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237  structures 1866  species 0  interactions 14799  sequences 375  architectures

Family: MCM (PF00493)

Summary: MCM P-loop domain

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This is the Wikipedia entry entitled "Minichromosome maintenance". More...

Minichromosome maintenance Edit Wikipedia article

MCM2-7 family
MCM DH overall structure.jpg
Overall Structure of the Mcm2-7 double hexamer[1]
Pfam clanCL0023
Pfam maps to the core ATP binding domain.

The minichromosome maintenance protein complex (MCM) is a DNA helicase essential for genomic DNA replication. Eukaryotic MCM consists of six gene products, Mcm2–7, which form a heterohexamer.[1][2] As a critical protein for cell division, MCM is also the target of various checkpoint pathways, such as the S-phase entry and S-phase arrest checkpoints. Both the loading and activation of MCM helicase are strictly regulated and are coupled to cell growth cycles. Deregulation of MCM function has been linked to genomic instability and a variety of carcinomas.[3][4]

History and structure

Homology shared by members of the Mcm2-7 protein family.[5] Homology among the six members of the family are indicated in black. Homology of each member across species is indicated in colour.

The minichromosome maintenance proteins were named after a yeast genetics screen for mutants defective in the regulation of DNA replication initiation.[6] The rationale behind this screen was that if replication origins were regulated in a manner analogous to transcription promoters, where transcriptional regulators showed promoter specificity, then replication regulators should also show origin specificity. Since eukaryotic chromosomes contain multiple replication origins and the plasmids contain only one, a slight defect in these regulators would have a dramatic effect on the replication of plasmids but little effect on chromosomes. In this screen, mutants conditional for plasmid loss were identified. In a secondary screen, these conditional mutants were selected for defects in plasmid maintenance against a collection of plasmids each carrying a different origin sequence. Two classes of mcm mutants were identified: Those that affected the stability of all minichromosomes and others that affected the stability of only a subset of the minichromosomes. The former were mutants defective in chromosome segregation such as mcm16, mcm20 and mcm21. Among the latter class of origin-specific mutants were mcm1, mcm2, mcm3, mcm5 and mcm10. Later on, others identified Mcm4, Mcm6 and Mcm7 in yeasts and other eukaryotes based on homology to Mcm2p, Mcm3p and Mcm5p expanding the MCM family to six, subsequently known as the Mcm2-7 family.[5] In archaea, the heterohexamer ring is replaced by a homohexamer made up of a single type mcm protein, pointing at a history of gene duplication and diversification.[7]

Mcm1[8][9] and Mcm10[10][11] are also involved in DNA replication, directly or indirectly, but have no sequence homology to the Mcm2-7 family.

Function in DNA replication initiation and elongation

MCM2-7 is required for both DNA replication initiation and elongation; its regulation at each stage is a central feature of eukaryotic DNA replication.[3] During G1 phase, the two head-to-head Mcm2-7 rings serve as the scaffold for the assembly of the bidirectional replication initiation complexes at the replication origin. During S phase, the Mcm2-7 complex forms the catalytic core of the Cdc45-MCM-GINS helicase - the DNA unwinding engine of the replisome.

G1/pre-replicative complex assembly

Site selection for replication origins is carried out by the Origin Recognition Complex (ORC), a six subunit complex (Orc1-6).[12][13] During the G1 phase of the cell cycle, Cdc6 is recruited by ORC to form a launching pad for the loading of two head-to-head Mcm2-7 hexamers, also known as the pre-replication complex (pre-RC).[14] There is genetic and biochemical evidence that the recruitment of the double hexamer may involve either one[15] or two[16] ORCs. Soluble Mcm2-7 hexamer forms a flexible left-handed open-ringed structure stabilised by Cdt1 prior to its loading onto chromatin,[2][17] one at a time.[18] The structure of the ORC-Cdc6-Cdt1-MCM (OCCM) intermediate formed after the loading of the first Cdt1-Mcm2-7 heptamer indicates that the winged helix domain at the C-terminal extensions (CTE) of the Mcm2-7 complex firmly anchor onto the surfaces created by the ORC-Cdc6 ring structure around origin DNA.[19] The fusion of the two head-to-head Mcm2-7 hexamers is believed to be facilitated by the removal of Cdt1, leaving the NTDs of the two MCM hexamers flexible for inter-ring interactions.[20][1] The loading of MCM2-7 onto DNA is an active process that requires ATP hydrolysis by both Orc1-6 and Cdc6.[21] This process is coined "Replication Licensing" as it is a prerequisite for DNA replication initiation in every cell division cycle.[22][23]

