UniProtKB - P33991 (MCM4_HUMAN)
DNA replication licensing factor MCM4
MCM4
Functioni
Miscellaneous
Catalytic activityi
- EC:3.6.4.12
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 510 – 517 | ATPSequence analysis | 8 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- DNA helicase activity Source: UniProtKB-EC
- DNA replication origin binding Source: GO_Central
- single-stranded DNA binding Source: GO_Central
GO - Biological processi
- DNA replication Source: Reactome
- DNA replication initiation Source: Reactome
- DNA strand elongation involved in DNA replication Source: GO_Central
- DNA unwinding involved in DNA replication Source: GO_Central
- double-strand break repair via break-induced replication Source: GO_Central
- mitotic DNA replication initiation Source: GO_Central
- pre-replicative complex assembly Source: Reactome
- pre-replicative complex assembly involved in nuclear cell cycle DNA replication Source: GO_Central
Keywordsi
Molecular function | DNA-binding, Helicase, Hydrolase |
Biological process | Cell cycle, DNA replication |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
PathwayCommonsi | P33991 |
Reactomei | R-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 |
SIGNORi | P33991 |
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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:6947, MCM4 |
MIMi | 602638, gene |
neXtProti | NX_P33991 |
VEuPathDBi | HostDB:ENSG00000104738.16 |
Subcellular locationi
Nucleus
- Nucleus By similarity
Other locations
- Chromosome By similarity
Note: Associated with chromatin before the formation of nuclei and detaches from it as DNA replication progresses.By similarity
Nucleus
- CMG complex Source: UniProtKB
- nucleoplasm Source: HPA
- nucleus Source: GO_Central
Other locations
- chromosome, telomeric region Source: BHF-UCL
- MCM complex Source: UniProtKB
- membrane Source: UniProtKB
Keywords - Cellular componenti
Chromosome, NucleusPathology & Biotechi
Involvement in diseasei
Immunodeficiency 54 (IMD54)3 Publications
Organism-specific databases
DisGeNETi | 4173 |
MalaCardsi | MCM4 |
MIMi | 609981, phenotype |
OpenTargetsi | ENSG00000104738 |
Orphaneti | 75391, Primary immunodeficiency with natural-killer cell deficiency and adrenal insufficiency |
PharmGKBi | PA30694 |
Miscellaneous databases
Pharosi | P33991, Tbio |
Chemistry databases
ChEMBLi | CHEMBL4105745 |
Genetic variation databases
BioMutai | MCM4 |
DMDMi | 68571766 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedCombined sources | |||
ChainiPRO_0000194101 | 2 – 863 | DNA replication licensing factor MCM4Add BLAST | 862 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylserineCombined sources | 1 | |
Modified residuei | 19 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 26 | PhosphoserineCombined sources | 1 | |
Modified residuei | 31 | PhosphoserineCombined sources | 1 | |
Modified residuei | 32 | PhosphoserineCombined sources | 1 | |
Modified residuei | 34 | PhosphoserineCombined sources | 1 | |
Modified residuei | 102 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 105 | PhosphoserineCombined sources | 1 | |
Modified residuei | 110 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 120 | PhosphoserineCombined sources | 1 | |
Modified residuei | 131 | PhosphoserineCombined sources | 1 | |
Modified residuei | 142 | PhosphoserineCombined sources | 1 | |
Modified residuei | 145 | PhosphoserineCombined sources | 1 | |
Modified residuei | 220 | N6-acetyllysineCombined sources | 1 | |
Cross-linki | 439 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources | ||
Modified residuei | 450 | N6-acetyllysineCombined sources | 1 | |
Cross-linki | 798 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources | ||
Modified residuei | 858 | N6-acetyllysineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
EPDi | P33991 |
jPOSTi | P33991 |
MassIVEi | P33991 |
MaxQBi | P33991 |
PaxDbi | P33991 |
PeptideAtlasi | P33991 |
PRIDEi | P33991 |
ProteomicsDBi | 54934 |
TopDownProteomicsi | P33991 |
PTM databases
iPTMneti | P33991 |
MetOSitei | P33991 |
PhosphoSitePlusi | P33991 |
SwissPalmi | P33991 |
Expressioni
Gene expression databases
Bgeei | ENSG00000104738, Expressed in testis and 230 other tissues |
ExpressionAtlasi | P33991, baseline and differential |
Genevisiblei | P33991, HS |
Organism-specific databases
HPAi | ENSG00000104738, Tissue enhanced (lymphoid) |
Interactioni
Subunit structurei
Component of the MCM2-7 complex (PubMed:16899510, PubMed:9305914). The complex forms a toroidal hexameric ring with the proposed subunit order MCM2-MCM6-MCM4-MCM7-MCM3-MCM5 (PubMed:16899510, PubMed:9305914).
