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Protein

Dynamin-like 120 kDa protein, mitochondrial

Gene

Opa1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Dynamin-related GTPase that is essential for normal mitochondrial morphology by regulating the equilibrium between mitochondrial fusion and mitochondrial fission (PubMed:11847212, PubMed:24616225, PubMed:26785494). Coexpression of isoform 1 with shorter alternative products is required for optimal activity in promoting mitochondrial fusion (By similarity). Binds lipid membranes enriched in negatively charged phospholipids, such as cardiolipin, and promotes membrane tubulation. The intrinsic GTPase activity is low, and is strongly increased by interaction with lipid membranes (By similarity). Plays a role in remodeling cristae and the release of cytochrome c during apoptosis (PubMed:16839884, PubMed:16839885). Proteolytic processing in response to intrinsic apoptotic signals may lead to disassembly of OPA1 oligomers and release of the caspase activator cytochrome C (CYCS) into the mitochondrial intermembrane space (PubMed:16839884, PubMed:16839885). Plays a role in mitochondrial genome maintenance (By similarity).By similarity5 Publications
Dynamin-like 120 kDa protein, form S1: Produced by cleavage at position S1 by OMA1 following stress conditions that induce loss of mitochondrial membrane potential, leading to negative regulation of mitochondrial fusion.2 Publications
Isoforms that contain the alternative exon 4b (present in isoform 2, but not in isoform 1) are required for mitochondrial genome maintenance, possibly by anchoring the mitochondrial nucleoids to the inner mitochondrial membrane.By similarity

Miscellaneous

Embryonic fibroblasts that lack Opa1 show a defect in apoptosis in response to intrinsic signals. This defect can be complemented by a soluble form of Opa1 targeted to the mitochondrial intermembrane space.1 Publication

Catalytic activityi

GTP + H2O = GDP + phosphate.By similarity

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi295 – 302GTPSequence analysis8
Nucleotide bindingi398 – 402GTPSequence analysis5
Nucleotide bindingi467 – 470GTPSequence analysis4

GO - Molecular functioni

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • cellular senescence Source: MGI
  • dynamin family protein polymerization involved in mitochondrial fission Source: GO_Central
  • GTP metabolic process Source: UniProtKB
  • inner mitochondrial membrane organization Source: UniProtKB
  • membrane tubulation Source: UniProtKB
  • mitochondrial fission Source: GO_Central
  • mitochondrial fusion Source: MGI
  • mitochondrial genome maintenance Source: UniProtKB
  • mitochondrion organization Source: MGI
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway Source: ParkinsonsUK-UCL
  • negative regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
  • negative regulation of release of cytochrome c from mitochondria Source: UniProtKB
  • neural tube closure Source: MGI
  • protein complex oligomerization Source: MGI
  • visual perception Source: UniProtKB

Keywordsi

Molecular functionHydrolase
Biological processApoptosis, Sensory transduction, Vision
LigandGTP-binding, Lipid-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi3.6.5.5 3474
ReactomeiR-MMU-169911 Regulation of Apoptosis

Names & Taxonomyi

Protein namesi
Recommended name:
Dynamin-like 120 kDa protein, mitochondrial (EC:3.6.5.5)
Alternative name(s):
Large GTP-binding protein
Short name:
LargeG
Optic atrophy protein 1 homolog
Cleaved into the following chain:
Gene namesi
Name:Opa1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 16

Organism-specific databases

MGIiMGI:1921393 Opa1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini88 – 96Mitochondrial matrixSequence analysis9
Transmembranei97 – 113HelicalSequence analysisAdd BLAST17
Topological domaini114 – 960Mitochondrial intermembraneSequence analysisAdd BLAST847

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion inner membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 87MitochondrionBy similarityAdd BLAST87
ChainiPRO_000000739888 – 960Dynamin-like 120 kDa protein, mitochondrialAdd BLAST873
ChainiPRO_0000253480195 – 960Dynamin-like 120 kDa protein, form S1By similarityAdd BLAST766

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei228N6-acetyllysineBy similarity1

