MUL1_HUMAN
ID MUL1_HUMAN Reviewed; 352 AA.
AC Q969V5; B5M497; Q7Z431; Q9H9B5;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Mitochondrial ubiquitin ligase activator of NFKB 1;
DE EC=2.3.2.27 {ECO:0000269|PubMed:18591963, ECO:0000269|PubMed:21597459, ECO:0000269|PubMed:22410793};
DE AltName: Full=E3 SUMO-protein ligase MUL1;
DE AltName: Full=E3 ubiquitin-protein ligase MUL1;
DE AltName: Full=Growth inhibition and death E3 ligase;
DE AltName: Full=Mitochondrial-anchored protein ligase;
DE AltName: Full=Protein Hades {ECO:0000303|PubMed:21597459};
DE AltName: Full=Putative NF-kappa-B-activating protein 266;
DE AltName: Full=RING finger protein 218;
DE AltName: Full=RING-type E3 ubiquitin transferase NFKB 1 {ECO:0000305};
GN Name=MUL1; Synonyms=C1orf166, GIDE, MAPL, MULAN, RNF218;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, SUBUNIT,
RP INTERACTION WITH MAP3K7, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DOMAIN,
RP AND MUTAGENESIS OF HIS-319.
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].
RC TISSUE=Lung;
RX PubMed=12761501; DOI=10.1038/sj.onc.1206406;
RA Matsuda A., Suzuki Y., Honda G., Muramatsu S., Matsuzaki O., Nagano Y.,
RA Doi T., Shimotohno K., Harada T., Nishida E., Hayashi H., Sugano S.;
RT "Large-scale identification and characterization of human genes that
RT activate NF-kappaB and MAPK signaling pathways.";
RL Oncogene 22:3307-3318(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Teratocarcinoma;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Melanoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Skin;
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 [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=18207745; DOI=10.1016/j.cub.2007.12.038;
RA Neuspiel M., Schauss A.C., Braschi E., Zunino R., Rippstein P.,
RA Rachubinski R.A., Andrade-Navarro M.A., McBride H.M.;
RT "Cargo-selected transport from the mitochondria to peroxisomes is mediated
RT by vesicular carriers.";
RL Curr. Biol. 18:102-108(2008).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, TOPOLOGY, AND
RP MUTAGENESIS OF ARG-260; LYS-261 AND CYS-339.
RX PubMed=18213395; DOI=10.1371/journal.pone.0001487;
RA Li W., Bengtson M.H., Ulbrich A., Matsuda A., Reddy V.A., Orth A.,
RA Chanda S.K., Batalov S., Joazeiro C.A.P.;
RT "Genome-wide and functional annotation of human E3 ubiquitin ligases
RT identifies MULAN, a mitochondrial E3 that regulates the organelle's
RT dynamics and signaling.";
RL PLoS ONE 3:E1487-E1487(2008).
RN [9]
RP FUNCTION AS SUMO LIGASE, INTERACTION WITH UBC9 AND DNM1L, AND PATHWAY.
RX PubMed=19407830; DOI=10.1038/embor.2009.86;
RA Braschi E., Zunino R., McBride H.M.;
RT "MAPL is a new mitochondrial SUMO E3 ligase that regulates mitochondrial
RT fission.";
RL EMBO Rep. 10:748-754(2009).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, INTERACTION WITH TP53, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF CYS-302 AND CYS-305.
RX PubMed=21597459; DOI=10.1038/cdd.2011.57;
RA Jung J.H., Bae S., Lee J.Y., Woo S.R., Cha H.J., Yoon Y., Suh K.S.,
RA Lee S.J., Park I.C., Jin Y.W., Lee K.H., An S., Lee J.H.;
RT "E3 ubiquitin ligase Hades negatively regulates the exonuclear function of
RT p53.";
RL Cell Death Differ. 18:1865-1875(2011).
RN [11]
RP FUNCTION IN UBIQUITINATION OF AKT1, AND CATALYTIC ACTIVITY.
