FZO_DROME
ID FZO_DROME Reviewed; 718 AA.
AC O18412; Q4V3Y6; Q9VCP7;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 2.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Transmembrane GTPase fzo;
DE EC=3.6.5.- {ECO:0000250|UniProtKB:Q8IWA4};
DE AltName: Full=Protein fuzzy onions;
GN Name=fzo; ORFNames=CG4568;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND MUTAGENESIS OF LYS-99 AND ARG-249.
RC TISSUE=Testis;
RX PubMed=9230308; DOI=10.1016/s0092-8674(00)80319-0;
RA Hales K.G., Fuller M.T.;
RT "Developmentally regulated mitochondrial fusion mediated by a conserved,
RT novel, predicted GTPase.";
RL Cell 90:121-129(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley;
RA Stapleton M., Carlson J.W., Chavez C., Frise E., George R.A., Pacleb J.M.,
RA Park S., Wan K.H., Yu C., Celniker S.E.;
RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=12128227; DOI=10.1016/s0925-4773(02)00141-7;
RA Hwa J.J., Hiller M.A., Fuller M.T., Santel A.;
RT "Differential expression of the Drosophila mitofusin genes fuzzy onions
RT (fzo) and dmfn.";
RL Mech. Dev. 116:213-216(2002).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18799731; DOI=10.1073/pnas.0803998105;
RA Deng H., Dodson M.W., Huang H., Guo M.;
RT "The Parkinson's disease genes pink1 and parkin promote mitochondrial
RT fission and/or inhibit fusion in Drosophila.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:14503-14508(2008).
CC -!- FUNCTION: Essential transmembrane GTPase, which mediates mitochondrial
CC fusion during spermatogenesis (PubMed:9230308, PubMed:18799731). In
CC early spermatocytes, fusion of mitochondria give rise to two organelles
CC named Nebenkern and constitutes an important step in mitochondria
CC morphology, which is balanced between fusion and fission
CC (PubMed:9230308, PubMed:18799731). Essential for fertility
CC (PubMed:9230308). {ECO:0000269|PubMed:18799731,
CC ECO:0000269|PubMed:9230308}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189;
CC Evidence={ECO:0000250|UniProtKB:Q8IWA4};
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000269|PubMed:9230308}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:9230308}.
CC -!- TISSUE SPECIFICITY: Specifically expressed in male germ cells, in
CC spermatocytes and early spermatids. Not expressed in other tissues.
CC {ECO:0000269|PubMed:12128227, ECO:0000269|PubMed:9230308}.
CC -!- DEVELOPMENTAL STAGE: Associated with mitochondria in spermatids during
CC a narrow developmental window. Mitochondria align on the spindle
CC equator throughout meiotic divisions, but it is not expressed on
CC mitochondria until the last of meiosis II. In postmeiotic haploid
CC spermatids, it is associated with aggregating mitochondria and highly
CC expressed on onion stage Nebenkerns. Expressed at lower levels
CC associated with early elongation stage mitochondrial derivatives. Not
CC detected on more elongated mitochondria.
CC -!- DISRUPTION PHENOTYPE: Defective mitochondrial fusion in spermatids
CC results in onion-staged nebenkerns with irregular borders that contain
CC many small mitochondria (PubMed:18799731). At the leaf-blade stage
CC nebenkerns contain many small mitochondria instead of the two
CC mitochondria derivatives seen in wild-type spermatids
CC (PubMed:18799731). {ECO:0000269|PubMed:18799731}.
CC -!- SIMILARITY: Belongs to the TRAFAC class dynamin-like GTPase
CC superfamily. Dynamin/Fzo/YdjA family. Mitofusin subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU01055}.
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DR EMBL; U95821; AAC24457.1; -; mRNA.
DR EMBL; AE014297; AAF56110.2; -; Genomic_DNA.
DR EMBL; BT023200; AAY55616.1; -; mRNA.
DR EMBL; BT023220; AAY55636.1; -; mRNA.
DR EMBL; BT023232; AAY55648.1; -; mRNA.
DR RefSeq; NP_732840.1; NM_170060.2.
DR AlphaFoldDB; O18412; -.
DR SMR; O18412; -.
DR BioGRID; 67689; 15.
DR IntAct; O18412; 1.
DR STRING; 7227.FBpp0083791; -.
DR PaxDb; O18412; -.
DR DNASU; 42745; -.
DR EnsemblMetazoa; FBtr0084399; FBpp0083791; FBgn0011596.
DR GeneID; 42745; -.
DR KEGG; dme:Dmel_CG4568; -.
DR CTD; 42745; -.
DR FlyBase; FBgn0011596; fzo.
DR VEuPathDB; VectorBase:FBgn0011596; -.
DR eggNOG; KOG0448; Eukaryota.
DR GeneTree; ENSGT00390000013727; -.
DR HOGENOM; CLU_021212_1_0_1; -.
DR InParanoid; O18412; -.
DR OMA; WDMASSQ; -.
DR OrthoDB; 216494at2759; -.
DR PhylomeDB; O18412; -.
