P58281 (OPA1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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:

1. Dynamin-like 120 kDa protein, form S1

Gene names

Name:

Opa1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	960 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Dynamin-related GTPase required for mitochondrial fusion and regulation of apoptosis. May form a diffusion barrier for proteins stored in mitochondrial cristae. 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. Ref.4 Ref.5 Ref.7 Ref.9 Dynamin-like 120 kDa protein, form S1: Inactive form produced by cleavage at S1 position by OMA1 following stress conditions that induce loss of mitochondrial membrane potential, leading to negative regulation of mitochondrial fusion. Ref.4 Ref.5 Ref.7 Ref.9
Catalytic activity	GTP + H2O = GDP + phosphate.
Subunit structure	Oligomeric complex consisting of membrane-bound and soluble forms of OPA1. Interacts with CHCHD3 and IMMT; these interactions occur preferentially with soluble OPA1 forms. Binds PARL. Ref.4 Ref.5 Ref.8
Subcellular location	Mitochondrion inner membrane; Single-pass membrane protein. Mitochondrion intermembrane space Ref.4.
Post-translational modification	PARL-dependent proteolytic processing releases an antiapoptotic soluble form not required for mitochondrial fusion. Cleaved by OMA1 at position S1 following stress conditions.
Disruption phenotype	Embryonic fibroblasts 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. Ref.4
Sequence similarities	Belongs to the dynamin family.
Sequence caution	The sequence AAH25160.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Apoptosis Sensory transduction Vision
Cellular component	Membrane Mitochondrion Mitochondrion inner membrane
Coding sequence diversity	Alternative splicing
Domain	Coiled coil Transit peptide Transmembrane Transmembrane helix
Ligand	GTP-binding Nucleotide-binding
Molecular function	Hydrolase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW inner mitochondrial membrane organization Inferred from sequence or structural similarity. Source: UniProtKB mitochondrial fusion Inferred from direct assay Ref.7. Source: MGI negative regulation of intrinsic apoptotic signaling pathway Inferred from mutant phenotype Ref.4. Source: UniProtKB negative regulation of release of cytochrome c from mitochondria Inferred from mutant phenotype Ref.4. Source: UniProtKB neural tube closure Inferred from mutant phenotype PubMed 15755804. Source: MGI response to stimulus Inferred from electronic annotation. Source: UniProtKB-KW visual perception Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	dendrite Inferred from direct assay Ref.1. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial crista Inferred from sequence or structural similarity. Source: UniProtKB mitochondrial intermembrane space Inferred from direct assay Ref.1. Source: UniProtKB mitochondrial outer membrane Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	GTP binding Inferred from electronic annotation. Source: UniProtKB-KW GTPase activity Traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P58281-1)

