MDB1_SCHPO
ID MDB1_SCHPO Reviewed; 624 AA.
AC O14079;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2012, sequence version 2.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=DNA damage response protein Mdb1 {ECO:0000305};
DE AltName: Full=BRCT domain protein Mdb1 {ECO:0000312|PomBase:SPACUNK4.14};
DE AltName: Full=Midzone and DNA break-localizing protein 1 {ECO:0000303|PubMed:24806815};
GN Name=mdb1 {ECO:0000303|PubMed:24806815};
GN ORFNames=SPAC2E11.14 {ECO:0000312|PDB:4S3H},
GN SPACUNK4.14 {ECO:0000312|EMBL:CAA20144.2, ECO:0000312|PomBase:SPACUNK4.14};
OS Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae;
OC Schizosaccharomyces.
OX NCBI_TaxID=284812;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=972 / ATCC 24843;
RX PubMed=11859360; DOI=10.1038/nature724;
RA Wood V., Gwilliam R., Rajandream M.A., Lyne M.H., Lyne R., Stewart A.,
RA Sgouros J.G., Peat N., Hayles J., Baker S.G., Basham D., Bowman S.,
RA Brooks K., Brown D., Brown S., Chillingworth T., Churcher C.M., Collins M.,
RA Connor R., Cronin A., Davis P., Feltwell T., Fraser A., Gentles S.,
RA Goble A., Hamlin N., Harris D.E., Hidalgo J., Hodgson G., Holroyd S.,
RA Hornsby T., Howarth S., Huckle E.J., Hunt S., Jagels K., James K.D.,
RA Jones L., Jones M., Leather S., McDonald S., McLean J., Mooney P.,
RA Moule S., Mungall K.L., Murphy L.D., Niblett D., Odell C., Oliver K.,
RA O'Neil S., Pearson D., Quail M.A., Rabbinowitsch E., Rutherford K.M.,
RA Rutter S., Saunders D., Seeger K., Sharp S., Skelton J., Simmonds M.N.,
RA Squares R., Squares S., Stevens K., Taylor K., Taylor R.G., Tivey A.,
RA Walsh S.V., Warren T., Whitehead S., Woodward J.R., Volckaert G., Aert R.,
RA Robben J., Grymonprez B., Weltjens I., Vanstreels E., Rieger M.,
RA Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Duesterhoeft A.,
RA Fritzc C., Holzer E., Moestl D., Hilbert H., Borzym K., Langer I., Beck A.,
RA Lehrach H., Reinhardt R., Pohl T.M., Eger P., Zimmermann W., Wedler H.,
RA Wambutt R., Purnelle B., Goffeau A., Cadieu E., Dreano S., Gloux S.,
RA Lelaure V., Mottier S., Galibert F., Aves S.J., Xiang Z., Hunt C.,
RA Moore K., Hurst S.M., Lucas M., Rochet M., Gaillardin C., Tallada V.A.,
RA Garzon A., Thode G., Daga R.R., Cruzado L., Jimenez J., Sanchez M.,
RA del Rey F., Benito J., Dominguez A., Revuelta J.L., Moreno S.,
RA Armstrong J., Forsburg S.L., Cerutti L., Lowe T., McCombie W.R.,
RA Paulsen I., Potashkin J., Shpakovski G.V., Ussery D., Barrell B.G.,
RA Nurse P.;
RT "The genome sequence of Schizosaccharomyces pombe.";
RL Nature 415:871-880(2002).
RN [2]
RP REVISION OF GENE MODEL.
RX PubMed=21511999; DOI=10.1126/science.1203357;
RA Rhind N., Chen Z., Yassour M., Thompson D.A., Haas B.J., Habib N.,
RA Wapinski I., Roy S., Lin M.F., Heiman D.I., Young S.K., Furuya K., Guo Y.,
RA Pidoux A., Chen H.M., Robbertse B., Goldberg J.M., Aoki K., Bayne E.H.,
RA Berlin A.M., Desjardins C.A., Dobbs E., Dukaj L., Fan L., FitzGerald M.G.,
RA French C., Gujja S., Hansen K., Keifenheim D., Levin J.Z., Mosher R.A.,
RA Mueller C.A., Pfiffner J., Priest M., Russ C., Smialowska A., Swoboda P.,
RA Sykes S.M., Vaughn M., Vengrova S., Yoder R., Zeng Q., Allshire R.,
RA Baulcombe D., Birren B.W., Brown W., Ekwall K., Kellis M., Leatherwood J.,
RA Levin H., Margalit H., Martienssen R., Nieduszynski C.A., Spatafora J.W.,
RA Friedman N., Dalgaard J.Z., Baumann P., Niki H., Regev A., Nusbaum C.;
RT "Comparative functional genomics of the fission yeasts.";
RL Science 332:930-936(2011).
