, FUNCTION,
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND INTERACTION WITH ERCC2
RP AND ERCC3.
RC TISSUE=Cervix carcinoma;
RX PubMed=11071939; DOI=10.1093/nar/28.22.4506;
RA Seroz T., Winkler G.S., Auriol J., Verhage R.A., Vermeulen W.,
RA Smit B., Brouwer J., Eker A.P.M., Weeda G., Egly J.-M.,
RA Hoeijmakers J.H.J.;
RT "Cloning of a human homolog of the yeast nucleotide excision repair
RT gene MMS19 and interaction with transcription repair factor TFIIH via
RT the XPB and XPD helicases.";
RL Nucleic Acids Res. 28:4506-4513(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT GLY-68, INTERACTION
RP WITH NCOA3, AND SUBCELLULAR LOCATION.
RX PubMed=11279242; DOI=10.1074/jbc.M101041200;
RA Wu X., Li H., Chen J.D.;
RT "The human homologue of the yeast DNA repair and TFIIH regulator MMS19
RT is an AF-1-specific coactivator of estrogen receptor.";
RL J. Biol. Chem. 276:23962-23968(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, AND VARIANT GLY-68.
RX PubMed=11328871; DOI=10.1093/nar/29.9.1884;
RA Queimado L., Rao M., Schultz R.A., Koonin E.V., Aravind L., Nardo T.,
RA Stefanini M., Friedberg E.C.;
RT "Cloning the human and mouse MMS19 genes and functional
RT complementation of a yeast mms19 deletion mutant.";
RL Nucleic Acids Res. 29:1884-1891(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 5 AND 6), NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 48-1030 (ISOFORM 4), NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 127-1030 (ISOFORM 2), AND VARIANTS
RP GLY-68 AND ASP-790.
RC TISSUE=Teratocarcinoma, Tongue, and Trachea;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLY-68; TRP-98;
RP ILE-197; HIS-306; VAL-365; PRO-409; GLU-434; ILE-526; VAL-558; ASP-790
RP AND HIS-983.
RG NIEHS SNPs program;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
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.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA 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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLY-68.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND
RP VARIANTS GLY-68 AND ASP-790.
RC TISSUE=Brain, Lymph, and Uterus;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-496, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [11]
RP FUNCTION, IDENTIFICATION IN MMXD COMPLEX, INTERACTION WITH FAM96B, AND
RP SUBCELLULAR LOCATION.
RX PubMed=20797633; DOI=10.1016/j.molcel.2010.07.029;
RA Ito S., Tan L.J., Andoh D., Narita T., Seki M., Hirano Y., Narita K.,
RA Kuraoka I., Hiraoka Y., Tanaka K.;
RT "MMXD, a TFIIH-independent XPD-MMS19 protein complex involved in
RT chromosome segregation.";
RL Mol. Cell 39:632-640(2010).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1027, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP FUNCTION, AND IDENTIFICATION IN THE CIA COMPLEX.
RX PubMed=22678362; DOI=10.1126/science.1219723;
RA Stehling O., Vashisht A.A., Mascarenhas J., Jonsson Z.O., Sharma T.,
RA Netz D.J., Pierik A.J., Wohlschlegel J.A., Lill R.;
RT "MMS19 assembles iron-sulfur proteins required for DNA metabolism and
RT genomic integrity.";
RL Science 337:195-199(2012).
RN [15]
RP FUNCTION, IDENTIFICATION IN THE CIA COMPLEX, AND SUBCELLULAR LOCATION.
RX PubMed=22678361; DOI=10.1126/science.1219664;
RA Gari K., Leon Ortiz A.M., Borel V., Flynn H., Skehel J.M.,
RA Boulton S.J.;
RT "MMS19 links cytoplasmic iron-sulfur cluster assembly to DNA
RT metabolism.";
RL Science 337:243-245(2012).
CC -!- FUNCTION: Key component of the cytosolic iron-sulfur protein
CC assembly (CIA) complex, a multiprotein complex that mediates the
CC incorporation of iron-sulfur cluster into apoproteins specifically
CC involved in DNA metabolism and genomic integrity. In the CIA
CC complex, MMS19 acts as an adapter between early-acting CIA
CC components and a subset of cellular target iron-sulfur proteins
CC such as ERCC2/XPD, FANCJ and RTEL1, thereby playing a key role in
CC nucleotide excision repair (NER) and RNA polymerase II (POL II)
CC transcription. As part of the mitotic spindle-associated MMXD
CC complex, plays a role in chromosome segregation, probably by
CC facilitating iron-sulfur cluster assembly into ERCC2/XPD.
CC Indirectly acts as a transcriptional coactivator of estrogen
CC receptor (ER), via its role in iron-sulfur insertion into some
CC component of the TFIIH-machinery.
CC -!- SUBUNIT: Component of the CIA complex. Component of the MMXD
CC complex, composed of CIAO1, ERCC2, FAM96B, MMS19 and SLC25A5.
CC Interacts with FAM96B; the interaction is direct. Interacts with
CC ERCC2/XPD; the interaction is direct. Interacts with ERCC3/XPB and
CC NCOA3/RAC3.
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm, cytoskeleton, spindle.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1;
CC IsoId=Q96T76-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96T76-7; Sequence=VSP_040312, VSP_040313;
CC Note=May be produced at very low levels due to a premature stop
CC codon in the mRNA, leading to nonsense-mediated mRNA decay;
CC Name=3;
CC IsoId=Q96T76-6; Sequence=VSP_040310, VSP_040311;
CC Note=No experimental confirmation available. May be produced at
CC very low levels due to a premature stop codon in the mRNA,
CC leading to nonsense-mediated mRNA decay;
CC Name=4;
CC IsoId=Q96T76-5; Sequence=VSP_015565;
CC Note=No experimental confirmation available;
CC Name=5;
CC IsoId=Q96T76-8; Sequence=VSP_044182;
CC Note=No experimental confirmation available;
CC Name=6;
CC IsoId=Q96T76-9; Sequence=VSP_044183;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed with higher expression
CC in testis.
CC -!- SIMILARITY: Belongs to the MET18/MMS19 family.
CC -!- SIMILARITY: Contains 7 HEAT repeats.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH80532.1; Type=Erroneous translation; Note=Wrong choice of CDS;
CC Sequence=BAB55315.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=BAB71223.1; Type=Erroneous translation; Note=Wrong choice of CDS;
CC Sequence=BAG51657.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=CAC29239.1; Type=Frameshift; Positions=373, 412;
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/mms19l/";
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DR EMBL; AJ306408; CAC29239.1; ALT_FRAME; mRNA.
DR EMBL; AF357881; AAK70402.1; -; mRNA.
DR EMBL; AF319947; AAK52668.1; -; mRNA.
DR EMBL; AK027710; BAB55315.1; ALT_INIT; mRNA.
DR EMBL; AK056244; BAG51657.1; ALT_INIT; mRNA.
DR EMBL; AK056581; BAB71223.1; ALT_SEQ; mRNA.
DR EMBL; AK298995; BAG61084.1; -; mRNA.
DR EMBL; AK304287; BAG65145.1; -; mRNA.
DR EMBL; AY974244; AAX59033.1; -; Genomic_DNA.
DR EMBL; AL355490; CAI40770.1; -; Genomic_DNA.
DR EMBL; AL359388; CAI40770.1; JOINED; Genomic_DNA.
DR EMBL; AL355490; CAQ10792.1; -; Genomic_DNA.
