MMS19_DROME
ID MMS19_DROME Reviewed; 959 AA.
AC Q95U54; Q968K4;
DT 07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=MMS19 nucleotide excision repair protein {ECO:0000305};
GN Name=Mms19 {ECO:0000312|FlyBase:FBgn0037301};
GN Synonyms=NEST:bs07f08 {ECO:0000312|FlyBase:FBgn0037301};
GN ORFNames=CG12005 {ECO:0000312|FlyBase:FBgn0037301};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227 {ECO:0000312|Proteomes:UP000000803};
RN [1] {ECO:0000312|EMBL:AAK52669.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
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 complementation of
RT a yeast mms19 deletion mutant.";
RL Nucleic Acids Res. 29:1884-1891(2001).
RN [2] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3] {ECO:0000312|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4] {ECO:0000312|EMBL:AAL13529.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAL13529.1};
RC TISSUE=Head {ECO:0000312|EMBL:AAL13529.1};
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [5] {ECO:0000305}
RP FUNCTION, INTERACTION WITH XPD-2 AND GALLA-2, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=29361561; DOI=10.1242/dev.156802;
RA Nag R.N., Niggli S., Sousa-Guimaraes S., Vazquez-Pianzola P., Suter B.;
RT "Mms19 is a mitotic gene that permits Cdk7 to be fully active as a Cdk-
RT activating kinase.";
RL Development 145:0-0(2018).
RN [6] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=33211700; DOI=10.1371/journal.pgen.1008913;
RA Chippalkatti R., Egger B., Suter B.;
RT "Mms19 promotes spindle microtubule assembly in Drosophila neural stem
RT cells.";
RL PLoS Genet. 16:e1008913-e1008913(2020).
CC -!- FUNCTION: Key component of the cytosolic iron-sulfur protein assembly
CC (CIA) complex, a multiprotein complex that mediates the incorporation
CC of iron-sulfur cluster into apoproteins specifically involved in DNA
CC metabolism and genomic integrity (By similarity). In the CIA complex,
CC MMS19 acts as an adapter between early-acting CIA components and a
CC subset of cellular target iron-sulfur proteins (By similarity).
CC Essential for diploid cell cycles, organ growth and development
CC (PubMed:29361561). Regulates mitosis by binding to Xpd and thereby
CC competing with the Xpd-mediated repression on the Cdk-activating kinase
CC (CAK) complex (PubMed:29361561). Regulates the centrosomal localization
CC of the MT regulator tacc, a downstream target of aurA kinase
CC (PubMed:33211700). Binds to microtubules (MT) (PubMed:33211700).
CC Regulates spindle and astral MT growth, MT stability and bundling
CC (PubMed:33211700). In neuroblasts, necessary for timely and coordinated
CC spindle assembly and orientation which is necessary for mitotic
CC progression (PubMed:33211700). In young embryos, the maternal protein
CC is important for progression through mitosis (PubMed:29361561).
CC {ECO:0000255|RuleBase:RU367072, ECO:0000269|PubMed:29361561,
CC ECO:0000269|PubMed:33211700}.
CC -!- SUBUNIT: Component of the CIA complex (By similarity). Interacts with
CC Xpd and galla-2 (PubMed:29361561). Binds to microtubules
CC (PubMed:33211700). {ECO:0000255|RuleBase:RU367072,
CC ECO:0000269|PubMed:29361561, ECO:0000269|PubMed:33211700}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, spindle
CC {ECO:0000255|RuleBase:RU367072, ECO:0000269|PubMed:29361561}. Nucleus
CC {ECO:0000255|RuleBase:RU367072, ECO:0000269|PubMed:29361561}. Cytoplasm
CC {ECO:0000269|PubMed:29361561}. Midbody {ECO:0000269|PubMed:29361561}.
CC Note=Localizes to the nucleus at the beginning of metaphase.
CC {ECO:0000269|PubMed:29361561}.
CC -!- TISSUE SPECIFICITY: Expressed in embryos (at protein level).
CC {ECO:0000269|PubMed:29361561}.
CC -!- DISRUPTION PHENOTYPE: Shows slowed larval development with lack of
CC imaginal disks and microcephaly with deformed and underdeveloped
CC optical lobes (PubMed:29361561, PubMed:33211700). Death occurs at the
CC third larval instar stage (PubMed:29361561, PubMed:33211700). Reduced
CC levels of Xpd in embryos (PubMed:29361561). Results in higher
CC proportion of neuroblasts in mitosis with shorter spindle and less
CC dense astral microtubules with defective assembly and orientation
CC (PubMed:33211700). Loss of maternal Mms19 causes cell cycle defects in
CC young embryos (PubMed:29361561). {ECO:0000269|PubMed:29361561,
CC ECO:0000269|PubMed:33211700}.
CC -!- SIMILARITY: Belongs to the MET18/MMS19 family.
CC {ECO:0000255|RuleBase:RU367072}.
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DR EMBL; AF319948; AAK52669.1; -; mRNA.
DR EMBL; AE014297; AAN13264.1; -; Genomic_DNA.
DR EMBL; AY058300; AAL13529.1; -; mRNA.
DR RefSeq; NP_649519.1; NM_141262.3.
DR AlphaFoldDB; Q95U54; -.
DR SMR; Q95U54; -.
DR IntAct; Q95U54; 1.
DR STRING; 7227.FBpp0078425; -.
DR PaxDb; Q95U54; -.
DR PRIDE; Q95U54; -.
