ID A0A3B3ITP6_HUMAN Unreviewed; 742 AA.
AC A0A3B3ITP6;
DT 05-DEC-2018, integrated into UniProtKB/TrEMBL.
DT 05-DEC-2018, sequence version 1.
DT 27-MAR-2024, entry version 31.
DE RecName: Full=DNA replication licensing factor MCM4 {ECO:0000256|RuleBase:RU368062};
DE EC=3.6.4.12 {ECO:0000256|RuleBase:RU368062};
GN Name=MCM4 {ECO:0000313|Ensembl:ENSP00000497881.1};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606 {ECO:0000313|Ensembl:ENSP00000497881.1, ECO:0000313|Proteomes:UP000005640};
RN [1] {ECO:0007829|PubMed:17081983}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [2] {ECO:0000313|Ensembl:ENSP00000497881.1, ECO:0000313|Proteomes:UP000005640}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Glockner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [3] {ECO:0007829|PubMed:18220336}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.D., Yates J.R.;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [4] {ECO:0007829|PubMed:18691976}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [5] {ECO:0007829|PubMed:18669648}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [6] {ECO:0007829|PubMed:19690332}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [7] {ECO:0007829|PubMed:19608861}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA 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 [8] {ECO:0007829|PubMed:20068231}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [9] {ECO:0007829|PubMed:21269460}
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., Burckstummer T.,
RA 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 [10] {ECO:0007829|PubMed:21406692}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [11] {ECO:0007829|PubMed:22814378}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [12] {ECO:0007829|PubMed:23186163}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=23186163;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [13] {ECO:0007829|PubMed:28112733}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [14] {ECO:0000313|Ensembl:ENSP00000497881.1}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (NOV-2023) to UniProtKB.
CC -!- FUNCTION: Acts as component of the MCM2-7 complex (MCM complex) which
CC is the replicative helicase essential for 'once per cell cycle' DNA
CC replication initiation and elongation in eukaryotic cells. The active
CC ATPase sites in the MCM2-7 ring are formed through the interaction
CC surfaces of two neighboring subunits such that a critical structure of
CC a conserved arginine finger motif is provided in trans relative to the
CC ATP-binding site of the Walker A box of the adjacent subunit. The six
CC ATPase active sites, however, are likely to contribute differentially
CC to the complex helicase activity. {ECO:0000256|RuleBase:RU368062}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.12;
CC Evidence={ECO:0000256|ARBA:ARBA00000600};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066;
CC Evidence={ECO:0000256|ARBA:ARBA00000600};
CC -!- SUBUNIT: Component of the MCM2-7 complex.
CC {ECO:0000256|RuleBase:RU368062}.
CC -!- SUBCELLULAR LOCATION: Chromosome {ECO:0000256|ARBA:ARBA00004286}.
CC Nucleus {ECO:0000256|ARBA:ARBA00004123}.
CC -!- SIMILARITY: Belongs to the MCM family. {ECO:0000256|ARBA:ARBA00008010,
CC ECO:0000256|RuleBase:RU004070}.
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DR EMBL; AC021236; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; A0A3B3ITP6; -.
DR SMR; A0A3B3ITP6; -.
DR MassIVE; A0A3B3ITP6; -.
DR PeptideAtlas; A0A3B3ITP6; -.
DR Antibodypedia; 1452; 522 antibodies from 36 providers.
DR Ensembl; ENST00000648407.1; ENSP00000497881.1; ENSG00000104738.19.
DR HGNC; HGNC:6947; MCM4.
DR VEuPathDB; HostDB:ENSG00000104738; -.
DR GeneTree; ENSGT01050000244824; -.
DR ChiTaRS; MCM4; human.
DR Proteomes; UP000005640; Chromosome 8.
DR Bgee; ENSG00000104738; Expressed in ventricular zone and 202 other cell types or tissues.
DR ExpressionAtlas; A0A3B3ITP6; baseline and differential.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0042555; C:MCM complex; IEA:UniProtKB-UniRule.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003678; F:DNA helicase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006270; P:DNA replication initiation; IEA:InterPro.
DR Gene3D; 2.20.28.10; -; 1.
DR Gene3D; 3.30.1640.10; mini-chromosome maintenance (MCM) complex, chain A, domain 1; 1.
DR Gene3D; 2.40.50.140; Nucleic acid-binding proteins; 1.
DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1.
DR InterPro; IPR031327; MCM.
