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Protein

DNA replication licensing factor MCM3

Gene

MCM3

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. Required for DNA replication and cell proliferation.

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.

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
  • helicase activity Source: UniProtKB-KW

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
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

EuPathDBiHostDB:ENSG00000112118.17
HGNCiHGNC:6945 MCM3
MIMi602693 gene
neXtProtiNX_P25205

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
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
ProteomicsDBi54265

PTM databases

iPTMnetiP25205
PhosphoSitePlusiP25205
SwissPalmiP25205

Miscellaneous databases

PMAP-CutDBiP25205

Expressioni

Gene expression databases

BgeeiENSG00000112118 Expressed in 229 organ(s), highest expression level in embryo
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

Protein-protein interaction databases

BioGridi110340, 132 interactors
ComplexPortaliCPX-2940 MCM complex
CORUMiP25205
DIPiDIP-31726N
IntActiP25205, 60 interactors
MINTiP25205
STRINGi9606.ENSP00000229854

Structurei

3D structure databases

ProteinModelPortaliP25205
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

Phylogenomic databases

eggNOGiKOG0479 Eukaryota
COG1241 LUCA
GeneTreeiENSGT00900000141082
HOGENOMiHOG000224126
HOVERGENiHBG104962
InParanoidiP25205
KOiK02541
OMAiYQSKVRE
OrthoDBiEOG091G02B0
PhylomeDBiP25205
TreeFamiTF106459

Family and domain databases

InterProiView protein in InterPro
IPR003593 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
PANTHERiPTHR11630 PTHR11630, 1 hit
PfamiView protein in Pfam
PF00493 MCM, 1 hit
PF14551 MCM_N, 1 hit
PF17207 MCM_OB, 1 hit
PRINTSiPR01657 MCMFAMILY
PR01659 MCMPROTEIN3
SMARTiView protein in SMART
SM00382 AAA, 1 hit
SM00350 MCM, 1 hit
SUPFAMiSSF50249 SSF50249, 1 hit
SSF52540 SSF52540, 2 hits
PROSITEiView protein in PROSITE
PS00847 MCM_1, 1 hit
PS50051 MCM_2, 1 hit

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

This entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.iShow all

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

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
J3KQ69J3KQ69_HUMAN
DNA replication licensing factor MC...
MCM3
818Annotation score:
Q7Z6P5Q7Z6P5_HUMAN
DNA replication licensing factor MC...
MCM3
328Annotation score:
M0QYS9M0QYS9_HUMAN
DNA replication licensing factor MC...
MCM3
77Annotation score:

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 dbSNP:rs2307332Ensembl.1
Natural variantiVAR_014811280D → V1 PublicationCorresponds to variant dbSNP:rs2307329Ensembl.1
Natural variantiVAR_014812287F → L1 PublicationCorresponds to variant dbSNP:rs2307328Ensembl.1
Natural variantiVAR_020516590I → L1 PublicationCorresponds to variant dbSNP:rs17240063Ensembl.1
Natural variantiVAR_020517774R → W1 PublicationCorresponds to variant dbSNP:rs2230239Ensembl.1
Natural variantiVAR_020427777E → K1 PublicationCorresponds to variant dbSNP:rs2230240Ensembl.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 No translation available.
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

Similar proteinsi

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 No translation available.
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
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110340, 132 interactors
ComplexPortaliCPX-2940 MCM complex
CORUMiP25205
DIPiDIP-31726N
IntActiP25205, 60 interactors
MINTiP25205
STRINGi9606.ENSP00000229854

PTM databases

iPTMnetiP25205
PhosphoSitePlusiP25205
SwissPalmiP25205

Polymorphism and mutation databases

BioMutaiMCM3
DMDMi19857543

Proteomic databases

EPDiP25205
MaxQBiP25205
PaxDbiP25205
PeptideAtlasiP25205
PRIDEiP25205
ProteomicsDBi54265

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
EuPathDBiHostDB:ENSG00000112118.17
GeneCardsiMCM3
HGNCiHGNC:6945 MCM3
HPAiCAB002162
HPA004789
HPA004790
MIMi602693 gene
neXtProtiNX_P25205
OpenTargetsiENSG00000112118
PharmGKBiPA30691
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0479 Eukaryota
COG1241 LUCA
GeneTreeiENSGT00900000141082
HOGENOMiHOG000224126
HOVERGENiHBG104962
InParanoidiP25205
KOiK02541
OMAiYQSKVRE
OrthoDBiEOG091G02B0
PhylomeDBiP25205
TreeFamiTF106459

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
SIGNORiP25205

Miscellaneous databases

ChiTaRSiMCM3 human
GeneWikiiMCM3
GenomeRNAii4172
PMAP-CutDBiP25205
PROiPR:P25205
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000112118 Expressed in 229 organ(s), highest expression level in embryo
CleanExiHS_MCM3
ExpressionAtlasiP25205 baseline and differential
GenevisibleiP25205 HS

Family and domain databases

InterProiView protein in InterPro
IPR003593 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
PANTHERiPTHR11630 PTHR11630, 1 hit
PfamiView protein in Pfam
PF00493 MCM, 1 hit
PF14551 MCM_N, 1 hit
PF17207 MCM_OB, 1 hit
PRINTSiPR01657 MCMFAMILY
PR01659 MCMPROTEIN3
SMARTiView protein in SMART
SM00382 AAA, 1 hit
SM00350 MCM, 1 hit
SUPFAMiSSF50249 SSF50249, 1 hit
SSF52540 SSF52540, 2 hits
PROSITEiView protein in PROSITE
PS00847 MCM_1, 1 hit
PS50051 MCM_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMCM3_HUMAN
AccessioniPrimary (citable) accession number: P25205
Secondary accession number(s): B4DWW4
, Q92660, Q9BTR3, Q9NUE7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: August 14, 2001
Last modified: September 12, 2018
This is version 212 of the entry and version 3 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, Direct protein sequencing, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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