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 e... See more...

Aliases for MARCHF4 Gene

Aliases for MARCHF4 Gene

  • Membrane Associated Ring-CH-Type Finger 4 2 3 5
  • Membrane-Associated Ring Finger (C3HC4) 4, E3 Ubiquitin Protein Ligase 2 3
  • Membrane-Associated RING Finger Protein 4 3 4
  • RING-Type E3 Ubiquitin Transferase MARCH4 3 4
  • Membrane-Associated RING-CH Protein IV 3 4
  • E3 Ubiquitin-Protein Ligase MARCH4 3 4
  • RING Finger Protein 174 3 4
  • MARCH-IV 3 4
  • MARCH4 3 5
  • RNF174 3 4
  • Membrane-Associated Ring Finger (C3HC4) 4 2
  • Membrane Associated Ring Finger 4 3
  • EC 2.3.2.27 4
  • KIAA1399 4

External Ids for MARCHF4 Gene

Previous HGNC Symbols for MARCHF4 Gene

  • MARCH4

Summaries for MARCHF4 Gene

Entrez Gene Summary for MARCHF4 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]

GeneCards Summary for MARCHF4 Gene

MARCHF4 (Membrane Associated Ring-CH-Type Finger 4) is a Protein Coding gene. Diseases associated with MARCHF4 include Frontotemporal Dementia. An important paralog of this gene is MARCHF9.

UniProtKB/Swiss-Prot Summary for MARCHF4 Gene

  • E3 ubiquitin-protein ligase that may mediate ubiquitination of MHC-I and CD4, and promote their subsequent endocytosis and sorting to lysosomes via multivesicular bodies. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates.

Additional gene information for MARCHF4 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for MARCHF4 Gene

Genomics for MARCHF4 Gene

GeneHancer (GH) Regulatory Elements for MARCHF4 Gene

Promoters and enhancers for MARCHF4 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH02J216370 Promoter/Enhancer 1.7 EPDnew Ensembl ENCODE 500.7 -0.1 -87 3.9 HNRNPK ZNF217 EP300 TCF12 NRF1 JUND FOS TEAD4 REST ZBTB10 MARCHF4 RF00994-555
GH02J216339 Promoter/Enhancer 1.7 FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 13.7 +28.9 28882 9.2 EP300 ZIC2 ZNF423 ZNF341 CTCF WT1 FOXA2 GABPA POLR2A SPI1 MARCHF4 ENSG00000235042 SMARCAL1 ENSG00000207303 ENSG00000233581
GH02J216315 Enhancer 1.1 FANTOM5 ENCODE CraniofacialAtlas 16.7 +56.2 56172 2.5 TCF12 JUND FOS ZIC2 NR2F2 MYC ZNF316 MAFF GABPA SMARCC1 MARCHF4 ENSG00000233581 ENSG00000207303
GH02J216306 Enhancer 1 FANTOM5 Ensembl ENCODE 15.9 +64.6 64550 2.7 ATF2 OSR2 WT1 PBX2 OVOL3 IKZF1 ZNF189 ZNF843 MEIS2 ATF1 MARCHF4 ENSG00000231092 ENSG00000235042 SMARCAL1 ENSG00000233581 ENSG00000207303
GH02J216215 Enhancer 1.2 Ensembl ENCODE dbSUPER 10.8 +155.7 155682 4 CTCF POLR2G JUND REST TOE1 EP300 MXI1 NCOR1 NEUROD1 GATA3 piR-51326 ENSG00000231092 MARCHF4 ENSG00000235042 SMARCAL1 LINC01963-001 LINC01963
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around MARCHF4 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for MARCHF4

Genomic Locations for MARCHF4 Gene

Genomic Locations for MARCHF4 Gene
chr2:216,257,862-216,372,483
(GRCh38/hg38)
Size:
114,622 bases
Orientation:
Minus strand
chr2:217,122,585-217,236,750
(GRCh37/hg19)
Size:
114,166 bases
Orientation:
Minus strand

Genomic View for MARCHF4 Gene

Genes around MARCHF4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MARCHF4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MARCHF4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MARCHF4 Gene

Proteins for MARCHF4 Gene

  • Protein details for MARCHF4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9P2E8-MARH4_HUMAN
    Recommended name:
    E3 ubiquitin-protein ligase MARCH4
    Protein Accession:
    Q9P2E8
    Secondary Accessions:
    • Q4KMN7
    • Q86WR8

    Protein attributes for MARCHF4 Gene

    Size:
    410 amino acids
    Molecular mass:
    45528 Da
    Quaternary structure:
    No Data Available
    SequenceCaution:
    • Sequence=BAA92637.1; Type=Erroneous initiation; Evidence={ECO:0000305};

neXtProt entry for MARCHF4 Gene

Post-translational modifications for MARCHF4 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for MARCHF4 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for MARCHF4 Gene

Domains & Families for MARCHF4 Gene

Gene Families for MARCHF4 Gene

Protein Domains for MARCHF4 Gene

Blocks:
  • Zn-finger, RING
  • RINGv
InterPro:
ProtoNet:

Graphical View of Domain Structure for InterPro Entry

Q9P2E8

UniProtKB/Swiss-Prot:

MARH4_HUMAN :
  • The RING-CH-type zinc finger domain is required for E3 ligase activity.
Domain:
  • The RING-CH-type zinc finger domain is required for E3 ligase activity.
genes like me logo Genes that share domains with MARCHF4: view

No data available for Suggested Antigen Peptide Sequences for MARCHF4 Gene

Function for MARCHF4 Gene

Molecular function for MARCHF4 Gene

UniProtKB/Swiss-Prot Function:
E3 ubiquitin-protein ligase that may mediate ubiquitination of MHC-I and CD4, and promote their subsequent endocytosis and sorting to lysosomes via multivesicular bodies. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27;.

Enzyme Numbers (IUBMB) for MARCHF4 Gene

Phenotypes From GWAS Catalog for MARCHF4 Gene

Gene Ontology (GO) - Molecular Function for MARCHF4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004842 ubiquitin-protein transferase activity IDA 14722266
GO:0008270 zinc ion binding IEA --
GO:0016740 transferase activity IEA --
GO:0046872 metal ion binding IEA --
genes like me logo Genes that share ontologies with MARCHF4: view
genes like me logo Genes that share phenotypes with MARCHF4: view

Animal Model Products

CRISPR Products

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for MARCHF4 Gene

Localization for MARCHF4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for MARCHF4 Gene

Golgi apparatus membrane; Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for MARCHF4 gene
Compartment Confidence
golgi apparatus 5
plasma membrane 2
extracellular 1
cytoskeleton 1
mitochondrion 1
nucleus 1
endoplasmic reticulum 1
endosome 1
cytosol 1
lysosome 1

Gene Ontology (GO) - Cellular Components for MARCHF4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000139 Golgi membrane IEA --
GO:0005794 Golgi apparatus IEA --
GO:0005795 Golgi stack IDA 14722266
GO:0005802 trans-Golgi network IDA 14722266
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with MARCHF4: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for MARCHF4 Gene

Pathways & Interactions for MARCHF4 Gene

PathCards logo

SuperPathways for MARCHF4 Gene

No Data Available

UniProtKB/Swiss-Prot Q9P2E8-MARH4_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

Gene Ontology (GO) - Biological Process for MARCHF4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0016567 protein ubiquitination IEA --
genes like me logo Genes that share ontologies with MARCHF4: view

No data available for Pathways by source and SIGNOR curated interactions for MARCHF4 Gene

Drugs & Compounds for MARCHF4 Gene

(3) Drugs for MARCHF4 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Phosphoric acid Approved Pharma 0
Adenosine monophosphate Approved, Investigational Nutra 0
ATP Investigational Nutra Agonist, Activator, Full agonist, Antagonist, Pore Blocker, Potentiation 0

(1) Additional Compounds for MARCHF4 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
pyrophosphate
  • [(ho)2P(O)OP(O)(OH)2]
  • Acide diphosphorique
  • Diphosphorsaeure
  • H4P2O7
  • PYROphosphATE
14000-31-8
genes like me logo Genes that share compounds with MARCHF4: view

Transcripts for MARCHF4 Gene

mRNA/cDNA for MARCHF4 Gene

1 REFSEQ mRNAs :
6 NCBI additional mRNA sequence :
1 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Alternative Splicing Database (ASD) splice patterns (SP) for MARCHF4 Gene

No ASD Table

Relevant External Links for MARCHF4 Gene

GeneLoc Exon Structure for
MARCHF4

Expression for MARCHF4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for MARCHF4

SOURCE GeneReport for Unigene cluster for MARCHF4 Gene:

Hs.170388

mRNA Expression by UniProt/SwissProt for MARCHF4 Gene:

Q9P2E8-MARH4_HUMAN
Tissue specificity: Expressed in brain and placenta.

