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Protein

DNA helicase MCM8

Gene

MCM8

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

Functioni

Component of the MCM8-MCM9 complex, a complex involved in the repair of double-stranded DNA breaks (DBSs) and DNA interstrand cross-links (ICLs) by homologous recombination (HR) (PubMed:23401855). Required for DNA resection by the MRE11-RAD50-NBN/NBS1 (MRN) complex by recruiting the MRN complex to the repair site and by promoting the complex nuclease activity (PubMed:26215093). Probably by regulating the localization of the MNR complex, indirectly regulates the recruitment of downstream effector RAD51 to DNA damage sites including DBSs and ICLs (PubMed:23401855). The MCM8-MCM9 complex is dispensable for DNA replication and S phase progression (PubMed:23401855). However, may play a non-essential for DNA replication: may be involved in the activation of the prereplicative complex (pre-RC) during G1 phase by recruiting CDC6 to the origin recognition complex (ORC) (PubMed:15684404). Probably by regulating HR, plays a key role during gametogenesis (By similarity). Stabilizes MCM9 protein (PubMed:23401855, PubMed:26215093).By similarity3 Publications

Caution

Was initially thought to play a role in DNA replication (PubMed:15684404). However, it was later shown that it is mainly involved in homologous recombination repair (PubMed:23401855).2 Publications

Catalytic activityi

ATP + H2O = ADP + phosphate.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi454 – 461ATPSequence analysis8

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • chromatin binding Source: UniProtKB
  • DNA binding Source: UniProtKB-KW
  • enzyme binding Source: UniProtKB
  • helicase activity Source: UniProtKB-KW
  • MutLbeta complex binding Source: UniProtKB
  • MutSalpha complex binding Source: UniProtKB
  • MutSbeta complex binding Source: UniProtKB

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-113507 E2F-enabled inhibition of pre-replication complex formation
R-HSA-176187 Activation of ATR in response to replication stress
R-HSA-176974 Unwinding of DNA
R-HSA-68689 CDC6 association with the ORC:origin complex
R-HSA-68827 CDT1 association with the CDC6:ORC:origin complex
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

Names & Taxonomyi

Protein namesi
Recommended name:
DNA helicase MCM8 (EC:3.6.4.121 Publication)
Alternative name(s):
Minichromosome maintenance 8
Gene namesi
Name:MCM8
Synonyms:C20orf154
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

EuPathDBiHostDB:ENSG00000125885.13
HGNCiHGNC:16147 MCM8
MIMi608187 gene
neXtProtiNX_Q9UJA3

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

Chromosome, Nucleus

Pathology & Biotechi

Involvement in diseasei

Premature ovarian failure 10 (POF10)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn ovarian disorder defined as the cessation of ovarian function under the age of 40 years. It is characterized by oligomenorrhea or amenorrhea, in the presence of elevated levels of serum gonadotropins and low estradiol.
See also OMIM:612885
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_073417149P → R in POF10; inhibits protein recruitment to sites of DNA damage; shows significant reduction in DNA-binding affinity for single-strand DNA. 1 PublicationCorresponds to variant dbSNP:rs606231343EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi456P → A: Decreases the formation of MRE11 and RPA1 foci in response to cisplatin-induced DNA damage. 1 Publication1

Keywords - Diseasei

Disease mutation, Premature ovarian failure

Organism-specific databases

DisGeNETi84515
MalaCardsiMCM8
MIMi612885 phenotype
OpenTargetsiENSG00000125885
Orphaneti619 NON RARE IN EUROPE: Primary ovarian failure
PharmGKBiPA25696

Polymorphism and mutation databases

BioMutaiMCM8
DMDMi27805609

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001941251 – 840DNA helicase MCM8Add BLAST840

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei630PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9UJA3
PaxDbiQ9UJA3
PeptideAtlasiQ9UJA3
PRIDEiQ9UJA3
ProteomicsDBi84610
84611 [Q9UJA3-2]
84612 [Q9UJA3-3]

PTM databases

iPTMnetiQ9UJA3
PhosphoSitePlusiQ9UJA3

Expressioni

Tissue specificityi

Highest levels in placenta, lung and pancreas. Low levels in skeletal muscle and kidney. Expressed in various tumors with highest levels in colon and lung cancers.1 Publication

Inductioni

By E2F1.1 Publication

Gene expression databases

BgeeiENSG00000125885 Expressed in 187 organ(s), highest expression level in testis
CleanExiHS_MCM8
GenevisibleiQ9UJA3 HS

Organism-specific databases

HPAiHPA045141

Interactioni

Subunit structurei

Component of the MCM8-MCM9 complex, which forms a hexamer composed of MCM8 and MCM9 (PubMed:23401855, PubMed:26300262). Interacts with the DNA mismatch repair (MMR) complex composed at least of MSH2, MSH3, MSH6, PMS1 and MLH1 (PubMed:26300262). Interacts with RAD51; the interaction recruits RAD51 to DNA damage sites (PubMed:23401855). Interacts with the MRN complex composed of MRE11, RAD50 and NBN/NBS1 (PubMed:26215093). Interacts with CDC6 and ORC2 (PubMed:15684404).4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MCMBPQ9BTE33EBI-8756095,EBI-749378

GO - Molecular functioni

Protein-protein interaction databases

BioGridi124109, 35 interactors
CORUMiQ9UJA3
IntActiQ9UJA3, 4 interactors
MINTiQ9UJA3
STRINGi9606.ENSP00000368174

Structurei

3D structure databases

ProteinModelPortaliQ9UJA3
SMRiQ9UJA3
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini402 – 609MCMAdd BLAST208

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi481 – 490Thr-rich10

Sequence similaritiesi

Belongs to the MCM family.Curated

Phylogenomic databases

eggNOGiKOG0480 Eukaryota
COG1241 LUCA
GeneTreeiENSGT00910000144163
HOGENOMiHOG000224129
HOVERGENiHBG031700
InParanoidiQ9UJA3
KOiK10737
OMAiHGMLMEF
OrthoDBiEOG091G01BH
PhylomeDBiQ9UJA3
TreeFamiTF323155

Family and domain databases

InterProiView protein in InterPro
IPR003593 AAA+_ATPase
IPR031327 MCM
IPR001208 MCM_dom
IPR033762 MCM_OB
IPR012340 NA-bd_OB-fold
IPR027417 P-loop_NTPase
PANTHERiPTHR11630 PTHR11630, 1 hit
PfamiView protein in Pfam
PF00493 MCM, 1 hit
PF17207 MCM_OB, 1 hit
PRINTSiPR01657 MCMFAMILY
SMARTiView protein in SMART
SM00382 AAA, 1 hit
SM00350 MCM, 1 hit
SUPFAMiSSF50249 SSF50249, 1 hit
SSF52540 SSF52540, 1 hit
PROSITEiView protein in PROSITE
PS50051 MCM_2, 1 hit

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: Q9UJA3-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MNGEYRGRGF GRGRFQSWKR GRGGGNFSGK WREREHRPDL SKTTGKRTSE
60 70 80 90 100
QTPQFLLSTK TPQSMQSTLD RFIPYKGWKL YFSEVYSDSS PLIEKIQAFE
110 120 130 140 150
KFFTRHIDLY DKDEIERKGS ILVDFKELTE GGEVTNLIPD IATELRDAPE
160 170 180 190 200
KTLACMGLAI HQVLTKDLER HAAELQAQEG LSNDGETMVN VPHIHARVYN
210 220 230 240 250
YEPLTQLKNV RANYYGKYIA LRGTVVRVSN IKPLCTKMAF LCAACGEIQS
260 270 280 290 300
FPLPDGKYSL PTKCPVPVCR GRSFTALRSS PLTVTMDWQS IKIQELMSDD
310 320 330 340 350
QREAGRIPRT IECELVHDLV DSCVPGDTVT ITGIVKVSNA EEGSRNKNDK
360 370 380 390 400
CMFLLYIEAN SISNSKGQKT KSSEDGCKHG MLMEFSLKDL YAIQEIQAEE
410 420 430 440 450
NLFKLIVNSL CPVIFGHELV KAGLALALFG GSQKYADDKN RIPIRGDPHI
460 470 480 490 500
LVVGDPGLGK SQMLQAACNV APRGVYVCGN TTTTSGLTVT LSKDSSSGDF
510 520 530 540 550
ALEAGALVLG DQGICGIDEF DKMGNQHQAL LEAMEQQSIS LAKAGVVCSL
560 570 580 590 600
PARTSIIAAA NPVGGHYNKA KTVSENLKMG SALLSRFDLV FILLDTPNEH
610 620 630 640 650
HDHLLSEHVI AIRAGKQRTI SSATVARMNS QDSNTSVLEV VSEKPLSERL
660 670 680 690 700
KVVPGETIDP IPHQLLRKYI GYARQYVYPR LSTEAARVLQ DFYLELRKQS
710 720 730 740 750
QRLNSSPITT RQLESLIRLT EARARLELRE EATKEDAEDI VEIMKYSMLG
760 770 780 790 800
TYSDEFGNLD FERSQHGSGM SNRSTAKRFI SALNNVAERT YNNIFQFHQL
810 820 830 840
RQIAKELNIQ VADFENFIGS LNDQGYLLKK GPKVYQLQTM
Length:840
Mass (Da):93,697
Last modified:June 1, 2001 - v2
Checksum:i6349339A92FEBF88
GO
Isoform 2 (identifier: Q9UJA3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     419-465: Missing.

Note: No experimental confirmation available.
Show »
Length:793
Mass (Da):88,756
Checksum:i39112134BB33E3B4
GO
Isoform 3 (identifier: Q9UJA3-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     342-357: Missing.

Note: No experimental confirmation available. According to PubMed:12771218, this isoform could be derived from an aberrant mRNA form found in placental choriocarcinoma.
Show »
Length:824
Mass (Da):91,784
Checksum:i829B4E10F9E00702
GO
Isoform 4 (identifier: Q9UJA3-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     408-418: NSLCPVIFGHE → KWSLALSPRLEYSGAISAHCNLHLPSSNSSPTSACRVAGTTGMRHQTQLLL

Note: No experimental confirmation available.
Show »
Length:880
Mass (Da):97,932
Checksum:iC14BC728273EEED6
GO

Sequence cautioni

The sequence BAB55260 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti590V → A in AAI01056 (PubMed:15489334).Curated1
Sequence conflicti788E → G in AAI01055 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01514563Q → K. Corresponds to variant dbSNP:rs236110Ensembl.1
Natural variantiVAR_050281101K → N. Corresponds to variant dbSNP:rs6117014Ensembl.1
Natural variantiVAR_073417149P → R in POF10; inhibits protein recruitment to sites of DNA damage; shows significant reduction in DNA-binding affinity for single-strand DNA. 1 PublicationCorresponds to variant dbSNP:rs606231343EnsemblClinVar.1
Natural variantiVAR_050282183N → S. Corresponds to variant dbSNP:rs16991591Ensembl.1
Natural variantiVAR_050283341E → K Decreases the formation of MRE11 and RPA1 foci in response to cisplatin-induced DNA damage. 1 PublicationCorresponds to variant dbSNP:rs16991615Ensembl.1
Natural variantiVAR_050284365S → N. Corresponds to variant dbSNP:rs28403619Ensembl.1
Natural variantiVAR_050285785N → S. Corresponds to variant dbSNP:rs16991638Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_041308342 – 357Missing in isoform 3. CuratedAdd BLAST16
Alternative sequenceiVSP_044179408 – 418NSLCPVIFGHE → KWSLALSPRLEYSGAISAHC NLHLPSSNSSPTSACRVAGT TGMRHQTQLLL in isoform 4. 1 PublicationAdd BLAST11
Alternative sequenceiVSP_015785419 – 465Missing in isoform 2. 1 PublicationAdd BLAST47

