Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

E3 ubiquitin-protein ligase MARCH5

Gene

MARCH5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 MFN1.4 Publications

Pathwayi

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri6 – 7570RING-CH-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. GTPase binding Source: UniProtKB
  2. ligase activity Source: UniProtKB-KW
  3. ubiquitin-protein transferase activity Source: UniProtKB
  4. zinc ion binding Source: InterPro

GO - Biological processi

  1. negative regulation of cell aging Source: UniProtKB
  2. positive regulation of mitochondrial fission Source: UniProtKB
  3. protein autoubiquitination Source: UniProtKB
  4. protein localization to mitochondrion Source: UniProtKB
  5. protein polyubiquitination Source: UniProtKB
  6. regulation of mitochondrial fission Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
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 namesi
Name:MARCH5
Synonyms:RNF153
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 10

Organism-specific databases

HGNCiHGNC:26025. MARCH5.

Subcellular locationi

Mitochondrion outer membrane; Multi-pass membrane protein. Endoplasmic reticulum membrane
Note: Authors show that the protein can be detected in endoplasmic reticulum (PubMed:14722266). Authors (PubMed:16874301) show its presence only in mitochondria (PubMed:16874301).2 Publications

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei99 – 11921HelicalSequence AnalysisAdd
BLAST
Transmembranei139 – 15921HelicalSequence AnalysisAdd
BLAST
Transmembranei209 – 22921HelicalSequence AnalysisAdd
BLAST
Transmembranei238 – 25821HelicalSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. endoplasmic reticulum Source: UniProtKB
  2. endoplasmic reticulum membrane Source: UniProtKB
  3. integral component of membrane Source: UniProtKB-KW
  4. membrane Source: UniProtKB
  5. mitochondrial outer membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Mitochondrion, Mitochondrion outer membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi43 – 431H → W: Loss of ubiquitin ligase activity, formation of highly interconnected mitochondria, change in mitochondria morphology that in turns triggers senescence, and perinuclear accumulation. 2 Publications
Mutagenesisi65 – 651C → S: Loss of E3 ubiquitin ligase activity. Formation of highly interconnected mitochondria and perinuclear accumulation; when associated with S-68. 2 Publications
Mutagenesisi68 – 681C → S: Loss of E3 ubiquitin ligase activity. Formation of highly interconnected mitochondria and perinuclear accumulation; when associated with S-65. 2 Publications

Organism-specific databases

PharmGKBiPA128394672.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 278278E3 ubiquitin-protein ligase MARCH5PRO_0000271769Add
BLAST

Post-translational modificationi

Autoubiquitinated leading to degradation (short half-life).1 Publication

Keywords - PTMi

Ubl conjugation

Proteomic databases

MaxQBiQ9NX47.
PaxDbiQ9NX47.
PeptideAtlasiQ9NX47.
PRIDEiQ9NX47.

PTM databases

PhosphoSiteiQ9NX47.

Expressioni

Tissue specificityi

Expressed in brain, heart, liver, lung, spleen, stomach, testis, skeletal and muscle.1 Publication

Gene expression databases

BgeeiQ9NX47.
CleanExiHS_MARCH5.
ExpressionAtlasiQ9NX47. baseline and differential.
GenevestigatoriQ9NX47.

Organism-specific databases

HPAiHPA052901.

Interactioni

Subunit structurei

Monomer and homodimer. Interacts with MFN1, MFN2, DNM1L and FIS1.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
DENRO435832EBI-2341610,EBI-716083
UBCP0CG482EBI-2341610,EBI-3390054

Protein-protein interaction databases

BioGridi120105. 27 interactions.
IntActiQ9NX47. 10 interactions.
MINTiMINT-2844053.
STRINGi9606.ENSP00000351813.

