Seroatlas · Human Serome Atlas

MCM4

DNA replication licensing factor MCM4

Also known as: CDC21, CDC54, hCdc21, MCM4_HUMAN, MGC33310, P1-Cdc21

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: P33991
Gene: MCM4
Ensembl: ENSG00000104738
Chromosome: 8
Canonical length: 863 aa
Protein class: Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted intracellular proteins
Subcellular location: Nucleoplasm

OverviewNCBI Gene

The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are essential for the initiation of eukaryotic genome replication. The hexameric protein complex formed by MCM proteins is a key component of the pre-replication complex (pre_RC) and may be involved in the formation of replication forks and in the recruitment of other DNA replication related proteins. The MCM complex consisting of this protein and MCM2, 6 and 7 proteins possesses DNA helicase activity, and may act as a DNA unwinding enzyme. The phosphorylation of this protein by CDC2 kinase reduces the DNA helicase activity and chromatin binding of the MCM complex. This gene is mapped to a region on the chromosome 8 head-to-head next to the PRKDC/DNA-PK, a DNA-activated protein kinase involved in the repair of DNA double-strand breaks. Alternatively spliced transcript variants encoding the same protein have been reported. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

863 residues, UniProt reviewed canonical sequence.

>P33991|MCM4
     1  MSSPASTPSR RGSRRGRATP AQTPRSEDAR SSPSQRRRGE DSTSTGELQP MPTSPGVDLQ
    61  SPAAQDVLFS SPPQMHSSAI PLDFDVSSPL TYGTPSSRVE GTPRSGVRGT PVRQRPDLGS
   121  AQKGLQVDLQ SDGAAAEDIV ASEQSLGQKL VIWGTDVNVA ACKENFQRFL QRFIDPLAKE
   181  EENVGIDITE PLYMQRLGEI NVIGEPFLNV NCEHIKSFDK NLYRQLISYP QEVIPTFDMA
   241  VNEIFFDRYP DSILEHQIQV RPFNALKTKN MRNLNPEDID QLITISGMVI RTSQLIPEMQ
   301  EAFFQCQVCA HTTRVEMDRG RIAEPSVCGR CHTTHSMALI HNRSLFSDKQ MIKLQESPED
   361  MPAGQTPHTV ILFAHNDLVD KVQPGDRVNV TGIYRAVPIR VNPRVSNVKS VYKTHIDVIH
   421  YRKTDAKRLH GLDEEAEQKL FSEKRVELLK ELSRKPDIYE RLASALAPSI YEHEDIKKGI
   481  LLQLFGGTRK DFSHTGRGKF RAEINILLCG DPGTSKSQLL QYVYNLVPRG QYTSGKGSSA
   541  VGLTAYVMKD PETRQLVLQT GALVLSDNGI CCIDEFDKMN ESTRSVLHEV MEQQTLSIAK
   601  AGIICQLNAR TSVLAAANPI ESQWNPKKTT IENIQLPHTL LSRFDLIFLL LDPQDEAYDR
   661  RLAHHLVALY YQSEEQAEEE LLDMAVLKDY IAYAHSTIMP RLSEEASQAL IEAYVDMRKI
   721  GSSRGMVSAY PRQLESLIRL AEAHAKVRLS NKVEAIDVEE AKRLHREALK QSATDPRTGI
   781  VDISILTTGM SATSRKRKEE LAEALKKLIL SKGKTPALKY QQLFEDIRGQ SDIAITKDMF
   841  EEALRALADD DFLTVTGKTV RLL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MCM4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Intracellular
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.36
Highest tissue expression: 52 nTPM

Expression across tissuesHPA

Tissue

bone marrow: 52 nTPM
thymus: 43 nTPM
tonsil: 39 nTPM
testis: 38 nTPM
lymph node: 35 nTPM
skin: 22 nTPM

Single-cell type

erythrocyte progenitors: 288 nCPM
early spermatids: 160 nCPM
late primary spermatocytes: 147 nCPM
megakaryocyte progenitors: 134 nCPM
monocyte progenitors: 124 nCPM
late spermatids: 111 nCPM

Immune cell

T-reg: 11 nTPM
memory CD8 T-cell: 5.7 nTPM
memory B-cell: 4.2 nTPM
gdT-cell: 4.1 nTPM
myeloid DC: 4.1 nTPM
NK-cell: 4.1 nTPM

Brain region

cerebellum: 13 nTPM
white matter: 13 nTPM
cerebral cortex: 13 nTPM
basal ganglia: 12 nTPM
hypothalamus: 12 nTPM
medulla oblongata: 12 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about MCM4.

Disease | AllUniProt

Conditions MCM4 is implicated in, by any mechanism.

Immunodeficiency 54 (IMD54) MIM:609981

Disease | GeneticClinVar

3 pathogenic / likely-pathogenic of 748 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Primary immunodeficiency with natural-killer cell deficiency and adrenal insufficiency

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.55
gnomAD pLI: 0
gnomAD missense Z: 0.14
DepMap mean gene effect: -1.28
DepMap dependency class: common

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 10% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

MCM domain
Nucleic acid-binding, OB-fold
Mini-chromosome maintenance, conserved site
P-loop containing nucleoside triphosphate hydrolase
MCM, N-terminal domain
Mini-chromosome maintenance protein
MCM OB domain
MCM, AAA-lid domain
MCM P-loop domain
MCM N-terminal domain
MCM OB domain
MCM AAA-lid domain
DNA replication licensing factor MCM4
MCM4, winged helix domain

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of MCM4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads MCM4 as an antibody target. Whether an autoantibody or antibody against MCM4 could matter depends on whether native MCM4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

MCM4 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label MCM4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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