Post-translational modificationi

PARL-dependent proteolytic processing releases an antiapoptotic soluble form not required for mitochondrial fusion. Cleaved by OMA1 at position S1 following stress conditions (PubMed:20038678, PubMed:22433842).2 Publications
Cleavage at position S2 is mediated by YME1L (PubMed:24616225, PubMed:26785494). Cleavage may occur in the sequence motif Leu-Gln-Gln-Gln-Ile-Gln (LQQQIQ) (By similarity). This motif is present in isoform 2, but is absent in the displayed isoform 1.By similarityCurated2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei194 – 195Cleavage at site S1By similarity2

Keywords - PTMi

Acetylation

Proteomic databases

MaxQBiP58281
PaxDbiP58281
PeptideAtlasiP58281
PRIDEiP58281

PTM databases

iPTMnetiP58281
PhosphoSitePlusiP58281

Expressioni

Tissue specificityi

Detected in brain (at protein level) (PubMed:11847212). Detected in brain, brain stem, heart, kidney, liver and skeletal muscle (PubMed:11847212).1 Publication

Gene expression databases

BgeeiENSMUSG00000038084
CleanExiMM_OPA1
ExpressionAtlasiP58281 baseline and differential
GenevisibleiP58281 MM

Interactioni

Subunit structurei

Oligomeric complex consisting of membrane-bound and soluble forms of OPA1 (PubMed:16839885). Interacts with CHCHD3 and IMMT; these interactions occur preferentially with soluble OPA1 forms (PubMed:21081504). Binds PARL (PubMed:16839884). Interacts with PRELID1 (By similarity).By similarity3 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi216522, 4 interactors
IntActiP58281, 16 interactors
MINTiP58281
STRINGi10090.ENSMUSP00000036993

Structurei

3D structure databases

ProteinModelPortaliP58281
SMRiP58281
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini285 – 561Dynamin-type GPROSITE-ProRule annotationAdd BLAST277

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni295 – 302G1 motifPROSITE-ProRule annotation8
Regioni321 – 324G2 motifPROSITE-ProRule annotation4
Regioni398 – 401G3 motifPROSITE-ProRule annotation4
Regioni467 – 470G4 motifPROSITE-ProRule annotation4
Regioni501 – 504G5 motifPROSITE-ProRule annotation4

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili210 – 254Sequence analysisAdd BLAST45
Coiled coili895 – 960Sequence analysisAdd BLAST66

Sequence similaritiesi

Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil, Transit peptide, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0447 Eukaryota
COG0699 LUCA
GeneTreeiENSGT00550000074851
HOVERGENiHBG019108
InParanoidiP58281
KOiK17079
OMAiYEDWKDG
OrthoDBiEOG091G01NV
PhylomeDBiP58281
TreeFamiTF314250

