MUL1_MOUSE
ID MUL1_MOUSE Reviewed; 352 AA.
AC Q8VCM5; A2AM82; A2AM84; B5M498; Q3TDK4; Q8BHF2; Q9DCV9;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 2.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Mitochondrial ubiquitin ligase activator of NFKB 1;
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:Q969V5};
DE AltName: Full=E3 ubiquitin-protein ligase MUL1;
DE AltName: Full=Growth inhibition and death E3 ligase;
DE AltName: Full=Protein Hades {ECO:0000250|UniProtKB:Q969V5};
DE AltName: Full=RING-type E3 ubiquitin transferase NFKB 1 {ECO:0000305};
GN Name=Mul1; Synonyms=Gide;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=18591963; DOI=10.1038/cr.2008.75;
RA Zhang B., Huang J., Li H.-L., Liu T., Wang Y.-Y., Waterman P., Mao A.-P.,
RA Xu L.-G., Zhai Z., Liu D., Marrack P., Shu H.-B.;
RT "GIDE is a mitochondrial E3 ubiquitin ligase that induces apoptosis and
RT slows growth.";
RL Cell Res. 18:900-910(2008).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J, and NOD;
RC TISSUE=Brain cortex, Head, Kidney, Liver, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION, AND TISSUE SPECIFICITY.
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 (By
CC similarity). E3 ubiquitin ligases accept ubiquitin from an E2
CC ubiquitin-conjugating enzyme in the form of a thioester and then
CC directly transfer the ubiquitin to targeted substrates (By similarity).
CC Can ubiquitinate AKT1 preferentially at 'Lys-284' involving 'Lys-48'-
CC linked polyubiquitination and seems to be involved in regulation of Akt
CC signaling by targeting phosphorylated Akt to proteosomal degradation
CC (By similarity). Mediates polyubiquitination of cytoplasmic TP53 at
CC 'Lys-27' which targets TP53 for proteasomal degradation, thus reducing
CC TP53 levels in the cytoplasm and mitochondrion (By similarity).
CC Proposed to preferentially act as a SUMO E3 ligase at physiological
CC concentrations (By similarity). Plays a role in the control of
CC mitochondrial morphology by promoting mitochondrial fragmentation, and
CC influences mitochondrial localization (By similarity). Likely to
CC promote mitochondrial fission through negatively regulating the
CC mitochondrial fusion proteins MFN1 and MFN2, acting in a pathway that
CC is parallel to the PRKN/PINK1 regulatory pathway (PubMed:24898855). May
CC also be involved in the sumoylation of the membrane fission protein
CC DNM1L (By similarity). Inhibits cell growth (By similarity). When
CC overexpressed, activates JNK through MAP3K7/TAK1 and induces caspase-
CC dependent apoptosis (By similarity). Involved in the modulation of
CC innate immune defense against viruses by inhibiting DDX58-dependent
CC antiviral response (By similarity). Can mediate DDX58 sumoylation and
CC disrupt its polyubiquitination (By similarity).
CC {ECO:0000250|UniProtKB:Q969V5, 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:0000250|UniProtKB:Q969V5};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q969V5}.
CC -!- PATHWAY: Protein modification; protein sumoylation.
CC {ECO:0000250|UniProtKB:Q969V5}.
CC -!- SUBUNIT: Homooligomer. Interacts with MAP3K7/TAK1. Interacts with UBC9.
CC Interacts with and sumoylates DNM1L. Interacts with MAVS. Interacts
CC with TP53 (via N-terminus); the interaction leads to ubiquitination and
CC proteasomal degradation of TP53. {ECO:0000250|UniProtKB:Q969V5}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000250|UniProtKB:Q969V5}; Multi-pass membrane protein
CC {ECO:0000255}. Peroxisome {ECO:0000250|UniProtKB:Q969V5}.
CC Note=Transported in mitochondrion-derived vesicles from the
CC mitochondrion to the peroxisome. {ECO:0000250|UniProtKB:Q969V5}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8VCM5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8VCM5-2; Sequence=VSP_034454, VSP_034455;
CC Name=3;
CC IsoId=Q8VCM5-3; Sequence=VSP_034453;
CC -!- TISSUE SPECIFICITY: Expressed in cortical neurons (at protein level).