Interacts with MCMBP (PubMed:17296731).
Component of the CMG helicase complex, composed of the MCM2-7 complex, the GINS complex and CDC45 (By similarity).
By similarity3 PublicationsBinary interactionsi
Hide detailsP33991
Protein-protein interaction databases
BioGRIDi | 110341, 176 interactors |
ComplexPortali | CPX-2940, MCM complex |
CORUMi | P33991 |
DIPi | DIP-31729N |
IntActi | P33991, 89 interactors |
MINTi | P33991 |
STRINGi | 9606.ENSP00000262105 |
Miscellaneous databases
RNActi | P33991, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 458 – 667 | MCMAdd BLAST | 210 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 642 – 645 | Arginine finger | 4 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0478, Eukaryota |
GeneTreei | ENSGT01010000222297 |
HOGENOMi | CLU_000995_7_1_1 |
InParanoidi | P33991 |
OMAi | YPPTRKL |
OrthoDBi | 266497at2759 |
PhylomeDBi | P33991 |
TreeFami | TF300463 |
Family and domain databases
InterProi | View protein in InterPro IPR031327, MCM IPR008047, MCM_4 IPR018525, MCM_CS IPR001208, MCM_dom IPR041562, MCM_lid IPR027925, MCM_N IPR033762, MCM_OB IPR012340, NA-bd_OB-fold IPR027417, P-loop_NTPase |
PANTHERi | PTHR11630, PTHR11630, 1 hit PTHR11630:SF66, PTHR11630:SF66, 1 hit |
Pfami | View protein in Pfam PF00493, MCM, 1 hit PF17855, MCM_lid, 1 hit PF14551, MCM_N, 1 hit PF17207, MCM_OB, 1 hit |
PRINTSi | PR01657, MCMFAMILY PR01660, MCMPROTEIN4 |
SMARTi | View protein in SMART SM00350, MCM, 1 hit |
SUPFAMi | SSF50249, SSF50249, 1 hit SSF52540, SSF52540, 1 hit |
PROSITEi | View protein in PROSITE PS00847, MCM_1, 1 hit PS50051, MCM_2, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 11 potential isoforms that are computationally mapped.Show allAlign All
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
Computationally mapped potential isoform sequencesi
There are 11 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A3B3IT92 | A0A3B3IT92_HUMAN | DNA helicase | MCM4 | 904 | Annotation score: | ||
A0A3B3IS57 | A0A3B3IS57_HUMAN | DNA helicase | MCM4 | 749 | Annotation score: | ||
A0A3B3ITP6 | A0A3B3ITP6_HUMAN | DNA helicase | MCM4 | 742 | Annotation score: | ||
A0A3B3IU45 | A0A3B3IU45_HUMAN | DNA helicase | MCM4 | 813 | Annotation score: | ||
E5RG31 | E5RG31_HUMAN | DNA helicase | MCM4 | 582 | Annotation score: | ||
A0A3B3IRR8 | A0A3B3IRR8_HUMAN | DNA helicase | MCM4 | 191 | Annotation score: | ||
A0A3B3ISC1 | A0A3B3ISC1_HUMAN | DNA replication licensing factor MC... | MCM4 | 107 | Annotation score: | ||
E5RFR3 | E5RFR3_HUMAN | DNA replication licensing factor MC... | MCM4 | 140 | Annotation score: | ||
E5RG53 | E5RG53_HUMAN | DNA replication licensing factor MC... | MCM4 | 81 | Annotation score: | ||
A0A3B3IS88 | A0A3B3IS88_HUMAN | DNA replication licensing factor MC... | MCM4 | 160 | Annotation score: | ||
There is more potential isoformShow all |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 62 | P → T in CAA52801 (PubMed:7601140).Curated | 1 | |
Sequence conflicti | 206 | P → Q in CAA52801 (PubMed:7601140).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_020500 | 460 | E → G1 PublicationCorresponds to variant dbSNP:rs17287663Ensembl. | 1 | |
Natural variantiVAR_020501 | 650 | L → 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 |
CCDSi | CCDS6143.1 |
PIRi | S65954 |
RefSeqi | NP_005905.2, NM_005914.3 NP_877423.1, NM_182746.2 |
Genome annotation databases
Ensembli | ENST00000262105; ENSP00000262105; ENSG00000104738 ENST00000649973; ENSP00000496964; ENSG00000104738 |
GeneIDi | 4173 |
KEGGi | hsa:4173 |
UCSCi | uc003xqk.3, human |
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 |
CCDSi | CCDS6143.1 |
PIRi | S65954 |