DR EMBL; AL359388; CAQ10792.1; JOINED; Genomic_DNA.
DR EMBL; AL359388; CAI14189.1; -; Genomic_DNA.
DR EMBL; AL355490; CAI14189.1; JOINED; Genomic_DNA.
DR EMBL; AL359388; CAQ08641.1; -; Genomic_DNA.
DR EMBL; AL355490; CAQ08641.1; JOINED; Genomic_DNA.
DR EMBL; CH471066; EAW49924.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49927.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49928.1; -; Genomic_DNA.
DR EMBL; BC002692; AAH02692.1; -; mRNA.
DR EMBL; BC006575; AAH06575.2; -; mRNA.
DR EMBL; BC009396; AAH09396.2; -; mRNA.
DR EMBL; BC080532; AAH80532.1; ALT_SEQ; mRNA.
DR EMBL; BC117129; AAI17130.1; -; mRNA.
DR RefSeq; NP_071757.4; NM_022362.4.
DR RefSeq; XP_005270096.1; XM_005270039.1.
DR UniGene; Hs.500721; -.
DR ProteinModelPortal; Q96T76; -.
DR IntAct; Q96T76; 5.
DR PhosphoSite; Q96T76; -.
DR DMDM; 150421597; -.
DR PaxDb; Q96T76; -.
DR PRIDE; Q96T76; -.
DR Ensembl; ENST00000327238; ENSP00000320059; ENSG00000155229.
DR Ensembl; ENST00000327277; ENSP00000322236; ENSG00000155229.
DR Ensembl; ENST00000355839; ENSP00000348097; ENSG00000155229.
DR Ensembl; ENST00000370782; ENSP00000359818; ENSG00000155229.
DR Ensembl; ENST00000415383; ENSP00000395045; ENSG00000155229.
DR Ensembl; ENST00000438925; ENSP00000412698; ENSG00000155229.
DR Ensembl; ENST00000441194; ENSP00000413801; ENSG00000155229.
DR GeneID; 64210; -.
DR KEGG; hsa:64210; -.
DR UCSC; uc001knr.3; human.
DR CTD; 64210; -.
DR GeneCards; GC10M099209; -.
DR H-InvDB; HIX0009091; -.
DR HGNC; HGNC:13824; MMS19.
DR HPA; HPA056299; -.
DR MIM; 614777; gene.
DR neXtProt; NX_Q96T76; -.
DR PharmGKB; PA162395974; -.
DR eggNOG; NOG320478; -.
DR HOVERGEN; HBG057358; -.
DR InParanoid; Q96T76; -.
DR KO; K15075; -.
DR OMA; LYPVAFS; -.
DR PhylomeDB; Q96T76; -.
DR Reactome; REACT_111217; Metabolism.
DR ChiTaRS; MMS19; human.
DR GeneWiki; MMS19; -.
DR GenomeRNAi; 64210; -.
DR NextBio; 66115; -.
DR PRO; PR:Q96T76; -.
DR ArrayExpress; Q96T76; -.
DR Bgee; Q96T76; -.
DR CleanEx; HS_MMS19; -.
DR Genevestigator; Q96T76; -.
DR GO; GO:0097361; C:CIA complex; IDA:UniProtKB.
DR GO; GO:0005675; C:holo TFIIH complex; NAS:UniProtKB.
DR GO; GO:0071817; C:MMXD complex; IDA:UniProtKB.
DR GO; GO:0030674; F:protein binding, bridging; NAS:UniProtKB.
DR GO; GO:0030159; F:receptor signaling complex scaffold activity; NAS:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; IMP:UniProtKB.
DR GO; GO:0007059; P:chromosome segregation; IMP:UniProtKB.
DR GO; GO:0016226; P:iron-sulfur cluster assembly; IMP:UniProtKB.
DR GO; GO:0006289; P:nucleotide-excision repair; NAS:UniProtKB.
DR GO; GO:0000160; P:phosphorelay signal transduction system; NAS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-dependent; IMP:UniProtKB.
DR GO; GO:0009725; P:response to hormone stimulus; NAS:UniProtKB.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR GO; GO:0006351; P:transcription, DNA-dependent; NAS:UniProtKB.
DR Gene3D; 1.25.10.10; -; 2.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR024687; Tscrpt_C.
DR Pfam; PF12460; MMS19_C; 1.
DR SUPFAM; SSF48371; SSF48371; 5.
DR PROSITE; PS50077; HEAT_REPEAT; FALSE_NEG.
PE 1: Evidence at protein level;
KW Acetylation; Activator; Alternative splicing; Chromosome partition;
KW Complete proteome; Cytoplasm; Cytoskeleton; DNA damage; DNA repair;
KW Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat;
KW Transcription; Transcription regulation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 1030 MMS19 nucleotide excision repair protein
FT homolog.
FT /FTId=PRO_0000096514.
FT REPEAT 43 81 HEAT 1.
FT REPEAT 253 291 HEAT 2.
FT REPEAT 387 426 HEAT 3.
FT REPEAT 866 904 HEAT 4.
FT REPEAT 908 946 HEAT 5.
FT REPEAT 949 987 HEAT 6.
FT REPEAT 990 1028 HEAT 7.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 496 496 N6-acetyllysine.
FT MOD_RES 1027 1027 Phosphoserine.
FT VAR_SEQ 1 1 M -> MRGEPVSSHRPYPLPRSLVRVM (in isoform
FT 5).
FT /FTId=VSP_044182.
FT VAR_SEQ 38 40 DVK -> GPL (in isoform 3).
FT /FTId=VSP_040310.
FT VAR_SEQ 41 1030 Missing (in isoform 3).
FT /FTId=VSP_040311.
FT VAR_SEQ 165 207 Missing (in isoform 6).
FT /FTId=VSP_044183.
FT VAR_SEQ 309 406 Missing (in isoform 4).
FT /FTId=VSP_015565.
FT VAR_SEQ 309 318 VFQTASERVE -> TAGTTCVNRT (in isoform 2).
FT /FTId=VSP_040312.
FT VAR_SEQ 319 1030 Missing (in isoform 2).
FT /FTId=VSP_040313.
FT VARIANT 68 68 A -> G (in dbSNP:rs2275586).
FT /FTId=VAR_023448.
FT VARIANT 98 98 R -> W (in dbSNP:rs29001280).
FT /FTId=VAR_023449.
FT VARIANT 197 197 V -> I (in dbSNP:rs29001285).
FT /FTId=VAR_023450.
FT VARIANT 306 306 R -> H (in dbSNP:rs29001306).
FT /FTId=VAR_023451.
FT VARIANT 365 365 M -> V (in dbSNP:rs29001309).
FT /FTId=VAR_023452.
FT VARIANT 409 409 Q -> P (in dbSNP:rs29001311).
FT /FTId=VAR_023453.
FT VARIANT 434 434 Q -> E (in dbSNP:rs29001314).
FT /FTId=VAR_023454.
FT VARIANT 526 526 V -> I (in dbSNP:rs17112809).
FT /FTId=VAR_023455.
FT VARIANT 558 558 A -> V (in dbSNP:rs12360068).
FT /FTId=VAR_023456.
FT VARIANT 790 790 G -> D (in dbSNP:rs3740526).
FT /FTId=VAR_023457.
FT VARIANT 983 983 R -> H (in dbSNP:rs29001332).
FT /FTId=VAR_023458.
FT CONFLICT 179 179 Q -> H (in Ref. 2; AAK70402).
