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Q9NX47 (MARH5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
E3 ubiquitin-protein ligase MARCH5

EC=6.3.2.-
Alternative name(s):
Membrane-associated RING finger protein 5
Membrane-associated RING-CH protein V
Short name=MARCH-V
Mitochondrial ubiquitin ligase
Short name=MITOL
RING finger protein 153
Gene names
Name:MARCH5
Synonyms:RNF153
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length278 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Mitochondrial E3 ubiquitin-protein ligase that plays a crucial role in the control of mitochondrial morphology by acting as a positive regulator of mitochondrial fission. May play a role in the prevention of cell senescence acting as a regulator of mitochondrial quality control. Promotes ubiquitination of FIS1, DNM1L and MFN1. Ref.6 Ref.7 Ref.8 Ref.9

Pathway

Protein modification; protein ubiquitination.

Subunit structure

Monomer and homodimer. Interacts with MFN1, MFN2, DNM1L and FIS1. Ref.1 Ref.6 Ref.7 Ref.9

Subcellular location

Mitochondrion outer membrane; Multi-pass membrane protein. Endoplasmic reticulum membrane. Note: Authors show that the protein can be detected in endoplasmic reticulum (Ref.5). Authors (Ref.6) show its presence only in mitochondria (Ref.6). Ref.1 Ref.5 Ref.6 Ref.7 Ref.8

Tissue specificity

Expressed in brain, heart, liver, lung, spleen, stomach, testis, skeletal and muscle. Ref.6

Domain

The RING-CH-type zinc finger domain is required for E3 ligase activity By similarity.

Post-translational modification

Autoubiquitinated leading to degradation (short half-life).

Miscellaneous

By binding to and ubiquitinating two ALS1 variants of SOD1 (mSOD1 variants Arg-86 and Ala-94) it attenuates their cytotoxicity.

Sequence similarities

Contains 1 RING-CH-type zinc finger.

Ontologies

Keywords
   Biological processUbl conjugation pathway
   Cellular componentEndoplasmic reticulum
Membrane
Mitochondrion
Mitochondrion outer membrane
   DomainTransmembrane
Transmembrane helix
Zinc-finger
   LigandMetal-binding
Zinc
   Molecular functionLigase
   PTMUbl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processnegative regulation of cell aging

Inferred from mutant phenotype Ref.9. Source: UniProtKB

positive regulation of mitochondrial fission

Inferred from mutant phenotype Ref.9. Source: UniProtKB

protein autoubiquitination

Inferred from direct assay Ref.6. Source: UniProtKB

protein localization to mitochondrion

Inferred from mutant phenotype Ref.7. Source: UniProtKB

protein polyubiquitination

Inferred from direct assay Ref.1. Source: UniProtKB

regulation of mitochondrial fission

Inferred from mutant phenotype Ref.6Ref.7. Source: UniProtKB

   Cellular_componentendoplasmic reticulum

Inferred from direct assay Ref.5. Source: UniProtKB

endoplasmic reticulum membrane

Inferred from direct assay Ref.5. Source: UniProtKB

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

mitochondrial outer membrane

Inferred from direct assay Ref.6Ref.7. Source: UniProtKB

   Molecular_functionGTPase binding

Inferred from physical interaction Ref.1. Source: UniProtKB

ubiquitin-protein ligase activity

Inferred from direct assay Ref.1. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 278278E3 ubiquitin-protein ligase MARCH5
PRO_0000271769

Regions

Transmembrane99 – 11921Helical; Potential
Transmembrane139 – 15921Helical; Potential
Transmembrane209 – 22921Helical; Potential
Transmembrane238 – 25821Helical; Potential
Zinc finger6 – 7570RING-CH-type

Experimental info

Mutagenesis431H → W: Loss of ubiquitin ligase activity, formation of highly interconnected mitochondria, change in mitochondria morphology that in turns triggers senescence, and perinuclear accumulation. Ref.7 Ref.9
Mutagenesis651C → S: Loss of E3 ubiquitin ligase activity. Formation of highly interconnected mitochondria and perinuclear accumulation; when associated with S-68. Ref.6 Ref.7
Mutagenesis681C → S: Loss of E3 ubiquitin ligase activity. Formation of highly interconnected mitochondria and perinuclear accumulation; when associated with S-65. Ref.6 Ref.7

Sequences

Sequence LengthMass (Da)Tools
Q9NX47 [UniParc].

Last modified October 1, 2000. Version 1.
Checksum: CB00A408E228A9EE

FASTA27831,232
        10         20         30         40         50         60 
MPDQALQQML DRSCWVCFAT DEDDRTAEWV RPCRCRGSTK WVHQACLQRW VDEKQRGNST 

        70         80         90        100        110        120 
ARVACPQCNA EYLIVFPKLG PVVYVLDLAD RLISKACPFA AAGIMVGSIY WTAVTYGAVT 

       130        140        150        160        170        180 
VMQVVGHKEG LDVMERADPL FLLIGLPTIP VMLILGKMIR WEDYVLRLWR KYSNKLQILN 

       190        200        210        220        230        240 
SIFPGIGCPV PRIPAEANPL ADHVSATRIL CGALVFPTIA TIVGKLMFSS VNSNLQRTIL 