Evidence on tissue expression from TISSUES for MARCHF4 Gene

  • Nervous system(4.2)
  • Liver(4.1)
  • Pancreas(4.1)
genes like me logo Genes that share expression patterns with MARCHF4: view

Primer Products

No data available for mRNA expression in normal human tissues , mRNA differential expression in normal tissues , Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for MARCHF4 Gene

Orthologs for MARCHF4 Gene

This gene was present in the common ancestor of chordates.

Orthologs for MARCHF4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia MARCH4 31 30
  • 100 (n)
OneToOne
cow
(Bos Taurus)
Mammalia MARCH4 31 30
  • 91.58 (n)
OneToOne
dog
(Canis familiaris)
Mammalia MARCH4 31 30
  • 91.54 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia March4 30
  • 88.77 (n)
mouse
(Mus musculus)
Mammalia March4 31 30
  • 88.72 (n)
OneToOne
Marchf4 17
oppossum
(Monodelphis domestica)
Mammalia MARCH4 31
  • 81 (a)
OneToOne
chicken
(Gallus gallus)
Aves MARCH4 31
  • 80 (a)
OneToOne
MAR-04 30
  • 77.91 (n)
lizard
(Anolis carolinensis)
Reptilia MARCH4 31
  • 79 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia march4 30
  • 71.31 (n)
zebrafish
(Danio rerio)
Actinopterygii zgc:153256 30
  • 64.28 (n)
march4 31
  • 55 (a)
OneToMany
MARCH4 (1 of 2) 31
  • 52 (a)
OneToMany
Dr.18480 30
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 27 (a)
OneToMany
Species where no ortholog for MARCHF4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for MARCHF4 Gene

ENSEMBL:
Gene Tree for MARCHF4 (if available)
TreeFam:
Gene Tree for MARCHF4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for MARCHF4: view image

Paralogs for MARCHF4 Gene

Paralogs for MARCHF4 Gene

genes like me logo Genes that share paralogs with MARCHF4: view

Variants for MARCHF4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for MARCHF4 Gene

SNP ID Clinical significance and condition Chr 02 pos Variation AA Info Type
rs145386484 Likely Benign: Frontotemporal dementia 216,370,222(-) C/G MISSENSE_VARIANT
rs756981946 Uncertain Significance: Frontotemporal dementia 216,283,615(-) T/C MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for MARCHF4 Gene

Structural Variations from Database of Genomic Variants (DGV) for MARCHF4 Gene

Variant ID Type Subtype PubMed ID
dgv630e201 CNV deletion 23290073
esv1006636 CNV deletion 20482838
esv2678065 CNV deletion 23128226
esv2721458 CNV deletion 23290073
esv2721460 CNV deletion 23290073
esv3560987 CNV deletion 23714750
esv3594292 CNV loss 21293372
nsv1001603 CNV gain 25217958
nsv1003877 CNV gain 25217958
nsv1005697 CNV loss 25217958
nsv1011506 CNV gain 25217958
nsv1148113 CNV deletion 26484159
nsv3160 CNV deletion 18451855
nsv507067 OTHER sequence alteration 20534489
nsv834537 CNV loss 17160897
nsv955059 CNV deletion 24416366
nsv999217 CNV gain 25217958

Variation tolerance for MARCHF4 Gene

Residual Variation Intolerance Score: 45.8% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for MARCHF4 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
MARCHF4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MARCHF4 Gene

Disorders for MARCHF4 Gene

MalaCards: The human disease database

(1) MalaCards diseases for MARCHF4 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
frontotemporal dementia
  • ftd
- elite association - COSMIC cancer census association via MalaCards
genes like me logo Genes that share disorders with MARCHF4: view

No data available for UniProtKB/Swiss-Prot , Genatlas and External Links for MARCHF4 Gene

Publications for MARCHF4 Gene

  1. Downregulation of major histocompatibility complex class I by human ubiquitin ligases related to viral immune evasion proteins. (PMID: 14722266) Bartee E … Früh K (Journal of virology 2004) 2 3 4 23 54
  2. Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro. (PMID: 10718198) Nagase T … Ohara O (DNA research : an international journal for rapid publication of reports on genes and genomes 2000) 2 3 4 54
  3. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4 54
  4. Genome-wide association analysis identifies susceptibility loci for migraine without aura. (PMID: 22683712) Freilinger T … International Headache Genetics Consortium (Nature genetics 2012) 3 54
  5. Membrane-Associated RING-CH proteins associate with Bap31 and target CD81 and CD44 to lysosomes. (PMID: 21151997) Bartee E … Früh K (PloS one 2010) 3 54

Products for MARCHF4 Gene

Sources for MARCHF4 Gene