FT CONFLICT 389 389 V -> D (in Ref. 2; AAK70402).
FT CONFLICT 394 394 L -> P (in Ref. 2; AAK70402).
FT CONFLICT 473 473 Q -> R (in Ref. 4; BAG51657).
FT CONFLICT 502 503 CR -> W (in Ref. 4; BAG51657).
FT CONFLICT 607 607 E -> K (in Ref. 4; BAG65145).
FT CONFLICT 640 640 E -> G (in Ref. 4; BAB55315).
FT CONFLICT 661 661 I -> V (in Ref. 4; BAG65145).
FT CONFLICT 741 741 L -> F (in Ref. 2; AAK70402).
SQ SEQUENCE 1030 AA; 113290 MW; 7EC22CF0E38EFE1D CRC64;
MAAAAAVEAA APMGALWGLV HDFVVGQQEG PADQVAADVK SGNYTVLQVV EALGSSLENP
EPRTRARAIQ LLSQVLLHCH TLLLEKEVVH LILFYENRLK DHHLVIPSVL QGLKALSLCV
ALPPGLAVSV LKAIFQEVHV QSLPQVDRHT VYNIITNFMR TREEELKSLG ADFTFGFIQV
MDGEKDPRNL LVAFRIVHDL ISRDYSLGPF VEELFEVTSC YFPIDFTPPP NDPHGIQRED
LILSLRAVLA STPRFAEFLL PLLIEKVDSE VLSAKLDSLQ TLNACCAVYG QKELKDFLPS
LWASIRREVF QTASERVEAE GLAALHSLTA CLSRSVLRAD AEDLLDSFLS NILQDCRHHL
CEPDMKLVWP SAKLLQAAAG ASARACDSVT SNVLPLLLEQ FHKHSQSSQR RTILEMLLGF
LKLQQKWSYE DKDQRPLNGF KDQLCSLVFM ALTDPSTQLQ LVGIRTLTVL GAQPDLLSYE
DLELAVGHLY RLSFLKEDSQ SCRVAALEAS GTLAALYPVA FSSHLVPKLA EELRVGESNL
TNGDEPTQCS RHLCCLQALS AVSTHPSIVK ETLPLLLQHL WQVNRGNMVA QSSDVIAVCQ
SLRQMAEKCQ QDPESCWYFH QTAIPCLLAL AVQASMPEKE PSVLRKVLLE DEVLAAMVSV
IGTATTHLSP ELAAQSVTHI VPLFLDGNVS FLPENSFPSR FQPFQDGSSG QRRLIALLMA
FVCSLPRNVE IPQLNQLMRE LLELSCCHSC PFSSTAAAKC FAGLLNKHPA GQQLDEFLQL
AVDKVEAGLG SGPCRSQAFT LLLWVTKALV LRYHPLSSCL TARLMGLLSD PELGPAAADG
FSLLMSDCTD VLTRAGHAEV RIMFRQRFFT DNVPALVQGF HAAPQDVKPN YLKGLSHVLN
RLPKPVLLPE LPTLLSLLLE ALSCPDCVVQ LSTLSCLQPL LLEAPQVMSL HVDTLVTKFL
NLSSSPSMAV RIAALQCMHA LTRLPTPVLL PYKPQVIRAL AKPLDDKKRL VRKEAVSARG
EWFLLGSPGS
//
ID MMS19_HUMAN Reviewed; 1030 AA.
AC Q96T76; B0QZ75; B3KPE5; B4DQX2; B4E2I3; D3DR55; F8W9Y2; Q17RZ8;
read moreAC Q5T455; Q66K82; Q7L4W8; Q969Z1; Q96DF1; Q96MR1; Q96RK5; Q96SK1;
AC Q9BUE2; Q9BYS9;
DT 13-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 26-JUN-2007, sequence version 2.
DT 22-JAN-2014, entry version 110.
DE RecName: Full=MMS19 nucleotide excision repair protein homolog;
DE Short=hMMS19;
DE AltName: Full=MET18 homolog;
DE AltName: Full=MMS19-like protein;
GN Name=MMS19; Synonyms=MMS19L;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT GLY-68, FUNCTION,
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND INTERACTION WITH ERCC2
RP AND ERCC3.
RC TISSUE=Cervix carcinoma;
RX PubMed=11071939; DOI=10.1093/nar/28.22.4506;
RA Seroz T., Winkler G.S., Auriol J., Verhage R.A., Vermeulen W.,
RA Smit B., Brouwer J., Eker A.P.M., Weeda G., Egly J.-M.,
RA Hoeijmakers J.H.J.;
RT "Cloning of a human homolog of the yeast nucleotide excision repair
RT gene MMS19 and interaction with transcription repair factor TFIIH via
RT the XPB and XPD helicases.";
RL Nucleic Acids Res. 28:4506-4513(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT GLY-68, INTERACTION
RP WITH NCOA3, AND SUBCELLULAR LOCATION.
RX PubMed=11279242; DOI=10.1074/jbc.M101041200;
RA Wu X., Li H., Chen J.D.;
RT "The human homologue of the yeast DNA repair and TFIIH regulator MMS19
RT is an AF-1-specific coactivator of estrogen receptor.";
RL J. Biol. Chem. 276:23962-23968(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, AND VARIANT GLY-68.
RX PubMed=11328871; DOI=10.1093/nar/29.9.1884;
RA Queimado L., Rao M., Schultz R.A., Koonin E.V., Aravind L., Nardo T.,
RA Stefanini M., Friedberg E.C.;
RT "Cloning the human and mouse MMS19 genes and functional
RT complementation of a yeast mms19 deletion mutant.";
RL Nucleic Acids Res. 29:1884-1891(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 5 AND 6), NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 48-1030 (ISOFORM 4), NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 127-1030 (ISOFORM 2), AND VARIANTS
RP GLY-68 AND ASP-790.
RC TISSUE=Teratocarcinoma, Tongue, and Trachea;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLY-68; TRP-98;
RP ILE-197; HIS-306; VAL-365; PRO-409; GLU-434; ILE-526; VAL-558; ASP-790
RP AND HIS-983.
RG NIEHS SNPs program;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
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.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA 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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLY-68.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND
RP VARIANTS GLY-68 AND ASP-790.
RC TISSUE=Brain, Lymph, and Uterus;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-496, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [11]
RP FUNCTION, IDENTIFICATION IN MMXD COMPLEX, INTERACTION WITH FAM96B, AND
RP SUBCELLULAR LOCATION.
RX PubMed=20797633; DOI=10.1016/j.molcel.2010.07.029;
RA Ito S., Tan L.J., Andoh D., Narita T., Seki M., Hirano Y., Narita K.,
RA Kuraoka I., Hiraoka Y., Tanaka K.;
RT "MMXD, a TFIIH-independent XPD-MMS19 protein complex involved in
RT chromosome segregation.";
RL Mol. Cell 39:632-640(2010).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1027, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP FUNCTION, AND IDENTIFICATION IN THE CIA COMPLEX.
RX PubMed=22678362; DOI=10.1126/science.1219723;
RA Stehling O., Vashisht A.A., Mascarenhas J., Jonsson Z.O., Sharma T.,
RA Netz D.J., Pierik A.J., Wohlschlegel J.A., Lill R.;
RT "MMS19 assembles iron-sulfur proteins required for DNA metabolism and
RT genomic integrity.";
RL Science 337:195-199(2012).
