Reviewed, UniProtKB/Swiss-Prot P25205 (MCM3_HUMAN)

Names and origin

Protein names

Recommended name:
    DNA replication licensing factor MCM3
Alternative name(s):
    DNA polymerase alpha holoenzyme-associated protein P1
    RLF subunit beta
    P102 protein
    P1-MCM3

Gene names

Name:

MCM3

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	808 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Acts as a factor that allows the DNA to undergo a single round of replication per cell cycle. Required for DNA replication and cell proliferation.
Subcellular location	Nucleus.
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17
Miscellaneous	Associated with the replication-specific DNA polymerase alpha.
Sequence similarities	Belongs to the MCM family. Contains 1 MCM domain.

Ontologies

Keywords
Biological process	Cell cycle DNA replication Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Ligand	ATP-binding DNA-binding Nucleotide-binding
PTM	Acetylation Phosphoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	DNA replication initiation Ref.8 Traceable author statement. Source: ProtInc cell cycle Inferred from electronic annotation. Source: UniProtKB-KW regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	alpha DNA polymerase:primase complex Ref.8 Traceable author statement. Source: ProtInc cytoplasm Inferred from direct assay. Source: HPA nucleoplasm Inferred from Experiment. Source: Reactome
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW DNA binding Ref.8 Traceable author statement. Source: ProtInc nucleoside-triphosphatase activity Inferred from electronic annotation. Source: InterPro protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDC5L	Q99459	1	EBI-355153,EBI-374880
CDC6	Q99741	1	EBI-355153,EBI-374862
CDC7	O00311	1	EBI-355153,EBI-374980
CDK2	P24941	1	EBI-355153,EBI-375096
ENSA	O43768	1	EBI-355153,EBI-714511
MCM10	Q7L590	1	EBI-355153,EBI-374912
MCM2	P49736	1	EBI-355153,EBI-374819
MCM5	P33992	2	EBI-355153,EBI-359410
MCM6	Q14566	1	EBI-355153,EBI-374900
ORC2L	Q13416	1	EBI-355153,EBI-374957
ORC4L	O43929	1	EBI-355153,EBI-374889
ORC5L	O43913	1	EBI-355153,EBI-374928
PAK2	Q13177	1	EBI-355153,EBI-1045887
PLK1	P53350	1	EBI-355153,EBI-476768
PNKP	Q96T60	1	EBI-355153,EBI-1045072
PTP4A3	O75365	1	EBI-355153,EBI-1043866
SNCG	O76070	1	EBI-355153,EBI-1053810
WDR8	Q9P2S5	1	EBI-355153,EBI-1054904