CC {ECO:0000269|PubMed:24898855}.
CC -!- DOMAIN: The zinc finger domain is required for E3 ligase activity.
CC {ECO:0000250|UniProtKB:Q969V5}.
CC -!- PTM: Ubiquitinated by PRKN during mitophagy, leading to its degradation
CC and enhancement of mitophagy. Deubiquitinated by USP30.
CC {ECO:0000250|UniProtKB:Q969V5}.
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DR EMBL; EU935009; ACH72646.1; -; mRNA.
DR EMBL; AK002416; BAB22084.1; -; mRNA.
DR EMBL; AK044088; BAC31768.1; -; mRNA.
DR EMBL; AK076419; BAC36332.1; -; mRNA.
DR EMBL; AK083295; BAC38848.1; -; mRNA.
DR EMBL; AK153956; BAE32279.1; -; mRNA.
DR EMBL; AK170149; BAE41597.1; -; mRNA.
DR EMBL; AL807249; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC019516; AAH19516.1; -; mRNA.
DR CCDS; CCDS18828.1; -. [Q8VCM5-1]
DR RefSeq; NP_080965.2; NM_026689.3. [Q8VCM5-1]
DR RefSeq; XP_006539197.1; XM_006539134.3. [Q8VCM5-3]
DR AlphaFoldDB; Q8VCM5; -.
DR SMR; Q8VCM5; -.
DR BioGRID; 212817; 2.
DR STRING; 10090.ENSMUSP00000039604; -.
DR iPTMnet; Q8VCM5; -.
DR PhosphoSitePlus; Q8VCM5; -.
DR EPD; Q8VCM5; -.
DR MaxQB; Q8VCM5; -.
DR PaxDb; Q8VCM5; -.
DR PeptideAtlas; Q8VCM5; -.
DR PRIDE; Q8VCM5; -.
DR ProteomicsDB; 290221; -. [Q8VCM5-1]
DR ProteomicsDB; 290222; -. [Q8VCM5-2]
DR ProteomicsDB; 290223; -. [Q8VCM5-3]
DR Antibodypedia; 2986; 280 antibodies from 30 providers.
DR DNASU; 68350; -.
DR Ensembl; ENSMUST00000044058; ENSMUSP00000039604; ENSMUSG00000041241. [Q8VCM5-1]
DR Ensembl; ENSMUST00000105813; ENSMUSP00000101439; ENSMUSG00000041241. [Q8VCM5-3]
DR Ensembl; ENSMUST00000105815; ENSMUSP00000101441; ENSMUSG00000041241. [Q8VCM5-2]
DR GeneID; 68350; -.
DR KEGG; mmu:68350; -.
DR UCSC; uc008vky.1; mouse. [Q8VCM5-1]
DR CTD; 79594; -.
DR MGI; MGI:1915600; Mul1.
DR VEuPathDB; HostDB:ENSMUSG00000041241; -.
DR eggNOG; KOG1571; Eukaryota.
DR GeneTree; ENSGT00390000012141; -.
DR HOGENOM; CLU_050604_1_0_1; -.
DR InParanoid; Q8VCM5; -.
DR OMA; LKAAPQY; -.
DR OrthoDB; 926101at2759; -.
DR PhylomeDB; Q8VCM5; -.
DR TreeFam; TF325195; -.
DR Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR Reactome; R-MMU-8951664; Neddylation.
DR Reactome; R-MMU-9755511; KEAP1-NFE2L2 pathway.
DR UniPathway; UPA00143; -.
DR UniPathway; UPA00886; -.
DR BioGRID-ORCS; 68350; 3 hits in 76 CRISPR screens.
DR ChiTaRS; Mul1; mouse.
DR PRO; PR:Q8VCM5; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q8VCM5; protein.
DR Bgee; ENSMUSG00000041241; Expressed in facial nucleus and 251 other tissues.
DR Genevisible; Q8VCM5; MM.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0031307; C:integral component of mitochondrial outer membrane; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005777; C:peroxisome; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0002039; F:p53 binding; ISS:UniProtKB.
DR GO; GO:0019789; F:SUMO transferase activity; ISO:MGI.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISS:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IBA:GO_Central.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0071360; P:cellular response to exogenous dsRNA; ISS:UniProtKB.
