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

    Gene ID: 10299, updated on 28-Oct-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
    mouse all
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    Genomic context

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    See MARCHF6 in Genome Data Viewer
    Location:
    5p15.2
    Exon count:
    31
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (10353695..10440388)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (10292877..10379523)
    RS_2024_09 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 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. 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
    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. 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
    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 (56) 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 endoplasmic reticulum mannose trimming TAS
    Traceable Author Statement
    more info
    		  
    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 endoplasmic reticulum quality control compartment IEA
    Inferred from Electronic Annotation
    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_2024_08

    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

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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