Late G1/early S - initiation

In late G1/early S phase, the pre-RC is activated for DNA unwinding by the cyclin-dependent kinases (CDKs) and DDK. This facilitates the loading of additional replication factors (e.g., Cdc45, MCM10, GINS, and DNA polymerases) and unwinding of the DNA at the origin.[3] Once pre-RC formation is complete, Orc1-6 and Cdc6 are no longer required for MCM2-7 retention at the origin, and they are dispensable for subsequent DNA replication.


Upon entry into S phase, the activity of the CDKs and the Dbf4-dependent kinase (DDK) Cdc7 promotes the assembly of replication forks, likely in part by activating MCM2-7 to unwind DNA. Following DNA polymerase loading, bidirectional DNA replication commences.

During S phase, Cdc6 and Cdt1 are degraded or inactivated to block additional pre-RC formation, and bidirectional DNA replication ensues. When the replication fork encounters lesions in the DNA, the S-phase checkpoint response slows or stops fork progression and stabilizes the association of MCM2-7 with the replication fork during DNA repair.[24]

Role in replication licensing

The replication licensing system acts to ensure that the no section of the genome is replicated more than once in a single cell cycle.[25]

The inactivation of any of at least five of the six MCM subunits during S phase quickly blocks ongoing elongation. As a critical mechanism to ensure only a single round of DNA replication, the loading of additional MCM2-7 complexes into pre-RCs is inactivated by redundant means after passage into S phase. [26]

MCM2-7 activity can also be regulated during elongation. The loss of replication fork integrity, an event precipitated by DNA damage, unusual DNA sequence, or insufficient deoxyribonucleotide precursors, can lead to the formation of DNA double-strand breaks and chromosome rearrangements. Normally, these replication problems trigger an S-phase checkpoint that minimizes genomic damage by blocking further elongation and physically stabilizing protein-DNA associations at the replication fork until the problem is fixed. This stabilization of the replication fork requires the physical interaction of MCM2-7 with Mrc1, Tof1, and Csm3 (M/T/C complex).[27] In the absence of these proteins, dsDNA unwinding and replisome movement powered by MCM2-7 continue, but DNA synthesis stops. At least part of this stop is due to the dissociation of polymerase ε from the replication fork.[27]

Biochemical structure

Each subunit in the MCM structure contains two large N- and C-terminal domains. The N-terminal domain consists of three small sub-domains and appears to be used mainly for structural organization.[28][1] The N-domain can coordinate with a neighboring subunit’s C-terminal AAA+ helicase domain through a long and conserved loop.[29][1] This conserved loop, named the allosteric control loop, has been shown to play a role in regulating interactions between N- and C-terminal regions by facilitating communication between the domains in response to ATP hydrolysis [10]. The N-domain also establishes the in vitro 3′→5′ directionality of MCM. [30][31]

Models of DNA unwinding

Regarding the physical mechanism of how a hexameric helicase unwinds DNA, two models have been proposed based on in vivo and in vitro data. In the "steric" model, the helicase tightly translocates along one strand of DNA while physically displacing the complementary strand. In the "pump" model, pairs of hexameric helicases unwind duplex DNA by either twisting it apart or extruding it through channels in the complex.

Steric model

The steric model hypothesizes that the helicase encircles dsDNA and, after local melting of the duplex DNA at the origin, translocates away from the origin, dragging a rigid proteinaceous "wedge" (either part of the helicase itself or another associated protein) that separates the DNA strands.[32]

Pump model

The pump model postulates that multiple helicases load at replication origins, translocate away from one another, and in some manner eventually become anchored in place. They then rotate dsDNA in opposite directions, resulting in the unwinding of the double helix in the intervening region.[33] The pump model has also been proposed to be restricted to the melting of origin DNA while the Mcm2-7 complexes are still anchored at the origin just before replication initiation.[1]

Role in cancer

Various MCMs have been shown to promote cell proliferation in vitro and in vivo especially in certain types of cancer cell lines. The association between MCMs and proliferation in cancer cell lines is mostly attributed to its ability to enhance DNA replication. The roles of MCM2 and MCM7 in cell proliferation have been demonstrated in various cellular contexts and even in human specimens. [26]