RN [3]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=16823372; DOI=10.1038/nbt1222;
RA Matsuyama A., Arai R., Yashiroda Y., Shirai A., Kamata A., Sekido S.,
RA Kobayashi Y., Hashimoto A., Hamamoto M., Hiraoka Y., Horinouchi S.,
RA Yoshida M.;
RT "ORFeome cloning and global analysis of protein localization in the fission
RT yeast Schizosaccharomyces pombe.";
RL Nat. Biotechnol. 24:841-847(2006).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-253 AND SER-283, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=18257517; DOI=10.1021/pr7006335;
RA Wilson-Grady J.T., Villen J., Gygi S.P.;
RT "Phosphoproteome analysis of fission yeast.";
RL J. Proteome Res. 7:1088-1097(2008).
RN [5]
RP REVISION OF GENE MODEL.
RX PubMed=21270388; DOI=10.1534/genetics.110.123497;
RA Bitton D.A., Wood V., Scutt P.J., Grallert A., Yates T., Smith D.L.,
RA Hagan I.M., Miller C.J.;
RT "Augmented annotation of the Schizosaccharomyces pombe genome reveals
RT additional genes required for growth and viability.";
RL Genetics 187:1207-1217(2011).
RN [6]
RP FUNCTION, INTERACTION WITH HTA1, SUBCELLULAR LOCATION, DOMAIN, DISRUPTION
RP PHENOTYPE, AND MUTAGENESIS OF SER-392 AND LYS-434.
RX PubMed=24806815; DOI=10.1371/journal.pone.0097028;
RA Wei Y., Wang H.T., Zhai Y., Russell P., Du L.L.;
RT "Mdb1, a fission yeast homolog of human MDC1, modulates DNA damage response
RT and mitotic spindle function.";
RL PLoS ONE 9:E97028-E97028(2014).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 1-104, IDENTIFICATION BY MASS
RP SPECTROMETRY, SUBUNIT, INTERACTION WITH HTA1, SUBCELLULAR LOCATION, DOMAIN,
RP AND MUTAGENESIS OF 1-MET--LYS-104 AND 105-MET--THR-624.
RX PubMed=26160178; DOI=10.1074/jbc.m115.642538;
RA Luo S., Xin X., Du L.L., Ye K., Wei Y.;
RT "Dimerization mediated by a divergent forkhead-associated domain is
RT essential for the DNA damage and spindle functions of fission yeast Mdb1.";
RL J. Biol. Chem. 290:21054-21066(2015).
CC -!- FUNCTION: Involved in DNA damage response (DDR) mediated through its
CC interaction with phosphorylated H2A proteins hta1 and hta2 which mark
CC the discrete foci of DNA damage. {ECO:0000269|PubMed:24806815}.
CC -!- SUBUNIT: Homodimer (PubMed:26160178). Interacts (via BRCT domain) with
CC hta1 peptide containing the S/T-Q motif in vitro; this interaction
CC requires phosphorylation of the hta1 peptide at the S/T-Q motif
CC (PubMed:24806815, PubMed:26160178). {ECO:0000269|PubMed:24806815,
CC ECO:0000269|PubMed:26160178}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16823372,
CC ECO:0000269|PubMed:24806815, ECO:0000269|PubMed:26160178}. Chromosome
CC {ECO:0000269|PubMed:24806815, ECO:0000269|PubMed:26160178}. Cytoplasm,
CC cytoskeleton, spindle {ECO:0000269|PubMed:24806815,
CC ECO:0000269|PubMed:26160178}. Note=Associated with chromatin.
CC Relocalizes to discrete nuclear foci at DNA double strand breaks (DSBs)
CC following DNA damage by the HO endonuclease and ionizing radiation
CC (IR). Focus formation requires interaction with phosphorylated hta1 and
CC hta2. During mitosis, localizes to spindles and concentrates at spindle
CC midzones at late mitosis. Localization to spindle midzones requires
CC ase1, but does not require phosphorylated hta1 nor hta2
CC (PubMed:24806815). Localizes to spindle midzones in anaphase
CC (PubMed:26160178). {ECO:0000269|PubMed:24806815,
CC ECO:0000269|PubMed:26160178}.
CC -!- DOMAIN: The N-terminus adopts a forkhead-associated (FHA) like fold.
CC {ECO:0000269|PubMed:26160178}.
CC -!- DOMAIN: BRCT domain is characteristic of proteins involved in DNA
CC damage signaling (By similarity). It is required for localization to
CC chromatin which flanks sites of DNA damage marked by phosphorylation of
CC hta1 and hta2. {ECO:0000250|UniProtKB:Q14676,
CC ECO:0000269|PubMed:24806815}.
