UniProtKB - P33993 (MCM7_HUMAN)
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Protein
DNA replication licensing factor MCM7
Gene
MCM7
Organism
Homo sapiens (Human)
Status
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 381 – 388 | ATPSequence analysis | 8 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- DNA helicase activity Source: Ensembl
- single-stranded DNA binding Source: Ensembl
GO - Biological processi
- cell proliferation Source: Ensembl
- cellular response to DNA damage stimulus Source: UniProtKB
- cellular response to epidermal growth factor stimulus Source: Ensembl
- cellular response to xenobiotic stimulus Source: Ensembl
- DNA replication Source: Reactome
- DNA replication initiation Source: InterPro
- DNA unwinding involved in DNA replication Source: Ensembl
- G1/S transition of mitotic cell cycle Source: Reactome
- regulation of phosphorylation Source: UniProtKB
- response to drug Source: Ensembl
Keywordsi
Molecular function | DNA-binding, Helicase, Hydrolase |
Biological process | Cell cycle, DNA replication |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
Reactomei | R-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. |
SIGNORi | P33993. |
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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000166508.17. |
HGNCi | HGNC:6950. MCM7. |
MIMi | 600592. gene. |
neXtProti | NX_P33993. |
Pathology & Biotechi
Organism-specific databases
DisGeNETi | 4176. |
OpenTargetsi | ENSG00000166508. |
PharmGKBi | PA30697. |
Polymorphism and mutation databases
DMDMi | 20981696. |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedCombined sources1 Publication | |||
ChainiPRO_0000194119 | 2 – 719 | DNA replication licensing factor MCM7Add BLAST | 718 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylalanineCombined sources1 Publication | 1 | |
Cross-linki | 15 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources | ||
Cross-linki | 28 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources | ||
Modified residuei | 121 | PhosphoserineCombined sources | 1 | |
Modified residuei | 314 | PhosphoserineCombined sources | 1 | |
Modified residuei | 365 | PhosphoserineCombined sources | 1 | |
Modified residuei | 500 | PhosphoserineCombined sources | 1 | |
Modified residuei | 678 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
O-glycosylated (O-GlcNAcylated), in a cell cycle-dependent manner.1 Publication
Keywords - PTMi
Acetylation, Glycoprotein, Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
EPDi | P33993. |
MaxQBi | P33993. |
PaxDbi | P33993. |
PeptideAtlasi | P33993. |
PRIDEi | P33993. |
PTM databases
iPTMneti | P33993. |
PhosphoSitePlusi | P33993. |
SwissPalmi | P33993. |
Expressioni
Gene expression databases
Bgeei | ENSG00000166508. |
CleanExi | HS_MCM2. HS_MCM7. |
ExpressionAtlasi | P33993. baseline and differential. |
Genevisiblei | P33993. HS. |
Organism-specific databases
HPAi | CAB002163. 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. Component of the replisome complex composed of at least DONSON, MCM2, MCM7, PCNA and TICRR (PubMed:28191891).Curated8 Publications
Binary interactionsi
Protein-protein interaction databases
BioGridi | 110344. 170 interactors. |
CORUMi | P33993. |
DIPi | DIP-27580N. |
IntActi | P33993. 197 interactors. |
MINTi | P33993. |
STRINGi | 9606.ENSP00000307288. |
Structurei
3D structure databases
ProteinModelPortali | P33993. |
SMRi | P33993. |
ModBasei | Search... |
MobiDBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 332 – 538 | MCMAdd BLAST | 207 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 521 – 564 | Interaction with RAD171 PublicationAdd BLAST | 44 | |
Regioni | 577 – 719 | Interaction with ATRIPAdd BLAST | 143 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 513 – 516 | Arginine finger | 4 |
Sequence similaritiesi
Belongs to the MCM family.Curated
Phylogenomic databases
eggNOGi | KOG0482. Eukaryota. COG1241. LUCA. |
GeneTreei | ENSGT00900000141136. |
HOGENOMi | HOG000224125. |
HOVERGENi | HBG000741. |
InParanoidi | P33993. |
KOi | K02210. |
OMAi | VKIQEMA. |
OrthoDBi | EOG091G02LB. |
PhylomeDBi | P33993. |
TreeFami | TF300400. |
Family and domain databases
InterProi | View 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. |
PANTHERi | PTHR11630. PTHR11630. 1 hit. PTHR11630:SF26. PTHR11630:SF26. 1 hit. |
Pfami | View protein in Pfam PF00493. MCM. 1 hit. PF14551. MCM_N. 1 hit. PF17207. MCM_OB. 1 hit. |
PRINTSi | PR01657. MCMFAMILY. PR01663. MCMPROTEIN7. |
SMARTi | View protein in SMART SM00382. AAA. 1 hit. SM00350. MCM. 1 hit. |
SUPFAMi | SSF50249. SSF50249. 2 hits. SSF52540. SSF52540. 1 hit. |
PROSITEi | View protein in PROSITE PS00847. MCM_1. 1 hit. PS50051. MCM_2. 1 hit. |
s (3)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 3 produced by isoformsialternative 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.
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
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 103 | I → L in CAA52803 (PubMed:15489334).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_029243 | 114 | R → Q. Corresponds to variant dbSNP:rs2307348Ensembl. | 1 | |
Natural variantiVAR_013297 | 144 | N → S1 PublicationCorresponds to variant dbSNP:rs2070215Ensembl. | 1 | |
Natural variantiVAR_014817 | 473 | G → S. Corresponds to variant dbSNP:rs2307347Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_044310 | 1 – 176 | Missing in isoform 3. 1 PublicationAdd BLAST | 176 | |
Alternative sequenceiVSP_003205 | 329 – 658 | Missing in isoform 2. 1 PublicationAdd BLAST | 330 |
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. |
CCDSi | CCDS5683.1. [P33993-1] CCDS5684.1. [P33993-3] |
PIRi | S70583. |
RefSeqi | NP_001265524.1. NM_001278595.1. [P33993-3] NP_005907.3. NM_005916.4. [P33993-1] NP_877577.1. NM_182776.2. [P33993-3] |
UniGenei | Hs.438720. |
Genome annotation databases
Ensembli | ENST00000303887; ENSP00000307288; ENSG00000166508. [P33993-1] ENST00000343023; ENSP00000344006; ENSG00000166508. [P33993-2] ENST00000354230; ENSP00000346171; ENSG00000166508. [P33993-3] ENST00000621318; ENSP00000483795; ENSG00000166508. [P33993-3] |
GeneIDi | 4176. |
KEGGi | hsa:4176. |
UCSCi | uc003usv.3. human. [P33993-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Entry informationi
Entry namei | MCM7_HUMAN | |
Accessioni | P33993Primary (citable) accession number: P33993 Secondary accession number(s): A4D2A1 Q96GL1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 1, 1994 |
Last sequence update: | May 15, 2002 | |
Last modified: | March 28, 2018 | |
This is version 195 of the entry and version 4 of the sequence. See complete history. | ||
Entry statusi | 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. |