Structurei

3D structure databases

ProteinModelPortaliQ9NX47.
SMRiQ9NX47. Positions 14-81.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

The RING-CH-type zinc finger domain is required for E3 ligase activity.PROSITE-ProRule annotation

Sequence similaritiesi

Contains 1 RING-CH-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri6 – 7570RING-CH-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Transmembrane, Transmembrane helix, Zinc-finger

Phylogenomic databases

eggNOGiNOG242263.
GeneTreeiENSGT00390000009948.
HOGENOMiHOG000247040.
HOVERGENiHBG059795.
InParanoidiQ9NX47.
KOiK10660.
OMAiNYPEQEG.
OrthoDBiEOG7CCBQZ.
PhylomeDBiQ9NX47.
TreeFamiTF316219.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR011016. Znf_RING-CH.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF12906. RINGv. 1 hit.
[Graphical view]
SMARTiSM00744. RINGv. 1 hit.
[Graphical view]
PROSITEiPS51292. ZF_RING_CH. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9NX47-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPDQALQQML DRSCWVCFAT DEDDRTAEWV RPCRCRGSTK WVHQACLQRW
60 70 80 90 100
VDEKQRGNST ARVACPQCNA EYLIVFPKLG PVVYVLDLAD RLISKACPFA
110 120 130 140 150
AAGIMVGSIY WTAVTYGAVT VMQVVGHKEG LDVMERADPL FLLIGLPTIP
160 170 180 190 200
VMLILGKMIR WEDYVLRLWR KYSNKLQILN SIFPGIGCPV PRIPAEANPL
210 220 230 240 250
ADHVSATRIL CGALVFPTIA TIVGKLMFSS VNSNLQRTIL GGIAFVAIKG
260 270
AFKVYFKQQQ YLRQAHRKIL NYPEQEEA
Length:278
Mass (Da):31,232
Last modified:October 1, 2000 - v1
Checksum:iCB00A408E228A9EE
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS7420.1.
RefSeqiNP_060294.1. NM_017824.4.
UniGeneiHs.573490.

Genome annotation databases

EnsembliENST00000358935; ENSP00000351813; ENSG00000198060.
GeneIDi54708.
KEGGihsa:54708.
UCSCiuc001khx.1. human.

Polymorphism databases

DMDMi74762759.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS7420.1.
RefSeqiNP_060294.1. NM_017824.4.
UniGeneiHs.573490.

3D structure databases

ProteinModelPortaliQ9NX47.
SMRiQ9NX47. Positions 14-81.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120105. 27 interactions.
IntActiQ9NX47. 10 interactions.
MINTiMINT-2844053.
STRINGi9606.ENSP00000351813.

PTM databases

PhosphoSiteiQ9NX47.

Polymorphism databases

DMDMi74762759.

Proteomic databases

MaxQBiQ9NX47.
PaxDbiQ9NX47.
PeptideAtlasiQ9NX47.
PRIDEiQ9NX47.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000358935; ENSP00000351813; ENSG00000198060.
GeneIDi54708.
KEGGihsa:54708.
UCSCiuc001khx.1. human.

Organism-specific databases

CTDi54708.
GeneCardsiGC10P094041.
HGNCiHGNC:26025. MARCH5.
HPAiHPA052901.
MIMi610637. gene.
neXtProtiNX_Q9NX47.
PharmGKBiPA128394672.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG242263.
GeneTreeiENSGT00390000009948.
HOGENOMiHOG000247040.
HOVERGENiHBG059795.
InParanoidiQ9NX47.
KOiK10660.
OMAiNYPEQEG.
OrthoDBiEOG7CCBQZ.
PhylomeDBiQ9NX47.
TreeFamiTF316219.

Enzyme and pathway databases

UniPathwayiUPA00143.

Miscellaneous databases

ChiTaRSiMARCH5. human.
GeneWikiiMARCH5.
GenomeRNAii54708.
NextBioi57269.
PROiQ9NX47.
SOURCEiSearch...

Gene expression databases

BgeeiQ9NX47.
CleanExiHS_MARCH5.
ExpressionAtlasiQ9NX47. baseline and differential.
GenevestigatoriQ9NX47.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR011016. Znf_RING-CH.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF12906. RINGv. 1 hit.
[Graphical view]
SMARTiSM00744. RINGv. 1 hit.
[Graphical view]
PROSITEiPS51292. ZF_RING_CH. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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.
    , 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. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  11. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  12. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

Entry informationi

Entry nameiMARH5_HUMAN
AccessioniPrimary (citable) accession number: Q9NX47
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 9, 2007
Last sequence update: October 1, 2000
Last modified: March 4, 2015
This is version 128 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Miscellaneous

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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.