RN [15]
RP FUNCTION, IDENTIFICATION IN THE CIA COMPLEX, AND SUBCELLULAR LOCATION.
RX PubMed=22678361; DOI=10.1126/science.1219664;
RA Gari K., Leon Ortiz A.M., Borel V., Flynn H., Skehel J.M.,
RA Boulton S.J.;
RT "MMS19 links cytoplasmic iron-sulfur cluster assembly to DNA
RT metabolism.";
RL Science 337:243-245(2012).
CC -!- FUNCTION: Key component of the cytosolic iron-sulfur protein
CC assembly (CIA) complex, a multiprotein complex that mediates the
CC incorporation of iron-sulfur cluster into apoproteins specifically
CC involved in DNA metabolism and genomic integrity. In the CIA
CC complex, MMS19 acts as an adapter between early-acting CIA
CC components and a subset of cellular target iron-sulfur proteins
CC such as ERCC2/XPD, FANCJ and RTEL1, thereby playing a key role in
CC nucleotide excision repair (NER) and RNA polymerase II (POL II)
CC transcription. As part of the mitotic spindle-associated MMXD
CC complex, plays a role in chromosome segregation, probably by
CC facilitating iron-sulfur cluster assembly into ERCC2/XPD.
CC Indirectly acts as a transcriptional coactivator of estrogen
CC receptor (ER), via its role in iron-sulfur insertion into some
CC component of the TFIIH-machinery.
CC -!- SUBUNIT: Component of the CIA complex. Component of the MMXD
CC complex, composed of CIAO1, ERCC2, FAM96B, MMS19 and SLC25A5.
CC Interacts with FAM96B; the interaction is direct. Interacts with
CC ERCC2/XPD; the interaction is direct. Interacts with ERCC3/XPB and
CC NCOA3/RAC3.
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm, cytoskeleton, spindle.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1;
CC IsoId=Q96T76-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96T76-7; Sequence=VSP_040312, VSP_040313;
CC Note=May be produced at very low levels due to a premature stop
CC codon in the mRNA, leading to nonsense-mediated mRNA decay;
CC Name=3;
CC IsoId=Q96T76-6; Sequence=VSP_040310, VSP_040311;
CC Note=No experimental confirmation available. May be produced at
CC very low levels due to a premature stop codon in the mRNA,
CC leading to nonsense-mediated mRNA decay;
CC Name=4;
CC IsoId=Q96T76-5; Sequence=VSP_015565;
CC Note=No experimental confirmation available;
CC Name=5;
CC IsoId=Q96T76-8; Sequence=VSP_044182;
CC Note=No experimental confirmation available;
CC Name=6;
CC IsoId=Q96T76-9; Sequence=VSP_044183;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed with higher expression
CC in testis.
CC -!- SIMILARITY: Belongs to the MET18/MMS19 family.
CC -!- SIMILARITY: Contains 7 HEAT repeats.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH80532.1; Type=Erroneous translation; Note=Wrong choice of CDS;
CC Sequence=BAB55315.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=BAB71223.1; Type=Erroneous translation; Note=Wrong choice of CDS;
CC Sequence=BAG51657.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=CAC29239.1; Type=Frameshift; Positions=373, 412;
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/mms19l/";
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DR EMBL; AJ306408; CAC29239.1; ALT_FRAME; mRNA.
DR EMBL; AF357881; AAK70402.1; -; mRNA.
DR EMBL; AF319947; AAK52668.1; -; mRNA.
DR EMBL; AK027710; BAB55315.1; ALT_INIT; mRNA.
DR EMBL; AK056244; BAG51657.1; ALT_INIT; mRNA.
DR EMBL; AK056581; BAB71223.1; ALT_SEQ; mRNA.
DR EMBL; AK298995; BAG61084.1; -; mRNA.
DR EMBL; AK304287; BAG65145.1; -; mRNA.
DR EMBL; AY974244; AAX59033.1; -; Genomic_DNA.
DR EMBL; AL355490; CAI40770.1; -; Genomic_DNA.
DR EMBL; AL359388; CAI40770.1; JOINED; Genomic_DNA.
DR EMBL; AL355490; CAQ10792.1; -; Genomic_DNA.
DR EMBL; AL359388; CAQ10792.1; JOINED; Genomic_DNA.
DR EMBL; AL359388; CAI14189.1; -; Genomic_DNA.
DR EMBL; AL355490; CAI14189.1; JOINED; Genomic_DNA.
DR EMBL; AL359388; CAQ08641.1; -; Genomic_DNA.
DR EMBL; AL355490; CAQ08641.1; JOINED; Genomic_DNA.
DR EMBL; CH471066; EAW49924.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49927.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49928.1; -; Genomic_DNA.
DR EMBL; BC002692; AAH02692.1; -; mRNA.
DR EMBL; BC006575; AAH06575.2; -; mRNA.
DR EMBL; BC009396; AAH09396.2; -; mRNA.
DR EMBL; BC080532; AAH80532.1; ALT_SEQ; mRNA.
DR EMBL; BC117129; AAI17130.1; -; mRNA.
DR RefSeq; NP_071757.4; NM_022362.4.
DR RefSeq; XP_005270096.1; XM_005270039.1.
DR UniGene; Hs.500721; -.
DR ProteinModelPortal; Q96T76; -.
DR IntAct; Q96T76; 5.
DR PhosphoSite; Q96T76; -.
DR DMDM; 150421597; -.
DR PaxDb; Q96T76; -.
DR PRIDE; Q96T76; -.
DR Ensembl; ENST00000327238; ENSP00000320059; ENSG00000155229.
DR Ensembl; ENST00000327277; ENSP00000322236; ENSG00000155229.
DR Ensembl; ENST00000355839; ENSP00000348097; ENSG00000155229.
DR Ensembl; ENST00000370782; ENSP00000359818; ENSG00000155229.
DR Ensembl; ENST00000415383; ENSP00000395045; ENSG00000155229.
DR Ensembl; ENST00000438925; ENSP00000412698; ENSG00000155229.
DR Ensembl; ENST00000441194; ENSP00000413801; ENSG00000155229.
DR GeneID; 64210; -.
DR KEGG; hsa:64210; -.
DR UCSC; uc001knr.3; human.
DR CTD; 64210; -.
DR GeneCards; GC10M099209; -.
DR H-InvDB; HIX0009091; -.
DR HGNC; HGNC:13824; MMS19.
DR HPA; HPA056299; -.
DR MIM; 614777; gene.
DR neXtProt; NX_Q96T76; -.
DR PharmGKB; PA162395974; -.
DR eggNOG; NOG320478; -.
DR HOVERGEN; HBG057358; -.
DR InParanoid; Q96T76; -.
DR KO; K15075; -.
DR OMA; LYPVAFS; -.
DR PhylomeDB; Q96T76; -.
DR Reactome; REACT_111217; Metabolism.
DR ChiTaRS; MMS19; human.
DR GeneWiki; MMS19; -.
DR GenomeRNAi; 64210; -.
DR NextBio; 66115; -.
DR PRO; PR:Q96T76; -.
DR ArrayExpress; Q96T76; -.
DR Bgee; Q96T76; -.
DR CleanEx; HS_MMS19; -.
DR Genevestigator; Q96T76; -.
DR GO; GO:0097361; C:CIA complex; IDA:UniProtKB.
DR GO; GO:0005675; C:holo TFIIH complex; NAS:UniProtKB.
DR GO; GO:0071817; C:MMXD complex; IDA:UniProtKB.