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: P58281-2)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 87	87	Mitochondrion By similarity
	Chain	88 – 960	873	Dynamin-like 120 kDa protein, mitochondrial		PRO_0000007398
	Chain	195 – 960	766	Dynamin-like 120 kDa protein, form S1 By similarity		PRO_0000253480
Regions
	Topological domain	88 – 96	9	Mitochondrial matrix Potential
	Transmembrane	97 – 113	17	Helical; Potential
	Topological domain	114 – 960	847	Mitochondrial intermembrane Potential
	Nucleotide binding	295 – 302	8	GTP Potential
	Nucleotide binding	398 – 402	5	GTP Potential
	Nucleotide binding	467 – 470	4	GTP Potential
	Coiled coil	210 – 254	45	Potential
	Coiled coil	895 – 960	66	Potential
Amino acid modifications
	Modified residue	228	1	N6-acetyllysine By similarity
	Modified residue	652	1	Phosphothreonine Ref.6
	Modified residue	929	1	Phosphothreonine By similarity
Natural variations
	Alternative sequence	208	1	K → KGLLGELILLQQQIQEHEEE ARRAAGQYSTSYAQQKRK in isoform 2.		VSP_021037
Experimental info
	Sequence conflict	236	1	L → P in BAC30002. Ref.2
	Sequence conflict	330 – 331	2	TL → NN in BAC32021. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified September 26, 2001. Version 1. Checksum: 0F103FB1FD570F49	FASTA	960	111,339
	10 20 30 40 50 60 MWRAGRAAVA CEVCQSLVKH SSGIQRNVPL QKLHLVSRSI YRSHHPALKL QRPQLRTPFQ 70 80 90 100 110 120 QFSSLTHLSL HKLKLSPIKY GYQPRRNFWP ARLAARLLKL RYIILGSAVG GGYTAKKTFD 130 140 150 160 170 180 EWKDMIPDLS DYKWIVPDFI WEIDEYIDLE KIRKALPSSE DLASLAPDLD KITESLSLLK 190 200 210 220 230 240 DFFTAGSPGE TAFRATDHGS ESDKHYRKVS DKEKIDQLQE ELLHTQLKYQ RILERLEKEN 250 260 270 280 290 300 KELRKLVLQK DDKGIHHRKL KKSLIDMYSE VLDVLSDYDA SYNTQDHLPR VVVVGDQSAG 310 320 330 340 350 360 KTSVLEMIAQ ARIFPRGSGE MMTRSPVKVT LSEGPHHVAL FKDSSREFDL TKEEDLAALR 370 380 390 400 410 420 HEIELRMRKN VKEGCTVSPE TISLNVKGPG LQRMVLVDLP GVINTVTSGM APDTKETIFS 430 440 450 460 470 480 ISKAYMQNPN AIILCIQDGS VDAERSIVTD LVSQMDPHGR RTIFVLTKVD LAEKNVASPS 490 500 510 520 530 540 RIQQIIEGKL FPMKALGYFA VVTGKGNSSE SIEAIREYEE EFFQNSKLLK TSMLKAHQVT 550 560 570 580 590 600 TRNLSLAVSD CFWKMVRESV EQQADSFKAT RFNLETEWKN NYPRLRELDR NELFEKAKNE 610 620 630 640 650 660 ILDEVISLSQ VTPKHWEEIL QQSLWERVST HVIENIYLPA AQTMNSGTFN TTVDIKLKQW 670 680 690 700 710 720 TDKQLPNKAV EVAWETLQEE FSRFMTEPKG KEHDDIFDKL KEAVKEESIK RHKWNDFAED 730 740 750 760 770 780 SLRVIQHNAL EDRSISDKQQ WDAAIYFMEE ALQGRLKDTE NAIENMIGPD WKKRWMYWKN 790 800 810 820 830 840 RTQEQCVHNE TKNELEKMLK VNDEHPAYLA SDEITTVRKN LESRGVEVDP SLIKDTWHQV 850 860 870 880 890 900 YRRHFLKTAL NHCNLCRRGF YYYQRHFIDS ELECNDVVLF WRIQRMLAIT ANTLRQQLTN 910 920 930 940 950 960 TEVRRLEKNV KEVLEDFAED GEKKVKLLTG KRVQLAEDLK KVREIQEKLD AFIEALHQEK
	Isoform 2 [UniParc]. Checksum: FADCB1430E585522	FASTA	997	115,593
	10 20 30 40 50 60 MWRAGRAAVA CEVCQSLVKH SSGIQRNVPL QKLHLVSRSI YRSHHPALKL QRPQLRTPFQ 70 80 90 100 110 120 QFSSLTHLSL HKLKLSPIKY GYQPRRNFWP ARLAARLLKL RYIILGSAVG GGYTAKKTFD 130 140 150 160 170 180 EWKDMIPDLS DYKWIVPDFI WEIDEYIDLE KIRKALPSSE DLASLAPDLD KITESLSLLK 190 200 210 220 230 240 DFFTAGSPGE TAFRATDHGS ESDKHYRKGL LGELILLQQQ IQEHEEEARR AAGQYSTSYA 250 260 270 280 290 300 QQKRKVSDKE KIDQLQEELL HTQLKYQRIL ERLEKENKEL RKLVLQKDDK GIHHRKLKKS 310 320 330 340 350 360 LIDMYSEVLD VLSDYDASYN TQDHLPRVVV VGDQSAGKTS VLEMIAQARI FPRGSGEMMT 370 380 390 400 410 420 RSPVKVTLSE GPHHVALFKD SSREFDLTKE EDLAALRHEI ELRMRKNVKE GCTVSPETIS 430 440 450 460 470 480 LNVKGPGLQR MVLVDLPGVI NTVTSGMAPD TKETIFSISK AYMQNPNAII LCIQDGSVDA 490 500 510 520 530 540 ERSIVTDLVS QMDPHGRRTI FVLTKVDLAE KNVASPSRIQ QIIEGKLFPM KALGYFAVVT 550 560 570 580 590 600 GKGNSSESIE AIREYEEEFF QNSKLLKTSM LKAHQVTTRN LSLAVSDCFW KMVRESVEQQ 610 620 630 640 650 660 ADSFKATRFN LETEWKNNYP RLRELDRNEL FEKAKNEILD EVISLSQVTP KHWEEILQQS 670 680 690 700 710 720 LWERVSTHVI ENIYLPAAQT MNSGTFNTTV DIKLKQWTDK QLPNKAVEVA WETLQEEFSR 730 740 750 760 770 780 FMTEPKGKEH DDIFDKLKEA VKEESIKRHK WNDFAEDSLR VIQHNALEDR SISDKQQWDA 790 800 810 820 830 840 AIYFMEEALQ GRLKDTENAI ENMIGPDWKK RWMYWKNRTQ EQCVHNETKN ELEKMLKVND 850 860 870 880 890 900 EHPAYLASDE ITTVRKNLES RGVEVDPSLI KDTWHQVYRR HFLKTALNHC NLCRRGFYYY 910 920 930 940 950 960 QRHFIDSELE CNDVVLFWRI QRMLAITANT LRQQLTNTEV RRLEKNVKEV LEDFAEDGEK 970 980 990 KVKLLTGKRV QLAEDLKKVR EIQEKLDAFI EALHQEK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structure of a dynamin-related mouse mitochondrial GTPase and its distribution in brain, subcellular localization, and effect on mitochondrial morphology." Misaka T., Miyashita T., Kubo Y. J. Biol. Chem. 277:15834-15842(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-365 (ISOFORM 2). Strain: C57BL/6J. Tissue: Blastocyst, Hypothalamus, Liver, Retina and Skin.
