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Q96E52 (OMA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 105. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Metalloendopeptidase OMA1, mitochondrial

EC=3.4.24.-
Alternative name(s):
Metalloprotease-related protein 1
Short name=MPRP-1
Overlapping with the m-AAA protease 1 homolog
Gene names
Name:OMA1
Synonyms:MPRP1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length524 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Metalloprotease that is part of the quality control system in the inner membrane of mitochondria. Following stress conditions that induce loss of mitochondrial membrane potential, mediates cleavage of OPA1 at S1 position, leading to OPA1 inactivation and negative regulation of mitochondrial fusion. Its role in mitochondrial quality control is essential for regulating lipid metabolism as well as to maintain body temperature and energy expenditure under cold-stress conditions. Ref.6

Cofactor

Binds 1 zinc ion per subunit Potential.

Subcellular location

Mitochondrion inner membrane; Multi-pass membrane protein Probable Ref.6.

Tissue specificity

Widely expressed, with strong expression in the heart, skeletal muscle, kidney and liver. Ref.1

Post-translational modification

In normal conditions, cleaved into an inactive 40 kDa form. Following CCCP treatment that induces loss of mitochondrial membrane potential, the 40 kDa form is reduced in favor of an active 60 kDa form. Ref.6

Sequence similarities

Belongs to the peptidase M48 family.

Caution

Was initially reported to localize in the endoplasmic reticulum (Ref.1). However, it was later shown that it localizes to mitochondrion (Ref.6).

Sequence caution

The sequence BAC03583.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence CAI13522.1 differs from that shown. Reason: Erroneous gene model prediction.

The sequence CAI13523.1 differs from that shown. Reason: Erroneous gene model prediction.

The sequence CAI13524.1 differs from that shown. Reason: Erroneous gene model prediction.

The sequence CAI13525.1 differs from that shown. Reason: Erroneous gene model prediction.

The sequence CAI13526.1 differs from that shown. Reason: Erroneous gene model prediction.

The sequence CAI22238.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
   Cellular componentMembrane
Mitochondrion
Mitochondrion inner membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainTransit peptide
Transmembrane
Transmembrane helix
   LigandMetal-binding
Zinc
   Molecular functionHydrolase
Metalloprotease
Protease
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcristae formation

Inferred from electronic annotation. Source: Ensembl

diet induced thermogenesis

Inferred from mutant phenotype PubMed 22433842. Source: UniProtKB

energy homeostasis

Inferred from mutant phenotype PubMed 22433842. Source: UniProtKB

glucose metabolic process

Inferred from mutant phenotype PubMed 22433842. Source: UniProtKB

lipid metabolic process

Inferred from mutant phenotype PubMed 22433842. Source: UniProtKB

misfolded or incompletely synthesized protein catabolic process

Inferred from mutant phenotype Ref.6. Source: UniProtKB

mitochondrial protein processing

Inferred from electronic annotation. Source: Ensembl

negative regulation of mitochondrial fusion

Inferred from mutant phenotype Ref.6PubMed 22433842. Source: UniProtKB

response to stress

Inferred from direct assay Ref.6. Source: UniProtKB

   Cellular_componentintegral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

mitochondrial inner membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

mitochondrial membrane

Inferred from direct assay Ref.6. Source: UniProtKB

   Molecular_functionmetal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

metalloendopeptidase activity

Inferred from mutant phenotype Ref.6PubMed 22433842. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q96E52-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q96E52-2)

The sequence of this isoform differs from the canonical sequence as follows:
     456-524: ALKIREMCNC...TYIVEKRTGS → LVREEKFIEQPEQIAELTLNSFIQNTEICRS
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 1313Mitochondrion Potential
Chain14 – 524511Metalloendopeptidase OMA1, mitochondrial
PRO_0000302809

Regions

Transmembrane196 – 21621Helical; Potential
Transmembrane341 – 36121Helical; Potential