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ439063 mRNA Translation: CAD27750.1
AY158211 mRNA Translation: AAO21222.1
AK027644 mRNA Translation: BAB55260.1 Different initiation.
AK314654 mRNA Translation: BAG37214.1
AL035461 Genomic DNA No translation available.
CH471133 Genomic DNA Translation: EAX10403.1
CH471133 Genomic DNA Translation: EAX10404.1
BC008830 mRNA Translation: AAH08830.2
BC080656 mRNA Translation: AAH80656.1
BC101054 mRNA Translation: AAI01055.1
BC101055 mRNA Translation: AAI01056.1
BC101056 mRNA Translation: AAI01057.1
BC101057 mRNA Translation: AAI01058.1
CCDSiCCDS13094.1 [Q9UJA3-1]
CCDS13095.1 [Q9UJA3-3]
CCDS63226.1 [Q9UJA3-2]
CCDS63227.1 [Q9UJA3-4]
RefSeqiNP_001268449.1, NM_001281520.1 [Q9UJA3-1]
NP_001268450.1, NM_001281521.1 [Q9UJA3-4]
NP_001268451.1, NM_001281522.1 [Q9UJA3-2]
NP_115874.3, NM_032485.5 [Q9UJA3-1]
NP_877954.1, NM_182802.2 [Q9UJA3-3]
XP_016883594.1, XM_017028105.1 [Q9UJA3-4]
UniGeneiHs.597484
Hs.656543

Genome annotation databases

EnsembliENST00000265187; ENSP00000265187; ENSG00000125885 [Q9UJA3-3]
ENST00000378883; ENSP00000368161; ENSG00000125885 [Q9UJA3-2]
ENST00000378886; ENSP00000368164; ENSG00000125885 [Q9UJA3-4]
ENST00000378896; ENSP00000368174; ENSG00000125885 [Q9UJA3-1]
ENST00000610722; ENSP00000478141; ENSG00000125885 [Q9UJA3-1]
GeneIDi84515
KEGGihsa:84515
UCSCiuc002wmi.5 human [Q9UJA3-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ439063 mRNA Translation: CAD27750.1
AY158211 mRNA Translation: AAO21222.1
AK027644 mRNA Translation: BAB55260.1 Different initiation.
AK314654 mRNA Translation: BAG37214.1
AL035461 Genomic DNA No translation available.
CH471133 Genomic DNA Translation: EAX10403.1
CH471133 Genomic DNA Translation: EAX10404.1
BC008830 mRNA Translation: AAH08830.2
BC080656 mRNA Translation: AAH80656.1
BC101054 mRNA Translation: AAI01055.1
BC101055 mRNA Translation: AAI01056.1
BC101056 mRNA Translation: AAI01057.1
BC101057 mRNA Translation: AAI01058.1
CCDSiCCDS13094.1 [Q9UJA3-1]
CCDS13095.1 [Q9UJA3-3]
CCDS63226.1 [Q9UJA3-2]
CCDS63227.1 [Q9UJA3-4]
RefSeqiNP_001268449.1, NM_001281520.1 [Q9UJA3-1]
NP_001268450.1, NM_001281521.1 [Q9UJA3-4]
NP_001268451.1, NM_001281522.1 [Q9UJA3-2]
NP_115874.3, NM_032485.5 [Q9UJA3-1]
NP_877954.1, NM_182802.2 [Q9UJA3-3]
XP_016883594.1, XM_017028105.1 [Q9UJA3-4]
UniGeneiHs.597484
Hs.656543

3D structure databases

ProteinModelPortaliQ9UJA3
SMRiQ9UJA3
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124109, 35 interactors
CORUMiQ9UJA3
IntActiQ9UJA3, 4 interactors
MINTiQ9UJA3
STRINGi9606.ENSP00000368174