CC -!- DISRUPTION PHENOTYPE: Strongly resistant to the microtubule
CC depolymerizing drug thiabendazole (TBZ). No effect on DNA damage
CC sensitivity in response to ionizing radiation (IR), ultraviolet (UV),
CC hydroxyurea (HU) or camptothecin (CPT) compared to wild-type.
CC {ECO:0000269|PubMed:24806815}.
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DR EMBL; CU329670; CAA20144.2; -; Genomic_DNA.
DR PIR; T41709; T41709.
DR RefSeq; NP_593964.2; NM_001019391.2.
DR PDB; 4S3H; X-ray; 2.70 A; A/B/C/D=1-104.
DR PDB; 6HM4; X-ray; 1.77 A; B=106-120.
DR PDB; 7P0L; X-ray; 1.97 A; A/B=384-581.
DR PDBsum; 4S3H; -.
DR PDBsum; 6HM4; -.
DR PDBsum; 7P0L; -.
DR AlphaFoldDB; O14079; -.
DR SMR; O14079; -.
DR BioGRID; 278975; 8.
DR STRING; 4896.SPACUNK4.14.1; -.
DR iPTMnet; O14079; -.
DR MaxQB; O14079; -.
DR PaxDb; O14079; -.
DR PRIDE; O14079; -.
DR EnsemblFungi; SPACUNK4.14.1; SPACUNK4.14.1:pep; SPACUNK4.14.
DR GeneID; 2542517; -.
DR KEGG; spo:SPACUNK4.14; -.
DR PomBase; SPACUNK4.14; mdb1.
DR VEuPathDB; FungiDB:SPACUNK4.14; -.
DR eggNOG; KOG2043; Eukaryota.
DR HOGENOM; CLU_430308_0_0_1; -.
DR InParanoid; O14079; -.
DR OMA; HSHACIN; -.
DR Reactome; R-SPO-3108214; SUMOylation of DNA damage response and repair proteins.
DR Reactome; R-SPO-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR PRO; PR:O14079; -.
DR Proteomes; UP000002485; Chromosome I.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:1990023; C:mitotic spindle midzone; IDA:PomBase.
DR GO; GO:0005634; C:nucleus; IDA:PomBase.
DR GO; GO:0035861; C:site of double-strand break; IDA:PomBase.
DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; ISS:PomBase.
DR Gene3D; 3.40.50.10190; -; 2.
DR InterPro; IPR001357; BRCT_dom.
DR InterPro; IPR036420; BRCT_dom_sf.
DR Pfam; PF00533; BRCT; 1.
DR SMART; SM00292; BRCT; 1.
DR SUPFAM; SSF52113; SSF52113; 1.
DR PROSITE; PS50172; BRCT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell cycle; Chromosome; Cytoplasm; Cytoskeleton; DNA damage;
KW Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..624
FT /note="DNA damage response protein Mdb1"
FT /id="PRO_0000116712"
FT DOMAIN 376..468
FT /note="BRCT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT REGION 177..237
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 249..386
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 591..624
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 193..237
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 249..265
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 283..307
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 308..352
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 353..386
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 253
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18257517"
FT MOD_RES 283
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18257517"
FT MUTAGEN 1..104
FT /note="Missing: Loss of in vitro interaction with
FT phosphorylated hta1 peptide containing the S/T-Q motif.
FT Completely abolishes both spontaneous and ionizing
FT radiation induced foci (IRIF) formation at nuclear DNA
FT double strand breaks (DSBs). Loss of mitotic spindle
FT midzone localization during anaphase. Cannot reverse the
FT thiabendazole (TBZ) resistant phenotype of the deletion
FT mutant of this protein."
FT /evidence="ECO:0000269|PubMed:26160178"
FT MUTAGEN 105..624
FT /note="Missing: Can form a homodimer. Loss of in vitro
FT interaction with phosphorylated hta1 peptide containing the
FT S/T-Q motif."
FT /evidence="ECO:0000269|PubMed:26160178"
FT MUTAGEN 392
FT /note="S->A: Loss of in vitro interaction with
FT phosphorylated hta1 peptide containing the S/T-Q motif.
FT Abolishes ionizing radiation induced foci (IRIF) formation
FT at nuclear DNA double strand breaks (DSBs). Localizes to
FT mitotic spindle during early mitosis. Loss of midzone
FT localization during late mitosis. Cannot reverse the
FT thiabendazole (TBZ) resistant phenotype of the deletion
FT mutant of this protein."
FT /evidence="ECO:0000269|PubMed:24806815"
FT MUTAGEN 434
FT /note="K->M: Loss of in vitro interaction with
FT phosphorylated hta1 peptide containing the S/T-Q motif.
