ID   GEMI_MOUSE              Reviewed;         206 AA.
AC   O88513;
DT   02-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1998, sequence version 1.
DT   27-MAR-2024, entry version 166.
DE   RecName: Full=Geminin;
GN   Name=Gmnn;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND DEVELOPMENTAL STAGE.
RX   PubMed=9635433; DOI=10.1016/s0092-8674(00)81209-x;
RA   McGarry T.J., Kirschner M.W.;
RT   "Geminin, an inhibitor of DNA replication, is degraded during mitosis.";
RL   Cell 93:1043-1053(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   FUNCTION, AND INTERACTION WITH CDT1.
RX   PubMed=12192004; DOI=10.1074/jbc.m206202200;
RA   Yanagi K., Mizuno T., You Z., Hanaoka F.;
RT   "Mouse geminin inhibits not only Cdt1-MCM6 interactions but also a novel
RT   intrinsic Cdt1 DNA binding activity.";
RL   J. Biol. Chem. 277:40871-40880(2002).
RN   [4]
RP   INTERACTION WITH CDT1.
RX   PubMed=15811859; DOI=10.1074/jbc.c500070200;
RA   Yanagi K., Mizuno T., Tsuyama T., Tada S., Iida Y., Sugimoto A., Eki T.,
RA   Enomoto T., Hanaoka F.;
RT   "Caenorhabditis elegans geminin homologue participates in cell cycle
RT   regulation and germ line development.";
RL   J. Biol. Chem. 280:19689-19694(2005).
RN   [5]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Spleen, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [6]
RP   X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 79-157 IN COMPLEX WITH CDT1,
RP   DOMAIN COILED COIL, AND SUBUNIT.
RX   PubMed=15286659; DOI=10.1038/nature02813;
RA   Lee C., Hong B., Choi J.M., Kim Y., Watanabe S., Ishimi Y., Enomoto T.,
RA   Tada S., Kim Y., Cho Y.;
RT   "Structural basis for inhibition of the replication licensing factor Cdt1
RT   by geminin.";
RL   Nature 430:913-917(2004).
CC   -!- FUNCTION: Inhibits DNA replication by preventing the incorporation of
CC       MCM complex into pre-replication complex (pre-RC) (PubMed:12192004,
CC       PubMed:9635433). It is degraded during the mitotic phase of the cell
CC       cycle. Its destruction at the metaphase-anaphase transition permits
CC       replication in the succeeding cell cycle (PubMed:12192004,
CC       PubMed:9635433). Inhibits histone acetyltransferase activity of
CC       KAT7/HBO1 in a CDT1-dependent manner, inhibiting histone H4 acetylation
CC       and DNA replication licensing (By similarity). Inhibits the
CC       transcriptional activity of a subset of Hox proteins, enrolling them in
CC       cell proliferative control (By similarity).
CC       {ECO:0000250|UniProtKB:O75496, ECO:0000269|PubMed:12192004,
CC       ECO:0000269|PubMed:9635433}.
CC   -!- SUBUNIT: Homotetramer (By similarity). Interacts with CDT1; this
CC       inhibits binding of the MCM complex to origins of replication
CC       (PubMed:12192004, PubMed:15286659, PubMed:15811859). The complex with
CC       CDT1 exists in two forms, a 'permissive' heterotrimer and an
CC       'inhibitory' heterohexamer (By similarity). Interacts (via coiled-coil
CC       domain) with IDAS (via coiled-coil domain); this targets GMNN to the
CC       nucleus (By similarity). The heterodimer formed by GMNN and MCIDAS has
CC       much lower affinity for CDT1 than the GMNN homodimer (By similarity).
CC       Interacts with a subset of Hox proteins, affinity increasing from
CC       anterior to posterior types, the strongest interaction being with
CC       HOXB1, HOXC9 and HOXD10 (By similarity). Interacts with LRWD1 from G1/S
CC       to mitosis (By similarity). {ECO:0000250|UniProtKB:O75496,
CC       ECO:0000269|PubMed:12192004, ECO:0000269|PubMed:15286659,
CC       ECO:0000269|PubMed:15811859}.
