Seroatlas · Human Serome Atlas

MARCHF4

E3 ubiquitin-protein ligase MARCHF4

Also known as: KIAA1399, MARCH-IV, MARCH4, MARH4_HUMAN, RNF174

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

Protein identityUniProt · HPA

UniProt accession
Q9P2E8
Gene
MARCHF4
Ensembl
ENSG00000144583
Chromosome
2
Canonical length
410 aa
Protein class
Enzymes, Metabolic proteins, Predicted membrane proteins

OverviewNCBI Gene

MARCH4 is a member of the MARCH family of membrane-bound E3 ubiquitin ligases (EC 6.3.2.19). MARCH enzymes add ubiquitin (see MIM 191339) to target lysines in substrate proteins, thereby signaling their vesicular transport between membrane compartments. MARCH4 reduces surface accumulation of several membrane glycoproteins by directing them to the endosomal compartment (Bartee et al., 2004 [PubMed 14722266]).[supplied by OMIM, Apr 2010]

Canonical amino-acid sequenceUniProt

410 residues, UniProt reviewed canonical sequence.

>Q9P2E8|MARCHF4
     1  MLMPLCGLLW WWWCCCSGWY CYGLCAPAPQ MLRHQGLLKC RCRMLFNDLK VFLLRRPPQA
    61  PLPMHGDPQP PGLAANNTLP ALGAGGWAGW RGPREVVGRE PPPVPPPPPL PPSSVEDDWG
   121  GPATEPPASL LSSASSDDFC KEKTEDRYSL GSSLDSGMRT PLCRICFQGP EQGELLSPCR
   181  CDGSVKCTHQ PCLIKWISER GCWSCELCYY KYHVIAISTK NPLQWQAISL TVIEKVQVAA
   241  AILGSLFLIA SISWLIWSTF SPSARWQRQD LLFQICYGMY GFMDVVCIGL IIHEGPSVYR
   301  IFKRWQAVNQ QWKVLNYDKT KDLEDQKAGG RTNPRTSSST QANIPSSEEE TAGTPAPEQG
   361  PAQAAGHPSG PLSHHHCAYT ILHILSHLRP HEQRSPPGSS RELVMRVTTV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MARCHF4 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
Other membrane
Secreted
No
Transmembrane segments
2
Mean surface accessibility (rSASA)
0.55
Highest tissue expression
7.2 nTPM

Expression across tissuesHPA

Tissue

  • basal ganglia: 7.2 nTPM
  • cerebral cortex: 5.5 nTPM
  • pituitary gland: 5.3 nTPM
  • amygdala: 4.7 nTPM
  • hippocampal formation: 4.1 nTPM
  • hypothalamus: 3.9 nTPM

Single-cell type

  • gonadotrophs: 183 nCPM
  • thyrotrophs: 144 nCPM
  • lactotrophs: 120 nCPM
  • brain inhibitory neurons: 102 nCPM
  • neuroendocrine cells: 97 nCPM
  • other brain neurons: 92 nCPM

Immune cell

  • basophil: 0 nTPM
  • classical monocyte: 0 nTPM
  • eosinophil: 0 nTPM
  • gdT-cell: 0 nTPM
  • intermediate monocyte: 0 nTPM
  • MAIT T-cell: 0 nTPM

Brain region

  • cerebral cortex: 17 nTPM
  • midbrain: 17 nTPM
  • basal ganglia: 16 nTPM
  • hippocampal formation: 13 nTPM
  • amygdala: 13 nTPM
  • hypothalamus: 12 nTPM

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)
0.57
gnomAD pLI
0.13
DepMap mean gene effect
-0.16
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% 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

KeywordsUniProt

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads MARCHF4 as an antibody target. Whether an autoantibody or antibody against MARCHF4 could matter depends on whether native MARCHF4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

MARCHF4 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 MARCHF4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/MARCHF4. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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