Seroatlas · Human Serome Atlas

MARCHF6

E3 ubiquitin-protein ligase MARCHF6

Also known as: MARCH-VI, MARCH6, MARH6_HUMAN, RNF176, TEB4

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

Protein identityUniProt · HPA

UniProt accession: O60337
Gene: MARCHF6
Ensembl: ENSG00000145495
Chromosome: 5
Canonical length: 910 aa
Protein class: Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins
Subcellular location: Endoplasmic reticulum

OverviewNCBI Gene

This gene encodes a member of a family of membrane-associated E3 ubiquitin ligases containing RING-CH-type zinc finger motifs. Ubiquitination of type II deiodinase by the encoded protein is an important regulatory step in thyroid hormone signalling. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

Canonical amino-acid sequenceUniProt

910 residues, UniProt reviewed canonical sequence.

>O60337|MARCHF6
     1  MDTAEEDICR VCRSEGTPEK PLYHPCVCTG SIKFIHQECL VQWLKHSRKE YCELCKHRFA
    61  FTPIYSPDMP SRLPIQDIFA GLVTSIGTAI RYWFHYTLVA FAWLGVVPLT ACRIYKCLFT
   121  GSVSSLLTLP LDMLSTENLL ADCLQGCFVV TCTLCAFISL VWLREQIVHG GAPIWLEHAA
   181  PPFNAAGHHQ NEAPAGGNGA ENVAADQPAN PPAENAVVGE NPDAQDDQAE EEEEDNEEED
   241  DAGVEDAADA NNGAQDDMNW NALEWDRAAE ELTWERMLGL DGSLVFLEHV FWVVSLNTLF
   301  ILVFAFCPYH IGHFSLVGLG FEEHVQASHF EGLITTIVGY ILLAITLIIC HGLATLVKFH
   361  RSRRLLGVCY IVVKVSLLVV VEIGVFPLIC GWWLDICSLE MFDATLKDRE LSFQSAPGTT
   421  MFLHWLVGMV YVFYFASFIL LLREVLRPGV LWFLRNLNDP DFNPVQEMIH LPIYRHLRRF
   481  ILSVIVFGSI VLLMLWLPIR IIKSVLPNFL PYNVMLYSDA PVSELSLELL LLQVVLPALL
   541  EQGHTRQWLK GLVRAWTVTA GYLLDLHSYL LGDQEENENS ANQQVNNNQH ARNNNAIPVV
   601  GEGLHAAHQA ILQQGGPVGF QPYRRPLNFP LRIFLLIVFM CITLLIASLI CLTLPVFAGR
   661  WLMSFWTGTA KIHELYTAAC GLYVCWLTIR AVTVMVAWMP QGRRVIFQKV KEWSLMIMKT
   721  LIVAVLLAGV VPLLLGLLFE LVIVAPLRVP LDQTPLFYPW QDWALGVLHA KIIAAITLMG
   781  PQWWLKTVIE QVYANGIRNI DLHYIVRKLA APVISVLLLS LCVPYVIASG VVPLLGVTAE
   841  MQNLVHRRIY PFLLMVVVLM AILSFQVRQF KRLYEHIKND KYLVGQRLVN YERKSGKQGS
   901  SPPPPQSSQE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MARCHF6 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: 14
Mean surface accessibility (rSASA): 0.39
Highest tissue expression: 72 nTPM

Expression across tissuesHPA

Tissue

bone marrow: 72 nTPM
parathyroid gland: 59 nTPM
tongue: 48 nTPM
skeletal muscle: 45 nTPM
cerebral cortex: 40 nTPM
pancreas: 38 nTPM

Single-cell type

neutrophils: 556 nCPM
neutrophil progenitors: 431 nCPM
endometrial ciliated cells: 339 nCPM
ependymal cells: 312 nCPM
pituicytes/fscs: 311 nCPM
enterocytes: 307 nCPM

Immune cell

basophil: 16 nTPM
MAIT T-cell: 13 nTPM
eosinophil: 13 nTPM
naive CD4 T-cell: 13 nTPM
naive CD8 T-cell: 12 nTPM
neutrophil: 12 nTPM

Brain region

white matter: 134 nTPM
hypothalamus: 133 nTPM
cerebellum: 127 nTPM
basal ganglia: 116 nTPM
cerebral cortex: 113 nTPM
thalamus: 111 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about MARCHF6.

Disease | AllUniProt

Conditions MARCHF6 is implicated in, by any mechanism.

Epilepsy, familial adult myoclonic, 3 (FAME3) MIM:613608

Disease | GeneticClinVar

2 pathogenic / likely-pathogenic of 141 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Epilepsy, familial adult myoclonic, 3

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): 0.15
gnomAD pLI: 1
DepMap mean gene effect: -0.25
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 11% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

endoplasmic reticulum
endoplasmic reticulum membrane
endoplasmic reticulum quality control compartment
membrane
ER ubiquitin ligase complex

Protein domainsUniProt · Pfam · InterPro

Zinc finger, RING-CH-type
Zinc finger, RING/FYVE/PHD-type
RING-variant domain
E3 ubiquitin-protein ligase MARCHF6-like, C-terminal domain
E3 ubiquitin-protein ligase MARCHF6-like, C-terminal domain

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of MARCHF6 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 MARCHF6 as an antibody target. Whether an autoantibody or antibody against MARCHF6 could matter depends on whether native MARCHF6 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

MARCHF6 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 MARCHF6 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Loading the interactive Seroatlas protein explorer...