DR Reactome; R-DME-5205685; PINK1-PRKN Mediated Mitophagy.
DR Reactome; R-DME-9013419; RHOT2 GTPase cycle.
DR Reactome; R-DME-983231; Factors involved in megakaryocyte development and platelet production.
DR BioGRID-ORCS; 42745; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 42745; -.
DR PRO; PR:O18412; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0011596; Expressed in testis and 12 other tissues.
DR Genevisible; O18412; DM.
DR GO; GO:0016021; C:integral component of membrane; TAS:FlyBase.
DR GO; GO:0031306; C:intrinsic component of mitochondrial outer membrane; IBA:GO_Central.
DR GO; GO:0005740; C:mitochondrial envelope; IDA:FlyBase.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; IMP:UniProtKB.
DR GO; GO:0008053; P:mitochondrial fusion; IMP:FlyBase.
DR GO; GO:0051646; P:mitochondrion localization; IBA:GO_Central.
DR GO; GO:0007287; P:Nebenkern assembly; IMP:FlyBase.
DR GO; GO:0010636; P:positive regulation of mitochondrial fusion; IMP:UniProtKB.
DR GO; GO:0030382; P:sperm mitochondrion organization; IMP:FlyBase.
DR GO; GO:0007283; P:spermatogenesis; TAS:FlyBase.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR045063; Dynamin_N.
DR InterPro; IPR006884; Fzo/mitofusin_HR2.
DR InterPro; IPR030381; G_DYNAMIN_dom.
DR InterPro; IPR027088; Mitofusin-1.
DR InterPro; IPR027094; Mitofusin_fam.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR10465; PTHR10465; 1.
DR PANTHER; PTHR10465:SF2; PTHR10465:SF2; 1.
DR Pfam; PF00350; Dynamin_N; 1.
DR Pfam; PF04799; Fzo_mitofusin; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS51718; G_DYNAMIN_2; 1.
PE 1: Evidence at protein level;
KW Coiled coil; Developmental protein; Differentiation; GTP-binding;
KW Hydrolase; Membrane; Mitochondrion; Mitochondrion outer membrane;
KW Nucleotide-binding; Reference proteome; Spermatogenesis; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..718
FT /note="Transmembrane GTPase fzo"
FT /id="PRO_0000127680"
FT TOPO_DOM 1..575
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 576..588
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 589..591
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000255"
FT TRANSMEM 592..614
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 615..718
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 83..364
FT /note="Dynamin-type G"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055"
FT REGION 93..100
FT /note="G1 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055"
FT REGION 119..120
FT /note="G2 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055"
FT REGION 189..192
FT /note="G3 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055"
FT REGION 248..251
FT /note="G4 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055"
FT REGION 283..286
FT /note="G5 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055"
FT COILED 366..402
FT /evidence="ECO:0000255"
FT COILED 664..687
FT /evidence="ECO:0000255"
FT BINDING 96..101
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8IWA4"
FT BINDING 248..251
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8IWA4"
FT BINDING 297
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8IWA4"
FT MUTAGEN 99
FT /note="K->T: Induces male infertility."
FT /evidence="ECO:0000269|PubMed:9230308"
FT MUTAGEN 249
FT /note="R->L: Induces male infertility."
FT /evidence="ECO:0000269|PubMed:9230308"
SQ SEQUENCE 718 AA; 81565 MW; 152CF237AFB333BD CRC64;
MAESDSGEST SSVSSFISSS SSSRLSEFVD AKTELQDIYH DLSNYLSNFL TILEETVLLK
DRQMLEHLCA FSSRVEAIAK VLSRDRMKVA FFGRTSNGKS AVINALLHEK ILPSAMGHTT
SCFCQVQANG SNETEHVKVE QEDEHMELSA LSQLASAHSP GALKPSTLLQ VNMAKNRCSI
LDYDVVLMDT PGVDVTAQLD DCLDSYCMDA DVFILVLNAE STVSRVERQF FKDVASKLSR
PNLFILNNRW DKASSLEPEM EQKVKDQHME RCVNLLVDEL GVYSTAQEAW ERIYHVSALE
ALHIRNGQIT NPSGQTQQRY QEFLRFENDF SNCLAVSALK TKFGPHLLSA QKILNQLKST
LICPFIEKVS RLIDENKERR ANLNAEIEDW LILMQEDREA LQYCFEELTE MTQRVGRCVL
NDQIKTLIPS SVLSFSQPFH PEFPAQIGQY QRSLCAHLDK LLEDRVLQCL SIPLQRKILD
IEKEIGLPIA ENSCDWQLIY GLDCQSYMSD FQPDLRFRFS LGFTALWHRL EGNLPLHASP
FRIQKLQNGH KKCSPLPPLV NGNHWQMLES LVKSKGSLGT VLLSAMAIRS FNWPIVLILG
GLVGSFYIYE YAAWTTAAQE RSFKSQYARL LQQRLRSDVQ QTVSGFELQL RQHLATVRNC
WEAQSNETLN DLNVRTAELT KQIQSMEVLQ LSLKKFRDKG QLLASRLGDF QETYLTKS