[3]	"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). Strain: Czech II. Tissue: Brain and Mammary gland.
[4]	"Mitochondrial rhomboid PARL regulates cytochrome c release during apoptosis via OPA1-dependent cristae remodeling." Cipolat S., Rudka T., Hartmann D., Costa V., Serneels L., Craessaerts K., Metzger K., Frezza C., Annaert W., D'Adamio L., Derks C., Dejaegere T., Pellegrini L., D'Hooge R., Scorrano L., De Strooper B. Cell 126:163-175(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PARL, DISRUPTION PHENOTYPE.
[5]	"OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion." Frezza C., Cipolat S., Martins de Brito O., Micaroni M., Beznoussenko G.V., Rudka T., Bartoli D., Polishuck R.S., Danial N.N., De Strooper B., Scorrano L. Cell 126:177-189(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBUNIT.
[6]	"Protein phosphorylation and expression profiling by Yin-yang multidimensional liquid chromatography (Yin-yang MDLC) mass spectrometry." Dai J., Jin W.-H., Sheng Q.-H., Shieh C.-H., Wu J.-R., Zeng R. J. Proteome Res. 6:250-262(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-652, MASS SPECTROMETRY. Tissue: Liver.
[7]	"Regulation of OPA1 processing and mitochondrial fusion by m-AAA protease isoenzymes and OMA1." Ehses S., Raschke I., Mancuso G., Bernacchia A., Geimer S., Tondera D., Martinou J.C., Westermann B., Rugarli E.I., Langer T. J. Cell Biol. 187:1023-1036(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION (DYNAMIN-LIKE 120 KDA PROTEIN; FORM S1), PROTEOLYTIC PROCESSING.
[8]	"ChChd3, an inner mitochondrial membrane protein, is essential for maintaining crista integrity and mitochondrial function." Darshi M., Mendiola V.L., Mackey M.R., Murphy A.N., Koller A., Perkins G.A., Ellisman M.H., Taylor S.S. J. Biol. Chem. 286:2918-2932(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CHCHD3, IMMT.
[9]	"Loss of mitochondrial protease OMA1 alters processing of the GTPase OPA1 and causes obesity and defective thermogenesis in mice." Quiros P.M., Ramsay A.J., Sala D., Fernandez-Vizarra E., Rodriguez F., Peinado J.R., Fernandez-Garcia M.S., Vega J.A., Enriquez J.A., Zorzano A., Lopez-Otin C. EMBO J. 31:2117-2133(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION (DYNAMIN-LIKE 120 KDA PROTEIN; FORM S1), PROTEOLYTIC PROCESSING.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00117657. IPI00403336.
RefSeq	NP_598513.1. NM_133752.3.
UniGene	Mm.274285.
3D structure databases
ProteinModelPortal	P58281.
SMR	P58281. Positions 283-601.
ModBase	Search...
Protein-protein interaction databases
IntAct	P58281. 4 interactions.
PTM databases
PhosphoSite	P58281.
Proteomic databases
PaxDb	P58281.
PRIDE	P58281.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000160597; ENSMUSP00000124223; ENSMUSG00000038084. ENSMUST00000161186; ENSMUSP00000123880; ENSMUSG00000038084.
GeneID	74143.
KEGG	mmu:74143.
UCSC	uc007ywf.2. mouse.
Organism-specific databases
CTD	4976.
MGI	MGI:1921393. Opa1.
Phylogenomic databases
eggNOG	COG0699.
GeneTree	ENSGT00550000074851.
HOVERGEN	HBG019108.
OMA	KRHKWNE.
OrthoDB	EOG4KKZ2B.
Gene expression databases
ArrayExpress	P58281.
Bgee	P58281.
CleanEx	MM_OPA1.
Genevestigator	P58281.
GermOnline	ENSMUSG00000038084. Mus musculus.
Family and domain databases
InterPro	IPR022812. Dynamin. IPR001401. Dynamin_GTPase. [Graphical view]
PANTHER	PTHR11566. PTHR11566. 1 hit.
Pfam	PF00350. Dynamin_N. 1 hit. [Graphical view]
PRINTS	PR00195. DYNAMIN.
SMART	SM00053. DYNc. 1 hit. [Graphical view]
PROSITE	PS00410. DYNAMIN. False negative. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	OPA1. mouse.
NextBio	339890.
SOURCE	Search...

Entry information

Entry name

OPA1_MOUSE

Accession

Primary (citable) accession number: P58281
Secondary accession number(s): A6H6Q3 , Q3ULA5, Q8BKU7, Q8BLL3, Q8BM08, Q8R3J7

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2001
Last sequence update:	September 26, 2001
Last modified:	May 1, 2013
This is version 99 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program