CC   -!- INTERACTION:
CC       O88513; Q8R4E9: Cdt1; NbExp=3; IntAct=EBI-445922, EBI-457043;
CC       O88513; P31311: Hoxa11; NbExp=2; IntAct=EBI-445922, EBI-445941;
CC       O88513; P28359: Hoxd10; NbExp=2; IntAct=EBI-445922, EBI-445929;
CC       O88513; Q8K214: Scmh1; NbExp=2; IntAct=EBI-445922, EBI-445955;
CC       O88513; Q9JIZ5: Tfap4; NbExp=2; IntAct=EBI-445922, EBI-15597718;
CC       O88513; Q9Y618: NCOR2; Xeno; NbExp=3; IntAct=EBI-445922, EBI-80830;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O75496}. Nucleus
CC       {ECO:0000250|UniProtKB:O75496}. Note=Mainly cytoplasmic but can be
CC       relocalized to the nucleus. {ECO:0000250|UniProtKB:O75496}.
CC   -!- DEVELOPMENTAL STAGE: Absent during G1 phase, accumulates during S, G2,
CC       and M phases, and disappears at the time of the metaphase-anaphase
CC       transition. {ECO:0000269|PubMed:9635433}.
CC   -!- PTM: Phosphorylated during mitosis. Phosphorylation at Ser-181 by CK2
CC       results in enhanced binding to Hox proteins and more potent inhibitory
CC       effect on Hox transcriptional activity. {ECO:0000250|UniProtKB:O75496}.
CC   -!- SIMILARITY: Belongs to the geminin family. {ECO:0000305}.
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DR   EMBL; AF068780; AAC24228.1; -; mRNA.
DR   EMBL; BC020061; AAH20061.1; -; mRNA.
DR   CCDS; CCDS26378.1; -.
DR   RefSeq; NP_065592.1; NM_020567.2.
DR   RefSeq; XP_006516786.1; XM_006516723.3.
DR   PDB; 2ZXX; X-ray; 2.80 A; A/B/D/E=79-157.
DR   PDBsum; 2ZXX; -.
DR   AlphaFoldDB; O88513; -.
DR   SMR; O88513; -.
DR   BioGRID; 208298; 18.
DR   DIP; DIP-32562N; -.
DR   IntAct; O88513; 16.
DR   STRING; 10090.ENSMUSP00000006898; -.
DR   iPTMnet; O88513; -.
DR   PhosphoSitePlus; O88513; -.
DR   EPD; O88513; -.
DR   PaxDb; 10090-ENSMUSP00000006898; -.
DR   ProteomicsDB; 272955; -.
DR   Pumba; O88513; -.
DR   Antibodypedia; 25345; 495 antibodies from 35 providers.
DR   DNASU; 57441; -.
DR   Ensembl; ENSMUST00000006898.10; ENSMUSP00000006898.4; ENSMUSG00000006715.12.
DR   Ensembl; ENSMUST00000110382.9; ENSMUSP00000106011.3; ENSMUSG00000006715.12.
DR   GeneID; 57441; -.
DR   KEGG; mmu:57441; -.
DR   UCSC; uc007pwg.1; mouse.
DR   AGR; MGI:1927344; -.
DR   CTD; 51053; -.
DR   MGI; MGI:1927344; Gmnn.
DR   VEuPathDB; HostDB:ENSMUSG00000006715; -.
DR   eggNOG; ENOG502SDC5; Eukaryota.
DR   GeneTree; ENSGT00940000153270; -.
DR   InParanoid; O88513; -.
DR   OMA; HWNDQLI; -.
DR   OrthoDB; 4119853at2759; -.
DR   PhylomeDB; O88513; -.
DR   TreeFam; TF101171; -.
DR   Reactome; R-MMU-68867; Assembly of the pre-replicative complex.
DR   Reactome; R-MMU-68962; Activation of the pre-replicative complex.
DR   Reactome; R-MMU-69052; Switching of origins to a post-replicative state.
DR   BioGRID-ORCS; 57441; 19 hits in 81 CRISPR screens.
