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Protein

DNA replication licensing factor MCM6

Gene

MCM6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.1 Publication

Catalytic activityi

ATP + H2O = ADP + phosphate.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi396 – 403ATPSequence analysis8

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • DNA helicase activity Source: Ensembl
  • single-stranded DNA binding Source: Ensembl

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Helicase, Hydrolase

Keywords - Biological processi

Cell cycle, DNA replication

Keywords - Ligandi

ATP-binding, DNA-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000076003-MONOMER.
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.
R-HSA-69300. Removal of licensing factors from origins.
SIGNORiQ14566.

Names & Taxonomyi

Protein namesi
Recommended name:
DNA replication licensing factor MCM6 (EC:3.6.4.12)
Alternative name(s):
p105MCM
Gene namesi
Name:MCM6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:6949. MCM6.

Subcellular locationi

  • Nucleus

  • Note: Binds to chromatin during G1 and detach from it during S phase.

GO - Cellular componenti

  • MCM complex Source: UniProtKB
  • nuclear chromosome, telomeric region Source: BHF-UCL
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi757E → A or D: Impairs interaction with CTD1. 1 Publication1
Mutagenesisi763E → A or D: Impairs interaction with CTD1. 1 Publication1
Mutagenesisi766L → A: Impairs interaction with CTD1. 1 Publication1

Organism-specific databases

DisGeNETi4175.
MalaCardsiMCM6.
MIMi223100. phenotype.
OpenTargetsiENSG00000076003.
Orphaneti319681. Lactase non-persistence in adulthood.
PharmGKBiPA30696.

Polymorphism and mutation databases

BioMutaiMCM6.
DMDMi2497824.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001941131 – 821DNA replication licensing factor MCM6Add BLAST821

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei13PhosphoserineCombined sources1
Modified residuei219PhosphoserineCombined sources1
Modified residuei271PhosphoserineCombined sources1
Modified residuei278PhosphothreonineCombined sources1
Modified residuei643N6-acetyllysineBy similarity1
Modified residuei689PhosphoserineBy similarity1
Modified residuei762PhosphoserineCombined sources1
Modified residuei791PhosphothreonineCombined sources1

Post-translational modificationi

O-glycosylated (O-GlcNAcylated), in a cell cycle-dependent manner.1 Publication

Keywords - PTMi

Acetylation, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ14566.
MaxQBiQ14566.
PaxDbiQ14566.
PeptideAtlasiQ14566.
PRIDEiQ14566.

PTM databases

iPTMnetiQ14566.
PhosphoSitePlusiQ14566.
SwissPalmiQ14566.

Miscellaneous databases

PMAP-CutDBQ14566.

Expressioni

Gene expression databases

BgeeiENSG00000076003.
CleanExiHS_MCM6.
GenevisibleiQ14566. HS.

Organism-specific databases

HPAiCAB009577.
HPA004818.

Interactioni

Subunit structurei

Component of the MCM2-7 complex. The complex forms a toroidal hexameric ring with the proposed subunit order MCM2-MCM6-MCM4-MCM7-MCM3-MCM5 (Probable). May interact with MCM10. Interacts with TIPIN. Interacts with CDT1. Interacts with MCMBP.Curated6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself2EBI-374900,EBI-374900
Q763532EBI-374900,EBI-6248077From a different organism.
CDKN2AP427714EBI-374900,EBI-375053
CDT1Q9H2114EBI-374900,EBI-456953
FAM161AQ3B8203EBI-374900,EBI-719941
MCM10Q7L5902EBI-374900,EBI-374912
MCM10Q7L590-23EBI-374900,EBI-10233517
MCM2P4973613EBI-374900,EBI-374819
MCM3P252053EBI-374900,EBI-355153
MCM7P339936EBI-374900,EBI-355924
MCMBPQ9BTE315EBI-374900,EBI-749378
NUDT2P505833EBI-374900,EBI-10096247
SNRPB2P085793EBI-374900,EBI-1053651
SSRP1Q089452EBI-374900,EBI-353771
ZBTB9Q96C003EBI-374900,EBI-395708

Protein-protein interaction databases

BioGridi110343. 90 interactors.
DIPiDIP-31727N.
IntActiQ14566. 48 interactors.
MINTiMINT-5004576.
STRINGi9606.ENSP00000264156.

Structurei

Secondary structure

1821
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi709 – 711Combined sources3
Beta strandi714 – 716Combined sources3
Helixi718 – 737Combined sources20
Beta strandi739 – 741Combined sources3
Helixi745 – 756Combined sources12
Turni757 – 759Combined sources3
Helixi763 – 782Combined sources20
Helixi793 – 796Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2KLQNMR-A708-821[»]
2LE8NMR-A708-821[»]
ProteinModelPortaliQ14566.
SMRiQ14566.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ14566.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini346 – 553MCMAdd BLAST208

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi528 – 531Arginine finger4

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG0480. Eukaryota.
COG1241. LUCA.
GeneTreeiENSGT00550000074860.
HOGENOMiHOG000224130.
HOVERGENiHBG006334.
InParanoidiQ14566.
KOiK02542.
OMAiEYFQRVT.
OrthoDBiEOG091G020Q.
PhylomeDBiQ14566.
TreeFamiTF105646.

Family and domain databases

Gene3Di2.20.28.10. 1 hit.
3.40.50.300. 1 hit.
InterProiIPR031327. MCM.
IPR008049. MCM6.
IPR018525. MCM_CS.
IPR001208. MCM_dom.
IPR027925. MCM_N.
IPR033762. MCM_OB.
IPR012340. NA-bd_OB-fold.
IPR027417. P-loop_NTPase.
IPR004039. Rubredoxin-type_fold.
[Graphical view]
PfamiPF00493. MCM. 1 hit.
PF14551. MCM_N. 1 hit.
PF17207. MCM_OB. 1 hit.
[Graphical view]
PRINTSiPR01657. MCMFAMILY.
PR01662. MCMPROTEIN6.
SMARTiSM00350. MCM. 1 hit.
[Graphical view]
SUPFAMiSSF50249. SSF50249. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEiPS00847. MCM_1. 1 hit.
PS50051. MCM_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q14566-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDLAAAAEPG AGSQHLEVRD EVAEKCQKLF LDFLEEFQSS DGEIKYLQLA
60 70 80 90 100
EELIRPERNT LVVSFVDLEQ FNQQLSTTIQ EEFYRVYPYL CRALKTFVKD
110 120 130 140 150
RKEIPLAKDF YVAFQDLPTR HKIRELTSSR IGLLTRISGQ VVRTHPVHPE
160 170 180 190 200
LVSGTFLCLD CQTVIRDVEQ QFKYTQPNIC RNPVCANRRR FLLDTNKSRF
210 220 230 240 250
VDFQKVRIQE TQAELPRGSI PRSLEVILRA EAVESAQAGD KCDFTGTLIV
260 270 280 290 300
VPDVSKLSTP GARAETNSRV SGVDGYETEG IRGLRALGVR DLSYRLVFLA
310 320 330 340 350
CCVAPTNPRF GGKELRDEEQ TAESIKNQMT VKEWEKVFEM SQDKNLYHNL
360 370 380 390 400
CTSLFPTIHG NDEVKRGVLL MLFGGVPKTT GEGTSLRGDI NVCIVGDPST
410 420 430 440 450
AKSQFLKHVE EFSPRAVYTS GKASSAAGLT AAVVRDEESH EFVIEAGALM
460 470 480 490 500
LADNGVCCID EFDKMDVRDQ VAIHEAMEQQ TISITKAGVK ATLNARTSIL
510 520 530 540 550
AAANPISGHY DRSKSLKQNI NLSAPIMSRF DLFFILVDEC NEVTDYAIAR
560 570 580 590 600
RIVDLHSRIE ESIDRVYSLD DIRRYLLFAR QFKPKISKES EDFIVEQYKH
610 620 630 640 650
LRQRDGSGVT KSSWRITVRQ LESMIRLSEA MARMHCCDEV QPKHVKEAFR
660 670 680 690 700
LLNKSIIRVE TPDVNLDQEE EIQMEVDEGA GGINGHADSP APVNGINGYN
710 720 730 740 750
EDINQESAPK ASLRLGFSEY CRISNLIVLH LRKVEEEEDE SALKRSELVN
760 770 780 790 800
WYLKEIESEI DSEEELINKK RIIEKVIHRL THYDHVLIEL TQAGLKGSTE
810 820
GSESYEEDPY LVVNPNYLLE D
Length:821
Mass (Da):92,889
Last modified:November 1, 1997 - v1
Checksum:iF94968EB25A3E501
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti377 – 387PKTTGEGTSLR → SKDNRRRDLSS in AAC50766 (PubMed:9516426).CuratedAdd BLAST11
Sequence conflicti495A → T in AAC50766 (PubMed:9516426).Curated1
Sequence conflicti738Missing in AAB48165 (PubMed:8977093).Curated1
Sequence conflicti790L → P in AAC50766 (PubMed:9516426).Curated1

Polymorphismi

Intronic variations in MCM6 upstream from the LCT gene are associated with adult-type hypolactasia [MIMi:223100] leading to lactose intolerance, or with lactase persistance. Lactose intolerance is a normal physiological phenomenon caused by developmental down-regulation of lactase activity during childhood or early adulthood. A non-coding variation in MCM6 affects the transcriptional regulation of the LCT gene resulting in down-regulation of lactase activity. However, the majority of Northern Europeans and some African populations have the ability to maintain lactase activity and digest lactose throughout life (lactase persistence).1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01481635E → V.Corresponds to variant rs3087355dbSNPEnsembl.1
Natural variantiVAR_016340806E → K.1 PublicationCorresponds to variant rs4988283dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D84557 mRNA. Translation: BAA12699.1.
U46838 mRNA. Translation: AAC50766.1.
AY220757 Genomic DNA. Translation: AAO26043.1.
AK312575 mRNA. Translation: BAG35469.1.
CH471058 Genomic DNA. Translation: EAX11621.1.
BC032374 mRNA. Translation: AAH32374.1.
AH005100 Genomic DNA. Translation: AAB48165.1.
CCDSiCCDS2179.1.
RefSeqiNP_005906.2. NM_005915.5.
UniGeneiHs.444118.

Genome annotation databases

EnsembliENST00000264156; ENSP00000264156; ENSG00000076003.
GeneIDi4175.
KEGGihsa:4175.
UCSCiuc002tuw.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D84557 mRNA. Translation: BAA12699.1.
U46838 mRNA. Translation: AAC50766.1.
AY220757 Genomic DNA. Translation: AAO26043.1.
AK312575 mRNA. Translation: BAG35469.1.
CH471058 Genomic DNA. Translation: EAX11621.1.
BC032374 mRNA. Translation: AAH32374.1.
AH005100 Genomic DNA. Translation: AAB48165.1.
CCDSiCCDS2179.1.
RefSeqiNP_005906.2. NM_005915.5.
UniGeneiHs.444118.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2KLQNMR-A708-821[»]
2LE8NMR-A708-821[»]
ProteinModelPortaliQ14566.
SMRiQ14566.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110343. 90 interactors.
DIPiDIP-31727N.
IntActiQ14566. 48 interactors.
MINTiMINT-5004576.
STRINGi9606.ENSP00000264156.

PTM databases

iPTMnetiQ14566.
PhosphoSitePlusiQ14566.
SwissPalmiQ14566.

Polymorphism and mutation databases

BioMutaiMCM6.
DMDMi2497824.

Proteomic databases

EPDiQ14566.
MaxQBiQ14566.
PaxDbiQ14566.
PeptideAtlasiQ14566.
PRIDEiQ14566.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264156; ENSP00000264156; ENSG00000076003.
GeneIDi4175.
KEGGihsa:4175.
UCSCiuc002tuw.5. human.

Organism-specific databases

CTDi4175.
DisGeNETi4175.
GeneCardsiMCM6.
HGNCiHGNC:6949. MCM6.
HPAiCAB009577.
HPA004818.
MalaCardsiMCM6.
MIMi223100. phenotype.
601806. gene.
neXtProtiNX_Q14566.
OpenTargetsiENSG00000076003.
Orphaneti319681. Lactase non-persistence in adulthood.
PharmGKBiPA30696.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0480. Eukaryota.
COG1241. LUCA.
GeneTreeiENSGT00550000074860.
HOGENOMiHOG000224130.
HOVERGENiHBG006334.
InParanoidiQ14566.
KOiK02542.
OMAiEYFQRVT.
OrthoDBiEOG091G020Q.
PhylomeDBiQ14566.
TreeFamiTF105646.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000076003-MONOMER.
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.
R-HSA-69300. Removal of licensing factors from origins.
SIGNORiQ14566.

Miscellaneous databases

ChiTaRSiMCM6. human.
EvolutionaryTraceiQ14566.
GeneWikiiMCM6.
GenomeRNAii4175.
PMAP-CutDBQ14566.
PROiQ14566.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000076003.
CleanExiHS_MCM6.
GenevisibleiQ14566. HS.

Family and domain databases

Gene3Di2.20.28.10. 1 hit.
3.40.50.300. 1 hit.
InterProiIPR031327. MCM.
IPR008049. MCM6.
IPR018525. MCM_CS.
IPR001208. MCM_dom.
IPR027925. MCM_N.
IPR033762. MCM_OB.
IPR012340. NA-bd_OB-fold.
IPR027417. P-loop_NTPase.
IPR004039. Rubredoxin-type_fold.
[Graphical view]
PfamiPF00493. MCM. 1 hit.
PF14551. MCM_N. 1 hit.
PF17207. MCM_OB. 1 hit.
[Graphical view]
PRINTSiPR01657. MCMFAMILY.
PR01662. MCMPROTEIN6.
SMARTiSM00350. MCM. 1 hit.
[Graphical view]
SUPFAMiSSF50249. SSF50249. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEiPS00847. MCM_1. 1 hit.
PS50051. MCM_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMCM6_HUMAN
AccessioniPrimary (citable) accession number: Q14566
Secondary accession number(s): B2R6H2, Q13504, Q99859
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: November 30, 2016
This is version 165 of the entry and version 1 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

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.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.