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Protein

DNA helicase MCM8

Gene

MCM8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Component of the MCM8-MCM9 complex, a complex involved in homologous recombination repair following DNA interstrand cross-links and plays a key role during gametogenesis. The MCM8-MCM9 complex probably acts as a hexameric helicase downstream of the Fanconi anemia proteins BRCA2 and RAD51 and is required to process aberrant forks into homologous recombination substrates and to orchestrate homologous recombination with resection, fork stabilization and fork restart. May also 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). Binds chromatin throughout the cell cycle.1 Publication

Catalytic activityi

ATP + H2O = ADP + phosphate.

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi454 – 4618ATPSequence analysis

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Helicase, Hydrolase

Keywords - Biological processi

Cell cycle, DNA damage, DNA repair, DNA replication

Keywords - Ligandi

ATP-binding, DNA-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.
R-HSA-69300. Removal of licensing factors from origins.

Names & Taxonomyi

Protein namesi
Recommended name:
DNA helicase MCM8 (EC:3.6.4.12)
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

HGNCiHGNC:16147. MCM8.

Subcellular locationi

GO - Cellular componenti

  • MCM8-MCM9 complex Source: UniProtKB
  • nucleoplasm Source: Reactome
  • nucleus Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti149 – 1491P → R in POF10; inhibits protein recruitment to sites of DNA damage; shows significant reduction in DNA-binding affinity for single-strand DNA. 1 Publication
Corresponds to variant rs606231343 [ dbSNP | Ensembl ].
VAR_073417

Keywords - Diseasei

Disease mutation, Premature ovarian failure

Organism-specific databases

MIMi612885. phenotype.
PharmGKBiPA25696.

Polymorphism and mutation databases

BioMutaiMCM8.
DMDMi27805609.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 840840DNA helicase MCM8PRO_0000194125Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei630 – 6301PhosphoserineCombined sources

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9UJA3.
PaxDbiQ9UJA3.
PeptideAtlasiQ9UJA3.
PRIDEiQ9UJA3.

PTM databases

iPTMnetiQ9UJA3.
PhosphoSiteiQ9UJA3.

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.
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. Interacts with CDC6 and ORC2.2 Publications

Binary interactionsi

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

Protein-protein interaction databases

BioGridi124109. 27 interactions.
IntActiQ9UJA3. 3 interactions.
STRINGi9606.ENSP00000368174.

Structurei

3D structure databases

ProteinModelPortaliQ9UJA3.
SMRiQ9UJA3. Positions 88-753.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini402 – 609208MCMAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi481 – 49010Thr-rich

Sequence similaritiesi

Belongs to the MCM family.Curated
Contains 1 MCM domain.Curated

Phylogenomic databases

eggNOGiKOG0480. Eukaryota.
COG1241. LUCA.
GeneTreeiENSGT00790000123057.
HOGENOMiHOG000224129.
HOVERGENiHBG031700.
InParanoidiQ9UJA3.
KOiK10737.
OMAiLIVNSLC.
OrthoDBiEOG091G01BH.
PhylomeDBiQ9UJA3.
TreeFamiTF323155.

Family and domain databases

Gene3Di2.40.50.140. 2 hits.
3.40.50.300. 1 hit.
InterProiIPR003593. AAA+_ATPase.
IPR031327. MCM.
IPR001208. MCM_dom.
IPR012340. NA-bd_OB-fold.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF00493. MCM. 1 hit.
[Graphical view]
PRINTSiPR01657. MCMFAMILY.
SMARTiSM00382. AAA. 1 hit.
SM00350. MCM. 1 hit.
[Graphical view]
SUPFAMiSSF50249. SSF50249. 1 hit.
SSF52540. SSF52540. 2 hits.
PROSITEiPS50051. MCM_2. 1 hit.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti590 – 5901V → A in AAI01056 (PubMed:15489334).Curated
Sequence conflicti788 – 7881E → G in AAI01055 (PubMed:15489334).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti63 – 631Q → K.
Corresponds to variant rs236110 [ dbSNP | Ensembl ].
VAR_015145
Natural varianti101 – 1011K → N.
Corresponds to variant rs6117014 [ dbSNP | Ensembl ].
VAR_050281
Natural varianti149 – 1491P → R in POF10; inhibits protein recruitment to sites of DNA damage; shows significant reduction in DNA-binding affinity for single-strand DNA. 1 Publication
Corresponds to variant rs606231343 [ dbSNP | Ensembl ].
VAR_073417
Natural varianti183 – 1831N → S.
Corresponds to variant rs16991591 [ dbSNP | Ensembl ].
VAR_050282
Natural varianti341 – 3411E → K.
Corresponds to variant rs16991615 [ dbSNP | Ensembl ].
VAR_050283
Natural varianti365 – 3651S → N.
Corresponds to variant rs28403619 [ dbSNP | Ensembl ].
VAR_050284
Natural varianti785 – 7851N → S.
Corresponds to variant rs16991638 [ dbSNP | Ensembl ].
VAR_050285

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei342 – 35716Missing in isoform 3. CuratedVSP_041308Add
BLAST
Alternative sequencei408 – 41811NSLCPVIFGHE → KWSLALSPRLEYSGAISAHC NLHLPSSNSSPTSACRVAGT TGMRHQTQLLL in isoform 4. 1 PublicationVSP_044179Add
BLAST
Alternative sequencei419 – 46547Missing in isoform 2. 1 PublicationVSP_015785Add
BLAST

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. Translation: CAI23480.1.
AL035461 Genomic DNA. Translation: CAB55276.2.
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]
UniGeneiHs.597484.

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

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. Translation: CAI23480.1.
AL035461 Genomic DNA. Translation: CAB55276.2.
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]
UniGeneiHs.597484.

3D structure databases

ProteinModelPortaliQ9UJA3.
SMRiQ9UJA3. Positions 88-753.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124109. 27 interactions.
IntActiQ9UJA3. 3 interactions.
STRINGi9606.ENSP00000368174.

PTM databases

iPTMnetiQ9UJA3.
PhosphoSiteiQ9UJA3.

Polymorphism and mutation databases

BioMutaiMCM8.
DMDMi27805609.

Proteomic databases

MaxQBiQ9UJA3.
PaxDbiQ9UJA3.
PeptideAtlasiQ9UJA3.
PRIDEiQ9UJA3.

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.
GeneCardsiMCM8.
HGNCiHGNC:16147. MCM8.
HPAiHPA045141.
MIMi608187. gene.
612885. phenotype.
neXtProtiNX_Q9UJA3.
PharmGKBiPA25696.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0480. Eukaryota.
COG1241. LUCA.
GeneTreeiENSGT00790000123057.
HOGENOMiHOG000224129.
HOVERGENiHBG031700.
InParanoidiQ9UJA3.
KOiK10737.
OMAiLIVNSLC.
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.
R-HSA-69300. Removal of licensing factors from origins.

Miscellaneous databases

ChiTaRSiMCM8. human.
GeneWikiiMCM8.
GenomeRNAii84515.
PROiQ9UJA3.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000125885.
CleanExiHS_MCM8.
GenevisibleiQ9UJA3. HS.

Family and domain databases

Gene3Di2.40.50.140. 2 hits.
3.40.50.300. 1 hit.
InterProiIPR003593. AAA+_ATPase.
IPR031327. MCM.
IPR001208. MCM_dom.
IPR012340. NA-bd_OB-fold.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF00493. MCM. 1 hit.
[Graphical view]
PRINTSiPR01657. MCMFAMILY.
SMARTiSM00382. AAA. 1 hit.
SM00350. MCM. 1 hit.
[Graphical view]
SUPFAMiSSF50249. SSF50249. 1 hit.
SSF52540. SSF52540. 2 hits.
PROSITEiPS50051. MCM_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMCM8_HUMAN
AccessioniPrimary (citable) accession number: Q9UJA3
Secondary accession number(s): B2RBG7
, D3DW08, E7EQU7, Q495R4, Q495R6, Q495R7, Q86US4, Q969I5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 17, 2003
Last sequence update: June 1, 2001
Last modified: September 7, 2016
This is version 147 of the entry and version 2 of the sequence. [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

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:22771115).2 Publications

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  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. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.