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62  structures 732  species 0  interactions 5047  sequences 104  architectures

Family: MCM (PF00493)

Summary: MCM2/3/5 family

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

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

Minichromosome maintenance Edit Wikipedia article

MCM2/3/5 family
PDB 1ltl EBI.jpg
Structure of MCM from archaeal M. Thermoautotrophicum.[1]
Identifiers
Symbol MCM
Pfam PF00493
Pfam clan CL0023
InterPro IPR001208
SMART SM00350
PROSITE PDOC00662
Potential role of Cdc6 at the initiation of DNA replication.[2]

Minichromosome maintenance protein complex (MCM) is a eukaryotic DNA helicase complex required for the process of DNA replication, specifically the formation and elongation of the replication fork. It is a hexamer of six related polypeptides (MCM2 through MCM7) that form a ring structure.[3][4][5] MCM is a component of the pre-replication complex that forms at the eukryotic origin of replication.

Control of MCM activity in the cell is partly achieved by its sumoylation. During cell cycle levels of chromatin-bound MCM sumoylation oscillate, loss of MCM sumoylation occurs immediately before DNA replication[6] Increased expression level of MCM proteins is observed in cells of different cancer types. MCMs could be useful markers of cancer cell proliferation[7][8].

See also

References

  1. ^ Fletcher RJ, Bishop BE, Leon RP, Sclafani RA, Ogata CM, Chen XS (March 2003). "The structure and function of MCM from archaeal M. Thermoautotrophicum". Nat. Struct. Biol. 10 (3): 160–7. doi:10.1038/nsb893. PMID 12548282. 
  2. ^ Borlado LR, Méndez J (February 2008). "CDC6: from DNA replication to cell cycle checkpoints and oncogenesis". Carcinogenesis 29 (2): 237–43. doi:10.1093/carcin/bgm268. PMID 18048387. 
  3. ^ a b Cortez D, Glick G, Elledge SJ (July 2004). "Minichromosome maintenance proteins are direct targets of the ATM and ATR checkpoint kinases". Proc. Natl. Acad. Sci. U.S.A. 101 (27): 10078–83. doi:10.1073/pnas.0403410101. PMC 454167. PMID 15210935. 
  4. ^ Carpentieri F, De Felice M, De Falco M, Rossi M, Pisani FM (April 2002). "Physical and functional interaction between the mini-chromosome maintenance-like DNA helicase and the single-stranded DNA binding protein from the crenarchaeon Sulfolobus solfataricus". J. Biol. Chem. 277 (14): 12118–27. doi:10.1074/jbc.M200091200. PMID 11821426. 
  5. ^ Brewster, Aaron; Chen, Xiaojiang (June 2010). "Insights into MCM functional mechanism: lessons learned from the archaeal MCM complex". Crit Rev Biochem Mol Biol 45 (3): 243–256. doi:10.3109/10409238.2010.484836. PMC 2953368. PMID 20441442. 
  6. ^ Baumann, Kim (2016). "DNA replication: SUMO wrestling to get the timing right". Nature Reviews Molecular Cell Biology 17 (3): 134–135. doi:10.1038/nrm.2016.15. ISSN 1471-0072. 
  7. ^ Valverde, Ludmila de F.; de Freitas, Raíza D.; Pereira, Thiago de A.; de Resende, Marina F.; Agra, Ivan M. G.; Dos Santos, Jean N.; Dos Reis, Mitermayer G.; Sales, Caroline B. S.; Gurgel Rocha, Clarissa A. (2016-06-02). "MCM3: A Novel Proliferation Marker in Oral Squamous Cell Carcinoma". Applied immunohistochemistry & molecular morphology: AIMM / official publication of the Society for Applied Immunohistochemistry. doi:10.1097/PAI.0000000000000397. ISSN 1533-4058. PMID 27258565. 
  8. ^ Nowinska, Katarzyna; Chmielewska, Magdalena; Piotrowska, Aleksandra; Pula, Bartosz; Pastuszewski, Wojciech; Krecicki, Tomasz; Podhorska-Okołow, Marzena; Zabel, Maciej; Dziegiel, Piotr (2016-02-01). "Correlation between levels of expression of minichromosome maintenance proteins, Ki-67 proliferation antigen and metallothionein I/II in laryngeal squamous cell cancer". International Journal of Oncology 48 (2): 635–645. doi:10.3892/ijo.2015.3273. ISSN 1791-2423. PMID 26648405. 

External links


This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

MCM2/3/5 family Provide feedback

No Pfam abstract.

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

External 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 six 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).

The presence of a putative ATP-binding domain implies that these proteins may be involved in an ATP-consuming step in the initiation of DNA replication in eukaryotes.

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 199 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_PrkA ABC_ATPase ABC_tran Adeno_IVa2 Adenylsucc_synt ADK AFG1_ATPase AIG1 APS_kinase Arf ArgK ArsA_ATPase ATP-synt_ab ATP_bind_1 ATP_bind_2 ATPase ATPase_2 Bac_DnaA CbiA CBP_BcsQ CDC73_C CLP1_P CMS1 CoaE CobA_CobO_BtuR CobU cobW CPT CTP_synth_N Cytidylate_kin Cytidylate_kin2 DAP3 DEAD DEAD_2 DLIC DNA_pack_C DNA_pack_N DNA_pol3_delta DNA_pol3_delta2 DnaB_C dNK DUF1611 DUF2075 DUF2326 DUF2478 DUF258 DUF2791 DUF2813 DUF3584 DUF463 DUF815 DUF853 DUF87 DUF927 Dynamin_N ERCC3_RAD25_C Exonuc_V_gamma FeoB_N Fer4_NifH Flavi_DEAD FTHFS FtsK_SpoIIIE G-alpha Gal-3-0_sulfotr GBP GTP_EFTU Gtr1_RagA Guanylate_kin GvpD HDA2-3 Helicase_C Helicase_C_2 Helicase_C_4 Helicase_RecD Herpes_Helicase Herpes_ori_bp Herpes_TK Hydin_ADK IIGP IPPT IPT IstB_IS21 KAP_NTPase KdpD Kinesin KTI12 Lon_2 LpxK MCM MEDS Mg_chelatase Microtub_bd MipZ MMR_HSR1 MobB MukB MutS_V Myosin_head NACHT NB-ARC NOG1 NTPase_1 NTPase_P4 ParA Parvo_NS1 PAXNEB PduV-EutP PhoH PIF1 Podovirus_Gp16 Polyoma_lg_T_C Pox_A32 PPK2 PPV_E1_C PRK Rad17 Rad51 Ras RecA ResIII RHD3 RHSP RNA12 RNA_helicase Roc RuvB_N SbcCD_C SecA_DEAD Septin Sigma54_activ_2 Sigma54_activat SKI SMC_N SNF2_N Spore_IV_A SRP54 SRPRB SulA Sulfotransfer_1 Sulfotransfer_2 Sulfotransfer_3 Sulphotransf T2SSE T4SS-DNA_transf Terminase_1 Terminase_3 Terminase_6 Terminase_GpA Thymidylate_kin TIP49 TK TniB Torsin TraG-D_C tRNA_lig_kinase TrwB_AAD_bind TsaE UvrD-helicase UvrD_C UvrD_C_2 Viral_helicase1 VirC1 VirE Zeta_toxin Zot

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(58)
Full
(5047)
Representative proteomes UniProt
(12448)
NCBI
(26224)
Meta
(815)
RP15
(1541)
RP35
(2874)
RP55
(4083)
RP75
(5098)
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PP/heatmap 1                

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  Seed
(58)
Full
(5047)
Representative proteomes UniProt
(12448)
NCBI
(26224)
Meta
(815)
RP15
(1541)
RP35
(2874)
RP55
(4083)
RP75
(5098)
Alignment:
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Sequence:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(58)
Full
(5047)
Representative proteomes UniProt
(12448)
NCBI
(26224)
Meta
(815)
RP15
(1541)
RP35
(2874)
RP55
(4083)
RP75
(5098)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

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...

Trees

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
Author: Bateman A, Finn RD
Number in seed: 58
Number in full: 5047
Average length of the domain: 303.00 aa
Average identity of full alignment: 41 %
Average coverage of the sequence by the domain: 40.86 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 17690987 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.2 25.2
Trusted cut-off 25.2 25.2
Noise cut-off 25.1 25.1
Model length: 331
Family (HMM) version: 21
Download: download the raw HMM for this family

Species distribution

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

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Structures

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 62 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 seqence.

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