Family and domain databases

CDDicd08771 DLP_1, 1 hit
InterProiView protein in InterPro
IPR001401 Dynamin_GTPase
IPR022812 Dynamin_SF
IPR030381 G_DYNAMIN_dom
IPR033047 Opa1
IPR027417 P-loop_NTPase
PANTHERiPTHR11566 PTHR11566, 1 hit
PTHR11566:SF67 PTHR11566:SF67, 1 hit
PfamiView protein in Pfam
PF00350 Dynamin_N, 1 hit
PRINTSiPR00195 DYNAMIN
SMARTiView protein in SMART
SM00053 DYNc, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
PROSITEiView protein in PROSITE
PS51718 G_DYNAMIN_2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P58281-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MWRAGRAAVA CEVCQSLVKH SSGIQRNVPL QKLHLVSRSI YRSHHPALKL
60 70 80 90 100
QRPQLRTPFQ QFSSLTHLSL HKLKLSPIKY GYQPRRNFWP ARLAARLLKL
110 120 130 140 150
RYIILGSAVG GGYTAKKTFD EWKDMIPDLS DYKWIVPDFI WEIDEYIDLE
160 170 180 190 200
KIRKALPSSE DLASLAPDLD KITESLSLLK DFFTAGSPGE TAFRATDHGS
210 220 230 240 250
ESDKHYRKVS DKEKIDQLQE ELLHTQLKYQ RILERLEKEN KELRKLVLQK
260 270 280 290 300
DDKGIHHRKL KKSLIDMYSE VLDVLSDYDA SYNTQDHLPR VVVVGDQSAG
310 320 330 340 350
KTSVLEMIAQ ARIFPRGSGE MMTRSPVKVT LSEGPHHVAL FKDSSREFDL
360 370 380 390 400
TKEEDLAALR HEIELRMRKN VKEGCTVSPE TISLNVKGPG LQRMVLVDLP
410 420 430 440 450
GVINTVTSGM APDTKETIFS ISKAYMQNPN AIILCIQDGS VDAERSIVTD
460 470 480 490 500
LVSQMDPHGR RTIFVLTKVD LAEKNVASPS RIQQIIEGKL FPMKALGYFA
510 520 530 540 550
VVTGKGNSSE SIEAIREYEE EFFQNSKLLK TSMLKAHQVT TRNLSLAVSD
560 570 580 590 600
CFWKMVRESV EQQADSFKAT RFNLETEWKN NYPRLRELDR NELFEKAKNE
610 620 630 640 650
ILDEVISLSQ VTPKHWEEIL QQSLWERVST HVIENIYLPA AQTMNSGTFN
660 670 680 690 700
TTVDIKLKQW TDKQLPNKAV EVAWETLQEE FSRFMTEPKG KEHDDIFDKL
710 720 730 740 750
KEAVKEESIK RHKWNDFAED SLRVIQHNAL EDRSISDKQQ WDAAIYFMEE
760 770 780 790 800
ALQGRLKDTE NAIENMIGPD WKKRWMYWKN RTQEQCVHNE TKNELEKMLK
810 820 830 840 850
VNDEHPAYLA SDEITTVRKN LESRGVEVDP SLIKDTWHQV YRRHFLKTAL
860 870 880 890 900
NHCNLCRRGF YYYQRHFIDS ELECNDVVLF WRIQRMLAIT ANTLRQQLTN
910 920 930 940 950
TEVRRLEKNV KEVLEDFAED GEKKVKLLTG KRVQLAEDLK KVREIQEKLD
960
AFIEALHQEK
Length:960
Mass (Da):111,339
Last modified:September 26, 2001 - v1
Checksum:i0F103FB1FD570F49
GO
Isoform 2 (identifier: P58281-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     208-208: K → KGLLGELILLQQQIQEHEEEARRAAGQYSTSYAQQKRK

Show »
Length:997
Mass (Da):115,593
Checksum:iFADCB1430E585522
GO

Sequence cautioni

The sequence AAH25160 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti236L → P in BAC30002 (PubMed:16141072).Curated1
Sequence conflicti330 – 331TL → NN in BAC32021 (PubMed:16141072).Curated2

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_021037208K → KGLLGELILLQQQIQEHEEE ARRAAGQYSTSYAQQKRK in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB044138 mRNA Translation: BAB59000.1
AK029157 mRNA Translation: BAC26331.1
AK038446 mRNA Translation: BAC30002.1
AK044657 mRNA Translation: BAC32021.1
AK050383 mRNA Translation: BAC34224.1
AK145620 mRNA Translation: BAE26544.1
BC025160 mRNA Translation: AAH25160.1 Different initiation.
BC138665 mRNA Translation: AAI38666.1
BC145959 mRNA Translation: AAI45960.1
CCDSiCCDS28096.1 [P58281-1]
RefSeqiNP_598513.1, NM_133752.3 [P58281-1]
XP_006522720.1, XM_006522657.2 [P58281-2]
UniGeneiMm.274285

Genome annotation databases

EnsembliENSMUST00000160597; ENSMUSP00000124223; ENSMUSG00000038084 [P58281-1]
ENSMUST00000161186; ENSMUSP00000123880; ENSMUSG00000038084 [P58281-2]
GeneIDi74143
KEGGimmu:74143
UCSCiuc007ywf.2 mouse [P58281-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiOPA1_MOUSE
AccessioniPrimary (citable) accession number: P58281
Secondary accession number(s): A6H6Q3
, Q3ULA5, Q8BKU7, Q8BLL3, Q8BM08, Q8R3J7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: September 26, 2001
Last modified: May 23, 2018
This is version 143 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families
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