FT Abolishes ionizing radiation induced foci (IRIF) formation
FT at nuclear DNA double strand breaks (DSBs). Loss of
FT localization to mitotic spindle and midzone during early
FT and late mitosis, respectively. Cannot reverse the
FT thiabendazole (TBZ) resistant phenotype of the deletion
FT mutant of this protein."
FT /evidence="ECO:0000269|PubMed:24806815"
FT STRAND 2..5
FT /evidence="ECO:0007829|PDB:4S3H"
FT STRAND 8..11
FT /evidence="ECO:0007829|PDB:4S3H"
FT STRAND 14..20
FT /evidence="ECO:0007829|PDB:4S3H"
FT STRAND 27..29
FT /evidence="ECO:0007829|PDB:4S3H"
FT STRAND 34..41
FT /evidence="ECO:0007829|PDB:4S3H"
FT STRAND 44..52
FT /evidence="ECO:0007829|PDB:4S3H"
FT STRAND 54..56
FT /evidence="ECO:0007829|PDB:4S3H"
FT STRAND 68..73
FT /evidence="ECO:0007829|PDB:4S3H"
FT STRAND 80..82
FT /evidence="ECO:0007829|PDB:4S3H"
FT STRAND 85..90
FT /evidence="ECO:0007829|PDB:4S3H"
FT STRAND 388..393
FT /evidence="ECO:0007829|PDB:7P0L"
FT HELIX 398..406
FT /evidence="ECO:0007829|PDB:7P0L"
FT STRAND 421..424
FT /evidence="ECO:0007829|PDB:7P0L"
FT STRAND 426..428
FT /evidence="ECO:0007829|PDB:7P0L"
FT HELIX 433..441
FT /evidence="ECO:0007829|PDB:7P0L"
FT STRAND 445..447
FT /evidence="ECO:0007829|PDB:7P0L"
FT HELIX 449..457
FT /evidence="ECO:0007829|PDB:7P0L"
FT HELIX 463..466
FT /evidence="ECO:0007829|PDB:7P0L"
FT HELIX 471..477
FT /evidence="ECO:0007829|PDB:7P0L"
FT TURN 489..492
FT /evidence="ECO:0007829|PDB:7P0L"
FT STRAND 494..497
FT /evidence="ECO:0007829|PDB:7P0L"
FT HELIX 499..503
FT /evidence="ECO:0007829|PDB:7P0L"
FT TURN 504..507
FT /evidence="ECO:0007829|PDB:7P0L"
FT HELIX 508..519
FT /evidence="ECO:0007829|PDB:7P0L"
FT HELIX 528..531
FT /evidence="ECO:0007829|PDB:7P0L"
FT STRAND 536..540
FT /evidence="ECO:0007829|PDB:7P0L"
FT STRAND 542..544
FT /evidence="ECO:0007829|PDB:7P0L"
FT HELIX 546..552
FT /evidence="ECO:0007829|PDB:7P0L"
FT TURN 553..555
FT /evidence="ECO:0007829|PDB:7P0L"
FT STRAND 558..560
FT /evidence="ECO:0007829|PDB:7P0L"
FT HELIX 562..570
FT /evidence="ECO:0007829|PDB:7P0L"
FT HELIX 575..578
FT /evidence="ECO:0007829|PDB:7P0L"
SQ SEQUENCE 624 AA; 70201 MW; 9B5749EF9FE4671B CRC64;
MEIQFGNQRC RMVNSGGFLA TDGSHLKEME TDDVLVEFLN IEHQLFIRNI RAIVKIADTT
VLPSASDKKL LYYVFDETRV RINDTPVIFS KLEEDNANVN EGSKMGVMTV PNTPQKPNLQ
QQKFEAINAN EDQIDYSSNL EQNYNSLIRQ GSDQVIPLSR FASEKSALEL EKELFSERIP
ESQSAAEPVL KVENSENDLD EKLVLDGQHV EGDHSSDTEE EVVSEDQKQL NKTDDESTFI
ESHQIYIQGE TKSPSSVSQS LSGDPSLKPA EVFDRKQSAE INSPIEKDVN PQQNISDSSI
KNNSIHSDEV NPEVRPDLTP SNENEESKRS APEIALKEKE STSQDESNRE AEEAPISTNY
SFPSSSLEDQ PDKNVQSSAV ENKNKHTNLV TSSFNLTKPM KSFIRRNGLR VQESVTDETD
FVILGSPPLR RTHKFLLATS LGIPLVSSQY LTDCIKSGKV LDFRSYKYKD EEAEAKWGFR
LDDIHRRTCF NGKRLYITKA IRDSMVGDSI HGLYSILETS GAEIVGDIKR AQEKDTIILA
QPDNDQEGRN MSATGLNVYK IELVALSILR DRIDFDEFLI DYDADSPTKV IGKRNVSKAS
RTGQGRKRSS RSSWNKPSAK EQRT