DR GO; GO:0030674; F:protein binding, bridging; NAS:UniProtKB.
DR GO; GO:0030159; F:receptor signaling complex scaffold activity; NAS:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; IMP:UniProtKB.
DR GO; GO:0007059; P:chromosome segregation; IMP:UniProtKB.
DR GO; GO:0016226; P:iron-sulfur cluster assembly; IMP:UniProtKB.
DR GO; GO:0006289; P:nucleotide-excision repair; NAS:UniProtKB.
DR GO; GO:0000160; P:phosphorelay signal transduction system; NAS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-dependent; IMP:UniProtKB.
DR GO; GO:0009725; P:response to hormone stimulus; NAS:UniProtKB.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR GO; GO:0006351; P:transcription, DNA-dependent; NAS:UniProtKB.
DR Gene3D; 1.25.10.10; -; 2.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR024687; Tscrpt_C.
DR Pfam; PF12460; MMS19_C; 1.
DR SUPFAM; SSF48371; SSF48371; 5.
DR PROSITE; PS50077; HEAT_REPEAT; FALSE_NEG.
PE 1: Evidence at protein level;
KW Acetylation; Activator; Alternative splicing; Chromosome partition;
KW Complete proteome; Cytoplasm; Cytoskeleton; DNA damage; DNA repair;
KW Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat;
KW Transcription; Transcription regulation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 1030 MMS19 nucleotide excision repair protein
FT homolog.
FT /FTId=PRO_0000096514.
FT REPEAT 43 81 HEAT 1.
FT REPEAT 253 291 HEAT 2.
FT REPEAT 387 426 HEAT 3.
FT REPEAT 866 904 HEAT 4.
FT REPEAT 908 946 HEAT 5.
FT REPEAT 949 987 HEAT 6.
FT REPEAT 990 1028 HEAT 7.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 496 496 N6-acetyllysine.
FT MOD_RES 1027 1027 Phosphoserine.
FT VAR_SEQ 1 1 M -> MRGEPVSSHRPYPLPRSLVRVM (in isoform
FT 5).
FT /FTId=VSP_044182.
FT VAR_SEQ 38 40 DVK -> GPL (in isoform 3).
FT /FTId=VSP_040310.
FT VAR_SEQ 41 1030 Missing (in isoform 3).
FT /FTId=VSP_040311.
FT VAR_SEQ 165 207 Missing (in isoform 6).
FT /FTId=VSP_044183.
FT VAR_SEQ 309 406 Missing (in isoform 4).
FT /FTId=VSP_015565.
FT VAR_SEQ 309 318 VFQTASERVE -> TAGTTCVNRT (in isoform 2).
FT /FTId=VSP_040312.
FT VAR_SEQ 319 1030 Missing (in isoform 2).
FT /FTId=VSP_040313.
FT VARIANT 68 68 A -> G (in dbSNP:rs2275586).
FT /FTId=VAR_023448.
FT VARIANT 98 98 R -> W (in dbSNP:rs29001280).
FT /FTId=VAR_023449.
FT VARIANT 197 197 V -> I (in dbSNP:rs29001285).
FT /FTId=VAR_023450.
FT VARIANT 306 306 R -> H (in dbSNP:rs29001306).
FT /FTId=VAR_023451.
FT VARIANT 365 365 M -> V (in dbSNP:rs29001309).
FT /FTId=VAR_023452.
FT VARIANT 409 409 Q -> P (in dbSNP:rs29001311).
FT /FTId=VAR_023453.
FT VARIANT 434 434 Q -> E (in dbSNP:rs29001314).
FT /FTId=VAR_023454.
FT VARIANT 526 526 V -> I (in dbSNP:rs17112809).
FT /FTId=VAR_023455.
FT VARIANT 558 558 A -> V (in dbSNP:rs12360068).
FT /FTId=VAR_023456.
FT VARIANT 790 790 G -> D (in dbSNP:rs3740526).
FT /FTId=VAR_023457.
FT VARIANT 983 983 R -> H (in dbSNP:rs29001332).
FT /FTId=VAR_023458.
FT CONFLICT 179 179 Q -> H (in Ref. 2; AAK70402).
FT CONFLICT 389 389 V -> D (in Ref. 2; AAK70402).
FT CONFLICT 394 394 L -> P (in Ref. 2; AAK70402).
FT CONFLICT 473 473 Q -> R (in Ref. 4; BAG51657).
FT CONFLICT 502 503 CR -> W (in Ref. 4; BAG51657).
FT CONFLICT 607 607 E -> K (in Ref. 4; BAG65145).
FT CONFLICT 640 640 E -> G (in Ref. 4; BAB55315).
FT CONFLICT 661 661 I -> V (in Ref. 4; BAG65145).
FT CONFLICT 741 741 L -> F (in Ref. 2; AAK70402).
SQ SEQUENCE 1030 AA; 113290 MW; 7EC22CF0E38EFE1D CRC64;
MAAAAAVEAA APMGALWGLV HDFVVGQQEG PADQVAADVK SGNYTVLQVV EALGSSLENP
EPRTRARAIQ LLSQVLLHCH TLLLEKEVVH LILFYENRLK DHHLVIPSVL QGLKALSLCV
ALPPGLAVSV LKAIFQEVHV QSLPQVDRHT VYNIITNFMR TREEELKSLG ADFTFGFIQV
MDGEKDPRNL LVAFRIVHDL ISRDYSLGPF VEELFEVTSC YFPIDFTPPP NDPHGIQRED
LILSLRAVLA STPRFAEFLL PLLIEKVDSE VLSAKLDSLQ TLNACCAVYG QKELKDFLPS
LWASIRREVF QTASERVEAE GLAALHSLTA CLSRSVLRAD AEDLLDSFLS NILQDCRHHL
CEPDMKLVWP SAKLLQAAAG ASARACDSVT SNVLPLLLEQ FHKHSQSSQR RTILEMLLGF
LKLQQKWSYE DKDQRPLNGF KDQLCSLVFM ALTDPSTQLQ LVGIRTLTVL GAQPDLLSYE
DLELAVGHLY RLSFLKEDSQ SCRVAALEAS GTLAALYPVA FSSHLVPKLA EELRVGESNL
TNGDEPTQCS RHLCCLQALS AVSTHPSIVK ETLPLLLQHL WQVNRGNMVA QSSDVIAVCQ
SLRQMAEKCQ QDPESCWYFH QTAIPCLLAL AVQASMPEKE PSVLRKVLLE DEVLAAMVSV
IGTATTHLSP ELAAQSVTHI VPLFLDGNVS FLPENSFPSR FQPFQDGSSG QRRLIALLMA
FVCSLPRNVE IPQLNQLMRE LLELSCCHSC PFSSTAAAKC FAGLLNKHPA GQQLDEFLQL
AVDKVEAGLG SGPCRSQAFT LLLWVTKALV LRYHPLSSCL TARLMGLLSD PELGPAAADG
FSLLMSDCTD VLTRAGHAEV RIMFRQRFFT DNVPALVQGF HAAPQDVKPN YLKGLSHVLN
RLPKPVLLPE LPTLLSLLLE ALSCPDCVVQ LSTLSCLQPL LLEAPQVMSL HVDTLVTKFL
NLSSSPSMAV RIAALQCMHA LTRLPTPVLL PYKPQVIRAL AKPLDDKKRL VRKEAVSARG
EWFLLGSPGS
//
MIM
614777
*RECORD*
*FIELD* NO
614777
*FIELD* TI
*614777 MMS19 NUCLEOTIDE EXCISION REPAIR, S. CEREVISIAE, HOMOLOG OF; MMS19
;;MMS19-LIKE PROTEIN; MMS19L
read more*FIELD* TX
DESCRIPTION
MMS19 has a critical role in the biogenesis of multiple Fe-S proteins
that function in genomic stability, RNA polymerase II function, and
telomere length regulation (Stehling et al., 2012; Gari et al., 2012).
