P33992 · MCM5_HUMAN
- ProteinDNA replication licensing factor MCM5
- GeneMCM5
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids734 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built (PubMed:16899510, PubMed:32453425, PubMed:34694004, PubMed:34700328, PubMed:35585232).
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 (PubMed:32453425).
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 (PubMed:32453425).
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 activity
- ATP + H2O = ADP + H+ + phosphateThis reaction proceeds in the forward direction.
Features
Showing features for binding site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | chromosome, telomeric region | |
Cellular Component | CMG complex | |
Cellular Component | MCM complex | |
Cellular Component | membrane | |
Cellular Component | nucleoplasm | |
Cellular Component | nucleus | |
Molecular Function | ATP binding | |
Molecular Function | ATP hydrolysis activity | |
Molecular Function | DNA replication origin binding | |
Molecular Function | helicase activity | |
Molecular Function | single-stranded DNA binding | |
Biological Process | DNA replication | |
Biological Process | DNA replication initiation | |
Biological Process | DNA unwinding involved in DNA replication | |
Biological Process | double-strand break repair via break-induced replication | |
Biological Process | regulation of DNA-templated DNA replication initiation |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameDNA replication licensing factor MCM5
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP33992
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Associated with chromatin before the formation of nuclei and detaches from it as DNA replication progresses.
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Meier-Gorlin syndrome 8 (MGORS8)
- Note
- 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 alsoMIM:617564
Natural variants in MGORS8
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_079198 | 466 | T>I | in MGORS8; dbSNP:rs1131692169 |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_014813 | 136 | in dbSNP:rs2307334 | |||
Sequence: S → T | ||||||
Natural variant | VAR_014814 | 180 | in dbSNP:rs2307340 | |||
Sequence: T → S | ||||||
Natural variant | VAR_014815 | 258 | in dbSNP:rs2230933 | |||
Sequence: V → I | ||||||
Natural variant | VAR_079198 | 466 | in MGORS8; dbSNP:rs1131692169 | |||
Sequence: T → I |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 859 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, modified residue, modified residue (large scale data), chain.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed | ||||
Sequence: M | |||||||
Modified residue | 2 | UniProt | N-acetylserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 2 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Chain | PRO_0000194107 | 2-734 | UniProt | DNA replication licensing factor MCM5 | |||
Sequence: SGFDDPGIFYSDSFGGDAQADEGQARKSQLQRRFKEFLRQYRVGTDRTGFTFKYRDELKRHYNLGEYWIEVEMEDLASFDEDLADYLYKQPAEHLQLLEEAAKEVADEVTRPRPSGEEVLQDIQVMLKSDASPSSIRSLKSDMMSHLVKIPGIIIAASAVRAKATRISIQCRSCRNTLTNIAMRPGLEGYALPRKCNTDQAGRPKCPLDPYFIMPDKCKCVDFQTLKLQELPDAVPHGEMPRHMQLYCDRYLCDKVVPGNRVTIMGIYSIKKFGLTTSRGRDRVGVGIRSSYIRVLGIQVDTDGSGRSFAGAVSPQEEEEFRRLAALPNVYEVISKSIAPSIFGGTDMKKAIACLLFGGSRKRLPDGLTRRGDINLLMLGDPGTAKSQLLKFVEKCSPIGVYTSGKGSSAAGLTASVMRDPSSRNFIMEGGAMVLADGGVVCIDEFDKMREDDRVAIHEAMEQQTISIAKAGITTTLNSRCSVLAAANSVFGRWDETKGEDNIDFMPTILSRFDMIFIVKDEHNEERDVMLAKHVITLHVSALTQTQAVEGEIDLAKLKKFIAYCRVKCGPRLSAEAAEKLKNRYIIMRSGARQHERDSDRRSSIPITVRQLEAIVRIAEALSKMKLQPFATEADVEEALRLFQVSTLDAALSGTLSGVEGFTSQEDQEMLSRIEKQLKRRFAIGSQVSEHSIIKDFTKQKYPEHAIHKVLQLMLRRGEIQHRMQRKVLYRLK | |||||||
Modified residue (large scale data) | 11 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 12 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 14 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 315 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 315 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 392 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 396 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 605 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 605 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 696 | UniProt | N6-acetyllysine | ||||
Sequence: K |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Component of the MCM2-7 complex (PubMed:16899510, PubMed:17296731).
The complex forms a toroidal hexameric ring with the proposed subunit order MCM2-MCM6-MCM4-MCM7-MCM3-MCM5 (PubMed:16899510, PubMed:17296731, PubMed:32453425).
Component of the CMG helicase complex, a hexameric ring of related MCM2-7 subunits stabilized by CDC45 and the tetrameric GINS complex (PubMed:32453425, PubMed:34694004, PubMed:34700328).
Interacts with ANKRD17 (PubMed:23711367).
Interacts with MCMBP (PubMed:17296731).
Interacts with TONSL; the interaction is direct (PubMed:26527279).
The complex forms a toroidal hexameric ring with the proposed subunit order MCM2-MCM6-MCM4-MCM7-MCM3-MCM5 (PubMed:16899510, PubMed:17296731, PubMed:32453425).
Component of the CMG helicase complex, a hexameric ring of related MCM2-7 subunits stabilized by CDC45 and the tetrameric GINS complex (PubMed:32453425, PubMed:34694004, PubMed:34700328).
Interacts with ANKRD17 (PubMed:23711367).
Interacts with MCMBP (PubMed:17296731).
Interacts with TONSL; the interaction is direct (PubMed:26527279).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P33992 | H4C9 P62805 | 2 | EBI-359410, EBI-302023 | |
BINARY | P33992 | L3MBTL1 Q9Y468 | 2 | EBI-359410, EBI-1265089 | |
BINARY | P33992 | MCM2 P49736 | 5 | EBI-359410, EBI-374819 | |
BINARY | P33992 | MCM3 P25205 | 8 | EBI-359410, EBI-355153 | |
BINARY | P33992 | MCM7 P33993 | 10 | EBI-359410, EBI-355924 | |
BINARY | P33992 | MCMBP Q9BTE3 | 16 | EBI-359410, EBI-749378 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 331-537 | MCM | ||||
Sequence: VYEVISKSIAPSIFGGTDMKKAIACLLFGGSRKRLPDGLTRRGDINLLMLGDPGTAKSQLLKFVEKCSPIGVYTSGKGSSAAGLTASVMRDPSSRNFIMEGGAMVLADGGVVCIDEFDKMREDDRVAIHEAMEQQTISIAKAGITTTLNSRCSVLAAANSVFGRWDETKGEDNIDFMPTILSRFDMIFIVKDEHNEERDVMLAKHVI |
Sequence similarities
Belongs to the MCM family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length734
- Mass (Da)82,286
- Last updated2001-08-14 v5
- ChecksumA80280E61749998D
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 41 | in Ref. 7; AAH03656 | ||||
Sequence: Q → R | ||||||
Sequence conflict | 434 | in Ref. 8 | ||||
Sequence: M → W | ||||||
Sequence conflict | 527 | in Ref. 3; BAA12176 | ||||
Sequence: E → V | ||||||
Sequence conflict | 591 | in Ref. 3; BAA12176 | ||||
Sequence: S → T | ||||||
Sequence conflict | 593-603 | in Ref. 3; BAA12176 | ||||
Sequence: ARQHERDSDRR → PVSTRGTVTA |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X74795 EMBL· GenBank· DDBJ | CAA52802.2 EMBL· GenBank· DDBJ | mRNA | ||
D83986 EMBL· GenBank· DDBJ | BAA12176.1 EMBL· GenBank· DDBJ | mRNA | ||
CR456517 EMBL· GenBank· DDBJ | CAG30403.1 EMBL· GenBank· DDBJ | mRNA | ||
AY212028 EMBL· GenBank· DDBJ | AAO21127.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
Z82244 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC000142 EMBL· GenBank· DDBJ | AAH00142.1 EMBL· GenBank· DDBJ | mRNA | ||
BC003656 EMBL· GenBank· DDBJ | AAH03656.1 EMBL· GenBank· DDBJ | mRNA |