Seroatlas · Human Serome Atlas

DNMT1

DNA (cytosine-5)-methyltransferase 1

Also known as: CXXC9, DNMT, DNMT1_HUMAN, MCMT

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

Protein identityUniProt · HPA

UniProt accession: P26358
Gene: DNMT1
Ensembl: ENSG00000130816
Chromosome: 19
Canonical length: 1616 aa
Protein class: Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins, Transcription factors
Subcellular location: Nucleoplasm
Quaternary structure: Homodimer

OverviewNCBI Gene

This gene encodes an enzyme that transfers methyl groups to cytosine nucleotides of genomic DNA. This protein is the major enzyme responsible for maintaining methylation patterns following DNA replication and shows a preference for hemi-methylated DNA. Methylation of DNA is an important component of mammalian epigenetic gene regulation. Aberrant methylation patterns are found in human tumors and associated with developmental abnormalities. Variation in this gene has been associated with cerebellar ataxia, deafness, and narcolepsy, and neuropathy, hereditary sensory, type IE. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

Canonical amino-acid sequenceUniProt

1616 residues, UniProt reviewed canonical sequence.

>P26358|DNMT1
     1  MPARTAPARV PTLAVPAISL PDDVRRRLKD LERDSLTEKE CVKEKLNLLH EFLQTEIKNQ
    61  LCDLETKLRK EELSEEGYLA KVKSLLNKDL SLENGAHAYN REVNGRLENG NQARSEARRV
   121  GMADANSPPK PLSKPRTPRR SKSDGEAKPE PSPSPRITRK STRQTTITSH FAKGPAKRKP
   181  QEESERAKSD ESIKEEDKDQ DEKRRRVTSR ERVARPLPAE EPERAKSGTR TEKEEERDEK
   241  EEKRLRSQTK EPTPKQKLKE EPDREARAGV QADEDEDGDE KDEKKHRSQP KDLAAKRRPE
   301  EKEPEKVNPQ ISDEKDEDEK EEKRRKTTPK EPTEKKMARA KTVMNSKTHP PKCIQCGQYL
   361  DDPDLKYGQH PPDAVDEPQM LTNEKLSIFD ANESGFESYE ALPQHKLTCF SVYCKHGHLC
   421  PIDTGLIEKN IELFFSGSAK PIYDDDPSLE GGVNGKNLGP INEWWITGFD GGEKALIGFS
   481  TSFAEYILMD PSPEYAPIFG LMQEKIYISK IVVEFLQSNS DSTYEDLINK IETTVPPSGL
   541  NLNRFTEDSL LRHAQFVVEQ VESYDEAGDS DEQPIFLTPC MRDLIKLAGV TLGQRRAQAR
   601  RQTIRHSTRE KDRGPTKATT TKLVYQIFDT FFAEQIEKDD REDKENAFKR RRCGVCEVCQ
   661  QPECGKCKAC KDMVKFGGSG RSKQACQERR CPNMAMKEAD DDEEVDDNIP EMPSPKKMHQ
   721  GKKKKQNKNR ISWVGEAVKT DGKKSYYKKV CIDAETLEVG DCVSVIPDDS SKPLYLARVT
   781  ALWEDSSNGQ MFHAHWFCAG TDTVLGATSD PLELFLVDEC EDMQLSYIHS KVKVIYKAPS
   841  ENWAMEGGMD PESLLEGDDG KTYFYQLWYD QDYARFESPP KTQPTEDNKF KFCVSCARLA
   901  EMRQKEIPRV LEQLEDLDSR VLYYSATKNG ILYRVGDGVY LPPEAFTFNI KLSSPVKRPR
   961  KEPVDEDLYP EHYRKYSDYI KGSNLDAPEP YRIGRIKEIF CPKKSNGRPN ETDIKIRVNK
  1021  FYRPENTHKS TPASYHADIN LLYWSDEEAV VDFKAVQGRC TVEYGEDLPE CVQVYSMGGP
  1081  NRFYFLEAYN AKSKSFEDPP NHARSPGNKG KGKGKGKGKP KSQACEPSEP EIEIKLPKLR
  1141  TLDVFSGCGG LSEGFHQAGI SDTLWAIEMW DPAAQAFRLN NPGSTVFTED CNILLKLVMA
  1201  GETTNSRGQR LPQKGDVEML CGGPPCQGFS GMNRFNSRTY SKFKNSLVVS FLSYCDYYRP
  1261  RFFLLENVRN FVSFKRSMVL KLTLRCLVRM GYQCTFGVLQ AGQYGVAQTR RRAIILAAAP
  1321  GEKLPLFPEP LHVFAPRACQ LSVVVDDKKF VSNITRLSSG PFRTITVRDT MSDLPEVRNG
  1381  ASALEISYNG EPQSWFQRQL RGAQYQPILR DHICKDMSAL VAARMRHIPL APGSDWRDLP
  1441  NIEVRLSDGT MARKLRYTHH DRKNGRSSSG ALRGVCSCVE AGKACDPAAR QFNTLIPWCL
  1501  PHTGNRHNHW AGLYGRLEWD GFFSTTVTNP EPMGKQGRVL HPEQHRVVSV RECARSQGFP
  1561  DTYRLFGNIL DKHRQVGNAV PPPLAKAIGL EIKLCMLAKA RESASAKIKE EEAAKD

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DNMT1 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): 0.34
Highest tissue expression: 24 nTPM

Expression across tissuesHPA

Tissue

lymph node: 24 nTPM
placenta: 24 nTPM
tonsil: 23 nTPM
bone marrow: 22 nTPM
thymus: 19 nTPM
appendix: 16 nTPM

Single-cell type

cytotrophoblasts: 570 nCPM
migrating cytotrophoblasts: 391 nCPM
syncytiotrophoblasts: 382 nCPM
erythrocyte progenitors: 318 nCPM
early primary spermatocytes: 285 nCPM
monocyte progenitors: 257 nCPM

Immune cell

NK-cell: 43 nTPM
plasmacytoid DC: 32 nTPM
gdT-cell: 30 nTPM
naive CD4 T-cell: 26 nTPM
MAIT T-cell: 25 nTPM
memory CD4 T-cell: 23 nTPM

Brain region

cerebellum: 48 nTPM
white matter: 46 nTPM
hypothalamus: 38 nTPM
pons: 34 nTPM
cerebral cortex: 33 nTPM
medulla oblongata: 32 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DNMT1.

Disease | AllUniProt

Conditions DNMT1 is implicated in, by any mechanism.

Neuropathy, hereditary sensory, 1E (HSN1E) MIM:614116
Cerebellar ataxia, deafness, and narcolepsy, autosomal dominant (ADCADN) MIM:604121

Disease | GeneticClinVar

13 pathogenic / likely-pathogenic of 1,731 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Hereditary sensory neuropathy-deafness-dementia syndrome
Autosomal dominant cerebellar ataxia, deafness and narcolepsy
Charcot-Marie-Tooth disease
Inborn genetic diseases
Pituitary stalk interruption syndrome

Disease | ImmuneIEDB

Conditions an epitope on DNMT1 was assayed in.

skin melanoma T cell

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): 0.14
gnomAD pLI: 1
gnomAD missense Z: 4.99
DepMap mean gene effect: -0.74
DepMap dependency class: common

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

DNA (cytosine-5-)-methyltransferase activity
DNA binding
DNA-methyltransferase activity
lncRNA binding
methyl-CpG binding
promoter-specific chromatin binding
zinc ion binding
histone H3K14ub reader activity
histone H3K18ub reader activity
histone H3K23ub reader activity

Cellular components

Protein domainsUniProt · Pfam · InterPro

Bromo adjacent homology (BAH) domain
C-5 cytosine methyltransferase
Zinc finger, CXXC-type
DMAP1-binding domain
DNA methylase, C-5 cytosine-specific, active site
S-adenosyl-L-methionine-dependent methyltransferase superfamily
DNA methylase, C-5 cytosine-specific, conserved site
Bromo adjacent homology (BAH) domain superfamily
DNA Cytosine-5 Methyltransferase
C-5 cytosine-specific DNA methylase
BAH domain
CXXC zinc finger domain
DMAP1-binding Domain
DNA (cytosine-5)-methyltransferase 1, replication foci domain
Cytosine specific DNA methyltransferase replication foci domain

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of DNMT1 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 DNMT1 as an antibody target. Whether an autoantibody or antibody against DNMT1 could matter depends on whether native DNMT1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

DNMT1 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 DNMT1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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