RefSeqi | NP_005905.2, NM_005914.3 NP_877423.1, NM_182746.2 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
6XTX | electron microscopy | 3.29 | 4 | 1-863 | [»] | |
6XTY | electron microscopy | 6.77 | 4 | 1-863 | [»] | |
SMRi | P33991 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 110341, 176 interactors |
ComplexPortali | CPX-2940, MCM complex |
CORUMi | P33991 |
DIPi | DIP-31729N |
IntActi | P33991, 89 interactors |
MINTi | P33991 |
STRINGi | 9606.ENSP00000262105 |
Chemistry databases
ChEMBLi | CHEMBL4105745 |
PTM databases
iPTMneti | P33991 |
MetOSitei | P33991 |
PhosphoSitePlusi | P33991 |
SwissPalmi | P33991 |
Genetic variation databases
BioMutai | MCM4 |
DMDMi | 68571766 |
Proteomic databases
EPDi | P33991 |
jPOSTi | P33991 |
MassIVEi | P33991 |
MaxQBi | P33991 |
PaxDbi | P33991 |
PeptideAtlasi | P33991 |
PRIDEi | P33991 |
ProteomicsDBi | 54934 |
TopDownProteomicsi | P33991 |
Protocols and materials databases
Antibodypediai | 1452, 440 antibodies |
Genome annotation databases
Ensembli | ENST00000262105; ENSP00000262105; ENSG00000104738 ENST00000649973; ENSP00000496964; ENSG00000104738 |
GeneIDi | 4173 |
KEGGi | hsa:4173 |
UCSCi | uc003xqk.3, human |
Organism-specific databases
CTDi | 4173 |
DisGeNETi | 4173 |
GeneCardsi | MCM4 |
HGNCi | HGNC:6947, MCM4 |
HPAi | ENSG00000104738, Tissue enhanced (lymphoid) |
MalaCardsi | MCM4 |
MIMi | 602638, gene 609981, phenotype |
neXtProti | NX_P33991 |
OpenTargetsi | ENSG00000104738 |
Orphaneti | 75391, Primary immunodeficiency with natural-killer cell deficiency and adrenal insufficiency |
PharmGKBi | PA30694 |
VEuPathDBi | HostDB:ENSG00000104738.16 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0478, Eukaryota |
GeneTreei | ENSGT01010000222297 |
HOGENOMi | CLU_000995_7_1_1 |
InParanoidi | P33991 |
OMAi | YPPTRKL |
OrthoDBi | 266497at2759 |
PhylomeDBi | P33991 |
TreeFami | TF300463 |
Enzyme and pathway databases
PathwayCommonsi | P33991 |
Reactomei | R-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 |
SIGNORi | P33991 |
Miscellaneous databases
BioGRID-ORCSi | 4173, 730 hits in 1007 CRISPR screens |
ChiTaRSi | MCM4, human |
GeneWikii | MCM4 |
GenomeRNAii | 4173 |
Pharosi | P33991, Tbio |
PROi | PR:P33991 |
RNActi | P33991, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000104738, Expressed in testis and 230 other tissues |
ExpressionAtlasi | P33991, baseline and differential |
Genevisiblei | P33991, HS |
Family and domain databases
InterProi | View protein in InterPro IPR031327, MCM IPR008047, MCM_4 IPR018525, MCM_CS IPR001208, MCM_dom IPR041562, MCM_lid IPR027925, MCM_N IPR033762, MCM_OB IPR012340, NA-bd_OB-fold IPR027417, P-loop_NTPase |
PANTHERi | PTHR11630, PTHR11630, 1 hit PTHR11630:SF66, PTHR11630:SF66, 1 hit |
Pfami | View protein in Pfam PF00493, MCM, 1 hit PF17855, MCM_lid, 1 hit PF14551, MCM_N, 1 hit PF17207, MCM_OB, 1 hit |
PRINTSi | PR01657, MCMFAMILY PR01660, MCMPROTEIN4 |
SMARTi | View protein in SMART SM00350, MCM, 1 hit |
SUPFAMi | SSF50249, SSF50249, 1 hit SSF52540, SSF52540, 1 hit |
PROSITEi | View protein in PROSITE PS00847, MCM_1, 1 hit PS50051, MCM_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | MCM4_HUMAN | |
Accessioni | P33991Primary (citable) accession number: P33991 Secondary accession number(s): Q8NEH1, Q99658 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 1, 1994 |
Last sequence update: | May 10, 2005 | |
Last modified: | April 7, 2021 | |
This is version 214 of the entry and version 5 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
3D-structure, Reference proteomeDocuments
- Human chromosome 8
Human chromosome 8: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families