CLONING
By searching databases for sequences similar to S. cerevisiae Mms19,
followed by RT-PCR and screening of a HeLa cell cDNA library, Seroz et
al. (2000) cloned MMS19. The deduced 1,030-amino acid protein has a
calculated molecular mass of 113 kD. MMS19 has an alanine- and
leucine-rich N terminus and several putative phosphorylation sites.
Northern blot analysis detected a 4-kb transcript in HeLa cells and in
all mouse tissues examined, with highest expression in testis.
By RT-PCR of HeLa cells and testis cDNA libraries, and 5-prime RACE,
Queimado et al. (2001) cloned 7 splice variants of MMS19. Two major
transcripts differ in their 5-prime UTRs and encode an identical
full-length protein of 1,030 amino acids. Other transcripts differ in
splicing of 5-prime exons and encode proteins that are 43, 158, or 201
amino acids shorter at their N-terminal ends. Full-length MMS19 contains
2 conserved globular domains. The N-terminal globular domain has a
highly conserved sequence of about 120 amino acids; a shorter globular
region at the C terminus contains 4 tightly spaced HEAT repeats that are
predicted to form tandem bihelical structures and function as scaffolds
for assembly of other protein subunits. Northern blot analysis detected
variable expression of major transcripts at 3.9 and 4.8 in all human
tissues examined. Each band appeared to be a heterogeneous collection of
alternatively spliced forms, and the difference in size appeared to be
due to use of alternate polyadenylation signals. Queimado et al. (2001)
also cloned Mms19 splice variants from mouse. The deduced full-length
mouse protein contains 1,031 amino acids and shares 90% sequence
identity with full-length human MMS19.
Wu et al. (2001) independently cloned MMS19 from a placenta cDNA
library. The deduced protein contains 1,030 amino acids. Northern blot
analysis detected a 4-kb MMS19 transcript in all cancer cell lines and
human tissues examined. Immunofluorescence analysis localized MMS19 to
the nucleus of HeLa cells.
Hatfield et al. (2006) identified 3 conserved domains in the full-length
MMS19 protein, which they called domains A, B, and C. The approximately
160-amino acid N-terminal A domain is followed immediately by the B
domain with 2 highly conserved motifs; the C domain constitutes the
C-terminal HEAT repeats. Alternative splicing deletes the A domain
and/or motif 1 of the B domain. Hatfield et al. (2006) also identified
MMS19 splice variants that lack exon 24, in addition to various other
5-prime exons, and these transcripts encode 3 different proteins lacking
domain C. RT-PCR detected transcripts lacking exon 24 in all normal
tissues examined; however, full-length MMS19 represented 80 to 90% of
all MMS19 transcripts.
GENE FUNCTION
By coimmunoprecipitation of HeLa cell lysates, Seroz et al. (2000) found
that MMS19 interacted specifically with the transcription factor IIH
(TFIIH) helicase subunits XPB (ERCC3; 133510) and XPD (ERCC2; 126340).
Queimado et al. (2001) found that expression of MMS19 complemented
ultraviolet (UV) radiation sensitivity and thermosensitivity, but not
methionine auxotrophy, in Mms19 mutant yeast.
Using yeast 2-hybrid analysis, Wu et al. (2001) found that the basic
helix-loop-helix (bHLH)-PAS domain of RAC3 (NCOA3; 601937) interacted
with the C-terminal domain of MMS19. Mutation analysis revealed that
MMS19 interacted with the PAS-A and PAS-B domains, but not the bHLH
domain, in a synergistic manner. Both the isolated C-terminal domain and
full-length MMS19 also interacted with estrogen receptors ESR-alpha
(ESR1; 133430) and ESR-beta (ESR2; 601663) in an estrogen-independent
manner, and activated an ESR reporter gene in an estrogen-dependent
manner. MMS19 also enhanced RAC3-dependent ESR activation. MMS19
specifically enhanced the activity of the N-terminal, but not the
C-terminal, transactivation domain of ESR-alpha. However, the isolated
C-terminal domain of MMS19 functioned in a dominant-negative manner,
which was reversed by coexpression of RAC3. Since the C-terminal domain
of MMS19 interacted with both ESR and RAC3, Wu et al. (2001) proposed
that the interactions may be mutually exclusive and regulatory.
Nucleotide excision repair (NER) and RNA polymerase II (see 180660)
transcription share TFIIH subunits, and yeast Mms19 has a role in both
processes. Using yeast complementation assays, Hatfield et al. (2006)
found that human MMS19 proteins lacking domain A functioned as
efficiently as full-length MMS19 in rescuing UV radiation-induced NER,
but not transcription, in yeast lacking Mms19. Conversely, MMS19
proteins lacking motif 1 of domain B were efficient in transcription,
but not in NER. MMS19 proteins lacking domain C (HEAT repeats) were
unable to fulfill either function. No human MMS19 construct complemented
the methionine auxotrophy in Mms19 mutant yeast, likely due to the
significant divergence between yeast and human cells in methionine
metabolism. Hatfield et al. (2006) proposed that the HEAT repeats
stabilize an MMS19-associated complex whereas domains A and B have
unique roles in NER and transcription.
Ito et al. (2010) showed that MSS19 coprecipitated with XPD, MIP18
(FAM96B; 614778), CIAO1 (604333) and ANT2 (SLC25A5; 300150) in a protein
complex that was required for chromosome segregation in human cell
lines.
Stehling et al. (2012) found that yeast Mms19 functioned late in
cytosolic Fe-S protein assembly in a complex with Cia1 (CIAO1) and Cia2,
which they called the cytosolic iron-sulfur protein assembly (CIA)
complex. Using RNA interference in HeLa cells, they found that MMS19 was
involved in biosynthesis of only a subset of human Fe-S proteins,
including DPYD (612779) and POLD1 (174761), but not IRP1 (ACO1; 100800)
or GPAT (PPAT; 172450). Using a proteomic approach, Stehling et al.
(2012) identified proteins that interacted with MMS19 in HEK293 cells,
including a number of known and putative Fe-S proteins such as CIAO1,
IOP1 (NARFL; 611118), and FAM96B, and they confirmed interaction between
MMS19, CIAO1, and FAM96B. Inactivation of MMS19, FAM96B, and IOP1
reduced HEK293 cell survival following UV irradiation or methyl
methanesulfonate treatment. Stehling et al. (2012) hypothesized that the
MMS19 complex acts late in Fe-S protein biogenesis to facilitate Fe-S
cluster transfer from the CIA scaffold complex CFD1 (NUBP2; 610779)-
NBP35 (NUBP1; 600280) to Fe-S target proteins. They proposed that the
apparent diverse functions of MMS19 could be understood by its central
role in Fe-S protein biogenesis.
Using coimmunoprecipitation and gel filtration studies, Gari et al.
