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P33991 (MCM4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 147. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
DNA replication licensing factor MCM4

EC=3.6.4.12
Alternative name(s):
CDC21 homolog
P1-CDC21
Gene names
Name:MCM4
Synonyms:CDC21
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length863 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity. Ref.7

Catalytic activity

ATP + H2O = ADP + phosphate.

Subunit structure

Component of the MCM2-7 complex. The complex forms a toroidal hexameric ring with the proposed subunit order MCM2-MCM6-MCM4-MCM7-MCM3-MCM5 (By simililarity). Interacts with MCMBP. Ref.7 Ref.9 Ref.10

Subcellular location

Nucleus By similarity.

Involvement in disease

Natural killer cell and glucocorticoid deficiency with DNA repair defect (NKGCD) [MIM:609981]: An autosomal recessive disorder characterized by severe intra- and extrauterine growth retardation, microcephaly, decreased numbers of natural killer cells, and recurrent viral infections, most often affecting the respiratory tract and leading to respiratory failure. Affected individuals also have adrenal insufficiency requiring corticosteroid replacement therapy and may have an increased susceptibility to cancer.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.18 Ref.19 Ref.20

Miscellaneous

Early fractionation of eukaryotic MCM proteins yielded a variety of dimeric, trimeric and tetrameric complexes with unclear biological significance. Specifically a MCM467 subcomplex is shown to have in vitro helicase activity which is inhibited by the MCM2 subunit. The MCM2-7 hexamer is the proposed physiological active complex.

Sequence similarities

Belongs to the MCM family.

Contains 1 MCM domain.

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.15
Chain2 – 863862DNA replication licensing factor MCM4
PRO_0000194101

Regions

Domain458 – 667210MCM
Nucleotide binding510 – 5178ATP Potential
Motif642 – 6454Arginine finger

Amino acid modifications

Modified residue21N-acetylserine Ref.15 Ref.17 Ref.21
Modified residue261Phosphoserine Ref.12
Modified residue311Phosphoserine Ref.12
Modified residue321Phosphoserine Ref.12 Ref.15
Modified residue341Phosphoserine Ref.12
Modified residue1201Phosphoserine Ref.8 Ref.11 Ref.15 Ref.17
Modified residue1311Phosphoserine Ref.13 Ref.15 Ref.17
Modified residue1421Phosphoserine Ref.15
Modified residue1451Phosphoserine Ref.15
Modified residue2201N6-acetyllysine Ref.14
Modified residue4501N6-acetyllysine Ref.14
Modified residue8581N6-acetyllysine By similarity

Natural variations

Natural variant4601E → G. Ref.2
Corresponds to variant rs17287663 [ dbSNP | Ensembl ].
VAR_020500
Natural variant6501L → M. Ref.1 Ref.3 Ref.6
Corresponds to variant rs762679 [ dbSNP | Ensembl ].
VAR_020501

Experimental info

Sequence conflict621P → T in CAA52801. Ref.1
Sequence conflict2061P → Q in CAA52801. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P33991 [UniParc].

Last modified May 10, 2005. Version 5.
Checksum: 96D9CA2A7D88D015

FASTA86396,558
        10         20         30         40         50         60 
MSSPASTPSR RGSRRGRATP AQTPRSEDAR SSPSQRRRGE DSTSTGELQP MPTSPGVDLQ 

        70         80         90        100        110        120 
SPAAQDVLFS SPPQMHSSAI PLDFDVSSPL TYGTPSSRVE GTPRSGVRGT PVRQRPDLGS 

       130        140        150        160        170        180 
AQKGLQVDLQ SDGAAAEDIV ASEQSLGQKL VIWGTDVNVA ACKENFQRFL QRFIDPLAKE 

       190        200        210        220        230        240 
EENVGIDITE PLYMQRLGEI NVIGEPFLNV NCEHIKSFDK NLYRQLISYP QEVIPTFDMA 

       250        260        270        280        290        300 
VNEIFFDRYP DSILEHQIQV RPFNALKTKN MRNLNPEDID QLITISGMVI RTSQLIPEMQ 

       310        320        330        340        350        360 
EAFFQCQVCA HTTRVEMDRG RIAEPSVCGR CHTTHSMALI HNRSLFSDKQ MIKLQESPED 

       370        380        390        400        410        420 
MPAGQTPHTV ILFAHNDLVD KVQPGDRVNV TGIYRAVPIR VNPRVSNVKS VYKTHIDVIH 

       430        440        450        460        470        480 
YRKTDAKRLH GLDEEAEQKL FSEKRVELLK ELSRKPDIYE RLASALAPSI YEHEDIKKGI 

       490        500        510        520        530        540 
LLQLFGGTRK DFSHTGRGKF RAEINILLCG DPGTSKSQLL QYVYNLVPRG QYTSGKGSSA 

       550        560        570        580        590        600 
VGLTAYVMKD PETRQLVLQT GALVLSDNGI CCIDEFDKMN ESTRSVLHEV MEQQTLSIAK 

       610        620        630        640        650        660 
AGIICQLNAR TSVLAAANPI ESQWNPKKTT IENIQLPHTL LSRFDLIFLL LDPQDEAYDR 

       670        680        690        700        710        720 
RLAHHLVALY YQSEEQAEEE LLDMAVLKDY IAYAHSTIMP RLSEEASQAL IEAYVDMRKI 

       730        740        750        760        770        780 
GSSRGMVSAY PRQLESLIRL AEAHAKVRLS NKVEAIDVEE AKRLHREALK QSATDPRTGI 

       790        800        810        820        830        840 
VDISILTTGM SATSRKRKEE LAEALKKLIL SKGKTPALKY QQLFEDIRGQ SDIAITKDMF 

       850        860 
EEALRALADD DFLTVTGKTV RLL 

« Hide

References

« Hide 'large scale' references
[1]"A human homologue of the yeast replication protein Cdc21. Interactions with other Mcm proteins."
Musahl C., Schulte D., Burkhart R., Knippers R.
Eur. J. Biochem. 230:1096-1101(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT MET-650.
[2]NIEHS SNPs program
Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLY-460.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT MET-650.
Tissue: Testis.
[4]"The promoters for human DNA-PKcs (PRKDC) and MCM4: divergently transcribed genes located at chromosome 8 band q11."
Connelly M.A., Zhang H., Kieleczawa J., Anderson C.W.
Genomics 47:71-83(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-712.
[5]"MCM4 and PRKDC, human genes encoding proteins MCM4 and DNA-PKcs, are close neighbours located on chromosome 8q12-->q13."
Ladenburger E.M., Fackelmayer F.O., Hameister H., Knippers R.
Cytogenet. Cell Genet. 77:268-270(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 1-23.
[6]"The P1 family: a new class of nuclear mammalian proteins related to the yeast Mcm replication proteins."
Hu B., Burkhart R., Schulte D., Musahl C., Knippers R.
Nucleic Acids Res. 21:5289-5293(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 440-863, VARIANT MET-650.
Tissue: Cervix.
[7]"A DNA helicase activity is associated with an MCM4, -6, and -7 protein complex."
Ishimi Y.
J. Biol. Chem. 272:24508-24513(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN THE MCM2-7 COMPLEX, FUNCTION.
[8]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-120, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"Essential role of phosphorylation of MCM2 by Cdc7/Dbf4 in the initiation of DNA replication in mammalian cells."
Tsuji T., Ficarro S.B., Jiang W.
Mol. Biol. Cell 17:4459-4472(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN THE MCM2-7 COMPLEX, ATPASE ACTIVITY OF THE MCM2-7 COMPLEX.
[10]"Identification and characterization of a novel component of the human minichromosome maintenance complex."
Sakwe A.M., Nguyen T., Athanasopoulos V., Shire K., Frappier L.
Mol. Cell. Biol. 27:3044-3055(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: HELICASE ACTIVITY OF THE MCM2-3 COMPLEX, INTERACTION WITH MCMBP, IDENTIFICATION IN THE MCM2-7 COMPLEX, IDENTIFICATION BY MASS SPECTROMETRY.
[11]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-120, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[12]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-26; SER-31; SER-32 AND SER-34, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[13]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-131, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[14]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-220 AND LYS-450, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-32; SER-120; SER-131; SER-142 AND SER-145, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[16]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-120 AND SER-131, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]"MCM4 mutation causes adrenal failure, short stature, and natural killer cell deficiency in humans."
Hughes C.R., Guasti L., Meimaridou E., Chuang C.H., Schimenti J.C., King P.J., Costigan C., Clark A.J., Metherell L.A.
J. Clin. Invest. 122:814-820(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN NKGCD.
[19]"Partial MCM4 deficiency in patients with growth retardation, adrenal insufficiency, and natural killer cell deficiency."
Gineau L., Cognet C., Kara N., Lach F.P., Dunne J., Veturi U., Picard C., Trouillet C., Eidenschenk C., Aoufouchi S., Alcais A., Smith O., Geissmann F., Feighery C., Abel L., Smogorzewska A., Stillman B., Vivier E., Casanova J.L., Jouanguy E.
J. Clin. Invest. 122:821-832(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN NKGCD.
[20]"Recessive mutations in MCM4/PRKDC cause a novel syndrome involving a primary immunodeficiency and a disorder of DNA repair."
Casey J.P., Nobbs M., McGettigan P., Lynch S., Ennis S.
J. Med. Genet. 49:242-245(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN NKGCD.
[21]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X74794 mRNA. Translation: CAA52801.1.
AY588245 Genomic DNA. Translation: AAS83108.1.
BC031061 mRNA. Translation: AAH31061.1.
U63630 Genomic DNA. Translation: AAC52018.1.
U90415 Genomic DNA. Translation: AAB51723.3.
PIRS65954.
RefSeqNP_005905.2. NM_005914.3.
NP_877423.1. NM_182746.2.
UniGeneHs.460184.

