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Protein

DNA replication licensing factor MCM6

Gene

MCM6

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.1 Publication

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.

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
  • identical protein binding Source: IntAct
  • single-stranded DNA binding Source: Ensembl

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
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

EuPathDBiHostDB:ENSG00000076003.4
HGNCiHGNC:6949 MCM6
MIMi601806 gene
neXtProtiNX_Q14566

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

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
ProteomicsDBi60047

PTM databases

iPTMnetiQ14566
PhosphoSitePlusiQ14566
SwissPalmiQ14566

Miscellaneous databases

PMAP-CutDBiQ14566

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

Show more details

GO - Molecular functioni

  • identical protein binding Source: IntAct

Protein-protein interaction databases

BioGridi110343, 115 interactors
ComplexPortaliCPX-2940 MCM complex
CORUMiQ14566
DIPiDIP-31727N
IntActiQ14566, 76 interactors
MINTiQ14566
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

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

Phylogenomic databases

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

Family and domain databases

InterProiView protein in InterPro
IPR031327 MCM
IPR008049 MCM6
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
PfamiView protein in Pfam
PF00493 MCM, 1 hit
PF14551 MCM_N, 1 hit
PF17207 MCM_OB, 1 hit
PRINTSiPR01657 MCMFAMILY
PR01662 MCMPROTEIN6
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

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 dbSNP:rs3087355Ensembl.1
Natural variantiVAR_016340806E → K1 PublicationCorresponds to variant dbSNP:rs4988283Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiMCM6_HUMAN
AccessioniPrimary (citable) accession number: Q14566
Secondary accession number(s): B2R6H2, Q13504, Q99859
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: July 18, 2018
This is version 181 of the entry and version 1 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

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

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