RX PubMed=22410793; DOI=10.1038/cr.2012.38;
RA Bae S., Kim S.Y., Jung J.H., Yoon Y., Cha H.J., Lee H., Kim K., Kim J.,
RA An I.S., Kim J., Um H.D., Park I.C., Lee S.J., Nam S.Y., Jin Y.W.,
RA Lee J.H., An S.;
RT "Akt is negatively regulated by the MULAN E3 ligase.";
RL Cell Res. 22:873-885(2012).
RN [12]
RP FUNCTION, AND INTERACTION WITH MAVS.
RX PubMed=23399697; DOI=10.1038/icb.2013.7;
RA Jenkins K., Khoo J.J., Sadler A., Piganis R., Wang D., Borg N.A.,
RA Hjerrild K., Gould J., Thomas B.J., Nagley P., Hertzog P.J., Mansell A.;
RT "Mitochondrially localised MUL1 is a novel modulator of antiviral
RT signaling.";
RL Immunol. Cell Biol. 91:321-330(2013).
RN [13]
RP FUNCTION.
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).
RN [14]
RP UBIQUITINATION AT LYS-52; LYS-273 AND LYS-299.
RX PubMed=25621951; DOI=10.1038/ncb3097;
RA Cunningham C.N., Baughman J.M., Phu L., Tea J.S., Yu C., Coons M.,
RA Kirkpatrick D.S., Bingol B., Corn J.E.;
RT "USP30 and parkin homeostatically regulate atypical ubiquitin chains on
RT mitochondria.";
RL Nat. Cell Biol. 17:160-169(2015).
CC -!- FUNCTION: Exhibits weak E3 ubiquitin-protein ligase activity
CC (PubMed:18591963, PubMed:19407830, PubMed:22410793). E3 ubiquitin
CC ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the
CC form of a thioester and then directly transfer the ubiquitin to
CC targeted substrates (PubMed:18591963, PubMed:19407830,
CC PubMed:22410793). Can ubiquitinate AKT1 preferentially at 'Lys-284'
CC involving 'Lys-48'-linked polyubiquitination and seems to be involved
CC in regulation of Akt signaling by targeting phosphorylated Akt to
CC proteosomal degradation (PubMed:22410793). Mediates polyubiquitination
CC of cytoplasmic TP53 at 'Lys-24' which targets TP53 for proteasomal
CC degradation, thus reducing TP53 levels in the cytoplasm and
CC mitochondrion (PubMed:21597459). Proposed to preferentially act as a
CC SUMO E3 ligase at physiological concentrations (PubMed:19407830). Plays
CC a role in the control of mitochondrial morphology by promoting
CC mitochondrial fragmentation, and influences mitochondrial localization
CC (PubMed:19407830, PubMed:18207745, PubMed:18213395). Likely to promote
CC mitochondrial fission through negatively regulating the mitochondrial
CC fusion proteins MFN1 and MFN2, acting in a pathway that is parallel to
CC the PRKN/PINK1 regulatory pathway (PubMed:24898855). May also be
CC involved in the sumoylation of the membrane fission protein DNM1L
CC (PubMed:18207745, PubMed:19407830). Inhibits cell growth
CC (PubMed:18591963, PubMed:22410793). When overexpressed, activates JNK
CC through MAP3K7/TAK1 and induces caspase-dependent apoptosis
CC (PubMed:23399697). Involved in the modulation of innate immune defense
CC against viruses by inhibiting DDX58-dependent antiviral response
CC (PubMed:23399697). Can mediate DDX58 sumoylation and disrupt its
CC polyubiquitination (PubMed:23399697). {ECO:0000269|PubMed:18207745,
CC ECO:0000269|PubMed:18213395, ECO:0000269|PubMed:18591963,
CC ECO:0000269|PubMed:19407830, ECO:0000269|PubMed:22410793,
CC ECO:0000269|PubMed:23399697, 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:18591963,
CC ECO:0000269|PubMed:21597459, ECO:0000269|PubMed:22410793};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:21597459}.
