MUL1_DROME
ID MUL1_DROME Reviewed; 338 AA.
AC Q9VZJ9;
DT 25-OCT-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Mitochondrial E3 ubiquitin protein ligase 1 {ECO:0000303|PubMed:24898855};
DE EC=2.3.2.27 {ECO:0000269|PubMed:24898855};
DE AltName: Full=Mitochondrial E3 ubiquitin protein transferase 1 {ECO:0000305};
GN Name=Mul1 {ECO:0000303|PubMed:24898855, ECO:0000312|FlyBase:FBgn0035483};
GN ORFNames=CG1134 {ECO:0000312|FlyBase:FBgn0035483};
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 {ECO:0000312|Proteomes:UP000000803};
RN [1] {ECO:0000312|Proteomes:UP000000803}
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 [2] {ECO:0000312|Proteomes:UP000000803}
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 [3] {ECO:0000312|EMBL:AAM29268.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Testis;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [4] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH MARF, UBIQUITINATION,
RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF HIS-307.
RX PubMed=24898855; DOI=10.7554/elife.01958;
RA Yun J., Puri R., Yang H., Lizzio M.A., Wu C., Sheng Z.H., Guo M.;
RT "MUL1 acts in parallel to the PINK1/parkin pathway in regulating mitofusin
RT and compensates for loss of PINK1/parkin.";
RL Elife 3:E01958-E01958(2014).
CC -!- FUNCTION: Exhibits weak E3 ubiquitin-protein ligase activity. E3
CC ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating
CC enzyme in the form of a thioester and then directly transfer the
CC ubiquitin to targeted substrates. Plays a role in the control of
CC mitochondrial morphology by promoting mitochondrial fission. Negatively
CC regulates the mitochondrial fusion protein marf by promoting its
CC ubiquitination, acting in a pathway that is parallel to the park/pink1
CC regulatory pathway. {ECO:0000269|PubMed:24898855}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000269|PubMed:24898855};
CC -!- SUBUNIT: Interacts with Marf. {ECO:0000269|PubMed:24898855}.
CC -!- INTERACTION:
CC Q9VZJ9; Q9VYX1: e(y)2; NbExp=4; IntAct=EBI-156824, EBI-2549759;
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000250|UniProtKB:Q969V5}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- PTM: Auto-ubiquitinated. {ECO:0000269|PubMed:24898855}.
CC -!- DISRUPTION PHENOTYPE: No gross morphological defects. Mitochondria are
CC slightly elongated. {ECO:0000269|PubMed:24898855}.
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DR EMBL; AE014296; AAF47822.1; -; Genomic_DNA.
DR EMBL; AE014296; ALI30453.1; -; Genomic_DNA.
DR EMBL; AY113263; AAM29268.1; -; mRNA.
DR RefSeq; NP_001303365.1; NM_001316436.1.
DR RefSeq; NP_647847.1; NM_139590.4.
DR AlphaFoldDB; Q9VZJ9; -.
DR IntAct; Q9VZJ9; 2.
DR STRING; 7227.FBpp0073049; -.
DR PaxDb; Q9VZJ9; -.
DR PRIDE; Q9VZJ9; -.
DR DNASU; 38472; -.
DR EnsemblMetazoa; FBtr0073193; FBpp0073049; FBgn0035483.
DR EnsemblMetazoa; FBtr0346806; FBpp0312381; FBgn0035483.
DR GeneID; 38472; -.
DR KEGG; dme:Dmel_CG1134; -.
DR UCSC; CG1134-RA; d. melanogaster.
DR CTD; 79594; -.
DR FlyBase; FBgn0035483; Mul1.
DR VEuPathDB; VectorBase:FBgn0035483; -.
DR eggNOG; KOG1571; Eukaryota.
DR GeneTree; ENSGT00390000012141; -.
DR HOGENOM; CLU_050604_1_0_1; -.
DR InParanoid; Q9VZJ9; -.
DR OMA; LKAAPQY; -.
DR OrthoDB; 926101at2759; -.
DR PhylomeDB; Q9VZJ9; -.
DR Reactome; R-DME-5689880; Ub-specific processing proteases.
DR Reactome; R-DME-8951664; Neddylation.
DR Reactome; R-DME-9755511; KEAP1-NFE2L2 pathway.
DR BioGRID-ORCS; 38472; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 38472; -.
DR PRO; PR:Q9VZJ9; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0035483; Expressed in testis and 25 other tissues.
DR GO; GO:0031307; C:integral component of mitochondrial outer membrane; ISS:FlyBase.
DR GO; GO:0005777; C:peroxisome; ISS:FlyBase.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISS:FlyBase.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; ISM:FlyBase.
DR GO; GO:0006996; P:organelle organization; IEA:InterPro.
DR GO; GO:0090141; P:positive regulation of mitochondrial fission; IMP:FlyBase.
DR GO; GO:0016567; P:protein ubiquitination; IMP:FlyBase.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR022170; MUL1-like.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF12483; GIDE; 1.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Isopeptide bond; Membrane; Metal-binding; Mitochondrion;
KW Mitochondrion outer membrane; Reference proteome; Transferase;
KW Transmembrane; Transmembrane helix; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..338
FT /note="Mitochondrial E3 ubiquitin protein ligase 1"
FT /id="PRO_0000442139"
FT TOPO_DOM 1..3
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q969V5"
FT TRANSMEM 4..24
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 25..227
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000250|UniProtKB:Q969V5"
FT TRANSMEM 228..248
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 249..338
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q969V5"
FT ZN_FING 290..326
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT MUTAGEN 307
FT /note="H->A: Abolishes ligase activity."
FT /evidence="ECO:0000269|PubMed:24898855"
SQ SEQUENCE 338 AA; 37844 MW; FD882A3020517AD2 CRC64;
MEFLHESVAL GVDLLILGLC AREYVHYKRT AKVLKAAPQY NIDGDLKSVV ERQRDKKIPY
AVIRGTVTPI GVPLRSSLVP SVSGVLQIVK LHEHRVTRGF AGFWTEQHKL LHESANEMPF
ELRNQSHGVE IVDALSAAVL DVDVVYDNYE PSNLSLFDHV FGFFSGVRQR GLQTTEEVLR
EGSFLTAIGE LELDGDTLRM QPSNEGPLFL TTATKSTLIK RFEDAKTTTI LKLVVCSTIS
AILVAFIAKK LYRKRKQERE EAKIRERLDT ERRERRARSR PHTLSQDQLC VVCSTNPKEI
ILLPCGHVCL CEDCAQKISV TCPVCRGSIV SKAAAFIA