DR GO; GO:0000266; P:mitochondrial fission; ISS:UniProtKB.
DR GO; GO:0051646; P:mitochondrion localization; ISS:UniProtKB.
DR GO; GO:0030308; P:negative regulation of cell growth; ISS:UniProtKB.
DR GO; GO:0071650; P:negative regulation of chemokine (C-C motif) ligand 5 production; ISS:UniProtKB.
DR GO; GO:0050689; P:negative regulation of defense response to virus by host; ISS:UniProtKB.
DR GO; GO:0045824; P:negative regulation of innate immune response; ISS:UniProtKB.
DR GO; GO:0010637; P:negative regulation of mitochondrial fusion; ISO:MGI.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; ISS:UniProtKB.
DR GO; GO:0060339; P:negative regulation of type I interferon-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:1904925; P:positive regulation of autophagy of mitochondrion in response to mitochondrial depolarization; IMP:ParkinsonsUK-UCL.
DR GO; GO:1903861; P:positive regulation of dendrite extension; IMP:ParkinsonsUK-UCL.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0090141; P:positive regulation of mitochondrial fission; ISO:MGI.
DR GO; GO:0033235; P:positive regulation of protein sumoylation; ISO:MGI.
DR GO; GO:0031648; P:protein destabilization; ISO:MGI.
DR GO; GO:0000209; P:protein polyubiquitination; ISS:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; ISO:MGI.
DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0051881; P:regulation of mitochondrial membrane potential; IGI:ParkinsonsUK-UCL.
DR GO; GO:1901028; P:regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway; ISS:UniProtKB.
DR GO; GO:0010821; P:regulation of mitochondrion organization; ISO:MGI.
DR GO; GO:0031647; P:regulation of protein stability; IMP:ParkinsonsUK-UCL.
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 PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Apoptosis; Isopeptide bond; Membrane; Metal-binding;
KW Mitochondrion; Mitochondrion outer membrane; Peroxisome;
KW Reference proteome; Transferase; Transmembrane; Transmembrane helix;
KW Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..352
FT /note="Mitochondrial ubiquitin ligase activator of NFKB 1"
FT /id="PRO_0000277662"
FT TOPO_DOM 1..8
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 9..29
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 30..238
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000255"
FT TRANSMEM 239..259
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 260..352
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT ZN_FING 302..340
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT CROSSLNK 52
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q969V5"
FT CROSSLNK 299
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q969V5"
FT VAR_SEQ 1..40
FT /note="MESGSRPSLGQVILLGTSSMVTAVLYSIYRQKAQVAQELK -> MVVVLCWL
FT EFHSPSAKDLFWQLYGRWTLEPKSYHQ (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_034453"
FT VAR_SEQ 111..123
FT /note="NDYSKIIHQRTNT -> CVSSGFYTSEVVV (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_034454"
FT VAR_SEQ 124..352
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_034455"
FT CONFLICT 38
FT /note="E -> V (in Ref. 2; BAE41597)"
FT /evidence="ECO:0000305"
FT CONFLICT 208
FT /note="V -> F (in Ref. 2; BAB22084)"
FT /evidence="ECO:0000305"
FT CONFLICT 242
FT /note="I -> V (in Ref. 1; ACH72646 and 4; AAH19516)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 352 AA; 39835 MW; 252530F1BD917871 CRC64;
MESGSRPSLG QVILLGTSSM VTAVLYSIYR QKAQVAQELK GAKKIHLGED LKGILSEAPG
KCVPYAVIEG AVRSVKETLN SQFVENCKGV IQRLSLQEHK MVWNRTTHLW NDYSKIIHQR
TNTVPFDLVP HEDGVAVSVR VLKPLDSVDL GLETVYEKFH PSVQSFTDAI GHYISGERPK
GIQETEEMLK VGATLTGIGE LVLDNNAVRL QPPKQGMQYY LSSQDFDSLL HRQESSVRLW
KILVLVFGFA TCATLFFILR KQYLHRQERL RQQQLQEEFL EHEAQLLSQA SPEDRESLKS
ACVVCLSNFK SCVFLECGHV CSCRQCYLAL PEPKRCPICR REITRVIPLY NS