MCM2 has been shown to be frequently expressed in proliferating premalignant lung cells. Its expression was associated with cells having a higher proliferation potential in non-dysplastic squamous epithelium, malignant fibrous histiocytomas, and endometrial carcinoma, while MCM2 expression was also correlated higher mitotic index in breast cancer specimens. [34]

Similarly, many research studies have shown the link between MCM7 expression and cell proliferation. Expression of MCM7 was significantly correlated with the expression of Ki67 in choriocarcinomas, lung cancer, papillary urothelial neoplasia, esophageal cancer, and endometrial cancer. Its expression was also associated with a higher proliferative index in prostatic intraepithelial neoplasia and cancer.[35]

See also


  1. ^ a b c d e f Li N, Zhai Y, Zhang Y, Li W, Yang M, Lei J, Tye BK, Gao N (August 2015). "Structure of the eukaryotic MCM complex at 3.8 Å". Nature. 524 (7564): 186–91. Bibcode:2015Natur.524..186L. doi:10.1038/nature14685. PMID 26222030. S2CID 4468690.
  2. ^ a b Zhai Y, Cheng E, Wu H, Li N, Yung PY, Gao N, Tye BK (March 2017). "Open-ringed structure of the Cdt1-Mcm2-7 complex as a precursor of the MCM double hexamer". Nature Structural & Molecular Biology. 24 (3): 300–308. doi:10.1038/nsmb.3374. PMID 28191894. S2CID 3929807.
  3. ^ a b c Bochman ML, Schwacha A (December 2009). "The Mcm complex: unwinding the mechanism of a replicative helicase". Microbiology and Molecular Biology Reviews. 73 (4): 652–83. doi:10.1128/mmbr.00019-09. PMC 2786579. PMID 19946136.
  4. ^ Shima N, Alcaraz A, Liachko I, Buske TR, Andrews CA, Munroe RJ, Hartford SA, Tye BK, Schimenti JC (January 2007). "A viable allele of Mcm4 causes chromosome instability and mammary adenocarcinomas in mice". Nature Genetics. 39 (1): 93–8. doi:10.1038/ng1936. PMID 17143284. S2CID 11433033.
  5. ^ a b Tye BK (June 1999). "MCM proteins in DNA replication". Annual Review of Biochemistry. 68 (1): 649–86. doi:10.1146/annurev.biochem.68.1.649. PMID 10872463.
  6. ^ Maine GT, Sinha P, Tye BK (March 1984). "Mutants of S. cerevisiae defective in the maintenance of minichromosomes". Genetics. 106 (3): 365–85. doi:10.1093/genetics/106.3.365. PMC 1224244. PMID 6323245.
  7. ^ Ausiannikava, Darya; Allers, Thorsten (31 January 2017). "Diversity of DNA Replication in the Archaea". Genes. 8 (2): 56. doi:10.3390/genes8020056. PMC 5333045. PMID 28146124.
  8. ^ Passmore S, Elble R, Tye BK (July 1989). "A protein involved in minichromosome maintenance in yeast binds a transcriptional enhancer conserved in eukaryotes". Genes & Development. 3 (7): 921–35. doi:10.1101/gad.3.7.921. PMID 2673922.
  9. ^ Chang VK, Fitch MJ, Donato JJ, Christensen TW, Merchant AM, Tye BK (February 2003). "Mcm1 binds replication origins". The Journal of Biological Chemistry. 278 (8): 6093–100. doi:10.1074/jbc.M209827200. PMID 12473677.
  10. ^ Merchant AM, Kawasaki Y, Chen Y, Lei M, Tye BK (June 1997). "A lesion in the DNA replication initiation factor Mcm10 induces pausing of elongation forks through chromosomal replication origins in Saccharomyces cerevisiae". Molecular and Cellular Biology. 17 (6): 3261–71. doi:10.1128/MCB.17.6.3261. PMC 232179. PMID 9154825.
  11. ^ Homesley L, Lei M, Kawasaki Y, Sawyer S, Christensen T, Tye BK (April 2000). "Mcm10 and the MCM2-7 complex interact to initiate DNA synthesis and to release replication factors from origins". Genes & Development. 14 (8): 913–26. doi:10.1101/gad.14.8.913. PMC 316538. PMID 10783164.
  12. ^ Bell SP, Stillman B (May 1992). "ATP-dependent recognition of eukaryotic origins of DNA replication by a multiprotein complex". Nature. 357 (6374): 128–34. Bibcode:1992Natur.357..128B. doi:10.1038/357128a0. PMID 1579162. S2CID 4346767.
  13. ^ Li N, Lam WH, Zhai Y, Cheng J, Cheng E, Zhao Y, Gao N, Tye BK (July 2018). "Structure of the origin recognition complex bound to DNA replication origin". Nature. 559 (7713): 217–222. Bibcode:2018Natur.559..217L. doi:10.1038/s41586-018-0293-x. PMID 29973722. S2CID 49577101.
  14. ^ Diffley JF, Cocker JH, Dowell SJ, Harwood J, Rowley A (1995). "Stepwise assembly of initiation complexes at budding yeast replication origins during the cell cycle". Journal of Cell Science. Supplement. 19: 67–72. doi:10.1242/jcs.1995.supplement_19.9. PMID 8655649.
  15. ^ Ticau S, Friedman LJ, Ivica NA, Gelles J, Bell SP (April 2015). "Single-molecule studies of origin licensing reveal mechanisms ensuring bidirectional helicase loading". Cell. 161 (3): 513–525. doi:10.1016/j.cell.2015.03.012. PMC 4445235. PMID 25892223.
  16. ^ Coster G, Diffley JF (July 2017). "Bidirectional eukaryotic DNA replication is established by quasi-symmetrical helicase loading". Science. 357 (6348): 314–318. Bibcode:2017Sci...357..314C. doi:10.1126/science.aan0063. PMC 5608077. PMID 28729513.
  17. ^ Frigola J, He J, Kinkelin K, Pye VE, Renault L, Douglas ME, Remus D, Cherepanov P, Costa A, Diffley JF (June 2017). "Cdt1 stabilizes an open MCM ring for helicase loading". Nature Communications. 8: 15720. Bibcode:2017NatCo...815720F. doi:10.1038/ncomms15720. PMC 5490006. PMID 28643783.
  18. ^ Ticau S, Friedman LJ, Champasa K, Corrêa IR, Gelles J, Bell SP (March 2017). "Mechanism and timing of Mcm2-7 ring closure during DNA replication origin licensing". Nature Structural & Molecular Biology. 24 (3): 309–315. doi:10.1038/nsmb.3375. PMC 5336523. PMID 28191892.
  19. ^ Yuan Z, Riera A, Bai L, Sun J, Nandi S, Spanos C, Chen ZA, Barbon M, Rappsilber J, Stillman B, Speck C, Li H (March 2017). "Structural basis of Mcm2-7 replicative helicase loading by ORC-Cdc6 and Cdt1". Nature Structural & Molecular Biology. 24 (3): 316–324. doi:10.1038/nsmb.3372. PMC 5503505. PMID 28191893.
  20. ^ Zhai Y, Li N, Jiang H, Huang X, Gao N, Tye BK (July 2017). "Unique Roles of the Non-identical MCM Subunits in DNA Replication Licensing". Molecular Cell. 67 (2): 168–179. doi:10.1016/j.molcel.2017.06.016. PMID 28732205.
  21. ^ Randell JC, Bowers JL, Rodríguez HK, Bell SP (January 2006). "Sequential ATP hydrolysis by Cdc6 and ORC directs loading of the Mcm2-7 helicase". Molecular Cell. 21 (1): 29–39. doi:10.1016/j.molcel.2005.11.023. PMID 16387651.
  22. ^ Tye BK (May 1994). "The MCM2-3-5 proteins: are they replication licensing factors?". Trends in Cell Biology. 4 (5): 160–6. doi:10.1016/0962-8924(94)90200-3. PMID 14731643.
  23. ^ Thömmes P, Kubota Y, Takisawa H, Blow JJ (June 1997). "The RLF-M component of the replication licensing system forms complexes containing all six MCM/P1 polypeptides". The EMBO Journal. 16 (11): 3312–9. doi:10.1093/emboj/16.11.3312. PMC 1169947. PMID 9214646.
  24. ^ Kamimura Y, Tak YS, Sugino A, Araki H (April 2001). "Sld3, which interacts with Cdc45 (Sld4), functions for chromosomal DNA replication in Saccharomyces cerevisiae". The EMBO Journal. 20 (8): 2097–107. doi:10.1093/emboj/20.8.2097. PMC 125422. PMID 11296242.
  25. ^ Tada S, Blow JJ (August 1998). "The replication licensing system". Biological Chemistry. 379 (8–9): 941–9. doi:10.1515/bchm.1998.379.8-9.941. PMC 3604913. PMID 9792427.
  26. ^ a b Neves H, Kwok HF (August 2017). "In sickness and in health: The many roles of the minichromosome maintenance proteins". Biochimica et Biophysica Acta (BBA) - Reviews on Cancer. 1868 (1): 295–308. doi:10.1016/j.bbcan.2017.06.001. PMID 28579200.
  27. ^ a b Katou Y, Kanoh Y, Bando M, Noguchi H, Tanaka H, Ashikari T, Sugimoto K, Shirahige K (August 2003). "S-phase checkpoint proteins Tof1 and Mrc1 form a stable replication-pausing complex". Nature. 424 (6952): 1078–83. Bibcode:2003Natur.424.1078K. doi:10.1038/nature01900. PMID 12944972. S2CID 4330982.
  28. ^ Liu W, Pucci B, Rossi M, Pisani FM, Ladenstein R (June 2008). "Structural analysis of the Sulfolobus solfataricus MCM protein N-terminal domain". Nucleic Acids Research. 36 (10): 3235–43. doi:10.1093/nar/gkn183. PMC 2425480. PMID 18417534.
  29. ^ Brewster AS, Chen XS (June 2010). "Insights into the MCM functional mechanism: lessons learned from the archaeal MCM complex". Critical Reviews in Biochemistry and Molecular Biology. 45 (3): 243–56. doi:10.3109/10409238.2010.484836. PMC 2953368. PMID 20441442.
  30. ^ Barry ER, McGeoch AT, Kelman Z, Bell SD (2007-02-01). "Archaeal MCM has separable processivity, substrate choice and helicase domains". Nucleic Acids Research. 35 (3): 988–98. doi:10.1093/nar/gkl1117. PMC 1807962. PMID 17259218.
  31. ^ Georgescu, Roxana; Yuan, Zuanning; Bai, Lin; de Luna Almeida Santos, Ruda; Sun, Jingchuan; Zhang, Dan; Yurieva, Olga; Li, Huilin; O’Donnell, Michael E. (31 January 2017). "Structure of eukaryotic CMG helicase at a replication fork and implications to replisome architecture and origin initiation". Proceedings of the National Academy of Sciences. 114 (5): E697–E706. doi:10.1073/pnas.1620500114. PMC 5293012. PMID 28096349.
  32. ^ Patel SS, Picha KM (2000-06-01). "Structure and function of hexameric helicases". Annual Review of Biochemistry. 69 (1): 651–97. doi:10.1146/annurev.biochem.69.1.651. PMID 10966472.
  33. ^ Laskey RA, Madine MA (January 2003). "A rotary pumping model for helicase function of MCM proteins at a distance from replication forks". EMBO Reports. 4 (1): 26–30. doi:10.1038/sj.embor.embor706. PMC 1315806. PMID 12524516.
  34. ^ Gonzalez MA, Pinder SE, Callagy G, Vowler SL, Morris LS, Bird K, Bell JA, Laskey RA, Coleman N (December 2003). "Minichromosome maintenance protein 2 is a strong independent prognostic marker in breast cancer". Journal of Clinical Oncology. 21 (23): 4306–13. doi:10.1200/jco.2003.04.121. PMID 14645419.
  35. ^ Guan B, Wang X, Yang J, Zhou C, Meng Y (August 2015). "Minichromosome maintenance complex component 7 has an important role in the invasion of papillary urothelial neoplasia". Oncology Letters. 10 (2): 946–950. doi:10.3892/ol.2015.3333. PMC 4509410. PMID 26622601.
  36. ^ Cortez D, Glick G, Elledge SJ (July 2004). "Minichromosome maintenance proteins are direct targets of the ATM and ATR checkpoint kinases". Proceedings of the National Academy of Sciences of the United States of America. 101 (27): 10078–83. doi:10.1073/pnas.0403410101. PMC 454167. PMID 15210935.

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MCM P-loop domain Provide feedback

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Literature references

  1. Koonin EV; , Nucleic Acids Res 1993;21:2541-2547.: A common set of conserved motifs in a vast variety of putative nucleic acid-dependent ATPases including MCM proteins involved in the initiation of eukaryotic DNA replication. PUBMED:8332451 EPMC:8332451

Internal database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001208

Proteins shown to be required for the initiation of eukaryotic DNA replication share a highly conserved domain of about 210 amino-acid residues [ PUBMED:1454522 , PUBMED:8265339 , PUBMED:14731643 ]. The latter shows some similarities [ PUBMED:8332451 ] with that of various other families of DNA-dependent ATPases. Eukaryotes seem to possess a family of eight proteins that contain this domain. They were first identified in yeast where most of them have a direct role in the initiation of chromosomal DNA replication by interacting directly with autonomously replicating sequences (ARS). They were thus called 'minichromosome maintenance proteins' with gene symbols prefixed by MCM. These six proteins are:

  • MCM2, also known as cdc19 (in S.pombe).
  • MCM3, also known as DNA polymerase alpha holoenzyme-associated protein P1, RLF beta subunit or ROA.
  • MCM4, also known as CDC54, cdc21 (in S.pombe) or dpa (in Drosophila).
  • MCM5, also known as CDC46 or nda4 (in S.pombe).
  • MCM6, also known as mis5 (in S.pombe).
  • MCM7, also known as CDC47 or Prolifera (in A.thaliana).
  • MCM8, also known as as REC (in Drosophila).
  • MCM

These proteins are evolutionarily related and belong to the AAA+ superfamily. They contain the Mcm family domain, which includes motifs that are required for ATP hydrolysis (such as the Walker A and B, and R-finger motifs). Mcm2-7 forms a hexameric complex which is the replicative helicase involved in replication initiation and elongation, whereas Mcm8 and Mcm9 from and separate one, conserved among many eukaryotes except yeast and C. elegans. Mcm8/9 complex play a role during replication elongation or recombination, being involved in the repair of double-stranded DNA breaks and DNA interstrand cross-links by homologous recombination. Drosophila is the only organism that has MCM8 without MCM9, involved in meiotic recombination [ PUBMED:22771115 , PUBMED:30743181 ].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan P-loop_NTPase (CL0023), which has the following description:

AAA family proteins often perform chaperone-like functions that assist in the assembly, operation, or disassembly of protein complexes [2].

The clan contains the following 245 members:

6PF2K AAA AAA-ATPase_like AAA_10 AAA_11 AAA_12 AAA_13 AAA_14 AAA_15 AAA_16 AAA_17 AAA_18 AAA_19 AAA_2 AAA_21 AAA_22 AAA_23 AAA_24 AAA_25 AAA_26 AAA_27 AAA_28 AAA_29 AAA_3 AAA_30 AAA_31 AAA_32 AAA_33 AAA_34 AAA_35 AAA_5 AAA_6 AAA_7 AAA_8 AAA_9 AAA_PrkA ABC_ATPase ABC_tran ABC_tran_Xtn Adeno_IVa2 Adenylsucc_synt ADK AFG1_ATPase AIG1 APS_kinase Arf ArsA_ATPase ATP-synt_ab ATP_bind_1 ATP_bind_2 ATPase ATPase_2 Bac_DnaA BCA_ABC_TP_C Beta-Casp bpMoxR BrxC_BrxD BrxL_ATPase Cas_Csn2 Cas_St_Csn2 CbiA CBP_BcsQ CDC73_C CENP-M CFTR_R CLP1_P CMS1 CoaE CobA_CobO_BtuR CobU cobW CPT CSM2 CTP_synth_N Cytidylate_kin Cytidylate_kin2 DAP3 DEAD DEAD_2 divDNAB DLIC DNA_pack_C DNA_pack_N DNA_pol3_delta DNA_pol3_delta2 DnaB_C dNK DO-GTPase1 DO-GTPase2 DUF1611 DUF2075 DUF2326 DUF2478 DUF257 DUF2813 DUF3584 DUF463 DUF4914 DUF5906 DUF6079 DUF815 DUF835 DUF87 DUF927 Dynamin_N Dynein_heavy Elong_Iki1 ELP6 ERCC3_RAD25_C Exonuc_V_gamma FeoB_N Fer4_NifH Flavi_DEAD FTHFS FtsK_SpoIIIE G-alpha Gal-3-0_sulfotr GBP GBP_C GpA_ATPase GpA_nuclease GTP_EFTU Gtr1_RagA Guanylate_kin GvpD_P-loop HDA2-3 Helicase_C Helicase_C_2 Helicase_C_4 Helicase_RecD HerA_C Herpes_Helicase Herpes_ori_bp Herpes_TK HydF_dimer HydF_tetramer Hydin_ADK IIGP IPPT IPT iSTAND IstB_IS21 KAP_NTPase KdpD Kinase-PPPase Kinesin KTI12 LAP1_C LpxK MCM MeaB MEDS Mg_chelatase Microtub_bd MipZ MMR_HSR1 MMR_HSR1_C MobB MukB Mur_ligase_M MutS_V Myosin_head NACHT NAT_N NB-ARC NOG1 NTPase_1 NTPase_P4 ORC3_N P-loop_TraG ParA Parvo_NS1 PAXNEB PduV-EutP PhoH PIF1 Ploopntkinase1 Ploopntkinase2 Ploopntkinase3 Podovirus_Gp16 Polyoma_lg_T_C Pox_A32 PPK2 PPV_E1_C PRK PSY3 Rad17 Rad51 Ras RecA ResIII RHD3_GTPase RhoGAP_pG1_pG2 RHSP RNA12 RNA_helicase Roc RsgA_GTPase RuvB_N SbcC_Walker_B SecA_DEAD Senescence Septin Sigma54_activ_2 Sigma54_activat SKI SMC_N SNF2-rel_dom SpoIVA_ATPase Spore_III_AA SRP54 SRPRB SulA Sulfotransfer_1 Sulfotransfer_2 Sulfotransfer_3 Sulfotransfer_4 Sulfotransfer_5 Sulphotransf SWI2_SNF2 T2SSE T4SS-DNA_transf TerL_ATPase Terminase_3 Terminase_6N Thymidylate_kin TIP49 TK TmcA_N TniB Torsin TraG-D_C tRNA_lig_kinase TrwB_AAD_bind TsaE UvrB UvrD-helicase UvrD_C UvrD_C_2 Viral_helicase1 VirC1 VirE YqeC Zeta_toxin Zot


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HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...


This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Prosite
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A , Finn RD
Number in seed: 56
Number in full: 14799
Average length of the domain: 205.40 aa
Average identity of full alignment: 48 %
Average coverage of the sequence by the domain: 26.65 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 23.3 23.3
Trusted cut-off 23.3 23.3
Noise cut-off 23.2 23.2
Model length: 224
Family (HMM) version: 26
Download: download the raw HMM for this family

Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

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Tree controls


The tree shows the occurrence of this domain across different species. More...


Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.


For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the MCM domain has been found. There are 237 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A0E4AYA7 View 3D Structure Click here
A0A0G2JY07 View 3D Structure Click here
A0A0R0F0P6 View 3D Structure Click here
A0A0R0GCD2 View 3D Structure Click here
A0A0R0J881 View 3D Structure Click here
A0A0R0L4I2 View 3D Structure Click here
A0A0R4IF39 View 3D Structure Click here
A0A0R4IF65 View 3D Structure Click here
A0A1D6F7C9 View 3D Structure Click here
A0A1D6FJ71 View 3D Structure Click here
A0A1D6FQ79 View 3D Structure Click here
A0A1D6FQT3 View 3D Structure Click here
A0A1D6FS08 View 3D Structure Click here
A0A1D6FSB6 View 3D Structure Click here
A0A1D6GII1 View 3D Structure Click here
A0A1D6HNE6 View 3D Structure Click here
A0A1D6JPN1 View 3D Structure Click here
A0A1D6LVG2 View 3D Structure Click here
A0A1D6LVG7 View 3D Structure Click here
A0A1D6M0G4 View 3D Structure Click here
A0A1D6M2M5 View 3D Structure Click here
A0A1D6MRL0 View 3D Structure Click here
A0A1D6MX99 View 3D Structure Click here
A0A1D6N7R2 View 3D Structure Click here
A0A1D6NMY4 View 3D Structure Click here
A0A1D6PT01 View 3D Structure Click here
A0A1D6QC12 View 3D Structure Click here
A0A1D8PFE6 View 3D Structure Click here
A0A1D8PHW4 View 3D Structure Click here
A0A1D8PIE7 View 3D Structure Click here
A0A1D8PS48 View 3D Structure Click here
A4FUD9 View 3D Structure Click here
A4HSF2 View 3D Structure Click here
A4HTX2 View 3D Structure Click here
A4I0T0 View 3D Structure Click here
A4I3G2 View 3D Structure Click here
A4I3W9 View 3D Structure Click here
A4I8B8 View 3D Structure Click here
A4I9B0 View 3D Structure Click here
A4IC27 View 3D Structure Click here