DR EnsemblMetazoa; FBtr0078778; FBpp0078425; FBgn0037301.
DR GeneID; 40626; -.
DR KEGG; dme:Dmel_CG12005; -.
DR UCSC; CG12005-RB; d. melanogaster.
DR CTD; 64210; -.
DR FlyBase; FBgn0037301; Mms19.
DR VEuPathDB; VectorBase:FBgn0037301; -.
DR eggNOG; KOG1967; Eukaryota.
DR GeneTree; ENSGT00390000015583; -.
DR HOGENOM; CLU_005943_2_0_1; -.
DR InParanoid; Q95U54; -.
DR OMA; FSFMPEF; -.
DR OrthoDB; 944339at2759; -.
DR PhylomeDB; Q95U54; -.
DR BioGRID-ORCS; 40626; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 40626; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0037301; Expressed in embryonic/larval hemocyte (Drosophila) and 31 other tissues.
DR ExpressionAtlas; Q95U54; baseline and differential.
DR GO; GO:0097361; C:CIA complex; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0030496; C:midbody; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005819; C:spindle; IDA:UniProtKB.
DR GO; GO:0055049; P:astral spindle assembly; IMP:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0007059; P:chromosome segregation; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0016226; P:iron-sulfur cluster assembly; IBA:GO_Central.
DR GO; GO:0031116; P:positive regulation of microtubule polymerization; IMP:UniProtKB.
DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0045840; P:positive regulation of mitotic nuclear division; IMP:UniProtKB.
DR GO; GO:0097428; P:protein maturation by iron-sulfur cluster transfer; IBA:GO_Central.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR039920; MET18/MMS19.
DR InterPro; IPR024687; MMS19_C.
DR InterPro; IPR029240; MMS19_N.
DR PANTHER; PTHR12891; PTHR12891; 1.
DR Pfam; PF12460; MMS19_C; 1.
DR Pfam; PF14500; MMS19_N; 1.
DR SUPFAM; SSF48371; SSF48371; 2.
PE 1: Evidence at protein level;
KW Cell cycle; Cell division; Chromosome partition; Cytoplasm; Cytoskeleton;
KW DNA damage; DNA repair; Mitosis; Nucleus; Reference proteome; Repeat.
FT CHAIN 1..959
FT /note="MMS19 nucleotide excision repair protein"
FT /evidence="ECO:0000305"
FT /id="PRO_0000452275"
FT REPEAT 794..828
FT /note="HEAT 1"
FT /evidence="ECO:0000250|UniProtKB:Q96T76"
FT REPEAT 832..871
FT /note="HEAT 2"
FT /evidence="ECO:0000250|UniProtKB:Q96T76"
FT REPEAT 874..915
FT /note="HEAT 3"
FT /evidence="ECO:0000250|UniProtKB:Q96T76"
FT REPEAT 918..956
FT /note="HEAT 4"
FT /evidence="ECO:0000250|UniProtKB:Q96T76"
FT CONFLICT 551
FT /note="T -> A (in Ref. 1; AAK52669)"
FT /evidence="ECO:0000305"
FT CONFLICT 710
FT /note="R -> S (in Ref. 1; AAK52669)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 959 AA; 107048 MW; 363EAF00E63F3B2C CRC64;
MTTPTRATLE KALKSDQKLV NSATQIAKDL TAKAYDISAL AEALGFALSS PDMEERVAGT
NLLSAVLIAL PQDLLQERQL EFLSTFYMDR LRDHHNVMPA IIDGIDALVH MKALPRAQIP
QILQSFFEHT TCQSQTRSDR TKLFHIFQYL TENFQDELQA MAGDFVYGLI NSIDGERDPR
NLDIIFSFMP EFLSTYPLLH LAEEMFEIFA CYFPIDFNPS KQDPAAITRD ELSKKLTNCL
VANNEFAEGT VVLAIEKLES ELLVAKLDSI ELLHQAAVKF PPSVLEPHFD QIWQALKTET
FPGNDNEEIL KASLKALSAL LERAAHIPDI SHSYQSSILG VILPHLSDVN QRLFHPATGI
ALVCVSGDAP YAADKILNSF LLKLQAADAS SEQRIKIYYI VSQVYKLSAL RGSLQKLDTT
IRESVQDDVI ASLRLIEQEE FDAKKEDLEL QKAALSVLNE SAPLLNEKQR ALIYKALVQL
VSHPSIDIDF TTLTVSLGAL QPVEVQSNFI DVCVRNFEIF STFVKRKIYT NLLPLMPQIA
FTQRILDLVM TQTFNDTTAE PVRLLALEAL NKLLLLADQR FIVDVQQESN LLHKLIELGQ
KTEGLSMQSL EQIAGALSRI TQQLPLSEQS AIVSEYLPGL NLSQSADLYI TKGLLGYLHK
DITLDDHFER LLTDLTQLSL NSDNEQLRVI AHHLLCSMVN KMESNPANLR KVKKITEQLK
VAIKKGDVRA VEILAWVGKG LVVAGFDEAA DVVGDLSDLL KHPSLSTAAA LGFDIIAAEY
PELDLPVVKF LYKQKLFHTI MGKMGSKLAN YCVHHLKAFV YVLKATPQAV IKLNIEQLGP
LLFKSLEEHN EAQSLCIALG ICEKFVAQQD TYFQGHLAHL IPSCLELSKY KAQHTMQVRI
AALQLLYDVT KYPTFVLLPH KVDVTLALAA ALDDPKRLVR NTAVKARNAW YLVGAPSPN
