P33992 (MCM5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
DNA replication licensing factor MCM5
EC=3.6.4.12

Alternative name(s):
CDC46 homolog
P1-CDC46

Gene names

Name:	MCM5
Synonyms:	CDC46

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	734 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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 By similarity. Interacts with MCMBP.
Catalytic activity	ATP + H2O = ADP + phosphate.
Subunit structure	Component of the MCM2-7 complex. The complex forms a toroidal hexameric ring with the proposed subunit order MCM2-MCM6-MCM4-MCM7-MCM3-MCM5 (By simililarity). Ref.9 Ref.10
Subcellular location	Nucleus.
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.
Sequence similarities	Belongs to the MCM family. Contains 1 MCM domain.

Ontologies

Keywords
Biological process	Cell cycle DNA replication
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Ligand	ATP-binding DNA-binding Nucleotide-binding
Molecular function	Helicase Hydrolase
PTM	Acetylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA duplex unwinding Inferred from electronic annotation. Source: GOC DNA replication initiation Inferred from electronic annotation. Source: InterPro DNA strand elongation involved in DNA replication Traceable author statement. Source: Reactome G1/S transition of mitotic cell cycle Traceable author statement. Source: Reactome M/G1 transition of mitotic cell cycle Traceable author statement. Source: Reactome S phase of mitotic cell cycle Traceable author statement. Source: Reactome cell cycle checkpoint Traceable author statement. Source: Reactome
Cellular_component	MCM complex Inferred from direct assay Ref.10. Source: UniProtKB nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW DNA binding Inferred from electronic annotation. Source: UniProtKB-KW DNA helicase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
HIST2H4B	P62805	2	EBI-359410,EBI-302023
MCM2	P49736	4	EBI-359410,EBI-374819
MCM3	P25205	3	EBI-359410,EBI-355153

