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MARCHF6 membrane associated ring-CH-type finger 6 [ Homo sapiens (human) ]

Gene ID: 10299, updated on 11-Apr-2024

Summary

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Official Symbol
MARCHF6provided by HGNC
Official Full Name
membrane associated ring-CH-type finger 6provided by HGNC
Primary source
HGNC:HGNC:30550
See related
Ensembl:ENSG00000145495 MIM:613297; AllianceGenome:HGNC:30550
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
TEB4; DOA10; FAME3; FCMTE3; MARCH6; RNF176; MARCH-VI
Summary
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]
Expression
Ubiquitous expression in brain (RPKM 18.9), bone marrow (RPKM 17.4) and 25 other tissues See more
Orthologs
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Genomic context

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Location:
5p15.2
Exon count:
31
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (10353695..10440388)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (10292877..10379523)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (10353807..10440500)

Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15917 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22352 Neighboring gene ReSE screen-validated silencer GRCh37_chr5:10300268-10300444 Neighboring gene carboxymethylenebutenolidase homolog Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:10307292-10307792 Neighboring gene CRISPRi-validated cis-regulatory element chr5.702 Neighboring gene Sharpr-MPRA regulatory region 12783 Neighboring gene uncharacterized LOC105374651 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15918 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:10333367-10334122 Neighboring gene MARCHF6 divergent transcript Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22353 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15919 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15920 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:10354472-10355043 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22354 Neighboring gene microRNA 10397 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr5:10420944-10422143 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15921 Neighboring gene ROPN1L antisense RNA 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:10457805-10458664 Neighboring gene rhophilin associated tail protein 1 like Neighboring gene uncharacterized LOC124900940

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. The E3 ubiquitin ligase MARCHF6 as a metabolic integrator in cholesterol synthesis and beyond. Scott NA, et al. Biochim Biophys Acta Mol Cell Biol Lipids, 2021 Jan. PMID 33049405
  2. Unstable TTTTA/TTTCA expansions in MARCH6 are associated with Familial Adult Myoclonic Epilepsy type 3. Florian RT, et al. Nat Commun, 2019 Oct 29. PMID 31664039, Free PMC Article
  3. Consulting prostate cancer cohort data uncovers transcriptional control: Regulation of the MARCH6 gene. Coates HW, et al. Biochim Biophys Acta Mol Cell Biol Lipids, 2019 Nov. PMID 31422115
  4. Cholesterol increases protein levels of the E3 ligase MARCH6 and thereby stimulates protein degradation. Sharpe LJ, et al. J Biol Chem, 2019 Feb 15. PMID 30545937, Free PMC Article
  5. Type 2 deiodinase at the crossroads of thyroid hormone action. Arrojo E Drigo R, et al. Int J Biochem Cell Biol, 2011 Oct. PMID 21679772, Free PMC Article

See all (51) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. MARCH6 promotes Papillary Thyroid Cancer development by destabilizing DHX9.
    Title: MARCH6 promotes Papillary Thyroid Cancer development by destabilizing DHX9.
  2. MARCH6 promotes hepatocellular carcinoma development through up-regulation of ATF2.
    Title: MARCH6 promotes hepatocellular carcinoma development through up-regulation of ATF2.
  3. The MARCH6-SQLE Axis Controls Endothelial Cholesterol Homeostasis and Angiogenic Sprouting.
    Title: The MARCH6-SQLE Axis Controls Endothelial Cholesterol Homeostasis and Angiogenic Sprouting.
  4. The E3 ubiquitin ligase MARCHF6 as a metabolic integrator in cholesterol synthesis and beyond.
    Title: The E3 ubiquitin ligase MARCHF6 as a metabolic integrator in cholesterol synthesis and beyond.
  5. the E3 ubiquitin ligase membrane-associated ring-CH-type finger 6 (MARCH6), known to control earlier rate-limiting steps in cholesterol synthesis, also control levels of LDM and the terminal cholesterol synthesis enzyme, 24-dehydrocholesterol reductase.
    Title: The cholesterol synthesis enzyme lanosterol 14α-demethylase is post-translationally regulated by the E3 ubiquitin ligase MARCH6.
  6. UBE2J2 as an important partner of MARCH6 for regulated degradation of the rate-limiting enzymes HMGCR and SQLE in cholesterol biosynthesis.
    Title: Differential use of E2 ubiquitin conjugating enzymes for regulated degradation of the rate-limiting enzymes HMGCR and SQLE in cholesterol biosynthesis.
  7. MARCH6 and AR expression are strongly correlated in primary prostate cancer tissues. This correlation is unrelated to androgen receptor signalling. MARCH6 and AR share common regulation by the transcription factor Sp1.
    Title: Consulting prostate cancer cohort data uncovers transcriptional control: Regulation of the MARCH6 gene.
  8. TTTTA/TTTCA repeat expansions in MARCH6 are associated with Familial Adult Myoclonic Epilepsy type 3.
    Title: Unstable TTTTA/TTTCA expansions in MARCH6 are associated with Familial Adult Myoclonic Epilepsy type 3.
  9. cholesterol reduced the levels of at least three known MARCH6 substrates, indicating that cholesterol-mediated MARCH6 stabilization increases its activity.
    Title: Cholesterol increases protein levels of the E3 ligase MARCH6 and thereby stimulates protein degradation.
  10. TRC8 and MARCH6 depletion altered the turnover of the tail-anchored protein heme oxygenase-1.
    Title: MARCH6 and TRC8 facilitate the quality control of cytosolic and tail-anchored proteins.
Submit: New GeneRIF Correction See all GeneRIFs (17)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Epilepsy, familial adult myoclonic, 3
MedGen: C3150860 OMIM: 613608 GeneReviews: Not available
not available

EBI GWAS Catalog

Description
A novel locus for body mass index on 5p15.2: a meta-analysis of two genome-wide association studies.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • KIAA0597, DKFZp586L081

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables enzyme binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables ubiquitin conjugating enzyme binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables ubiquitin protein ligase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables ubiquitin protein ligase activity TAS
Traceable Author Statement
more info
 PubMed 
enables ubiquitin-protein transferase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables ubiquitin-protein transferase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables ubiquitin-specific protease binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables zinc ion binding IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in ERAD pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in ERAD pathway TAS
Traceable Author Statement
more info
 PubMed 
involved_in proteasomal protein catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein K48-linked ubiquitination IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein ubiquitination IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
part_of ER ubiquitin ligase complex IC
Inferred by Curator
more info
 PubMed 
located_in endoplasmic reticulum IDA
Inferred from Direct Assay
more info
  
is_active_in endoplasmic reticulum membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in endoplasmic reticulum membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in endoplasmic reticulum membrane TAS
Traceable Author Statement
more info
  
located_in membrane HDA PubMed 
located_in membrane IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
E3 ubiquitin-protein ligase MARCHF6
Names
E3 ubiquitin-protein ligase MARCH6
RING finger protein 176
RING-type E3 ubiquitin transferase MARCH6
RING-type E3 ubiquitin transferase MARCHF6
doa10 homolog
membrane associated ring finger 6
membrane-associated RING finger protein 6
membrane-associated RING-CH finger protein 6
membrane-associated RING-CH protein VI
membrane-associated ring finger (C3HC4) 6, E3 ubiquitin protein ligase
NP_001257589.1
NP_001257590.1
NP_005876.2
XP_011512234.1
XP_011512236.1
XP_011512238.1
XP_016864433.1
XP_047272567.1
XP_047272568.1
XP_047272569.1
XP_047272570.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001270660.2 → NP_001257589.1  E3 ubiquitin-protein ligase MARCHF6 isoform 2

