Q26454 (MCM4_DROME) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
DNA replication licensing factor MCM4
EC=3.6.4.12

Alternative name(s):
Protein disc proliferation abnormal

Gene names

Name:	dpa
ORF Names:	CG1616

Organism

Drosophila melanogaster (Fruit fly)

Taxonomic identifier

7227 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Arthropoda › Hexapoda › Insecta › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Ephydroidea › Drosophilidae › Drosophila › Sophophora

Protein attributes

Sequence length	866 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. Required for DNA replication and cell proliferation. Essential role in mitotic DNA replication but not in endoreplication. Ref.4 Ref.7
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).
Subcellular location	Nucleus By similarity.
Sequence similarities	Belongs to the MCM family. Contains 1 MCM domain.

Ontologies

Keywords
Biological process	DNA replication
Cellular component	Nucleus
Ligand	ATP-binding DNA-binding Nucleotide-binding
Molecular function	Helicase Hydrolase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	DNA-dependent DNA replication initiation Inferred from electronic annotation. Source: InterPro mitotic spindle organization Inferred from mutant phenotype. Source: FlyBase
Cellular component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW DNA binding Inferred from electronic annotation. Source: UniProtKB-KW helicase activity Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Mcm6	Q9V461	3	EBI-175772,EBI-869161

