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Protein

DNA replication licensing factor MCM5

Gene

MCM5

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 (By similarity). Interacts with MCMBP.By similarity

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 bindingi381 – 388ATPSequence analysis8

GO - Molecular functioni

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

Names & Taxonomyi

Protein namesi
Recommended name:
DNA replication licensing factor MCM5 (EC:3.6.4.12)
Alternative name(s):
CDC46 homolog
P1-CDC46
Gene namesi
Name:MCM5
Synonyms:CDC46
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

EuPathDBiHostDB:ENSG00000100297.15
HGNCiHGNC:6948 MCM5
MIMi602696 gene
neXtProtiNX_P33992

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

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Meier-Gorlin syndrome 8 (MGORS8)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of Meier-Gorlin syndrome, a syndrome characterized by bilateral microtia, aplasia/hypoplasia of the patellae, and severe intrauterine and postnatal growth retardation with short stature and poor weight gain. Additional clinical findings include anomalies of cranial sutures, microcephaly, apparently low-set and simple ears, microstomia, full lips, highly arched or cleft palate, micrognathia, genitourinary tract anomalies, and various skeletal anomalies. While almost all cases have primordial dwarfism with substantial prenatal and postnatal growth retardation, not all cases have microcephaly, and microtia and absent/hypoplastic patella are absent in some. Despite the presence of microcephaly, intellect is usually normal. MGORS8 inheritance is autosomal recessive.
See also OMIM:617564
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_079198466T → I in MGORS8. 1 Publication1

Keywords - Diseasei

Disease mutation, Dwarfism

Organism-specific databases

DisGeNETi4174
MalaCardsiMCM5
MIMi617564 phenotype
OpenTargetsiENSG00000100297
PharmGKBiPA30695

Polymorphism and mutation databases

BioMutaiMCM5
DMDMi19858646

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001941072 – 734DNA replication licensing factor MCM5Add BLAST733

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1
Modified residuei315PhosphoserineCombined sources1
Modified residuei392N6-acetyllysineCombined sources1
Modified residuei396N6-acetyllysineCombined sources1
Modified residuei605PhosphoserineCombined sources1
Modified residuei696N6-acetyllysineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP33992
MaxQBiP33992
PaxDbiP33992
PeptideAtlasiP33992
PRIDEiP33992

PTM databases

iPTMnetiP33992
PhosphoSitePlusiP33992
SwissPalmiP33992

Miscellaneous databases

PMAP-CutDBP33992

Expressioni

Gene expression databases

BgeeiENSG00000100297
CleanExiHS_MCM5
ExpressionAtlasiP33992 baseline and differential
GenevisibleiP33992 HS

Organism-specific databases

HPAiCAB000101
HPA000845
HPA052880

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). Interacts with ANKRD17.Curated3 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi110342, 247 interactors
CORUMiP33992
DIPiDIP-27578N
IntActiP33992, 56 interactors
MINTiP33992
STRINGi9606.ENSP00000216122

Structurei

3D structure databases

ProteinModelPortaliP33992
SMRiP33992
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini331 – 537MCMAdd BLAST207

Sequence similaritiesi

Belongs to the MCM family.Curated

Phylogenomic databases

eggNOGiKOG0481 Eukaryota
COG1241 LUCA
GeneTreeiENSGT00550000074928
HOGENOMiHOG000224128
HOVERGENiHBG104907
InParanoidiP33992
KOiK02209
OMAiIHKVLQL
OrthoDBiEOG091G027N
PhylomeDBiP33992
TreeFamiTF105653

Family and domain databases

InterProiView protein in InterPro
IPR031327 MCM
IPR008048 MCM5
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
PR01661 MCMPROTEIN5
SMARTiView protein in SMART
SM00350 MCM, 1 hit
SUPFAMiSSF50249 SSF50249, 1 hit
SSF52540 SSF52540, 1 hit
PROSITEiView protein in PROSITE
PS00847 MCM_1, 1 hit
PS50051 MCM_2, 1 hit

Sequencei

Sequence statusi: Complete.