    See identical proteins and their annotated locations for NP_001257589.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate in-frame exon in the coding region, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.
    Source sequence(s)
    AC092336, AK300034, BX116291, DB072938
    Consensus CDS
    CCDS59487.1
    UniProtKB/Swiss-Prot
    O60337
    Related
    ENSP00000414643.2, ENST00000449913.6
    Conserved Domains (2) summary
    COG5183
    Location:334 → 845
    SSM4; E3 ubiquitin-protein ligase DOA10 [Posttranslational modification, protein turnover, chaperones]
    cd16702
    Location:8 → 57
    RING_CH-C4HC3_MARCH6; RING-CH finger, H2 subclass (C4HC3-type), found in membrane-associated RING-CH6 (MARCH6)

  2. NM_001270661.2 → NP_001257590.1  E3 ubiquitin-protein ligase MARCHF6 isoform 3

    See identical proteins and their annotated locations for NP_001257590.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks three alternate in-frame exons in the coding region, compared to variant 1. The encoded isoform (3) is shorter than isoform 1.
    Source sequence(s)
    AC092336, AK296585, BX116291, DB072938
    Consensus CDS
    CCDS59488.1
    UniProtKB/Swiss-Prot
    O60337
    Related
    ENSP00000425930.1, ENST00000503788.5
    Conserved Domains (1) summary
    COG5183
    Location:277 → 788
    SSM4; E3 ubiquitin-protein ligase DOA10 [Posttranslational modification, protein turnover, chaperones]

  3. NM_005885.4 → NP_005876.2  E3 ubiquitin-protein ligase MARCHF6 isoform 1

    See identical proteins and their annotated locations for NP_005876.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AB011169, AC092336, BX116291, DB072938
    Consensus CDS
    CCDS34135.1
    UniProtKB/Swiss-Prot
    A5PKZ4, B4DKJ2, B4DT33, D3DTC8, O14670, O60337, Q86X77
    Related
    ENSP00000274140.4, ENST00000274140.10
    Conserved Domains (1) summary
    cd16702
    Location:8 → 57
    RING_CH-C4HC3_MARCH6; RING-CH finger, H2 subclass (C4HC3-type), found in membrane-associated RING-CH6 (MARCH6)

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

    Range
    10353695..10440388
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047416612.1 → XP_047272568.1  E3 ubiquitin-protein ligase MARCHF6 isoform X3

  2. XM_011513934.3 → XP_011512236.1  E3 ubiquitin-protein ligase MARCHF6 isoform X4

    Conserved Domains (1) summary
    cd16702
    Location:8 → 57
    RING_CH-C4HC3_MARCH6; RING-CH finger, H2 subclass (C4HC3-type), found in membrane-associated RING-CH6 (MARCH6)

  3. XM_011513936.4 → XP_011512238.1  E3 ubiquitin-protein ligase MARCHF6 isoform X6

    Conserved Domains (1) summary
    smart00744
    Location:8 → 56
    RINGv; The RING-variant domain is a C4HC3 zinc-finger like motif found in a number of cellular and viral proteins

  4. XM_017008944.3 → XP_016864433.1  E3 ubiquitin-protein ligase MARCHF6 isoform X8

  5. XM_011513932.3 → XP_011512234.1  E3 ubiquitin-protein ligase MARCHF6 isoform X1

    Conserved Domains (1) summary
    COG5183
    Location:314 → 825
    SSM4; E3 ubiquitin-protein ligase DOA10 [Posttranslational modification, protein turnover, chaperones]

  6. XM_047416611.1 → XP_047272567.1  E3 ubiquitin-protein ligase MARCHF6 isoform X2

  7. XM_047416613.1 → XP_047272569.1  E3 ubiquitin-protein ligase MARCHF6 isoform X5

  8. XM_047416614.1 → XP_047272570.1  E3 ubiquitin-protein ligase MARCHF6 isoform X7

    Related
    ENSP00000424512.1, ENST00000510792.1

RNA

  1. XR_925577.3 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060929.1 Alternate T2T-CHM13v2.0

    Range
    10292877..10379523
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O60337.2 GenPept UniProtKB/Swiss-Prot:O60337

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