Sites

Active site3281 By similarity
Metal binding3271Zinc; catalytic By similarity
Metal binding3311Zinc; catalytic Probable
Metal binding3921Zinc; catalytic By similarity

Natural variations

Alternative sequence456 – 52469ALKIR…KRTGS → LVREEKFIEQPEQIAELTLN SFIQNTEICRS in isoform 2.
VSP_027958
Natural variant671N → K.
Corresponds to variant rs34466938 [ dbSNP | Ensembl ].
VAR_034958
Natural variant691H → Y in a patient with amyotrophic lateral sclerosis. Ref.8
Corresponds to variant rs75220198 [ dbSNP | Ensembl ].
VAR_065755
Natural variant1171P → L. Ref.8
Corresponds to variant rs17117720 [ dbSNP | Ensembl ].
VAR_034959
Natural variant2111F → C.
Corresponds to variant rs17117699 [ dbSNP | Ensembl ].
VAR_034960
Natural variant2261L → V in a colorectal cancer sample; somatic mutation. Ref.7
VAR_035708
Natural variant2721E → G in a patient with amyotrophic lateral sclerosis. Ref.8
VAR_065756
Natural variant3291I → L. Ref.8
Corresponds to variant rs17117678 [ dbSNP | Ensembl ].
VAR_034961
Natural variant3651D → Y. Ref.8
Corresponds to variant rs77980955 [ dbSNP | Ensembl ].
VAR_065757

Experimental info

Mutagenesis3311H → A: Abolishes ability to cleave OPA1 at S1 position. Ref.6

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 1, 2001. Version 1.
Checksum: F8F9B37489B0EFF1

FASTA52460,120
        10         20         30         40         50         60 
MSFICGLQSA ARNHVFFRFN SLSNWRKCNT LASTSRGCHQ VQVNHIVNKY QGLGVNQCDR 

        70         80         90        100        110        120 
WSFLPGNFHF YSTFNNKRTG GLSSTKSKEI WRITSKCTVW NDAFSRQLLI KEVTAVPSLS 

       130        140        150        160        170        180 
VLHPLSPASI RAIRNFHTSP RFQAAPVPLL LMILKPVQKL FAIIVGRGIR KWWQALPPNK 

       190        200        210        220        230        240 
KEVVKENIRK NKWKLFLGLS SFGLLFVVFY FTHLEVSPIT GRSKLLLLGK EQFRLLSELE 

       250        260        270        280        290        300 
YEAWMEEFKN DMLTEKDARY LAVKEVLCHL IECNKDVPGI SQINWVIHVV DSPIINAFVL 

       310        320        330        340        350        360 
PNGQMFVFTG FLNSVTDIHQ LSFLLGHEIA HAVLGHAAEK AGMVHLLDFL GMIFLTMIWA 

       370        380        390        400        410        420 
ICPRDSLALL CQWIQSKLQE YMFNRPYSRK LEAEADKIGL LLAAKACADI RASSVFWQQM 

       430        440        450        460        470        480 
EFVDSLHGQP KMPEWLSTHP SHGNRVEYLD RLIPQALKIR EMCNCPPLSN PDPRLLFKLS 

       490        500        510        520 
TKHFLEESEK EDLNITKKQK MDTLPIQKQE QIPLTYIVEK RTGS 

« Hide

Isoform 2 [UniParc].

Checksum: F2D48060E2D25826
Show »

FASTA48655,744

References

« Hide 'large scale' references
[1]"Identification of a human cDNA sequence which encodes a novel membrane-associated protein containing a zinc metalloprotease motif."
Bao Y.-C., Tsuruga H., Hirai M., Yasuda K., Yokoi N., Kitamura T., Kumagai H.
DNA Res. 10:123-128(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
[2]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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] (ISOFORM 1).
Tissue: Liver.
[5]"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] OF 160-524 (ISOFORM 2).
Tissue: Substantia nigra.
[6]"Inducible proteolytic inactivation of OPA1 mediated by the OMA1 protease in mammalian cells."
Head B., Griparic L., Amiri M., Gandre-Babbe S., van der Bliek A.M.
J. Cell Biol. 187:959-966(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING, MUTAGENESIS OF HIS-331.
[7]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] VAL-226.
[8]"Resequencing of 29 candidate genes in patients with familial and sporadic amyotrophic lateral sclerosis."
Daoud H., Valdmanis P.N., Gros-Louis F., Belzil V., Spiegelman D., Henrion E., Diallo O., Desjarlais A., Gauthier J., Camu W., Dion P.A., Rouleau G.A.
Arch. Neurol. 68:587-593(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS TYR-69; LEU-117; GLY-272; LEU-329 AND TYR-365.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB048348 mRNA. Translation: BAC79381.1.
AL365187 Genomic DNA. Translation: CAI13522.1. Sequence problems.
AL365187 Genomic DNA. Translation: CAI13523.1. Sequence problems.
AL365187 Genomic DNA. Translation: CAI13524.1. Sequence problems.
AL365187 Genomic DNA. Translation: CAI13525.1. Sequence problems.
AL365187, AL109845 Genomic DNA. Translation: CAI13526.1. Sequence problems.
AL109845, AL365187 Genomic DNA. Translation: CAI22238.1. Sequence problems.
AL365187, AL109845 Genomic DNA. Translation: CAI13527.1.
AL109845, AL365187 Genomic DNA. Translation: CAI22239.1.
CH471059 Genomic DNA. Translation: EAX06631.1.
CH471059 Genomic DNA. Translation: EAX06632.1.
CH471059 Genomic DNA. Translation: EAX06633.1.
BC012915 mRNA. Translation: AAH12915.1.
AK091101 mRNA. Translation: BAC03583.1. Different initiation.
RefSeqNP_660286.1. NM_145243.3.
UniGeneHs.425769.

3D structure databases

ProteinModelPortalQ96E52.
SMRQ96E52. Positions 253-455.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ96E52. 1 interaction.
STRING9606.ENSP00000360270.

Protein family/group databases

MEROPSM48.017.

PTM databases

PhosphoSiteQ96E52.

Polymorphism databases

DMDM74751828.

Proteomic databases

PaxDbQ96E52.
PRIDEQ96E52.

Protocols and materials databases

DNASU115209.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000358603; ENSP00000351417; ENSG00000162600. [Q96E52-2]
ENST00000371226; ENSP00000360270; ENSG00000162600. [Q96E52-1]
GeneID115209.
KEGGhsa:115209.
UCSCuc001cyx.1. human. [Q96E52-2]
uc001cyy.3. human. [Q96E52-1]

Organism-specific databases

CTD115209.
GeneCardsGC01M058881.
H-InvDBHIX0077405.
HGNCHGNC:29661. OMA1.
HPAHPA055120.
neXtProtNX_Q96E52.
PharmGKBPA134911478.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0501.
HOVERGENHBG096685.
InParanoidQ96E52.
OMAQKQEQIP.
PhylomeDBQ96E52.
TreeFamTF329133.

Gene expression databases

BgeeQ96E52.
CleanExHS_OMA1.
GenevestigatorQ96E52.

Family and domain databases

InterProIPR001915. Peptidase_M48.
[Graphical view]
PfamPF01435. Peptidase_M48. 1 hit.
[Graphical view]
PROSITEPS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi115209.
NextBio79540.
PROQ96E52.

Entry information

Entry nameOMA1_HUMAN
AccessionPrimary (citable) accession number: Q96E52
Secondary accession number(s): D3DQ54 expand/collapse secondary AC list , Q5T3G6, Q5T3G7, Q5T3G8, Q5T3G9, Q5T3H0, Q8NBB3
Entry history
Integrated into UniProtKB/Swiss-Prot: September 11, 2007
Last sequence update: December 1, 2001
Last modified: April 16, 2014
This is version 105 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

Peptidase families

Classification of peptidase families and list of entries

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM