OPA1

Protein identityUniProt · HPA

UniProt accession

O60313

Gene

OPA1

Ensembl

ENSG00000198836

Chromosome

3

Canonical length

960 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Transporters

Subcellular location

Nucleoplasm,Mitochondria

OverviewNCBI Gene

The protein encoded by this gene is a nuclear-encoded mitochondrial protein with similarity to dynamin-related GTPases. The encoded protein localizes to the inner mitochondrial membrane and helps regulate mitochondrial stability and energy output. This protein also sequesters cytochrome c. Mutations in this gene have been associated with optic atrophy type 1, which is a dominantly inherited optic neuropathy resulting in progressive loss of visual acuity, leading in many cases to legal blindness. [provided by RefSeq, Aug 2017]

Canonical amino-acid sequenceUniProt

960 residues, UniProt reviewed canonical sequence.

>O60313|OPA1
     1  MWRLRRAAVA CEVCQSLVKH SSGIKGSLPL QKLHLVSRSI YHSHHPTLKL QRPQLRTSFQ
    61  QFSSLTNLPL RKLKFSPIKY GYQPRRNFWP ARLATRLLKL RYLILGSAVG GGYTAKKTFD
   121  QWKDMIPDLS EYKWIVPDIV WEIDEYIDFE KIRKALPSSE DLVKLAPDFD KIVESLSLLK
   181  DFFTSGSPEE TAFRATDRGS ESDKHFRKVS DKEKIDQLQE ELLHTQLKYQ RILERLEKEN
   241  KELRKLVLQK DDKGIHHRKL KKSLIDMYSE VLDVLSDYDA SYNTQDHLPR VVVVGDQSAG
   301  KTSVLEMIAQ ARIFPRGSGE MMTRSPVKVT LSEGPHHVAL FKDSSREFDL TKEEDLAALR
   361  HEIELRMRKN VKEGCTVSPE TISLNVKGPG LQRMVLVDLP GVINTVTSGM APDTKETIFS
   421  ISKAYMQNPN AIILCIQDGS VDAERSIVTD LVSQMDPHGR RTIFVLTKVD LAEKNVASPS
   481  RIQQIIEGKL FPMKALGYFA VVTGKGNSSE SIEAIREYEE EFFQNSKLLK TSMLKAHQVT
   541  TRNLSLAVSD CFWKMVRESV EQQADSFKAT RFNLETEWKN NYPRLRELDR NELFEKAKNE
   601  ILDEVISLSQ VTPKHWEEIL QQSLWERVST HVIENIYLPA AQTMNSGTFN TTVDIKLKQW
   661  TDKQLPNKAV EVAWETLQEE FSRFMTEPKG KEHDDIFDKL KEAVKEESIK RHKWNDFAED
   721  SLRVIQHNAL EDRSISDKQQ WDAAIYFMEE ALQARLKDTE NAIENMVGPD WKKRWLYWKN
   781  RTQEQCVHNE TKNELEKMLK CNEEHPAYLA SDEITTVRKN LESRGVEVDP SLIKDTWHQV
   841  YRRHFLKTAL NHCNLCRRGF YYYQRHFVDS ELECNDVVLF WRIQRMLAIT ANTLRQQLTN
   901  TEVRRLEKNV KEVLEDFAED GEKKIKLLTG KRVQLAEDLK KVREIQEKLD AFIEALHQEK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against OPA1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.37

Highest tissue expression

42 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about OPA1.

Disease | AllUniProt

Conditions OPA1 is implicated in, by any mechanism.

• Optic atrophy 1 (OPA1) MIM:165500
• Optic atrophy plus syndrome (DOA+) MIM:125250
• Behr syndrome (BEHRS) MIM:210000
• Mitochondrial DNA depletion syndrome 14, cardioencephalomyopathic type (MTDPS14) MIM:616896

Disease | GeneticClinVar

374 pathogenic / likely-pathogenic of 1,797 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Optic atrophy
• Autosomal dominant optic atrophy classic form
• Optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy
• OPA1-related disorder
• Abortive cerebellar ataxia

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.29

gnomAD pLI

0.99

gnomAD missense Z

1.97

DepMap mean gene effect

-0.46

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 15% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• apoptotic process
• axonal transport of mitochondrion
• cellular senescence
• cristae formation
• GTP metabolic process
• inner mitochondrial membrane organization
• membrane tubulation
• mitochondrial fission
• mitochondrial fusion
• mitochondrion organization
• negative regulation of apoptotic process
• negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway
• negative regulation of release of cytochrome c from mitochondria
• neural tube closure
• peroxisome fission
• positive regulation of interleukin-17 production
• positive regulation of T-helper 17 cell lineage commitment
• protein complex oligomerization
• visual perception
• mitochondrial inner membrane fusion

Molecular functions

• cardiolipin binding
• GTP binding
• GTPase activity
• GTPase-dependent fusogenic activity
• magnesium ion binding
• microtubule binding
• phosphatidic acid binding
• membrane bending activity

Cellular components

• axon cytoplasm
• cytoplasm
• cytosol
• dendrite
• membrane
• microtubule
• mitochondrial crista
• mitochondrial inner membrane
• mitochondrial intermembrane space
• mitochondrial membrane
• mitochondrial outer membrane
• mitochondrion
• nucleoplasm

Protein domainsUniProt · Pfam · InterPro

• Dynamin, GTPase domain
• Dynamin
• P-loop containing nucleoside triphosphate hydrolase
• Dynamin-type guanine nucleotide-binding (G) domain
• Dynamin, N-terminal
• Dynamin family
• Dynamin-like GTPase OPA1, C-terminal
• Dynamin-like GTPase OPA1 C-terminal

KeywordsUniProt

• Acetylation
• Apoptosis
• Cardiomyopathy
• Coiled coil
• Deafness
• Disulfide bond
• GTP-binding
• Hydrolase
• Lipid-binding
• Membrane
• Mitochondrion
• Mitochondrion inner membrane
• Neurodegeneration
• Nucleotide-binding
• Primary mitochondrial disease
• Sensory transduction
• Transit peptide
• Transmembrane
• Transmembrane helix
• Vision

InteractionsUniProt · HPA

Protein binding partners of OPA1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CHCHD3
• IMMT
• PRELID1
• RCC1L
• NME4
• BNIP3
• GID8