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Protein

DNA replication licensing factor MCM3

Gene

MCM3

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. Required for DNA replication and cell proliferation.

Catalytic activityi

ATP + H2O = ADP + phosphate.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi345 – 352ATPSequence analysis8

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • DNA binding Source: ProtInc
  • DNA helicase activity Source: InterPro

GO - Biological processi

  • DNA replication Source: Reactome
  • DNA replication initiation Source: ProtInc
  • G1/S transition of mitotic cell cycle Source: Reactome
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:ENSG00000112118-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.
SIGNORiP25205.

Names & Taxonomyi

Protein namesi
Recommended name:
DNA replication licensing factor MCM3 (EC:3.6.4.12)
Alternative name(s):
DNA polymerase alpha holoenzyme-associated protein P1
P1-MCM3
RLF subunit beta
p102
Gene namesi
Name:MCM3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:6945. MCM3.

Subcellular locationi

GO - Cellular componenti

  • alpha DNA polymerase:primase complex Source: ProtInc
  • centrosome Source: HPA
  • intracellular membrane-bounded organelle Source: HPA
  • MCM complex Source: UniProtKB
  • membrane Source: UniProtKB
  • nuclear chromosome, telomeric region Source: BHF-UCL
  • nucleoplasm Source: HPA
  • nucleus Source: BHF-UCL
  • perinuclear region of cytoplasm Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi535S → A: 50% reduction in phosphorylation by ATM or ATR. 1 Publication1

Organism-specific databases

DisGeNETi4172.
OpenTargetsiENSG00000112118.
PharmGKBiPA30691.

Polymorphism and mutation databases

BioMutaiMCM3.
DMDMi19857543.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00001940932 – 808DNA replication licensing factor MCM3Add BLAST807

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1 Publication1
Modified residuei160PhosphoserineCombined sources1
Modified residuei275PhosphoserineCombined sources1
Modified residuei293N6-acetyllysineBy similarity1
Modified residuei535Phosphoserine; by ATM1 Publication1
Modified residuei547N6-acetyllysineBy similarity1
Modified residuei611PhosphoserineCombined sources1
Modified residuei668PhosphoserineCombined sources1
Modified residuei672PhosphoserineCombined sources1
Modified residuei674PhosphothreonineCombined sources1
Modified residuei681PhosphoserineCombined sources1
Modified residuei708PhosphotyrosineCombined sources1
Modified residuei711PhosphoserineCombined sources1
Modified residuei713PhosphothreonineCombined sources1
Modified residuei722PhosphothreonineCombined sources1
Modified residuei725PhosphothreonineCombined sources1
Modified residuei728PhosphoserineBy similarity1
Modified residuei734PhosphoserineBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Acetylation, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP25205.
MaxQBiP25205.
PaxDbiP25205.
PeptideAtlasiP25205.
PRIDEiP25205.

PTM databases

iPTMnetiP25205.
PhosphoSitePlusiP25205.
SwissPalmiP25205.

Miscellaneous databases

PMAP-CutDBP25205.

Expressioni

Gene expression databases

BgeeiENSG00000112118.
CleanExiHS_MCM3.
ExpressionAtlasiP25205. baseline and differential.
GenevisibleiP25205. HS.

Organism-specific databases

HPAiCAB002162.
HPA004789.
HPA004790.

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). Associated with the replication-specific DNA polymerase alpha. Interacts with MCMBP. Interacts with ANKRD17.Curated3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
HIST2H4BP628052EBI-355153,EBI-302023
MCM2P497365EBI-355153,EBI-374819
MCM5P339924EBI-355153,EBI-359410
MCM6Q145663EBI-355153,EBI-374900
MCMBPQ9BTE311EBI-355153,EBI-749378
ORC2Q134162EBI-355153,EBI-374957

Protein-protein interaction databases

BioGridi110340. 116 interactors.
DIPiDIP-31726N.
IntActiP25205. 48 interactors.
MINTiMINT-1201900.
STRINGi9606.ENSP00000229854.

Structurei

3D structure databases

ProteinModelPortaliP25205.
SMRiP25205.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini295 – 502MCMAdd BLAST208

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi477 – 480Arginine finger4

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG0479. Eukaryota.
COG1241. LUCA.
GeneTreeiENSGT00550000075022.
HOGENOMiHOG000224126.
HOVERGENiHBG104962.
InParanoidiP25205.
KOiK02541.
OMAiLGSMVCV.
OrthoDBiEOG091G02B0.
PhylomeDBiP25205.
TreeFamiTF106459.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR003593. AAA+_ATPase.
IPR031327. MCM.
IPR008046. Mcm3.
IPR018525. MCM_CS.
IPR001208. MCM_dom.
IPR027925. MCM_N.
IPR033762. MCM_OB.
IPR012340. NA-bd_OB-fold.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF00493. MCM. 1 hit.
PF14551. MCM_N. 1 hit.
PF17207. MCM_OB. 1 hit.
[Graphical view]
PRINTSiPR01657. MCMFAMILY.
PR01659. MCMPROTEIN3.
SMARTiSM00382. AAA. 1 hit.
SM00350. MCM. 1 hit.
[Graphical view]
SUPFAMiSSF50249. SSF50249. 1 hit.
SSF52540. SSF52540. 2 hits.
PROSITEiPS00847. MCM_1. 1 hit.
PS50051. MCM_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P25205-1) [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
MAGTVVLDDV ELREAQRDYL DFLDDEEDQG IYQSKVRELI SDNQYRLIVN
60 70 80 90 100
VNDLRRKNEK RANRLLNNAF EELVAFQRAL KDFVASIDAT YAKQYEEFYV
110 120 130 140 150
GLEGSFGSKH VSPRTLTSCF LSCVVCVEGI VTKCSLVRPK VVRSVHYCPA
160 170 180 190 200
TKKTIERRYS DLTTLVAFPS SSVYPTKDEE NNPLETEYGL SVYKDHQTIT
210 220 230 240 250
IQEMPEKAPA GQLPRSVDVI LDDDLVDKAK PGDRVQVVGT YRCLPGKKGG
260 270 280 290 300
YTSGTFRTVL IACNVKQMSK DAQPSFSAED IAKIKKFSKT RSKDIFDQLA
310 320 330 340 350
KSLAPSIHGH DYVKKAILCL LLGGVERDLE NGSHIRGDIN ILLIGDPSVA
360 370 380 390 400
KSQLLRYVLC TAPRAIPTTG RGSSGVGLTA AVTTDQETGE RRLEAGAMVL
410 420 430 440 450
ADRGVVCIDE FDKMSDMDRT AIHEVMEQGR VTIAKAGIHA RLNARCSVLA
460 470 480 490 500
AANPVYGRYD QYKTPMENIG LQDSLLSRFD LLFIMLDQMD PEQDREISDH
510 520 530 540 550
VLRMHRYRAP GEQDGDAMPL GSAVDILATD DPNFSQEDQQ DTQIYEKHDN
560 570 580 590 600
LLHGTKKKKE KMVSAAFMKK YIHVAKIIKP VLTQESATYI AEEYSRLRSQ
610 620 630 640 650
DSMSSDTART SPVTARTLET LIRLATAHAK ARMSKTVDLQ DAEEAVELVQ
660 670 680 690 700
YAYFKKVLEK EKKRKKRSED ESETEDEEEK SQEDQEQKRK RRKTRQPDAK
710 720 730 740 750
DGDSYDPYDF SDTEEEMPQV HTPKTADSQE TKESQKVELS ESRLKAFKVA
760 770 780 790 800
LLDVFREAHA QSIGMNRLTE SINRDSEEPF SSVEIQAALS KMQDDNQVMV

SEGIIFLI
Length:808
Mass (Da):90,981
Last modified:August 14, 2001 - v3
Checksum:iC967C068B7090558
GO
Isoform 2 (identifier: P25205-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MLPRSPPLPRGNLWWREEFGSFRAGVESSWEPPRDFGGGSSLAAGM

Note: No experimental confirmation available.
Show »
Length:853
Mass (Da):95,908
Checksum:iE3EFA82D0E088CF1
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti230 – 231KP → NA in BAA07267 (PubMed:7758114).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_014810105S → G.Corresponds to variant rs2307332dbSNPEnsembl.1
Natural variantiVAR_014811280D → V.1 PublicationCorresponds to variant rs2307329dbSNPEnsembl.1
Natural variantiVAR_014812287F → L.1 PublicationCorresponds to variant rs2307328dbSNPEnsembl.1
Natural variantiVAR_020516590I → L.1 PublicationCorresponds to variant rs17240063dbSNPEnsembl.1
Natural variantiVAR_020517774R → W.1 PublicationCorresponds to variant rs2230239dbSNPEnsembl.1
Natural variantiVAR_020427777E → K.1 PublicationCorresponds to variant rs2230240dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0570501M → MLPRSPPLPRGNLWWREEFG SFRAGVESSWEPPRDFGGGS SLAAGM in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X62153 mRNA. Translation: CAA44078.2.
D38073 mRNA. Translation: BAA07267.1.
AK301704 mRNA. Translation: BAG63176.1.
AY621074 Genomic DNA. Translation: AAT27321.1.
AL034343 Genomic DNA. Translation: CAB75298.1.
CH471081 Genomic DNA. Translation: EAX04367.1.
BC001626 mRNA. Translation: AAH01626.1.
BC003509 mRNA. Translation: AAH03509.2.
CCDSiCCDS4940.2. [P25205-2]
PIRiS62594.
RefSeqiNP_001257401.1. NM_001270472.1.
NP_002379.3. NM_002388.4. [P25205-2]
UniGeneiHs.179565.

Genome annotation databases

EnsembliENST00000229854; ENSP00000229854; ENSG00000112118. [P25205-1]
ENST00000596288; ENSP00000472940; ENSG00000112118. [P25205-2]
ENST00000616552; ENSP00000480987; ENSG00000112118. [P25205-2]
GeneIDi4172.
KEGGihsa:4172.
UCSCiuc003pan.2. human. [P25205-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X62153 mRNA. Translation: CAA44078.2.
D38073 mRNA. Translation: BAA07267.1.
AK301704 mRNA. Translation: BAG63176.1.
AY621074 Genomic DNA. Translation: AAT27321.1.
AL034343 Genomic DNA. Translation: CAB75298.1.
CH471081 Genomic DNA. Translation: EAX04367.1.
BC001626 mRNA. Translation: AAH01626.1.
BC003509 mRNA. Translation: AAH03509.2.
CCDSiCCDS4940.2. [P25205-2]
PIRiS62594.
RefSeqiNP_001257401.1. NM_001270472.1.
NP_002379.3. NM_002388.4. [P25205-2]
UniGeneiHs.179565.

3D structure databases

ProteinModelPortaliP25205.
SMRiP25205.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110340. 116 interactors.
DIPiDIP-31726N.
IntActiP25205. 48 interactors.
MINTiMINT-1201900.
STRINGi9606.ENSP00000229854.

PTM databases

iPTMnetiP25205.
PhosphoSitePlusiP25205.
SwissPalmiP25205.

Polymorphism and mutation databases

BioMutaiMCM3.
DMDMi19857543.

Proteomic databases

EPDiP25205.
MaxQBiP25205.
PaxDbiP25205.
PeptideAtlasiP25205.
PRIDEiP25205.

Protocols and materials databases

DNASUi4172.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000229854; ENSP00000229854; ENSG00000112118. [P25205-1]
ENST00000596288; ENSP00000472940; ENSG00000112118. [P25205-2]
ENST00000616552; ENSP00000480987; ENSG00000112118. [P25205-2]
GeneIDi4172.
KEGGihsa:4172.
UCSCiuc003pan.2. human. [P25205-1]

Organism-specific databases

CTDi4172.
DisGeNETi4172.
GeneCardsiMCM3.
HGNCiHGNC:6945. MCM3.
HPAiCAB002162.
HPA004789.
HPA004790.
MIMi602693. gene.
neXtProtiNX_P25205.
OpenTargetsiENSG00000112118.
PharmGKBiPA30691.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0479. Eukaryota.
COG1241. LUCA.
GeneTreeiENSGT00550000075022.
HOGENOMiHOG000224126.
HOVERGENiHBG104962.
InParanoidiP25205.
KOiK02541.
OMAiLGSMVCV.
OrthoDBiEOG091G02B0.
PhylomeDBiP25205.
TreeFamiTF106459.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000112118-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.
SIGNORiP25205.

Miscellaneous databases

ChiTaRSiMCM3. human.
GeneWikiiMCM3.
GenomeRNAii4172.
PMAP-CutDBP25205.
PROiP25205.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000112118.
CleanExiHS_MCM3.
ExpressionAtlasiP25205. baseline and differential.
GenevisibleiP25205. HS.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR003593. AAA+_ATPase.
IPR031327. MCM.
IPR008046. Mcm3.
IPR018525. MCM_CS.
IPR001208. MCM_dom.
IPR027925. MCM_N.
IPR033762. MCM_OB.
IPR012340. NA-bd_OB-fold.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF00493. MCM. 1 hit.
PF14551. MCM_N. 1 hit.
PF17207. MCM_OB. 1 hit.
[Graphical view]
PRINTSiPR01657. MCMFAMILY.
PR01659. MCMPROTEIN3.
SMARTiSM00382. AAA. 1 hit.
SM00350. MCM. 1 hit.
[Graphical view]
SUPFAMiSSF50249. SSF50249. 1 hit.
SSF52540. SSF52540. 2 hits.
PROSITEiPS00847. MCM_1. 1 hit.
PS50051. MCM_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMCM3_HUMAN
AccessioniPrimary (citable) accession number: P25205
Secondary accession number(s): B4DWW4
, Q92660, Q9BTR3, Q9NUE7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: August 14, 2001
Last modified: November 30, 2016
This is version 194 of the entry and version 3 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. The MCM2-7 hexamer is the proposed physiological active complex.

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: 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.