DR InterPro; IPR008047; MCM_4.
DR InterPro; IPR018525; MCM_CS.
DR InterPro; IPR001208; MCM_dom.
DR InterPro; IPR027925; MCM_N.
DR InterPro; IPR033762; MCM_OB.
DR InterPro; IPR012340; NA-bd_OB-fold.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR11630; DNA REPLICATION LICENSING FACTOR MCM FAMILY MEMBER; 1.
DR PANTHER; PTHR11630:SF66; DNA REPLICATION LICENSING FACTOR MCM4; 1.
DR Pfam; PF00493; MCM; 1.
DR Pfam; PF14551; MCM_N; 1.
DR Pfam; PF17207; MCM_OB; 1.
DR PRINTS; PR01657; MCMFAMILY.
DR PRINTS; PR01660; MCMPROTEIN4.
DR SMART; SM00350; MCM; 1.
DR SUPFAM; SSF50249; Nucleic acid-binding proteins; 1.
DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR PROSITE; PS00847; MCM_1; 1.
DR PROSITE; PS50051; MCM_2; 1.
PE 1: Evidence at protein level;
KW ATP-binding {ECO:0000256|ARBA:ARBA00022840, ECO:0000256|RuleBase:RU004070};
KW Cell cycle {ECO:0000256|ARBA:ARBA00023306};
KW Chromosome {ECO:0000256|ARBA:ARBA00022454};
KW DNA replication {ECO:0000256|ARBA:ARBA00022705,
KW ECO:0000256|RuleBase:RU368062};
KW DNA-binding {ECO:0000256|RuleBase:RU004070};
KW Helicase {ECO:0000256|ARBA:ARBA00022806, ECO:0000256|RuleBase:RU368062};
KW Hydrolase {ECO:0000256|ARBA:ARBA00022801, ECO:0000256|RuleBase:RU368062};
KW Nucleotide-binding {ECO:0000256|ARBA:ARBA00022741,
KW ECO:0000256|RuleBase:RU004070};
KW Nucleus {ECO:0000256|ARBA:ARBA00023242, ECO:0000256|RuleBase:RU368062};
KW Proteomics identification {ECO:0007829|EPD:A0A3B3ITP6,
KW ECO:0007829|MaxQB:A0A3B3ITP6};
KW Reference proteome {ECO:0000313|Proteomes:UP000005640}.
FT DOMAIN 458..666
FT /note="MCM"
FT /evidence="ECO:0000259|PROSITE:PS50051"
FT REGION 1..60
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 91..126
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 44..60
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 742 AA; 83054 MW; 6884621DBB9A5742 CRC64;
MSSPASTPSR RGSRRGRATP AQTPRSEDAR SSPSQRRRGE DSTSTGELQP MPTSPGVDLQ
SPAAQDVLFS SPPQMHSSAI PLDFDVSSPL TYGTPSSRVE GTPRSGVRGT PVRQRPDLGS
AQKGLQVDLQ SDGAAAEDIV ASEQSLGQKL VIWGTDVNVA ACKENFQRFL QRFIDPLAKE
EENVGIDITE PLYMQRLGEI NVIGEPFLNV NCEHIKSFDK NLYRQLISYP QEVIPTFDMA
VNEIFFDRYP DSILEHQIQV RPFNALKTKN MRNLNPEDID QLITISGMVI RTSQLIPEMQ
EAFFQCQVCA HTTRVEMDRG RIAEPSVCGR CHTTHSMALI HNRSLFSDKQ MIKLQESPED
MPAGQTPHTV ILFAHNDLVD KVQPGDRVNV TGIYRAVPIR VNPRVSNVKS VYKTHIDVIH
YRKTDAKRLH GLDEEAEQKL FSEKRVELLK ELSRKPDIYE RLASALAPSI YEHEDIKKGI
LLQLFGGTRK DFSHTGRGKF RAEINILLCG DPGTSKSQLL QYVYNLVPRG QYTSGKGSSA
VGLTAYVMKD PETRQLVLQT GALVLSDNGI CCIDEFDKMN ESTRSVLHEV MEQQTLSIAK
AGIICQLNAR TSVLAAANPI ESQWNPKKTT IENIQLPHTL LSRFDLIFLL LDPQDEAYDR
RLAHHLVALY YQSEEQAEEE LLDMAVLKDY IAYAHSTIMP RLSEEASQAL IEAITKDMFE
EALRALADDD FLTVTGKTVR LL
//