       250        260        270 
GGIAFVAIKG AFKVYFKQQQ YLRQAHRKIL NYPEQEEA 

« Hide

References

« Hide 'large scale' references
[1]"MARCH-V is a novel mitofusin 2- and Drp1-binding protein able to change mitochondrial morphology."
Nakamura N., Kimura Y., Tokuda M., Honda S., Hirose S.
EMBO Rep. 7:1019-1022(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH MFN2 AND DNM1L, SUBCELLULAR LOCATION.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Uterus.
[5]"Downregulation of major histocompatibility complex class I by human ubiquitin ligases related to viral immune evasion proteins."
Bartee E., Mansouri M., Hovey Nerenberg B.T., Gouveia K., Frueh K.
J. Virol. 78:1109-1120(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[6]"A novel mitochondrial ubiquitin ligase plays a critical role in mitochondrial dynamics."
Yonashiro R., Ishido S., Kyo S., Fukuda T., Goto E., Matsuki Y., Ohmura-Hoshino M., Sada K., Hotta H., Yamamura H., Inatome R., Yanagi S.
EMBO J. 25:3618-3626(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS AN E3 UBIQUITIN LIGASE FOR FIS1 AND DNM1L AND AS A REGULATOR OF MITOCHONDRIAL FISSION, AUTOUBIQUITINATION, PTM, SUBCELLULAR LOCATION, INTERACTION WITH FIS1 AND DNM1L, TISSUE SPECIFICITY, MUTAGENESIS OF CYS-65 AND CYS-68.
[7]"The mitochondrial E3 ubiquitin ligase MARCH5 is required for Drp1 dependent mitochondrial division."
Karbowski M., Neutzner A., Youle R.J.
J. Cell Biol. 178:71-84(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS A REGULATOR OF MITOCHONDRIAL MORPHOLOGY, MUTAGENESIS OF HIS-43; CYS-65 AND CYS-68, SUBUNIT, SUBCELLULAR LOCATION.
[8]"Mitochondrial ubiquitin ligase MITOL ubiquitinates mutant SOD1 and attenuates mutant SOD1-induced reactive oxygen species generation."
Yonashiro R., Sugiura A., Miyachi M., Fukuda T., Matsushita N., Inatome R., Ogata Y., Suzuki T., Dohmae N., Yanagi S.
Mol. Biol. Cell 20:4524-4530(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS A REGULATOR OF MITOCHONDRIAL QUALITY CONTROL, SUBCELLULAR LOCATION.
[9]"Loss of MARCH5 mitochondrial E3 ubiquitin ligase induces cellular senescence through dynamin-related protein 1 and mitofusin 1."
Park Y.Y., Lee S., Karbowski M., Neutzner A., Youle R.J., Cho H.
J. Cell Sci. 123:619-626(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS AN E3 UBIQUITIN LIGASE FOR MFN1 AND AS A POSITIVE REGULATOR OF MITOCHONDRIAL FISSION, MUTAGENESIS OF HIS-43, INTERACTION WITH MFN1.
[10]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB191202 mRNA. Translation: BAF02285.1.
AK000452 mRNA. Translation: BAA91173.1.
AL158040, AL161652 Genomic DNA. Translation: CAI13639.1.
AL161652, AL158040 Genomic DNA. Translation: CAI15361.1.
BC015480 mRNA. Translation: AAH15480.1.
RefSeqNP_060294.1. NM_017824.4.
UniGeneHs.573490.

3D structure databases

ProteinModelPortalQ9NX47.
SMRQ9NX47. Positions 14-81.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid120105. 22 interactions.
IntActQ9NX47. 10 interactions.
MINTMINT-2844053.
STRING9606.ENSP00000351813.

PTM databases

PhosphoSiteQ9NX47.

Polymorphism databases

DMDM74762759.

Proteomic databases

PaxDbQ9NX47.
PeptideAtlasQ9NX47.
PRIDEQ9NX47.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000358935; ENSP00000351813; ENSG00000198060.
GeneID54708.
KEGGhsa:54708.
UCSCuc001khx.1. human.

Organism-specific databases

CTD54708.
GeneCardsGC10P094041.
HGNCHGNC:26025. MARCH5.
HPAHPA052901.
MIM610637. gene.
neXtProtNX_Q9NX47.
PharmGKBPA128394672.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG242263.
HOGENOMHOG000247040.
HOVERGENHBG059795.
InParanoidQ9NX47.
KOK10660.
OMAYRSCWVC.
OrthoDBEOG7CCBQZ.
PhylomeDBQ9NX47.
TreeFamTF316219.

Enzyme and pathway databases

UniPathwayUPA00143.

Gene expression databases

ArrayExpressQ9NX47.
BgeeQ9NX47.
CleanExHS_MARCH5.
GenevestigatorQ9NX47.

Family and domain databases

Gene3D3.30.40.10. 1 hit.
InterProIPR011016. Znf_RING-CH.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamPF12906. RINGv. 1 hit.
[Graphical view]
SMARTSM00744. RINGv. 1 hit.
[Graphical view]
PROSITEPS51292. ZF_RING_CH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMARCH5. human.
GeneWikiMARCH5.
GenomeRNAi54708.
NextBio57269.
PROQ9NX47.
SOURCESearch...

Entry information

Entry nameMARH5_HUMAN
AccessionPrimary (citable) accession number: Q9NX47
Entry history
Integrated into UniProtKB/Swiss-Prot: January 9, 2007
Last sequence update: October 1, 2000
Last modified: April 16, 2014
This is version 119 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM