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UniProtKB - P33993 (MCM7_HUMAN)

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Protein

DNA replication licensing factor MCM7

Gene

MCM7

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 S-phase checkpoint activation upon UV-induced damage.3 Publications

Miscellaneous

Early fractionation of eukaryotic MCM proteins yielded a variety of dimeric, trimeric and tetrameric complexes with unclear biological significance. Specifically a MCM467 subcomplex is shown to have in vitro helicase activity which is inhibited by the MCM2 subunit. 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

Complete GO annotation...

GO - Biological processi

Complete GO annotation...

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.
R-HSA-69300. Removal of licensing factors from origins.
SIGNORiP33993.

Names & Taxonomyi

Protein namesi
Recommended name:
DNA replication licensing factor MCM7 (EC:3.6.4.12)
Alternative name(s):
CDC47 homolog
P1.1-MCM3
Gene namesi
Name:MCM7
Synonyms:CDC47, MCM2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:6950. MCM7.

Subcellular locationi

GO - Cellular componenti

  • chromatin Source: ProtInc
  • cytosol Source: HPA
  • MCM complex Source: UniProtKB
  • membrane Source: UniProtKB
  • nuclear chromosome, telomeric region Source: BHF-UCL
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi4176.
OpenTargetsiENSG00000166508.
PharmGKBiPA30697.

Polymorphism and mutation databases

DMDMi20981696.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00001941192 – 719DNA replication licensing factor MCM7Add BLAST718

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1 Publication1
Modified residuei121PhosphoserineCombined sources1
Modified residuei314PhosphoserineCombined sources1
Modified residuei365PhosphoserineCombined sources1
Modified residuei500PhosphoserineCombined sources1
Modified residuei678PhosphoserineCombined sources1

Post-translational modificationi

O-glycosylated (O-GlcNAcylated), in a cell cycle-dependent manner.1 Publication

Keywords - PTMi

Acetylation, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP33993.
MaxQBiP33993.
PaxDbiP33993.
PeptideAtlasiP33993.
PRIDEiP33993.

PTM databases

iPTMnetiP33993.
PhosphoSitePlusiP33993.
SwissPalmiP33993.

Expressioni

Gene expression databases

BgeeiENSG00000166508.
CleanExiHS_MCM2.
HS_MCM7.
ExpressionAtlasiP33993. baseline and differential.
GenevisibleiP33993. HS.

Organism-specific databases

HPAiCAB002163.
CAB016312.
HPA003898.

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 the ATR-ATRIP complex and with RAD17. Interacts with TIPIN. Interacts with MCMBP. Interacts with ANKRD17.Curated7 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi110344. 161 interactors.
DIPiDIP-27580N.
IntActiP33993. 179 interactors.
MINTiMINT-5005969.
STRINGi9606.ENSP00000307288.

Structurei

3D structure databases

ProteinModelPortaliP33993.
SMRiP33993.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini332 – 538MCMAdd BLAST207

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni521 – 564Interaction with RAD171 PublicationAdd BLAST44
Regioni577 – 719Interaction with ATRIPAdd BLAST143

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi513 – 516Arginine finger4

Sequence similaritiesi

Belongs to the MCM family.Curated

Phylogenomic databases

eggNOGiKOG0482. Eukaryota.
COG1241. LUCA.
GeneTreeiENSGT00870000136551.
HOGENOMiHOG000224125.
HOVERGENiHBG000741.
InParanoidiP33993.
KOiK02210.
OMAiVKIQEMA.
OrthoDBiEOG091G02LB.
PhylomeDBiP33993.
TreeFamiTF300400.

Family and domain databases

InterProiView protein in InterPro
IPR003593. AAA+_ATPase.
IPR031327. MCM.
IPR008050. MCM7.
IPR018525. MCM_CS.
IPR001208. MCM_dom.
IPR027925. MCM_N.
IPR033762. MCM_OB.
IPR012340. NA-bd_OB-fold.
IPR027417. P-loop_NTPase.
PANTHERiPTHR11630:SF78. PTHR11630:SF78. 1 hit.
PfamiView protein in Pfam
PF00493. MCM. 1 hit.
PF14551. MCM_N. 1 hit.
PF17207. MCM_OB. 1 hit.
PRINTSiPR01657. MCMFAMILY.
PR01663. MCMPROTEIN7.
SMARTiView protein in SMART
SM00382. AAA. 1 hit.
SM00350. MCM. 1 hit.
SUPFAMiSSF50249. SSF50249. 2 hits.
SSF52540. SSF52540. 1 hit.
PROSITEiView protein in PROSITE
PS00847. MCM_1. 1 hit.
PS50051. MCM_2. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P33993-1) [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
MALKDYALEK EKVKKFLQEF YQDDELGKKQ FKYGNQLVRL AHREQVALYV 
        60         70         80         90        100
DLDDVAEDDP ELVDSICENA RRYAKLFADA VQELLPQYKE REVVNKDVLD 
       110        120        130        140        150
VYIEHRLMME QRSRDPGMVR SPQNQYPAEL MRRFELYFQG PSSNKPRVIR 
       160        170        180        190        200
EVRADSVGKL VTVRGIVTRV SEVKPKMVVA TYTCDQCGAE TYQPIQSPTF 
       210        220        230        240        250
MPLIMCPSQE CQTNRSGGRL YLQTRGSRFI KFQEMKMQEH SDQVPVGNIP 
       260        270        280        290        300
RSITVLVEGE NTRIAQPGDH VSVTGIFLPI LRTGFRQVVQ GLLSETYLEA 
       310        320        330        340        350
HRIVKMNKSE DDESGAGELT REELRQIAEE DFYEKLAASI APEIYGHEDV 
       360        370        380        390        400
KKALLLLLVG GVDQSPRGMK IRGNINICLM GDPGVAKSQL LSYIDRLAPR 
       410        420        430        440        450
SQYTTGRGSS GVGLTAAVLR DSVSGELTLE GGALVLADQG VCCIDEFDKM 
       460        470        480        490        500
AEADRTAIHE VMEQQTISIA KAGILTTLNA RCSILAAANP AYGRYNPRRS 
       510        520        530        540        550
LEQNIQLPAA LLSRFDLLWL IQDRPDRDND LRLAQHITYV HQHSRQPPSQ 
       560        570        580        590        600
FEPLDMKLMR RYIAMCREKQ PMVPESLADY ITAAYVEMRR EAWASKDATY 
       610        620        630        640        650
TSARTLLAIL RLSTALARLR MVDVVEKEDV NEAIRLMEMS KDSLLGDKGQ 
       660        670        680        690        700
TARTQRPADV IFATVRELVS GGRSVRFSEA EQRCVSRGFT PAQFQAALDE 
       710 
YEELNVWQVN ASRTRITFV
Length:719
Mass (Da):81,308
Last modified:May 15, 2002 - v4
Checksum:i330A1DEFAEFBFB88
GO
Isoform 2 (identifier: P33993-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     329-658: Missing.

Note: No experimental confirmation available.
Show »
Length:389
Mass (Da):44,649
Checksum:iCCAA37CB2DA54063
GO
Isoform 3 (identifier: P33993-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-176: Missing.

Show »
Length:543
Mass (Da):60,643
Checksum:i4CAA41B4F392F50C
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti103I → L in CAA52803 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_029243114R → Q. Corresponds to variant dbSNP:rs2307348Ensembl.1
Natural variantiVAR_013297144N → S1 PublicationCorresponds to variant dbSNP:rs2070215Ensembl.1
Natural variantiVAR_014817473G → S. Corresponds to variant dbSNP:rs2307347Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0443101 – 176Missing in isoform 3. 1 PublicationAdd BLAST176
Alternative sequenceiVSP_003205329 – 658Missing in isoform 2. 1 PublicationAdd BLAST330

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D55716 mRNA. Translation: BAA09534.1.
AK055379 mRNA. Translation: BAG51508.1.
AC073842 Genomic DNA. No translation available.
CH236956 Genomic DNA. Translation: EAL23855.1.
CH236956 Genomic DNA. Translation: EAL23856.1.
CH471091 Genomic DNA. Translation: EAW76598.1.
CH471091 Genomic DNA. Translation: EAW76599.1.
BC009398 mRNA. Translation: AAH09398.1.
BC013375 mRNA. Translation: AAH13375.1.
X74796 mRNA. Translation: CAA52803.1.
D28480 mRNA. Translation: BAA05839.1.
CCDSiCCDS5683.1. [P33993-1]
CCDS5684.1. [P33993-3]
PIRiS70583.
RefSeqiNP_001265524.1. NM_001278595.1. [P33993-3]
NP_005907.3. NM_005916.4. [P33993-1]
NP_877577.1. NM_182776.2. [P33993-3]
UniGeneiHs.438720.

Genome annotation databases

EnsembliENST00000303887; ENSP00000307288; ENSG00000166508. [P33993-1]
ENST00000343023; ENSP00000344006; ENSG00000166508. [P33993-2]
ENST00000354230; ENSP00000346171; ENSG00000166508. [P33993-3]
ENST00000621318; ENSP00000483795; ENSG00000166508. [P33993-3]
GeneIDi4176.
KEGGihsa:4176.
UCSCiuc003usv.3. human. [P33993-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiMCM7_HUMAN
AccessioniPrimary (citable) accession number: P33993
Secondary accession number(s): A4D2A1
, A4D2A2, E9PGN9, Q15076, Q96D34, Q96GL1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: May 15, 2002
Last modified: July 5, 2017
This is version 187 of the entry and version 4 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

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families