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 866	866	DNA replication licensing factor MCM4		PRO_0000194104
Regions
	Domain	460 – 669	210	MCM
	Nucleotide binding	512 – 519	8	ATP Potential
	Motif	644 – 647	4	Arginine finger
Amino acid modifications
	Modified residue	55	1	Phosphoserine Ref.5 Ref.6
	Modified residue	81	1	Phosphoserine Ref.6
	Modified residue	87	1	Phosphothreonine Ref.6
Experimental info
	Mutagenesis	518	1	K → A: Slihgtly reduces complex helicase activity. Ref.7
	Sequence conflict	435	1	D → E in AAB35644. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q26454 [UniParc]. Last modified November 2, 2001. Version 2. Checksum: CF6ED69D2ADDA04E	FASTA	866	96,610
	10 20 30 40 50 60 MSSPARSPSV GGATPKQGAR TPTRGIASQD VETPMRMGPG RAVRPSDNIS LPPTSPGNIS 70 80 90 100 110 120 LPATSPARGL GANMSEIDLS SPLNYGTPSS MGSIRTPRSG IRGTPLRARP DIRTDKRIRQ 130 140 150 160 170 180 VAIGGGSGLE PIPEKGSETT DPVSESSQAP QLVVWGTNVV VSQCKSKFKS FIMRFIDPSA 190 200 210 220 230 240 EQDEISENID VNQPLYLQKL EEIHTLEEPY LNLNCAHLKT FDQDLYRQLI CYPQEVIPGF 250 260 270 280 290 300 DMAINEMFFE RYPAALLEHQ IQVRPFNADK TRNMRSLNPE DMDQLISISG MVIRSSNVIP 310 320 330 340 350 360 EMREAFFSCN ICSFSTTVEV DRGRINQPTL CTNCNTNHCF RLIHNRSEFT DKQLVKLQES 370 380 390 400 410 420 PDDMAAGQTP HNVLLYAHND LVDKVQPGDR VTVTGIYRAT PLKTGGLSSS VKSVYKTHVD 430 440 450 460 470 480 VVHFRKVDNK RLYEDEEGKD HIFPPERVEL LQLLAKKPDI YDRLARAIAP SIYENDDIKK 490 500 510 520 530 540 GILLQLFGGT KKKHATLGRQ NFRSEIHLLL CGDPGTSKSQ MLQYVFNLVP RSQYTSGRGS 550 560 570 580 590 600 SAVGLTAYVT KDPETRQLVL QTGALVLADN GVCCIDEFDK MNDSTRSVLH EVMEQQTLSI 610 620 630 640 650 660 AKAGIICQLN ARTSILAAAN PAESQWNKRK NIIDNVQLPH TLLSRFDLIF LVLDPQDEIF 670 680 690 700 710 720 DKRLASHLVS LYYVTRHEEE DTMFDMSVLR DYIAYAREHL SPTLSDEAQQ RLIQAYVDMR 730 740 750 760 770 780 KVGAGRGQIS AYPRQLESLI RLSEAHAKVR LSNQVELLDV EEAWRLHREA LKQSATDPLS 790 800 810 820 830 840 GKIDVGILTT GLSTAARKKR ADLVAAIKEN LKKKGKVLTV PYQKLFSDIK EGSQIMITRE 850 860 QFEDALKEVQ DEGAIVVMGK NTIRIC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"dpa, a member of the MCM family, is required for mitotic DNA replication but not endoreplication in Drosophila." Feger G., Vaessin H., Su T.T., Wolff E., Jan L.Y., Jan Y.N. EMBO J. 14:5387-5398(1995) [PubMed: 7489728] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The genome sequence of Drosophila melanogaster." Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D. , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C. Science 287:2185-2195(2000) [PubMed: 10731132] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Berkeley.
[3]	"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review." Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. , Drysdale R.A., Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E. Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed: 12537572] [Abstract] Cited for: GENOME REANNOTATION. Strain: Berkeley.
[4]	"Isolation of the Cdc45/Mcm2-7/GINS (CMG) complex, a candidate for the eukaryotic DNA replication fork helicase." Moyer S.E., Lewis P.W., Botchan M.R. Proc. Natl. Acad. Sci. U.S.A. 103:10236-10241(2006) [PubMed: 16798881] [Abstract] Cited for: IDENTIFICATION IN THE MCM2-7 COMPLEX, FUNCTION OF THE MCM2-7 COMPLEX.
[5]	"An integrated chemical, mass spectrometric and computational strategy for (quantitative) phosphoproteomics: application to Drosophila melanogaster Kc167 cells." Bodenmiller B., Mueller L.N., Pedrioli P.G.A., Pflieger D., Juenger M.A., Eng J.K., Aebersold R., Tao W.A. Mol. Biosyst. 3:275-286(2007) [PubMed: 17372656] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-55, MASS SPECTROMETRY.
[6]	"Phosphoproteome analysis of Drosophila melanogaster embryos." Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P. J. Proteome Res. 7:1675-1682(2008) [PubMed: 18327897] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-55; SER-81 AND THR-87, MASS SPECTROMETRY. Tissue: Embryo.
[7]	"Activation of the MCM2-7 helicase by association with Cdc45 and GINS proteins." Ilves I., Petojevic T., Pesavento J.J., Botchan M.R. Mol. Cell 37:247-258(2010) [PubMed: 20122406] [Abstract] Cited for: RECONSTITUTION OF THE MCM2-7 COMPLEX, FUNCTION OF THE MCM2-7 COMPLEX, MUTAGENESIS OF LYS-518.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	S80255 mRNA. Translation: AAB35644.1. AE013599 Genomic DNA. Translation: AAF59242.1.
PIR	S59872.
RefSeq	NP_477185.1. NM_057837.3.
UniGene	Dm.21562.
3D structure databases
ProteinModelPortal	Q26454.
SMR	Q26454. Positions 163-774.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-35346N.
IntAct	Q26454. 3 interactions.
STRING	Q26454.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblMetazoa	FBtr0088982; FBpp0088055; FBgn0015929.
GeneID	35679.
KEGG	dme:Dmel_CG1616.
NMPDR	fig|7227.3.peg.3663.
Organism-specific databases
CTD	103997.
FlyBase	FBgn0015929. dpa.
Phylogenomic databases
eggNOG	inNOG07968.
InParanoid	Q26454.
OMA	HTVILFA.
OrthoDB	EOG4Q574C.
PhylomeDB	Q26454.
Gene expression databases
ArrayExpress	Q26454.
Bgee	Q26454.
GermOnline	CG1616. Drosophila melanogaster.
Family and domain databases
InterPro	IPR003593. ATPase_AAA+_core. IPR008047. MCM_4. IPR018525. MCM_CS. IPR001208. MCM_DNA-dep_ATPase. IPR012340. NA-bd_OB-fold. IPR016027. NA-bd_OB-fold-like. [Graphical view]
Gene3D	G3DSA:2.40.50.140. OB_NA_bd_sub. 2 hits.
KO	K02212.
Pfam	PF00493. MCM. 1 hit. [Graphical view]
PRINTS	PR01657. MCMFAMILY. PR01660. MCMPROTEIN4.
SMART	SM00382. AAA. 1 hit. 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
NextBio	794682.

Entry information

Entry name

MCM4_DROME

Accession

Primary (citable) accession number: Q26454
Secondary accession number(s): Q9V4M5

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 2, 2001
Last modified:	January 25, 2012
This is version 95 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Drosophila annotation project