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Protein

DNA replication licensing factor MCM4

Gene

MCM4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.2 Publications

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.Curated

Catalytic activityi

ATP + H2O = ADP + phosphate.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi510 – 517ATPSequence analysis8

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDNA-binding, Helicase, Hydrolase
Biological processCell cycle, DNA replication
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-176187 Activation of ATR in response to replication stress
R-HSA-176974 Unwinding of DNA
R-HSA-68867 Assembly of the pre-replicative complex
R-HSA-68949 Orc1 removal from chromatin
R-HSA-68962 Activation of the pre-replicative complex
R-HSA-69052 Switching of origins to a post-replicative state
SIGNORiP33991

Names & Taxonomyi

Protein namesi
Recommended name:
DNA replication licensing factor MCM4 (EC:3.6.4.12)
Alternative name(s):
CDC21 homolog
P1-CDC21
Gene namesi
Name:MCM4
Synonyms:CDC21
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000104738.16
HGNCiHGNC:6947 MCM4
MIMi602638 gene
neXtProtiNX_P33991

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Immunodeficiency 54 (IMD54)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
See also OMIM:609981

Organism-specific databases

DisGeNETi4173
MalaCardsiMCM4
MIMi609981 phenotype
OpenTargetsiENSG00000104738
Orphaneti75391 Primary immunodeficiency with natural-killer cell deficiency and adrenal insufficiency
PharmGKBiPA30694

Polymorphism and mutation databases

BioMutaiMCM4
DMDMi68571766

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001941012 – 863DNA replication licensing factor MCM4Add BLAST862

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1
Modified residuei19PhosphothreonineBy similarity1
Modified residuei26PhosphoserineCombined sources1
Modified residuei31PhosphoserineCombined sources1
Modified residuei32PhosphoserineCombined sources1
Modified residuei34PhosphoserineCombined sources1
Modified residuei102PhosphothreonineCombined sources1
Modified residuei105PhosphoserineCombined sources1
Modified residuei110PhosphothreonineCombined sources1
Modified residuei120PhosphoserineCombined sources1
Modified residuei131PhosphoserineCombined sources1
Modified residuei142PhosphoserineCombined sources1
Modified residuei145PhosphoserineCombined sources1
Modified residuei220N6-acetyllysineCombined sources1
Cross-linki439Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei450N6-acetyllysineCombined sources1
Cross-linki798Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei858N6-acetyllysineBy similarity1

Post-translational modificationi

Sumoylated; SUMO2 modified in response to stress caused by inhibition of proteasome activity (in vitro).By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP33991
MaxQBiP33991
PaxDbiP33991
PeptideAtlasiP33991
PRIDEiP33991
ProteomicsDBi54934
TopDownProteomicsiP33991

PTM databases

iPTMnetiP33991
PhosphoSitePlusiP33991
SwissPalmiP33991

Miscellaneous databases

PMAP-CutDBiP33991

Expressioni

Gene expression databases

BgeeiENSG00000104738 Expressed in 218 organ(s), highest expression level in testis
CleanExiHS_MCM4
ExpressionAtlasiP33991 baseline and differential
GenevisibleiP33991 HS

Organism-specific databases

HPAiCAB004497
HPA004873
HPA031052

Interactioni

Subunit structurei

Component of the MCM2-7 complex (PubMed:9305914, PubMed:16899510). The complex forms a toroidal hexameric ring with the proposed subunit order MCM2-MCM6-MCM4-MCM7-MCM3-MCM5 (Probable). Interacts with MCMBP (PubMed:17296731).Curated3 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi110341, 128 interactors
ComplexPortaliCPX-2940 MCM complex
CORUMiP33991
DIPiDIP-31729N
IntActiP33991, 73 interactors
MINTiP33991
STRINGi9606.ENSP00000262105

Structurei

3D structure databases

ProteinModelPortaliP33991
SMRiP33991
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini458 – 667MCMAdd BLAST210

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi642 – 645Arginine finger4

Sequence similaritiesi

Belongs to the MCM family.Curated

Phylogenomic databases

eggNOGiKOG0478 Eukaryota
COG1241 LUCA
GeneTreeiENSGT00910000144163
HOGENOMiHOG000224127
HOVERGENiHBG102781
InParanoidiP33991
KOiK02212
OMAiKNTIRIC
OrthoDBiEOG091G02V8
PhylomeDBiP33991
TreeFamiTF300463