(2012) independently found that human MMS19 formed a stable CIA complex
with CIAO1, IOP1, and FAM96B. Knockdown of MMS19 via small interfering
RNA reduced the stability of FAM96B. MMS19 knockdown also decreased
cellular content of XPD, reduced association of XPD with TFIIH, and
increased association of XPD with CIAO1, suggesting that the interaction
of MMS19 with Fe-S proteins may be transient and possibly involves the
apoform of proteins prior to Fe-S cluster incorporation. Consistent with
this, chelation of Fe increased the levels of Fe-S proteins that
coimmunoprecipitated with MMS19, with the effect on DNA polymerase delta
(see 174761) being the most pronounced.
GENE STRUCTURE
Queimado et al. (2001) determined that the MMS19 gene contains at least
32 exons and spans over 40 kb. Exon 1 is noncoding, and translation is
initiated in exons 2 and 7. The 3-prime UTR contains 2 polyadenylation
signal motifs and is rich in Alu elements.
MAPPING
Using FISH, Seroz et al. (2000) mapped the MMS19 gene to chromosome
10q24-q25. Queimado et al. (2001) mapped the gene to chromosome 10q24 by
FISH and radiation hybrid analysis.
ANIMAL MODEL
Gari et al. (2012) found that knockdown of Mms19 in mice was embryonic
lethal prior to the implantation stage.
*FIELD* RF
1. Gari, K.; Ortiz, A. M. L.; Borel, V.; Flynn, H.; Skehel, J. M.;
Boulton, S. J.: MMS19 links cytoplasmic iron-sulfur cluster assembly
to DNA metabolism. Science 337: 243-245, 2012.
2. Hatfield, M. D.; Reis, A. M. C.; Obeso, D.; Cook, J. R.; Thompson,
D. M.; Rao, M.; Friedberg, E. C.; Queimado, L.: Identification of
MMS19 domains with distinct functions in NER and transcription. DNA
Repair 5: 914-924, 2006.
3. Ito, S.; Tan, L. J.; Andoh, D.; Narita, T.; Seki, M.; Hirano, Y.;
Narita, K.; Kuraoka, I.; Hiraoka, Y.; Tanaka, K.: MMXD, a TFIIH-independent
XPD-MMS19 protein complex involved in chromosome segregation. Molec.
Cell 39: 632-640, 2010.
4. Queimado, L.; Rao, M.; Schultz, R. A.; Koonin, E. V.; Aravind,
L.; Nardo, T.; Stefanini, M.; Friedberg, E. C.: Cloning the human
and mouse MMS19 genes and functional complementation of a yeast mms19
deletion mutant. Nucleic Acids Res. 29: 1884-1891, 2001.
5. Seroz, T.; Winkler, G. S.; Auriol, J.; Verhage, R. A.; Vermeulen,
W.; Smit, B.; Brouwer, J.; Eker, A. P. M. Weeda, G.; Egly, J.-M.;
Hoeijmakers, J. H. J.: Cloning of a human homolog of the yeast nucleotide
excision repair gene MMS19 and interaction with transcription repair
factor TFIIH via the XPB and XPD helicases. Nucleic Acids Res. 28:
4506-4513, 2000.
6. Stehling, O.; Vashisht, A. A.; Mascarenhas, J.; Jonsson, Z. O.;
Sharma, T.; Netz, D. J. A.; Pierik, A. J.; Wohlschlegel, J. A.; Lill,
R.: MMS19 assembles iron-sulfur proteins required for DNA metabolism
and genomic integrity. Science 337: 195-199, 2012.
7. Wu, X.; Li, H.; Chen, J. D.: The human homologue of the yeast
DNA repair and TFIIH regulator MMS19 is an AF-1-specific coactivator
of estrogen receptor. J. Biol. Chem. 276: 23962-23968, 2001.
*FIELD* CD
Patricia A. Hartz: 8/20/2012
*FIELD* ED
carol: 08/20/2012
carol: 8/20/2012
*RECORD*
*FIELD* NO
614777
*FIELD* TI
*614777 MMS19 NUCLEOTIDE EXCISION REPAIR, S. CEREVISIAE, HOMOLOG OF; MMS19
;;MMS19-LIKE PROTEIN; MMS19L
read more*FIELD* TX
DESCRIPTION
MMS19 has a critical role in the biogenesis of multiple Fe-S proteins
that function in genomic stability, RNA polymerase II function, and
telomere length regulation (Stehling et al., 2012; Gari et al., 2012).
CLONING
By searching databases for sequences similar to S. cerevisiae Mms19,
followed by RT-PCR and screening of a HeLa cell cDNA library, Seroz et
al. (2000) cloned MMS19. The deduced 1,030-amino acid protein has a
calculated molecular mass of 113 kD. MMS19 has an alanine- and
leucine-rich N terminus and several putative phosphorylation sites.
Northern blot analysis detected a 4-kb transcript in HeLa cells and in
all mouse tissues examined, with highest expression in testis.
By RT-PCR of HeLa cells and testis cDNA libraries, and 5-prime RACE,
Queimado et al. (2001) cloned 7 splice variants of MMS19. Two major
transcripts differ in their 5-prime UTRs and encode an identical
full-length protein of 1,030 amino acids. Other transcripts differ in
splicing of 5-prime exons and encode proteins that are 43, 158, or 201
amino acids shorter at their N-terminal ends. Full-length MMS19 contains
2 conserved globular domains. The N-terminal globular domain has a
highly conserved sequence of about 120 amino acids; a shorter globular
region at the C terminus contains 4 tightly spaced HEAT repeats that are
predicted to form tandem bihelical structures and function as scaffolds
for assembly of other protein subunits. Northern blot analysis detected
variable expression of major transcripts at 3.9 and 4.8 in all human
tissues examined. Each band appeared to be a heterogeneous collection of
alternatively spliced forms, and the difference in size appeared to be
due to use of alternate polyadenylation signals. Queimado et al. (2001)
also cloned Mms19 splice variants from mouse. The deduced full-length
mouse protein contains 1,031 amino acids and shares 90% sequence
identity with full-length human MMS19.
Wu et al. (2001) independently cloned MMS19 from a placenta cDNA
library. The deduced protein contains 1,030 amino acids. Northern blot
analysis detected a 4-kb MMS19 transcript in all cancer cell lines and
human tissues examined. Immunofluorescence analysis localized MMS19 to
the nucleus of HeLa cells.
Hatfield et al. (2006) identified 3 conserved domains in the full-length
MMS19 protein, which they called domains A, B, and C. The approximately
160-amino acid N-terminal A domain is followed immediately by the B
domain with 2 highly conserved motifs; the C domain constitutes the
C-terminal HEAT repeats. Alternative splicing deletes the A domain
and/or motif 1 of the B domain. Hatfield et al. (2006) also identified
MMS19 splice variants that lack exon 24, in addition to various other
5-prime exons, and these transcripts encode 3 different proteins lacking
domain C. RT-PCR detected transcripts lacking exon 24 in all normal
tissues examined; however, full-length MMS19 represented 80 to 90% of
all MMS19 transcripts.
GENE FUNCTION
By coimmunoprecipitation of HeLa cell lysates, Seroz et al. (2000) found
that MMS19 interacted specifically with the transcription factor IIH
(TFIIH) helicase subunits XPB (ERCC3; 133510) and XPD (ERCC2; 126340).
Queimado et al. (2001) found that expression of MMS19 complemented
ultraviolet (UV) radiation sensitivity and thermosensitivity, but not
methionine auxotrophy, in Mms19 mutant yeast.