3D structure databases

ProteinModelPortalP33991.
SMRP33991. Positions 161-770.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110341. 59 interactions.
DIPDIP-31729N.
IntActP33991. 47 interactions.
MINTMINT-1202120.
STRING9606.ENSP00000262105.

PTM databases

PhosphoSiteP33991.

Polymorphism databases

DMDM68571766.

Proteomic databases

PaxDbP33991.
PeptideAtlasP33991.
PRIDEP33991.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000262105; ENSP00000262105; ENSG00000104738.
ENST00000523944; ENSP00000430194; ENSG00000104738.
GeneID4173.
KEGGhsa:4173.
UCSCuc003xqk.2. human.

Organism-specific databases

CTD4173.
GeneCardsGC08P048873.
H-InvDBHIX0007492.
HGNCHGNC:6947. MCM4.
HPACAB004497.
HPA004873.
HPA031052.
MIM602638. gene.
609981. phenotype.
neXtProtNX_P33991.
Orphanet75391. Immunodeficiency with natural-killer cell deficiency.
PharmGKBPA30694.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1241.
HOGENOMHOG000224127.
HOVERGENHBG102781.
InParanoidP33991.
KOK02212.
OMAMHSSAIP.
OrthoDBEOG78D7JF.
PhylomeDBP33991.
TreeFamTF300463.

Enzyme and pathway databases

ReactomeREACT_115566. Cell Cycle.
REACT_21300. Mitotic M-M/G1 phases.
REACT_383. DNA Replication.

Gene expression databases

ArrayExpressP33991.
BgeeP33991.
CleanExHS_MCM4.
GenevestigatorP33991.

Family and domain databases

Gene3D2.20.28.10. 1 hit.
2.40.50.140. 2 hits.
3.40.50.300. 1 hit.
InterProIPR003593. AAA+_ATPase.
IPR008047. MCM_4.
IPR018525. MCM_CS.
IPR001208. MCM_DNA-dep_ATPase.
IPR027925. MCM_N.
IPR012340. NA-bd_OB-fold.
IPR027417. P-loop_NTPase.
IPR004039. Rubredoxin-type_fold.
[Graphical view]
PfamPF00493. MCM. 1 hit.
PF14551. MCM_N. 1 hit.
[Graphical view]
PRINTSPR01657. MCMFAMILY.
PR01660. MCMPROTEIN4.
SMARTSM00382. AAA. 1 hit.
SM00350. MCM. 1 hit.
[Graphical view]
SUPFAMSSF50249. SSF50249. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEPS00847. MCM_1. 1 hit.
PS50051. MCM_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMCM4. human.
GeneWikiMCM4.
GenomeRNAi4173.
NextBio16436.
PMAP-CutDBP33991.
PROP33991.
SOURCESearch...

Entry information

Entry nameMCM4_HUMAN
AccessionPrimary (citable) accession number: P33991
Secondary accession number(s): Q8NEH1, Q99658
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: May 10, 2005
Last modified: April 16, 2014
This is version 147 of the entry and version 5 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM