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Protein

DNA replication licensing factor MCM4

Gene

MCM4

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.2 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.Curated

Catalytic activityi

ATP + H2O = ADP + phosphate.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi510 – 517ATPSequence analysis8

GO - Molecular functioni

GO - Biological processi

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.
SIGNORiP33991.

Names & Taxonomyi

Protein namesi
Recommended name:
DNA replication licensing factor MCM4 (EC:3.6.4.12)
Alternative name(s):
CDC21 homolog
P1-CDC21
Gene namesi
Name:MCM4
Synonyms:CDC21
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:6947. MCM4.

Subcellular locationi

GO - Cellular componenti

  • MCM complex Source: UniProtKB
  • membrane Source: UniProtKB
  • nuclear chromosome, telomeric region Source: BHF-UCL
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Natural killer cell and glucocorticoid deficiency with DNA repair defect (NKGCD)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive disorder characterized by severe intra- and extrauterine growth retardation, microcephaly, decreased numbers of natural killer cells, and recurrent viral infections, most often affecting the respiratory tract and leading to respiratory failure. Affected individuals also have adrenal insufficiency requiring corticosteroid replacement therapy and may have an increased susceptibility to cancer.
See also OMIM:609981

Organism-specific databases

DisGeNETi4173.
MalaCardsiMCM4.
MIMi609981. phenotype.
OpenTargetsiENSG00000104738.
Orphaneti75391. Immunodeficiency with natural-killer cell deficiency and adrenal insufficiency.
PharmGKBiPA30694.

Polymorphism and mutation databases

BioMutaiMCM4.
DMDMi68571766.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001941012 – 863DNA replication licensing factor MCM4Add BLAST862

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1
Modified residuei19PhosphothreonineBy similarity1
Modified residuei26PhosphoserineCombined sources1
Modified residuei31PhosphoserineCombined sources1
Modified residuei32PhosphoserineCombined sources1
Modified residuei34PhosphoserineCombined sources1
Modified residuei102PhosphothreonineCombined sources1
Modified residuei105PhosphoserineCombined sources1
Modified residuei110PhosphothreonineCombined sources1
Modified residuei120PhosphoserineCombined sources1
Modified residuei131PhosphoserineCombined sources1
Modified residuei142PhosphoserineCombined sources1
Modified residuei145PhosphoserineCombined sources1
Modified residuei220N6-acetyllysineCombined sources1
Cross-linki439Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei450N6-acetyllysineCombined sources1
Cross-linki798Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei858N6-acetyllysineBy similarity1

Post-translational modificationi

Sumoylated; SUMO2 modified in response to stress caused by inhibition of proteasome activity (in vitro).By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP33991.
MaxQBiP33991.
PaxDbiP33991.
PeptideAtlasiP33991.
PRIDEiP33991.
TopDownProteomicsiP33991.

PTM databases

iPTMnetiP33991.
PhosphoSitePlusiP33991.
SwissPalmiP33991.

Miscellaneous databases

PMAP-CutDBiP33991.

Expressioni

Gene expression databases

BgeeiENSG00000104738.
CleanExiHS_MCM4.
ExpressionAtlasiP33991. baseline and differential.
GenevisibleiP33991. HS.

Organism-specific databases

HPAiCAB004497.
HPA004873.
HPA031052.

Interactioni

Subunit structurei

Component of the MCM2-7 complex (PubMed:9305914, PubMed:16899510). The complex forms a toroidal hexameric ring with the proposed subunit order MCM2-MCM6-MCM4-MCM7-MCM3-MCM5 (Probable). Interacts with MCMBP (PubMed:17296731).Curated3 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi110341. 96 interactors.
DIPiDIP-31729N.
IntActiP33991. 67 interactors.
MINTiMINT-1202120.
STRINGi9606.ENSP00000262105.

Structurei

3D structure databases

ProteinModelPortaliP33991.
SMRiP33991.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini458 – 667MCMAdd BLAST210

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi642 – 645Arginine finger4

Sequence similaritiesi

Belongs to the MCM family.Curated

Phylogenomic databases

eggNOGiKOG0478. Eukaryota.
COG1241. LUCA.
GeneTreeiENSGT00880000137967.
HOGENOMiHOG000224127.
HOVERGENiHBG102781.
InParanoidiP33991.
KOiK02212.
OMAiKNTIRIC.
OrthoDBiEOG091G02V8.
PhylomeDBiP33991.
TreeFamiTF300463.

Family and domain databases

InterProiView protein in InterPro
IPR031327. MCM.
IPR008047. MCM_4.
IPR018525. MCM_CS.
IPR001208. MCM_dom.
IPR027925. MCM_N.
IPR033762. MCM_OB.
IPR012340. NA-bd_OB-fold.
IPR027417. P-loop_NTPase.
PfamiView protein in Pfam
PF00493. MCM. 1 hit.
PF14551. MCM_N. 1 hit.
PF17207. MCM_OB. 1 hit.
PRINTSiPR01657. MCMFAMILY.
PR01660. MCMPROTEIN4.
SMARTiView protein in SMART
SM00350. MCM. 1 hit.
SUPFAMiSSF50249. SSF50249. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEiView protein in PROSITE
PS00847. MCM_1. 1 hit.
PS50051. MCM_2. 1 hit.

Sequencei

Sequence statusi: Complete.

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

P33991-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSSPASTPSR RGSRRGRATP AQTPRSEDAR SSPSQRRRGE DSTSTGELQP
60 70 80 90 100
MPTSPGVDLQ SPAAQDVLFS SPPQMHSSAI PLDFDVSSPL TYGTPSSRVE
110 120 130 140 150
GTPRSGVRGT PVRQRPDLGS AQKGLQVDLQ SDGAAAEDIV ASEQSLGQKL
160 170 180 190 200
VIWGTDVNVA ACKENFQRFL QRFIDPLAKE EENVGIDITE PLYMQRLGEI
210 220 230 240 250
NVIGEPFLNV NCEHIKSFDK NLYRQLISYP QEVIPTFDMA VNEIFFDRYP
260 270 280 290 300
DSILEHQIQV RPFNALKTKN MRNLNPEDID QLITISGMVI RTSQLIPEMQ
310 320 330 340 350
EAFFQCQVCA HTTRVEMDRG RIAEPSVCGR CHTTHSMALI HNRSLFSDKQ
360 370 380 390 400
MIKLQESPED MPAGQTPHTV ILFAHNDLVD KVQPGDRVNV TGIYRAVPIR
410 420 430 440 450
VNPRVSNVKS VYKTHIDVIH YRKTDAKRLH GLDEEAEQKL FSEKRVELLK
460 470 480 490 500
ELSRKPDIYE RLASALAPSI YEHEDIKKGI LLQLFGGTRK DFSHTGRGKF
510 520 530 540 550
RAEINILLCG DPGTSKSQLL QYVYNLVPRG QYTSGKGSSA VGLTAYVMKD
560 570 580 590 600
PETRQLVLQT GALVLSDNGI CCIDEFDKMN ESTRSVLHEV MEQQTLSIAK
610 620 630 640 650
AGIICQLNAR TSVLAAANPI ESQWNPKKTT IENIQLPHTL LSRFDLIFLL
660 670 680 690 700
LDPQDEAYDR RLAHHLVALY YQSEEQAEEE LLDMAVLKDY IAYAHSTIMP
710 720 730 740 750
RLSEEASQAL IEAYVDMRKI GSSRGMVSAY PRQLESLIRL AEAHAKVRLS
760 770 780 790 800
NKVEAIDVEE AKRLHREALK QSATDPRTGI VDISILTTGM SATSRKRKEE
810 820 830 840 850
LAEALKKLIL SKGKTPALKY QQLFEDIRGQ SDIAITKDMF EEALRALADD
860
DFLTVTGKTV RLL
Length:863
Mass (Da):96,558
Last modified:May 10, 2005 - v5
Checksum:i96D9CA2A7D88D015
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti62P → T in CAA52801 (PubMed:7601140).Curated1
Sequence conflicti206P → Q in CAA52801 (PubMed:7601140).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_020500460E → G1 PublicationCorresponds to variant dbSNP:rs17287663Ensembl.1
Natural variantiVAR_020501650L → M3 PublicationsCorresponds to variant dbSNP:rs762679Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X74794 mRNA. Translation: CAA52801.1.
AY588245 Genomic DNA. Translation: AAS83108.1.
BC031061 mRNA. Translation: AAH31061.1.
U63630 Genomic DNA. Translation: AAC52018.1.
U90415 Genomic DNA. Translation: AAB51723.3.
CCDSiCCDS6143.1.
PIRiS65954.
RefSeqiNP_005905.2. NM_005914.3.
NP_877423.1. NM_182746.2.
UniGeneiHs.460184.

Genome annotation databases

EnsembliENST00000262105; ENSP00000262105; ENSG00000104738.
ENST00000523944; ENSP00000430194; ENSG00000104738.
GeneIDi4173.
KEGGihsa:4173.
UCSCiuc003xqk.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiMCM4_HUMAN
AccessioniPrimary (citable) accession number: P33991
Secondary accession number(s): Q8NEH1, Q99658
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: May 10, 2005
Last modified: August 30, 2017
This is version 182 of the entry and version 5 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, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: 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