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.7
	Chain	2 – 808	807	DNA replication licensing factor MCM3		PRO_0000194093
Regions
	Domain	295 – 502	208	MCM
	Nucleotide binding	345 – 352	8	ATP Potential
Amino acid modifications
	Modified residue	2	1	N-acetylalanine Ref.7
	Modified residue	160	1	Phosphoserine Ref.17
	Modified residue	535	1	Phosphoserine; by ATM Ref.9
	Modified residue	668	1	Phosphoserine Ref.17
	Modified residue	672	1	Phosphoserine Ref.11 Ref.12 Ref.15 Ref.17
	Modified residue	674	1	Phosphothreonine Ref.11 Ref.12 Ref.15 Ref.17
	Modified residue	681	1	Phosphoserine Ref.15 Ref.17
	Modified residue	704	1	Phosphoserine Ref.14
	Modified residue	711	1	Phosphoserine Ref.11 Ref.14 Ref.16 Ref.17
	Modified residue	713	1	Phosphothreonine Ref.10 Ref.11 Ref.13 Ref.14 Ref.17
	Modified residue	722	1	Phosphothreonine Ref.10 Ref.11 Ref.13 Ref.16 Ref.17
	Modified residue	728	1	Phosphoserine Ref.15
	Modified residue	734	1	Phosphoserine Ref.15
Natural variations
	Natural variant	105	1	S → G: dbSNP rs2307332.		VAR_014810
	Natural variant	280	1	D → V: dbSNP rs2307329. Ref.4		VAR_014811
	Natural variant	287	1	F → L: dbSNP rs2307328. Ref.4		VAR_014812
	Natural variant	590	1	I → L: dbSNP rs17240063. Ref.4		VAR_020516
	Natural variant	774	1	R → W: dbSNP rs2230239. Ref.4		VAR_020517
	Natural variant	777	1	E → K: dbSNP rs2230240. Ref.4		VAR_020427
Experimental info
	Mutagenesis	535	1	S → A: 50% reduction in phosphorylation by ATM or ATR. Ref.9
	Sequence conflict	230 – 231	2	KP → NA in BAA07267. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P25205-1 [UniParc]. Last modified August 14, 2001. Version 3. Checksum: C967C068B7090558	FASTA	808	90,981
	10 20 30 40 50 60 MAGTVVLDDV ELREAQRDYL DFLDDEEDQG IYQSKVRELI SDNQYRLIVN VNDLRRKNEK 70 80 90 100 110 120 RANRLLNNAF EELVAFQRAL KDFVASIDAT YAKQYEEFYV GLEGSFGSKH VSPRTLTSCF 130 140 150 160 170 180 LSCVVCVEGI VTKCSLVRPK VVRSVHYCPA TKKTIERRYS DLTTLVAFPS SSVYPTKDEE 190 200 210 220 230 240 NNPLETEYGL SVYKDHQTIT IQEMPEKAPA GQLPRSVDVI LDDDLVDKAK PGDRVQVVGT 250 260 270 280 290 300 YRCLPGKKGG YTSGTFRTVL IACNVKQMSK DAQPSFSAED IAKIKKFSKT RSKDIFDQLA 310 320 330 340 350 360 KSLAPSIHGH DYVKKAILCL LLGGVERDLE NGSHIRGDIN ILLIGDPSVA KSQLLRYVLC 370 380 390 400 410 420 TAPRAIPTTG RGSSGVGLTA AVTTDQETGE RRLEAGAMVL ADRGVVCIDE FDKMSDMDRT 430 440 450 460 470 480 AIHEVMEQGR VTIAKAGIHA RLNARCSVLA AANPVYGRYD QYKTPMENIG LQDSLLSRFD 490 500 510 520 530 540 LLFIMLDQMD PEQDREISDH VLRMHRYRAP GEQDGDAMPL GSAVDILATD DPNFSQEDQQ 550 560 570 580 590 600 DTQIYEKHDN LLHGTKKKKE KMVSAAFMKK YIHVAKIIKP VLTQESATYI AEEYSRLRSQ 610 620 630 640 650 660 DSMSSDTART SPVTARTLET LIRLATAHAK ARMSKTVDLQ DAEEAVELVQ YAYFKKVLEK 670 680 690 700 710 720 EKKRKKRSED ESETEDEEEK SQEDQEQKRK RRKTRQPDAK DGDSYDPYDF SDTEEEMPQV 730 740 750 760 770 780 HTPKTADSQE TKESQKVELS ESRLKAFKVA LLDVFREAHA QSIGMNRLTE SINRDSEEPF 790 800 SSVEIQAALS KMQDDNQVMV SEGIIFLI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The P1 family: a new class of nuclear mammalian proteins related to the yeast Mcm replication proteins." Hu B., Burkhart R., Schulte D., Musahl C., Knippers R. Nucleic Acids Res. 21:5289-5293(1993) [PubMed: 8265339] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Cervix.
[2]	Goehring F., Jehnichen P., Hemmer W.H. Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[3]	"Identification of the yeast MCM3-related protein as a component of Xenopus DNA replication licensing factor." Kubota Y., Mimura S., Nishimoto S., Takisawa H., Nojima H. Cell 81:601-609(1995) [PubMed: 7758114] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Cervix.
[4]	NIEHS SNPs program Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS VAL-280; LEU-287; LEU-590; TRP-774 AND LYS-777.
[5]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lymph and Pancreas.
[7]	Bienvenut W.V., Glen H., Brunton V.G., Frame M.C. Submitted (JUL-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-13; 47-55; 337-351 AND 749-756, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, MASS SPECTROMETRY. Tissue: Osteosarcoma.