CC -!- PATHWAY: Protein modification; protein sumoylation.
CC {ECO:0000269|PubMed:19407830}.
CC -!- SUBUNIT: Homooligomer (PubMed:18591963). Interacts with MAP3K7/TAK1
CC (PubMed:18591963). Interacts with UBC9 (PubMed:19407830). Interacts
CC with and sumoylates DNM1L (PubMed:19407830). Interacts with MAVS
CC (PubMed:23399697). Interacts with TP53 (via N-terminus); the
CC interaction leads to ubiquitination and proteasomal degradation of TP53
CC (PubMed:21597459). {ECO:0000269|PubMed:18591963,
CC ECO:0000269|PubMed:19407830, ECO:0000269|PubMed:21597459,
CC ECO:0000269|PubMed:23399697}.
CC -!- INTERACTION:
CC Q969V5; Q92624: APPBP2; NbExp=6; IntAct=EBI-744120, EBI-743771;
CC Q969V5; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-744120, EBI-10171774;
CC Q969V5; Q9BRK0: REEP2; NbExp=3; IntAct=EBI-744120, EBI-11337973;
CC Q969V5; Q9C026: TRIM9; NbExp=3; IntAct=EBI-744120, EBI-720828;
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000269|PubMed:18207745, ECO:0000269|PubMed:18213395,
CC ECO:0000269|PubMed:18591963, ECO:0000269|PubMed:21597459}; Multi-pass
CC membrane protein {ECO:0000255}. Peroxisome
CC {ECO:0000269|PubMed:18207745}. Note=Transported in mitochondrion-
CC derived vesicles from the mitochondrion to the peroxisome.
CC {ECO:0000269|PubMed:18207745}.
CC -!- TISSUE SPECIFICITY: Widely expressed with highest levels in the heart,
CC skeletal muscle, placenta, kidney and liver. Barely detectable in colon
CC and thymus. {ECO:0000269|PubMed:18213395, ECO:0000269|PubMed:18591963}.
CC -!- DOMAIN: The zinc finger domain is required for E3 ligase activity.
CC {ECO:0000269|PubMed:18591963}.
CC -!- PTM: Ubiquitinated by PRKN during mitophagy, leading to its degradation
CC and enhancement of mitophagy. Deubiquitinated by USP30.
CC {ECO:0000269|PubMed:25621951}.
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DR EMBL; EU935008; ACH72645.1; -; mRNA.
DR EMBL; AB097015; BAC77368.1; -; mRNA.
DR EMBL; AK022937; BAB14317.1; -; mRNA.
DR EMBL; AL833889; CAD38745.1; -; mRNA.
DR EMBL; AL391357; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC010101; AAH10101.1; -; mRNA.
DR EMBL; BC014010; AAH14010.1; -; mRNA.
DR CCDS; CCDS208.1; -.
DR RefSeq; NP_078820.2; NM_024544.2.
DR PDB; 6K2K; NMR; -; A=297-352.
DR PDB; 6M2C; X-ray; 2.70 A; E/F/G/H=298-352.
DR PDB; 6M2D; X-ray; 1.79 A; A/B/C/D/E/F=297-352.
DR PDBsum; 6K2K; -.
DR PDBsum; 6M2C; -.
DR PDBsum; 6M2D; -.
DR AlphaFoldDB; Q969V5; -.
DR SMR; Q969V5; -.
DR BioGRID; 122734; 102.
DR IntAct; Q969V5; 38.
DR MINT; Q969V5; -.
DR STRING; 9606.ENSP00000264198; -.
DR iPTMnet; Q969V5; -.
DR PhosphoSitePlus; Q969V5; -.
DR BioMuta; MUL1; -.
DR DMDM; 74760689; -.
DR EPD; Q969V5; -.
DR jPOST; Q969V5; -.
DR MassIVE; Q969V5; -.
DR MaxQB; Q969V5; -.
DR PaxDb; Q969V5; -.
DR PeptideAtlas; Q969V5; -.
DR PRIDE; Q969V5; -.
DR ProteomicsDB; 75853; -.
DR Antibodypedia; 2986; 280 antibodies from 30 providers.
DR DNASU; 79594; -.
DR Ensembl; ENST00000264198.5; ENSP00000264198.3; ENSG00000090432.7.
DR GeneID; 79594; -.
DR KEGG; hsa:79594; -.
DR MANE-Select; ENST00000264198.5; ENSP00000264198.3; NM_024544.3; NP_078820.2.
DR UCSC; uc001bdi.5; human.
DR CTD; 79594; -.
DR DisGeNET; 79594; -.
DR GeneCards; MUL1; -.
DR HGNC; HGNC:25762; MUL1.
DR HPA; ENSG00000090432; Low tissue specificity.
DR MIM; 612037; gene.
DR neXtProt; NX_Q969V5; -.
DR OpenTargets; ENSG00000090432; -.
DR PharmGKB; PA162396329; -.
DR VEuPathDB; HostDB:ENSG00000090432; -.
DR eggNOG; KOG1571; Eukaryota.
DR GeneTree; ENSGT00390000012141; -.
DR HOGENOM; CLU_050604_1_0_1; -.
DR InParanoid; Q969V5; -.
DR OMA; LKAAPQY; -.
DR OrthoDB; 926101at2759; -.
DR PhylomeDB; Q969V5; -.
DR TreeFam; TF325195; -.
DR BRENDA; 2.3.2.27; 2681.
DR PathwayCommons; Q969V5; -.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR Reactome; R-HSA-8951664; Neddylation.
DR Reactome; R-HSA-9755511; KEAP1-NFE2L2 pathway.
DR SignaLink; Q969V5; -.
DR SIGNOR; Q969V5; -.
DR UniPathway; UPA00143; -.
DR UniPathway; UPA00886; -.
DR BioGRID-ORCS; 79594; 13 hits in 1118 CRISPR screens.
DR GenomeRNAi; 79594; -.
DR Pharos; Q969V5; Tbio.
DR PRO; PR:Q969V5; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q969V5; protein.
DR Bgee; ENSG00000090432; Expressed in apex of heart and 163 other tissues.
DR ExpressionAtlas; Q969V5; baseline and differential.
DR Genevisible; Q969V5; HS.
DR GO; GO:0030424; C:axon; IMP:ParkinsonsUK-UCL.
DR GO; GO:0031307; C:integral component of mitochondrial outer membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; IMP:ParkinsonsUK-UCL.
DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0002039; F:p53 binding; IPI:UniProtKB.
DR GO; GO:0019789; F:SUMO transferase activity; IDA:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
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; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0071360; P:cellular response to exogenous dsRNA; IDA:UniProtKB.
DR GO; GO:0000266; P:mitochondrial fission; IMP:UniProtKB.
DR GO; GO:0051646; P:mitochondrion localization; IMP:UniProtKB.
DR GO; GO:0030308; P:negative regulation of cell growth; IDA:UniProtKB.
DR GO; GO:0071650; P:negative regulation of chemokine (C-C motif) ligand 5 production; IMP:UniProtKB.
DR GO; GO:0050689; P:negative regulation of defense response to virus by host; IMP:UniProtKB.
DR GO; GO:0045824; P:negative regulation of innate immune response; IMP:UniProtKB.
DR GO; GO:0010637; P:negative regulation of mitochondrial fusion; IDA:UniProtKB.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; IDA:UniProtKB.
DR GO; GO:0060339; P:negative regulation of type I interferon-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:1904925; P:positive regulation of autophagy of mitochondrion in response to mitochondrial depolarization; IEA:Ensembl.
DR GO; GO:1903861; P:positive regulation of dendrite extension; IEA:Ensembl.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; HMP:UniProtKB.