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 734	734	DNA replication licensing factor MCM5		PRO_0000194107
Regions
	Domain	331 – 537	207	MCM
	Nucleotide binding	381 – 388	8	ATP Potential
Amino acid modifications
	Modified residue	392	1	N6-acetyllysine Ref.11
	Modified residue	396	1	N6-acetyllysine Ref.11
	Modified residue	696	1	N6-acetyllysine Ref.11
Natural variations
	Natural variant	136	1	S → T. Ref.5 Corresponds to variant rs2307334 [ dbSNP | Ensembl ].		VAR_014813
	Natural variant	180	1	T → S. Ref.5 Corresponds to variant rs2307340 [ dbSNP | Ensembl ].		VAR_014814
	Natural variant	258	1	V → I. Ref.5 Corresponds to variant rs2230933 [ dbSNP | Ensembl ].		VAR_014815
Experimental info
	Sequence conflict	41	1	Q → R in AAH03656. Ref.7
	Sequence conflict	434	1	M → W Ref.8
	Sequence conflict	527	1	E → V in BAA12176. Ref.3
	Sequence conflict	591	1	S → T in BAA12176. Ref.3
	Sequence conflict	593 – 603	11	ARQHERDSDRR → PVSTRGTVTA in BAA12176. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P33992 [UniParc]. Last modified August 14, 2001. Version 5. Checksum: A80280E61749998D	FASTA	734	82,286
	10 20 30 40 50 60 MSGFDDPGIF YSDSFGGDAQ ADEGQARKSQ LQRRFKEFLR QYRVGTDRTG FTFKYRDELK 70 80 90 100 110 120 RHYNLGEYWI EVEMEDLASF DEDLADYLYK QPAEHLQLLE EAAKEVADEV TRPRPSGEEV 130 140 150 160 170 180 LQDIQVMLKS DASPSSIRSL KSDMMSHLVK IPGIIIAASA VRAKATRISI QCRSCRNTLT 190 200 210 220 230 240 NIAMRPGLEG YALPRKCNTD QAGRPKCPLD PYFIMPDKCK CVDFQTLKLQ ELPDAVPHGE 250 260 270 280 290 300 MPRHMQLYCD RYLCDKVVPG NRVTIMGIYS IKKFGLTTSR GRDRVGVGIR SSYIRVLGIQ 310 320 330 340 350 360 VDTDGSGRSF AGAVSPQEEE EFRRLAALPN VYEVISKSIA PSIFGGTDMK KAIACLLFGG 370 380 390 400 410 420 SRKRLPDGLT RRGDINLLML GDPGTAKSQL LKFVEKCSPI GVYTSGKGSS AAGLTASVMR 430 440 450 460 470 480 DPSSRNFIME GGAMVLADGG VVCIDEFDKM REDDRVAIHE AMEQQTISIA KAGITTTLNS 490 500 510 520 530 540 RCSVLAAANS VFGRWDETKG EDNIDFMPTI LSRFDMIFIV KDEHNEERDV MLAKHVITLH 550 560 570 580 590 600 VSALTQTQAV EGEIDLAKLK KFIAYCRVKC GPRLSAEAAE KLKNRYIIMR SGARQHERDS 610 620 630 640 650 660 DRRSSIPITV RQLEAIVRIA EALSKMKLQP FATEADVEEA LRLFQVSTLD AALSGTLSGV 670 680 690 700 710 720 EGFTSQEDQE MLSRIEKQLK RRFAIGSQVS EHSIIKDFTK QKYPEHAIHK VLQLMLRRGE 730 IQHRMQRKVL YRLK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Hu B. Submitted (JUL-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Cervix carcinoma.
[2]	Goehring F., Jehnichen P., Hemmer W.H. Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[3]	"Homo sapiens DNA replication licensing factor (huMCM5)." Mimura S., Nishimoto S., Kubota Y., Takisawa H., Nojima H. Submitted (MAR-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"A genome annotation-driven approach to cloning the human ORFeome." Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I. Genome Biol. 5:R84.1-R84.11(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	NIEHS SNPs program Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-136; SER-180 AND ILE-258.
[6]	"The DNA sequence of human chromosome 22." Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H. Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lymph and Placenta.
[8]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 352-590. Tissue: Cervix.
[9]	"Essential role of phosphorylation of MCM2 by Cdc7/Dbf4 in the initiation of DNA replication in mammalian cells." Tsuji T., Ficarro S.B., Jiang W. Mol. Biol. Cell 17:4459-4472(2006) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE MCM2-7 COMPLEX, ATPASE ACTIVITY OF THE MCM2-7 COMPLEX.
[10]	"Identification and characterization of a novel component of the human minichromosome maintenance complex." Sakwe A.M., Nguyen T., Athanasopoulos V., Shire K., Frappier L. Mol. Cell. Biol. 27:3044-3055(2007) [PubMed] [Europe PMC] [Abstract] Cited for: MASS SPECTROMETRY, INTERACTION WITH MCMBP, IDENTIFICATION IN THE MCM2-7 COMPLEX.
[11]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-392; LYS-396 AND LYS-696, MASS SPECTROMETRY.
[12]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	X74795 mRNA. Translation: CAA52802.2. D83986 mRNA. Translation: BAA12176.1. CR456517 mRNA. Translation: CAG30403.1. AY212028 Genomic DNA. Translation: AAO21127.1. Z82244 Genomic DNA. No translation available. BC000142 mRNA. Translation: AAH00142.1. BC003656 mRNA. Translation: AAH03656.1.
IPI	IPI00018350.
PIR	I38080.
RefSeq	NP_006730.2. NM_006739.3.
UniGene	Hs.517582.
3D structure databases
ProteinModelPortal	P33992.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-27578N.
IntAct	P33992. 17 interactions.
MINT	MINT-5004198.
STRING	9606.ENSP00000216122.
PTM databases
PhosphoSite	P33992.
Polymorphism databases
DMDM	19858646.
Proteomic databases
PaxDb	P33992.
PeptideAtlas	P33992.
PRIDE	P33992.
Protocols and materials databases
DNASU	4174.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000216122; ENSP00000216122; ENSG00000100297.
GeneID	4174.
KEGG	hsa:4174.
UCSC	uc003anu.4. human.
Organism-specific databases
CTD	4174.
GeneCards	GC22P035797.
HGNC	HGNC:6948. MCM5.
HPA	CAB000101. HPA000845.
MIM	602696. gene.
neXtProt	NX_P33992.
PharmGKB	PA30695.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1241.
HOGENOM	HOG000224128.
HOVERGEN	HBG104907.
InParanoid	P33992.
KO	K02209.
OMA	KKSIACL.
OrthoDB	EOG4Z0B52.
PhylomeDB	P33992.
Enzyme and pathway databases
Reactome	REACT_115566. Cell Cycle. REACT_21300. Mitotic M-M/G1 phases. REACT_383. DNA Replication.
Gene expression databases
ArrayExpress	P33992.
Bgee	P33992.
CleanEx	HS_MCM5.
Genevestigator	P33992.
GermOnline	ENSG00000100297. Homo sapiens.
Family and domain databases
Gene3D	2.40.50.140. 2 hits.
InterPro	IPR008048. MCM5. IPR018525. MCM_CS. IPR001208. MCM_DNA-dep_ATPase. IPR012340. NA-bd_OB-fold. [Graphical view]
Pfam	PF00493. MCM. 1 hit. [Graphical view]
PRINTS	PR01657. MCMFAMILY. PR01661. MCMPROTEIN5.
SMART	SM00350. MCM. 1 hit. [Graphical view]
SUPFAM	SSF50249. Nucleic_acid_OB. 1 hit.
PROSITE	PS00847. MCM_1. 1 hit. PS50051. MCM_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	MCM5. human.
GenomeRNAi	4174.
NextBio	16442.
PMAP-CutDB	P33992.
SOURCE	Search...

Entry information

Entry name

MCM5_HUMAN

Accession

Primary (citable) accession number: P33992
Secondary accession number(s): O60785 , Q14578, Q9BTJ4, Q9BWL8

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	August 14, 2001
Last modified:	May 1, 2013
This is version 143 of the entry and version 5 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.