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

P33992-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSGFDDPGIF YSDSFGGDAQ ADEGQARKSQ LQRRFKEFLR QYRVGTDRTG
60 70 80 90 100
FTFKYRDELK RHYNLGEYWI EVEMEDLASF DEDLADYLYK QPAEHLQLLE
110 120 130 140 150
EAAKEVADEV TRPRPSGEEV LQDIQVMLKS DASPSSIRSL KSDMMSHLVK
160 170 180 190 200
IPGIIIAASA VRAKATRISI QCRSCRNTLT NIAMRPGLEG YALPRKCNTD
210 220 230 240 250
QAGRPKCPLD PYFIMPDKCK CVDFQTLKLQ ELPDAVPHGE MPRHMQLYCD
260 270 280 290 300
RYLCDKVVPG NRVTIMGIYS IKKFGLTTSR GRDRVGVGIR SSYIRVLGIQ
310 320 330 340 350
VDTDGSGRSF AGAVSPQEEE EFRRLAALPN VYEVISKSIA PSIFGGTDMK
360 370 380 390 400
KAIACLLFGG SRKRLPDGLT RRGDINLLML GDPGTAKSQL LKFVEKCSPI
410 420 430 440 450
GVYTSGKGSS AAGLTASVMR DPSSRNFIME GGAMVLADGG VVCIDEFDKM
460 470 480 490 500
REDDRVAIHE AMEQQTISIA KAGITTTLNS RCSVLAAANS VFGRWDETKG
510 520 530 540 550
EDNIDFMPTI LSRFDMIFIV KDEHNEERDV MLAKHVITLH VSALTQTQAV
560 570 580 590 600
EGEIDLAKLK KFIAYCRVKC GPRLSAEAAE KLKNRYIIMR SGARQHERDS
610 620 630 640 650
DRRSSIPITV RQLEAIVRIA EALSKMKLQP FATEADVEEA LRLFQVSTLD
660 670 680 690 700
AALSGTLSGV EGFTSQEDQE MLSRIEKQLK RRFAIGSQVS EHSIIKDFTK
710 720 730
QKYPEHAIHK VLQLMLRRGE IQHRMQRKVL YRLK
Length:734
Mass (Da):82,286
Last modified:August 14, 2001 - v5
Checksum:iA80280E61749998D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti41Q → R in AAH03656 (PubMed:15489334).Curated1
Sequence conflicti434M → W (PubMed:8265339).Curated1
Sequence conflicti527E → V in BAA12176 (Ref. 3) Curated1
Sequence conflicti591S → T in BAA12176 (Ref. 3) Curated1
Sequence conflicti593 – 603ARQHERDSDRR → PVSTRGTVTA in BAA12176 (Ref. 3) CuratedAdd BLAST11

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_014813136S → T1 PublicationCorresponds to variant dbSNP:rs2307334Ensembl.1
Natural variantiVAR_014814180T → S1 PublicationCorresponds to variant dbSNP:rs2307340Ensembl.1
Natural variantiVAR_014815258V → I1 PublicationCorresponds to variant dbSNP:rs2230933Ensembl.1
Natural variantiVAR_079198466T → I in MGORS8. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS13915.1
PIRiI38080
RefSeqiNP_006730.2, NM_006739.3
UniGeneiHs.517582

Genome annotation databases

EnsembliENST00000216122; ENSP00000216122; ENSG00000100297
GeneIDi4174
KEGGihsa:4174
UCSCiuc003anu.5 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiMCM5_HUMAN
AccessioniPrimary (citable) accession number: P33992
Secondary accession number(s): O60785
, Q14578, Q9BTJ4, Q9BWL8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: August 14, 2001
Last modified: May 23, 2018
This is version 195 of the entry and version 5 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, Reference proteome

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