DR GO; GO:0090141; P:positive regulation of mitochondrial fission; IDA:UniProtKB.
DR GO; GO:0033235; P:positive regulation of protein sumoylation; IDA:UniProtKB.
DR GO; GO:0031648; P:protein destabilization; IMP:ParkinsonsUK-UCL.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IMP:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0051881; P:regulation of mitochondrial membrane potential; IEA:Ensembl.
DR GO; GO:1901028; P:regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway; IDA:UniProtKB.
DR GO; GO:0010821; P:regulation of mitochondrion organization; 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 3D-structure; 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_0000277660"
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:0000269|PubMed:25621951"
FT CROSSLNK 273
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25621951"
FT CROSSLNK 299
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25621951"
FT MUTAGEN 260
FT /note="R->A: Protein is targeted to the ER; when associated
FT with A-261."
FT /evidence="ECO:0000269|PubMed:18213395"
FT MUTAGEN 261
FT /note="K->A: Protein is targeted to the ER; when associated
FT with A-260."
FT /evidence="ECO:0000269|PubMed:18213395"
FT MUTAGEN 302
FT /note="C->S: Failure to reduce TP53 levels and abolishes
FT ligase activity; when associated with S-305."
FT /evidence="ECO:0000269|PubMed:21597459"
FT MUTAGEN 305
FT /note="C->S: Failure to reduce TP53 levels and abolishes
FT ligase activity; when associated with S-302."
FT /evidence="ECO:0000269|PubMed:21597459"
FT MUTAGEN 319
FT /note="H->A: Abolishes ligase activity. No effect on
FT mitochondrial localization."
FT /evidence="ECO:0000269|PubMed:18591963"
FT MUTAGEN 339
FT /note="C->A: Abolishes ligase activity."
FT /evidence="ECO:0000269|PubMed:18213395"
FT CONFLICT 240
FT /note="W -> C (in Ref. 3; BAB14317)"
FT /evidence="ECO:0000305"
FT CONFLICT 349
FT /note="L -> P (in Ref. 1; ACH72645 and 2; BAC77368)"
FT /evidence="ECO:0000305"
FT HELIX 297..300
FT /evidence="ECO:0007829|PDB:6M2D"
FT TURN 303..305
FT /evidence="ECO:0007829|PDB:6M2D"
FT STRAND 306..309
FT /evidence="ECO:0007829|PDB:6M2D"
FT STRAND 312..315
FT /evidence="ECO:0007829|PDB:6M2D"
FT TURN 316..318
FT /evidence="ECO:0007829|PDB:6M2C"
FT STRAND 319..322
FT /evidence="ECO:0007829|PDB:6M2C"
FT HELIX 324..329
FT /evidence="ECO:0007829|PDB:6M2D"
FT TURN 337..339
FT /evidence="ECO:0007829|PDB:6M2D"
FT STRAND 345..350
FT /evidence="ECO:0007829|PDB:6M2D"
SQ SEQUENCE 352 AA; 39800 MW; 6EF2B8BBFCE1801F CRC64;
MESGGRPSLC QFILLGTTSV VTAALYSVYR QKARVSQELK GAKKVHLGED LKSILSEAPG
KCVPYAVIEG AVRSVKETLN SQFVENCKGV IQRLTLQEHK MVWNRTTHLW NDCSKIIHQR
TNTVPFDLVP HEDGVDVAVR VLKPLDSVDL GLETVYEKFH PSIQSFTDVI GHYISGERPK
GIQETEEMLK VGATLTGVGE LVLDNNSVRL QPPKQGMQYY LSSQDFDSLL QRQESSVRLW
KVLALVFGFA TCATLFFILR KQYLQRQERL RLKQMQEEFQ EHEAQLLSRA KPEDRESLKS
ACVVCLSSFK SCVFLECGHV CSCTECYRAL PEPKKCPICR QAITRVIPLY NS