Using yeast 2-hybrid analysis, Wu et al. (2001) found that the basic
helix-loop-helix (bHLH)-PAS domain of RAC3 (NCOA3; 601937) interacted
with the C-terminal domain of MMS19. Mutation analysis revealed that
MMS19 interacted with the PAS-A and PAS-B domains, but not the bHLH
domain, in a synergistic manner. Both the isolated C-terminal domain and
full-length MMS19 also interacted with estrogen receptors ESR-alpha
(ESR1; 133430) and ESR-beta (ESR2; 601663) in an estrogen-independent
manner, and activated an ESR reporter gene in an estrogen-dependent
manner. MMS19 also enhanced RAC3-dependent ESR activation. MMS19
specifically enhanced the activity of the N-terminal, but not the
C-terminal, transactivation domain of ESR-alpha. However, the isolated
C-terminal domain of MMS19 functioned in a dominant-negative manner,
which was reversed by coexpression of RAC3. Since the C-terminal domain
of MMS19 interacted with both ESR and RAC3, Wu et al. (2001) proposed
that the interactions may be mutually exclusive and regulatory.
Nucleotide excision repair (NER) and RNA polymerase II (see 180660)
transcription share TFIIH subunits, and yeast Mms19 has a role in both
processes. Using yeast complementation assays, Hatfield et al. (2006)
found that human MMS19 proteins lacking domain A functioned as
efficiently as full-length MMS19 in rescuing UV radiation-induced NER,
but not transcription, in yeast lacking Mms19. Conversely, MMS19
proteins lacking motif 1 of domain B were efficient in transcription,
but not in NER. MMS19 proteins lacking domain C (HEAT repeats) were
unable to fulfill either function. No human MMS19 construct complemented
the methionine auxotrophy in Mms19 mutant yeast, likely due to the
significant divergence between yeast and human cells in methionine
metabolism. Hatfield et al. (2006) proposed that the HEAT repeats
stabilize an MMS19-associated complex whereas domains A and B have
unique roles in NER and transcription.
Ito et al. (2010) showed that MSS19 coprecipitated with XPD, MIP18
(FAM96B; 614778), CIAO1 (604333) and ANT2 (SLC25A5; 300150) in a protein
complex that was required for chromosome segregation in human cell
lines.
Stehling et al. (2012) found that yeast Mms19 functioned late in
cytosolic Fe-S protein assembly in a complex with Cia1 (CIAO1) and Cia2,
which they called the cytosolic iron-sulfur protein assembly (CIA)
complex. Using RNA interference in HeLa cells, they found that MMS19 was
involved in biosynthesis of only a subset of human Fe-S proteins,
including DPYD (612779) and POLD1 (174761), but not IRP1 (ACO1; 100800)
or GPAT (PPAT; 172450). Using a proteomic approach, Stehling et al.
(2012) identified proteins that interacted with MMS19 in HEK293 cells,
including a number of known and putative Fe-S proteins such as CIAO1,
IOP1 (NARFL; 611118), and FAM96B, and they confirmed interaction between
MMS19, CIAO1, and FAM96B. Inactivation of MMS19, FAM96B, and IOP1
reduced HEK293 cell survival following UV irradiation or methyl
methanesulfonate treatment. Stehling et al. (2012) hypothesized that the
MMS19 complex acts late in Fe-S protein biogenesis to facilitate Fe-S
cluster transfer from the CIA scaffold complex CFD1 (NUBP2; 610779)-
NBP35 (NUBP1; 600280) to Fe-S target proteins. They proposed that the
apparent diverse functions of MMS19 could be understood by its central
role in Fe-S protein biogenesis.
Using coimmunoprecipitation and gel filtration studies, Gari et al.
(2012) independently found that human MMS19 formed a stable CIA complex
with CIAO1, IOP1, and FAM96B. Knockdown of MMS19 via small interfering
RNA reduced the stability of FAM96B. MMS19 knockdown also decreased
cellular content of XPD, reduced association of XPD with TFIIH, and
increased association of XPD with CIAO1, suggesting that the interaction
of MMS19 with Fe-S proteins may be transient and possibly involves the
apoform of proteins prior to Fe-S cluster incorporation. Consistent with
this, chelation of Fe increased the levels of Fe-S proteins that
coimmunoprecipitated with MMS19, with the effect on DNA polymerase delta
(see 174761) being the most pronounced.
GENE STRUCTURE
Queimado et al. (2001) determined that the MMS19 gene contains at least
32 exons and spans over 40 kb. Exon 1 is noncoding, and translation is
initiated in exons 2 and 7. The 3-prime UTR contains 2 polyadenylation
signal motifs and is rich in Alu elements.
MAPPING
Using FISH, Seroz et al. (2000) mapped the MMS19 gene to chromosome
10q24-q25. Queimado et al. (2001) mapped the gene to chromosome 10q24 by
FISH and radiation hybrid analysis.
ANIMAL MODEL
Gari et al. (2012) found that knockdown of Mms19 in mice was embryonic
lethal prior to the implantation stage.
*FIELD* RF
1. Gari, K.; Ortiz, A. M. L.; Borel, V.; Flynn, H.; Skehel, J. M.;
Boulton, S. J.: MMS19 links cytoplasmic iron-sulfur cluster assembly
to DNA metabolism. Science 337: 243-245, 2012.
2. Hatfield, M. D.; Reis, A. M. C.; Obeso, D.; Cook, J. R.; Thompson,
D. M.; Rao, M.; Friedberg, E. C.; Queimado, L.: Identification of
MMS19 domains with distinct functions in NER and transcription. DNA
Repair 5: 914-924, 2006.
3. Ito, S.; Tan, L. J.; Andoh, D.; Narita, T.; Seki, M.; Hirano, Y.;
Narita, K.; Kuraoka, I.; Hiraoka, Y.; Tanaka, K.: MMXD, a TFIIH-independent
XPD-MMS19 protein complex involved in chromosome segregation. Molec.
Cell 39: 632-640, 2010.
4. Queimado, L.; Rao, M.; Schultz, R. A.; Koonin, E. V.; Aravind,
L.; Nardo, T.; Stefanini, M.; Friedberg, E. C.: Cloning the human
and mouse MMS19 genes and functional complementation of a yeast mms19
deletion mutant. Nucleic Acids Res. 29: 1884-1891, 2001.
5. Seroz, T.; Winkler, G. S.; Auriol, J.; Verhage, R. A.; Vermeulen,
W.; Smit, B.; Brouwer, J.; Eker, A. P. M. Weeda, G.; Egly, J.-M.;
Hoeijmakers, J. H. J.: Cloning of a human homolog of the yeast nucleotide
excision repair gene MMS19 and interaction with transcription repair
factor TFIIH via the XPB and XPD helicases. Nucleic Acids Res. 28:
4506-4513, 2000.
6. Stehling, O.; Vashisht, A. A.; Mascarenhas, J.; Jonsson, Z. O.;
Sharma, T.; Netz, D. J. A.; Pierik, A. J.; Wohlschlegel, J. A.; Lill,
R.: MMS19 assembles iron-sulfur proteins required for DNA metabolism
and genomic integrity. Science 337: 195-199, 2012.
7. Wu, X.; Li, H.; Chen, J. D.: The human homologue of the yeast
DNA repair and TFIIH regulator MMS19 is an AF-1-specific coactivator
of estrogen receptor. J. Biol. Chem. 276: 23962-23968, 2001.
*FIELD* CD
Patricia A. Hartz: 8/20/2012
*FIELD* ED
carol: 08/20/2012
carol: 8/20/2012