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

Summary

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

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_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

MARCH6 promotes Papillary Thyroid Cancer development by destabilizing DHX9.
Title: MARCH6 promotes Papillary Thyroid Cancer development by destabilizing DHX9.
MARCH6 promotes hepatocellular carcinoma development through up-regulation of ATF2.
Title: MARCH6 promotes hepatocellular carcinoma development through up-regulation of ATF2.
The MARCH6-SQLE Axis Controls Endothelial Cholesterol Homeostasis and Angiogenic Sprouting.
Title: The MARCH6-SQLE Axis Controls Endothelial Cholesterol Homeostasis and Angiogenic Sprouting.
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.
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.
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.
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.
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.
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.
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 EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D5S1654E (e-PCR)
- UniSTS:46341

SHGC-37071 (e-PCR)
- UniSTS:49162

WI-22102 (e-PCR)
- UniSTS:23571

D5S438E (e-PCR)
- UniSTS:79640

D5S1598E (e-PCR)
- UniSTS:43827

WI-11573 (e-PCR)
- UniSTS:61516

RH35927 (e-PCR)
- UniSTS:27984

D5S1646E (e-PCR)
- UniSTS:3165

D5S1645E (e-PCR)
- UniSTS:33135

WI-17007 (e-PCR)
- UniSTS:2161

SHGC-79719 (e-PCR)
- UniSTS:103304

RH12605 (e-PCR)
- UniSTS:9120

SGC35190 (e-PCR)
- UniSTS:25252

WIAF-1507 (e-PCR)
- UniSTS:3262

SHGC-145385 (e-PCR)
- UniSTS:174541

RH92217 (e-PCR)
- UniSTS:86739

RH27917 (e-PCR)
- UniSTS:91875

RH68720 (e-PCR)
- UniSTS:22763

G19766 (e-PCR)
- UniSTS:51955

A001X45 (e-PCR)
- UniSTS:51956

G62792 (e-PCR)
- UniSTS:139769

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 more info	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

EC 2.3.2.27

NP_001257590.1

EC 2.3.2.27

NP_005876.2

EC 2.3.2.27

XP_011512234.1

EC 2.3.2.27

XP_011512236.1

EC 2.3.2.27

XP_011512238.1

EC 2.3.2.27

XP_016864433.1

EC 2.3.2.27

XP_047272567.1

EC 2.3.2.27

XP_047272568.1

EC 2.3.2.27

XP_047272569.1

EC 2.3.2.27

XP_047272570.1

EC 2.3.2.27

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)

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)
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]
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

NC_000005.10 Reference GRCh38.p14 Primary Assembly

Range

10353695..10440388

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047416612.1 → XP_047272568.1 E3 ubiquitin-protein ligase MARCHF6 isoform X3
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)
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
XM_017008944.3 → XP_016864433.1 E3 ubiquitin-protein ligase MARCHF6 isoform X8
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]
XM_047416611.1 → XP_047272567.1 E3 ubiquitin-protein ligase MARCHF6 isoform X2
XM_047416613.1 → XP_047272569.1 E3 ubiquitin-protein ligase MARCHF6 isoform X5
XM_047416614.1 → XP_047272570.1 E3 ubiquitin-protein ligase MARCHF6 isoform X7

Related

ENSP00000424512.1, ENST00000510792.1