DR   EvolutionaryTrace; O88513; -.
DR   PRO; PR:O88513; -.
DR   Proteomes; UP000000589; Chromosome 13.
DR   RNAct; O88513; Protein.
DR   Bgee; ENSMUSG00000006715; Expressed in primitive streak and 267 other cell types or tissues.
DR   ExpressionAtlas; O88513; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR   GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
DR   GO; GO:0017053; C:transcription repressor complex; IEA:Ensembl.
DR   GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR   GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
DR   GO; GO:0042826; F:histone deacetylase binding; ISS:UniProtKB.
DR   GO; GO:0003714; F:transcription corepressor activity; IDA:UniProtKB.
DR   GO; GO:0009887; P:animal organ morphogenesis; IDA:MGI.
DR   GO; GO:0071163; P:DNA replication preinitiation complex assembly; IEA:Ensembl.
DR   GO; GO:0045786; P:negative regulation of cell cycle; IDA:UniProtKB.
DR   GO; GO:0008156; P:negative regulation of DNA replication; IDA:UniProtKB.
DR   GO; GO:2000104; P:negative regulation of DNA-templated DNA replication; IEA:Ensembl.
DR   GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB.
DR   GO; GO:0065003; P:protein-containing complex assembly; IDA:UniProtKB.
DR   GO; GO:0030174; P:regulation of DNA-templated DNA replication initiation; IEA:Ensembl.
DR   GO; GO:0007346; P:regulation of mitotic cell cycle; IEA:Ensembl.
DR   CDD; cd22589; geminin_CC; 1.
DR   DisProt; DP02412; -.
DR   Gene3D; 1.20.5.1180; Geminin coiled-coil domain; 1.
DR   IDEAL; IID50306; -.
DR   InterPro; IPR022786; Geminin/Multicilin.
DR   PANTHER; PTHR13372; GEMININ; 1.
DR   PANTHER; PTHR13372:SF4; GEMININ; 1.
DR   Pfam; PF07412; Geminin; 1.
DR   SUPFAM; SSF111469; Geminin coiled-coil domain; 1.
DR   Genevisible; O88513; MM.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Cell cycle; Coiled coil; Cytoplasm;
KW   DNA replication inhibitor; Nucleus; Phosphoprotein; Reference proteome.
FT   CHAIN           1..206
FT                   /note="Geminin"
FT                   /id="PRO_0000148730"
FT   REGION          1..42
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          79..158
FT                   /note="Necessary and sufficient for interaction with IDAS
FT                   and CDT1"
FT                   /evidence="ECO:0000250"
FT   REGION          157..206
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          167..187
FT                   /note="Homeodomain binding"
FT                   /evidence="ECO:0000250"
FT   COILED          91..141
FT   COMPBIAS        1..20
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        165..182
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        191..206
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         27
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:O75496"
FT   MOD_RES         36
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:O75496"
FT   MOD_RES         63
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:O75496"
FT   MOD_RES         64
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:O75496"
FT   MOD_RES         181
FT                   /note="Phosphoserine; by CK2"
FT                   /evidence="ECO:0000250|UniProtKB:O75496"
FT   TURN            82..86
FT                   /evidence="ECO:0007829|PDB:2ZXX"
FT   HELIX           95..136
FT                   /evidence="ECO:0007829|PDB:2ZXX"
FT   HELIX           139..154
FT                   /evidence="ECO:0007829|PDB:2ZXX"
SQ   SEQUENCE   206 AA;  23300 MW;  B87153A5D5BCF5CF CRC64;
     MNLSMKQKQE GAQENVKNSP VPRRTLKMIQ PSADGSLVGR ENELPKGLFK RKLWDDQLAS
     QTSSCGPEAN ENKDVGDLTQ EAFDLISKEN PSSQYWKEVA EQRRKALYEA LKENEKLHKE
     IEQKDSEIAR LRKENKDLAE VAEHVQYMAE VIERLSNEPL DNFESPDSQE FDSEEEAVEY
     SELEDSGAGT CAEETVSSST DARPCT
//