Family and domain databases

InterProiView protein in InterPro
IPR031327 MCM
IPR008047 MCM_4
IPR018525 MCM_CS
IPR001208 MCM_dom
IPR027925 MCM_N
IPR033762 MCM_OB
IPR012340 NA-bd_OB-fold
IPR027417 P-loop_NTPase
PANTHERiPTHR11630 PTHR11630, 1 hit
PTHR11630:SF66 PTHR11630:SF66, 1 hit
PfamiView protein in Pfam
PF00493 MCM, 1 hit
PF14551 MCM_N, 1 hit
PF17207 MCM_OB, 1 hit
PRINTSiPR01657 MCMFAMILY
PR01660 MCMPROTEIN4
SMARTiView protein in SMART
SM00350 MCM, 1 hit
SUPFAMiSSF50249 SSF50249, 1 hit
SSF52540 SSF52540, 1 hit
PROSITEiView protein in PROSITE
PS00847 MCM_1, 1 hit
PS50051 MCM_2, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 5 potential isoforms that are computationally mapped.Show allAlign All

P33991-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MSSPASTPSR RGSRRGRATP AQTPRSEDAR SSPSQRRRGE DSTSTGELQP
60 70 80 90 100
MPTSPGVDLQ SPAAQDVLFS SPPQMHSSAI PLDFDVSSPL TYGTPSSRVE
110 120 130 140 150
GTPRSGVRGT PVRQRPDLGS AQKGLQVDLQ SDGAAAEDIV ASEQSLGQKL
160 170 180 190 200
VIWGTDVNVA ACKENFQRFL QRFIDPLAKE EENVGIDITE PLYMQRLGEI
210 220 230 240 250
NVIGEPFLNV NCEHIKSFDK NLYRQLISYP QEVIPTFDMA VNEIFFDRYP
260 270 280 290 300
DSILEHQIQV RPFNALKTKN MRNLNPEDID QLITISGMVI RTSQLIPEMQ
310 320 330 340 350
EAFFQCQVCA HTTRVEMDRG RIAEPSVCGR CHTTHSMALI HNRSLFSDKQ
360 370 380 390 400
MIKLQESPED MPAGQTPHTV ILFAHNDLVD KVQPGDRVNV TGIYRAVPIR
410 420 430 440 450
VNPRVSNVKS VYKTHIDVIH YRKTDAKRLH GLDEEAEQKL FSEKRVELLK
460 470 480 490 500
ELSRKPDIYE RLASALAPSI YEHEDIKKGI LLQLFGGTRK DFSHTGRGKF
510 520 530 540 550
RAEINILLCG DPGTSKSQLL QYVYNLVPRG QYTSGKGSSA VGLTAYVMKD
560 570 580 590 600
PETRQLVLQT GALVLSDNGI CCIDEFDKMN ESTRSVLHEV MEQQTLSIAK
610 620 630 640 650
AGIICQLNAR TSVLAAANPI ESQWNPKKTT IENIQLPHTL LSRFDLIFLL
660 670 680 690 700
LDPQDEAYDR RLAHHLVALY YQSEEQAEEE LLDMAVLKDY IAYAHSTIMP
710 720 730 740 750
RLSEEASQAL IEAYVDMRKI GSSRGMVSAY PRQLESLIRL AEAHAKVRLS
760 770 780 790 800
NKVEAIDVEE AKRLHREALK QSATDPRTGI VDISILTTGM SATSRKRKEE
810 820 830 840 850
LAEALKKLIL SKGKTPALKY QQLFEDIRGQ SDIAITKDMF EEALRALADD
860
DFLTVTGKTV RLL
Length:863
Mass (Da):96,558
Last modified:May 10, 2005 - v5
Checksum:i96D9CA2A7D88D015
GO

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E5RFJ8E5RFJ8_HUMAN
DNA replication licensing factor MC...
MCM4
211Annotation score:
E5RG31E5RG31_HUMAN
DNA replication licensing factor MC...
MCM4
278Annotation score:
E5RG53E5RG53_HUMAN
DNA replication licensing factor MC...
MCM4
81Annotation score:
E5RFR3E5RFR3_HUMAN
DNA replication licensing factor MC...
MCM4
140Annotation score:
E5RHP5E5RHP5_HUMAN
DNA replication licensing factor MC...
MCM4
27Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti62P → T in CAA52801 (PubMed:7601140).Curated1
Sequence conflicti206P → Q in CAA52801 (PubMed:7601140).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_020500460E → G1 PublicationCorresponds to variant dbSNP:rs17287663Ensembl.1
Natural variantiVAR_020501650L → M3 PublicationsCorresponds to variant dbSNP:rs762679EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS6143.1
PIRiS65954
RefSeqiNP_005905.2, NM_005914.3
NP_877423.1, NM_182746.2
UniGeneiHs.460184

Genome annotation databases

EnsembliENST00000262105; ENSP00000262105; ENSG00000104738
ENST00000523944; ENSP00000430194; ENSG00000104738
GeneIDi4173
KEGGihsa:4173
UCSCiuc003xqk.3 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS6143.1
PIRiS65954
RefSeqiNP_005905.2, NM_005914.3
NP_877423.1, NM_182746.2
UniGeneiHs.460184

3D structure databases

ProteinModelPortaliP33991
SMRiP33991
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110341, 128 interactors
ComplexPortaliCPX-2940 MCM complex
CORUMiP33991
DIPiDIP-31729N
IntActiP33991, 73 interactors
MINTiP33991
STRINGi9606.ENSP00000262105

PTM databases

iPTMnetiP33991
PhosphoSitePlusiP33991
SwissPalmiP33991

Polymorphism and mutation databases

BioMutaiMCM4
DMDMi68571766

Proteomic databases

EPDiP33991
MaxQBiP33991
PaxDbiP33991
PeptideAtlasiP33991
PRIDEiP33991
ProteomicsDBi54934
TopDownProteomicsiP33991

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000262105; ENSP00000262105; ENSG00000104738
ENST00000523944; ENSP00000430194; ENSG00000104738
GeneIDi4173
KEGGihsa:4173
UCSCiuc003xqk.3 human

Organism-specific databases

CTDi4173
DisGeNETi4173
EuPathDBiHostDB:ENSG00000104738.16
GeneCardsiMCM4
H-InvDBiHIX0007492
HGNCiHGNC:6947 MCM4
HPAiCAB004497
HPA004873
HPA031052
MalaCardsiMCM4
MIMi602638 gene
609981 phenotype
neXtProtiNX_P33991
OpenTargetsiENSG00000104738
Orphaneti75391 Primary immunodeficiency with natural-killer cell deficiency and adrenal insufficiency
PharmGKBiPA30694
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0478 Eukaryota
COG1241 LUCA
GeneTreeiENSGT00910000144163
HOGENOMiHOG000224127
HOVERGENiHBG102781
InParanoidiP33991
KOiK02212
OMAiKNTIRIC
OrthoDBiEOG091G02V8
PhylomeDBiP33991
TreeFamiTF300463

Enzyme and pathway databases

ReactomeiR-HSA-176187 Activation of ATR in response to replication stress
R-HSA-176974 Unwinding of DNA
R-HSA-68867 Assembly of the pre-replicative complex
R-HSA-68949 Orc1 removal from chromatin
R-HSA-68962 Activation of the pre-replicative complex
R-HSA-69052 Switching of origins to a post-replicative state
SIGNORiP33991

Miscellaneous databases

ChiTaRSiMCM4 human
GeneWikiiMCM4
GenomeRNAii4173
PMAP-CutDBiP33991
PROiPR:P33991
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000104738 Expressed in 218 organ(s), highest expression level in testis
CleanExiHS_MCM4
ExpressionAtlasiP33991 baseline and differential
GenevisibleiP33991 HS

Family and domain databases

InterProiView protein in InterPro
IPR031327 MCM
IPR008047 MCM_4
IPR018525 MCM_CS
IPR001208 MCM_dom
IPR027925 MCM_N
IPR033762 MCM_OB
IPR012340 NA-bd_OB-fold
IPR027417 P-loop_NTPase
PANTHERiPTHR11630 PTHR11630, 1 hit
PTHR11630:SF66 PTHR11630:SF66, 1 hit
PfamiView protein in Pfam
PF00493 MCM, 1 hit
PF14551 MCM_N, 1 hit
PF17207 MCM_OB, 1 hit
PRINTSiPR01657 MCMFAMILY
PR01660 MCMPROTEIN4
SMARTiView protein in SMART
SM00350 MCM, 1 hit
SUPFAMiSSF50249 SSF50249, 1 hit
SSF52540 SSF52540, 1 hit
PROSITEiView protein in PROSITE
PS00847 MCM_1, 1 hit
PS50051 MCM_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMCM4_HUMAN
AccessioniPrimary (citable) accession number: P33991
Secondary accession number(s): Q8NEH1, Q99658
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: May 10, 2005
Last modified: November 7, 2018
This is version 195 of the entry and version 5 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
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