[8]	"Properties of the nuclear P1 protein, a mammalian homologue of the yeast Mcm3 replication protein." Thoemmes P., Fett R., Schray B., Burkhart R., Barnes M., Kennedy C., Brown N.C., Knippers R. Nucleic Acids Res. 20:1069-1074(1992) [PubMed: 1549468] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 563-808.
[9]	"Minichromosome maintenance proteins are direct targets of the ATM and ATR checkpoint kinases." Cortez D., Glick G., Elledge S.J. Proc. Natl. Acad. Sci. U.S.A. 101:10078-10083(2004) [PubMed: 15210935] [Abstract] Cited for: PHOSPHORYLATION AT SER-535, MUTAGENESIS OF SER-535.
[10]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-713 AND THR-722, MASS SPECTROMETRY. Tissue: Epithelium.
[11]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-672; THR-674; SER-711; THR-713 AND THR-722, MASS SPECTROMETRY. Tissue: Epithelium.
[12]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-672 AND THR-674, MASS SPECTROMETRY. Tissue: Epithelium.
[13]	"Toward a global characterization of the phosphoproteome in prostate cancer cells: identification of phosphoproteins in the LNCaP cell line." Giorgianni F., Zhao Y., Desiderio D.M., Beranova-Giorgianni S. Electrophoresis 28:2027-2034(2007) [PubMed: 17487921] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-713 AND THR-722, MASS SPECTROMETRY.
[14]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-704; SER-711 AND THR-713, MASS SPECTROMETRY.
[15]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-672; THR-674; SER-681; SER-728 AND SER-734, MASS SPECTROMETRY.
[16]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-711 AND THR-722, MASS SPECTROMETRY.
[17]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-160; SER-668; SER-672; THR-674; SER-681; SER-711; THR-713 AND THR-722, MASS SPECTROMETRY.
[18]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases
EMBLGenBankDDBJ	X62153 mRNA. Translation: CAA44078.2. D38073 mRNA. Translation: BAA07267.1. AY621074 Genomic DNA. Translation: AAT27321.1. AL034343 Genomic DNA. Translation: CAB75298.1. BC001626 mRNA. Translation: AAH01626.1. BC003509 mRNA. Translation: AAH03509.2.
IPI	IPI00013214.
PIR	S62594.
RefSeq	NP_002379.2.
UniGene	Hs.179565
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	P25205. 31 interactions.
PTM databases
PhosphoSite	P25205.
Proteomic databases
PeptideAtlas	P25205.
PRIDE	P25205.
Genome annotation databases
Ensembl	ENSG00000112118. Homo sapiens. [Contig view]
GeneID	4172.
KEGG	hsa:4172.
Organism-specific databases
GeneCards	GC06M052236.
H-InvDB	HIX0005950.
HGNC	HGNC:6945. MCM3.
HPA	CAB002162. HPA004789. HPA004790.
MIM	602693. gene.
PharmGKB	PA30691.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P25205.
HOVERGEN	P25205.
OMA	P25205. QVMVSEG.
Enzyme and pathway databases
Reactome	REACT_152. Cell Cycle, Mitotic. REACT_1538. Cell Cycle Checkpoints. REACT_383. DNA Replication.
Gene expression databases
ArrayExpress	P25205.
Bgee	P25205.
CleanEx	HS_MCM3.
GermOnline	ENSG00000112118. Homo sapiens.
Family and domain databases
InterPro	IPR003593. ATPase_AAA+_core. IPR001208. DNA-dep_ATPase_MCM. IPR018525. DNA-dep_ATPase_MCM_CS. IPR008046. MCM_3. IPR012340. NA-bd_OB-fold. [Graphical view]
Gene3D	G3DSA:2.40.50.140. OB_NA_bd_sub. 1 hit.
Pfam	PF00493. MCM. 1 hit. [Graphical view]
PRINTS	PR01657. MCMFAMILY. PR01659. MCMPROTEIN3.
ProDom	PD001041. MCM. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00382. AAA. 1 hit. SM00350. MCM. 1 hit. [Graphical view]
PROSITE	PS00847. MCM_1. 1 hit. PS50051. MCM_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	16432.
PMAP-CutDB	P25205.
SOURCE	Search...

Entry information

Entry name

MCM3_HUMAN

Accession

Primary (citable) accession number: P25205
Secondary accession number(s): Q92660, Q9BTR3, Q9NUE7

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1992
Last sequence update:	August 14, 2001
Last modified:	June 16, 2009
This is version 107 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)