PTM databases

iPTMnetiQ9UJA3
PhosphoSitePlusiQ9UJA3

Polymorphism and mutation databases

BioMutaiMCM8
DMDMi27805609

Proteomic databases

EPDiQ9UJA3
PaxDbiQ9UJA3
PeptideAtlasiQ9UJA3
PRIDEiQ9UJA3
ProteomicsDBi84610
84611 [Q9UJA3-2]
84612 [Q9UJA3-3]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000265187; ENSP00000265187; ENSG00000125885 [Q9UJA3-3]
ENST00000378883; ENSP00000368161; ENSG00000125885 [Q9UJA3-2]
ENST00000378886; ENSP00000368164; ENSG00000125885 [Q9UJA3-4]
ENST00000378896; ENSP00000368174; ENSG00000125885 [Q9UJA3-1]
ENST00000610722; ENSP00000478141; ENSG00000125885 [Q9UJA3-1]
GeneIDi84515
KEGGihsa:84515
UCSCiuc002wmi.5 human [Q9UJA3-1]

Organism-specific databases

CTDi84515
DisGeNETi84515
EuPathDBiHostDB:ENSG00000125885.13
GeneCardsiMCM8
HGNCiHGNC:16147 MCM8
HPAiHPA045141
MalaCardsiMCM8
MIMi608187 gene
612885 phenotype
neXtProtiNX_Q9UJA3
OpenTargetsiENSG00000125885
Orphaneti619 NON RARE IN EUROPE: Primary ovarian failure
PharmGKBiPA25696
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0480 Eukaryota
COG1241 LUCA
GeneTreeiENSGT00910000144163
HOGENOMiHOG000224129
HOVERGENiHBG031700
InParanoidiQ9UJA3
KOiK10737
OMAiHGMLMEF
OrthoDBiEOG091G01BH
PhylomeDBiQ9UJA3
TreeFamiTF323155

Enzyme and pathway databases

ReactomeiR-HSA-113507 E2F-enabled inhibition of pre-replication complex formation
R-HSA-176187 Activation of ATR in response to replication stress
R-HSA-176974 Unwinding of DNA
R-HSA-68689 CDC6 association with the ORC:origin complex
R-HSA-68827 CDT1 association with the CDC6:ORC:origin complex
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

Miscellaneous databases

ChiTaRSiMCM8 human
GeneWikiiMCM8
GenomeRNAii84515
PROiPR:Q9UJA3
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000125885 Expressed in 187 organ(s), highest expression level in testis
CleanExiHS_MCM8
GenevisibleiQ9UJA3 HS

Family and domain databases

InterProiView protein in InterPro
IPR003593 AAA+_ATPase
IPR031327 MCM
IPR001208 MCM_dom
IPR033762 MCM_OB
IPR012340 NA-bd_OB-fold
IPR027417 P-loop_NTPase
PANTHERiPTHR11630 PTHR11630, 1 hit
PfamiView protein in Pfam
PF00493 MCM, 1 hit
PF17207 MCM_OB, 1 hit
PRINTSiPR01657 MCMFAMILY
SMARTiView protein in SMART
SM00382 AAA, 1 hit
SM00350 MCM, 1 hit
SUPFAMiSSF50249 SSF50249, 1 hit
SSF52540 SSF52540, 1 hit
PROSITEiView protein in PROSITE
PS50051 MCM_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMCM8_HUMAN
AccessioniPrimary (citable) accession number: Q9UJA3
Secondary accession number(s): B2RBG7
, D3DW08, E7EQU7, Q495R4, Q495R6, Q495R7, Q86US4, Q969I5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 17, 2003
Last sequence update: June 1, 2001
Last modified: November 7, 2018
This is version 170 of the entry and version 2 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 20
    Human chromosome 20: entries, gene names and cross-references to MIM
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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