Q9NX47 (MARH5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	278 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Ubl conjugation pathway
Cellular component	Endoplasmic reticulum Membrane Mitochondrion Mitochondrion outer membrane
Domain	Transmembrane Transmembrane helix Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase
PTM	Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	negative 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 in mitochondrion Inferred from mutant phenotype Ref.7. Source: UniProtKB protein polyubiquitination Inferred from direct assay Ref.1. Source: UniProtKB
Cellular component	endoplasmic reticulum membrane Inferred from direct assay Ref.5. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial outer membrane Inferred from direct assay Ref.6Ref.7. Source: UniProtKB
Molecular function	GTPase 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...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 278	278	E3 ubiquitin-protein ligase MARCH5		PRO_0000271769
Regions
	Transmembrane	99 – 119	21	Helical; Potential
	Transmembrane	139 – 159	21	Helical; Potential
	Transmembrane	209 – 229	21	Helical; Potential
	Transmembrane	238 – 258	21	Helical; Potential
	Zinc finger	6 – 75	70	RING-CH-type
Experimental info
	Mutagenesis	43	1	H → 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
	Mutagenesis	65	1	C → S: Loss of E3 ubiquitin ligase activity. Formation of highly interconnected mitochondria and perinuclear accumulation; when associated with S-68. Ref.6 Ref.7
	Mutagenesis	68	1	C → 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		Length	Mass (Da)
	Q9NX47 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: CB00A408E228A9EE	FASTA	278	31,232
	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

References

	« Hide 'large scale' referencesShow '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: 16936636] [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. , 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: 14702039] [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. , 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: 15164054] [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: 15489334] [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: 14722266] [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: 16874301] [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: 17606867] [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: 19741096] [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: 20103533] [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: 21269460] [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.
IPI	IPI00414168.
RefSeq	NP_060294.1. NM_017824.4.
UniGene	Hs.573490.
3D structure databases
ProteinModelPortal	Q9NX47.
SMR	Q9NX47. Positions 5-77.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9NX47. 5 interactions.
MINT	MINT-2844053.
STRING	Q9NX47.
Polymorphism databases
DMDM	74762759.
Proteomic databases
PeptideAtlas	Q9NX47.
PRIDE	Q9NX47.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000358935; ENSP00000351813; ENSG00000198060.
GeneID	54708.
KEGG	hsa:54708.
UCSC	uc001khx.1. human.
Organism-specific databases
CTD	54708.
GeneCards	GC10P094041.
H-InvDB	HIX0009041.
HGNC	HGNC:26025. MARCH5.
MIM	610637. gene.
neXtProt	NX_Q9NX47.
PharmGKB	PA128394672.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG05126.
GeneTree	ENSGT00390000009948.
HOGENOM	HBG715518.
HOVERGEN	HBG059795.
InParanoid	Q9NX47.
OMA	VSCPQCN.
OrthoDB	EOG4M3992.
PhylomeDB	Q9NX47.
Gene expression databases
ArrayExpress	Q9NX47.
Bgee	Q9NX47.
CleanEx	HS_MARCH5.
Genevestigator	Q9NX47.
Family and domain databases
InterPro	IPR011016. Znf_RING-CH. IPR013083. Znf_RING/FYVE/PHD. [Graphical view]
Gene3D	G3DSA:3.30.40.10. Znf_RING/FYVE/PHD. 1 hit.
KO	K10660.
SMART	SM00744. RINGv. 1 hit. [Graphical view]
PROSITE	PS51292. ZF_RING_CH. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	57269.
SOURCE	Search...

Entry information

Entry name

MARH5_HUMAN

Accession

Primary (citable) accession number: Q9NX47

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 9, 2007
Last sequence update:	October 1, 2000
Last modified:	January 25, 2012
This is version 100 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.