MUL1_MACFA
ID MUL1_MACFA Reviewed; 352 AA.
AC Q4R7G8;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 88.
DE RecName: Full=Mitochondrial ubiquitin ligase activator of NFKB 1;
DE EC=2.3.2.27;
DE AltName: Full=E3 ubiquitin-protein ligase MUL1;
DE AltName: Full=Protein Hades {ECO:0000250|UniProtKB:Q969V5};
DE AltName: Full=RING-type E3 ubiquitin transferase NFKB 1 {ECO:0000305};
GN Name=MUL1; ORFNames=QtsA-15365;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RG International consortium for macaque cDNA sequencing and analysis;
RT "DNA sequences of macaque genes expressed in brain or testis and its
RT evolutionary implications.";
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
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. Can ubiquitinate AKT1 preferentially
CC at 'Lys-284' involving 'Lys-48'-linked polyubiquitination and seems to
CC be involved in regulation of Akt signaling by targeting phosphorylated
CC Akt to proteosomal degradation. Mediates polyubiquitination of
CC cytoplasmic TP53 at 'Lys-24' which targets TP53 for proteasomal
CC degradation, thus reducing TP53 levels in the cytoplasm and
CC mitochondrion. Proposed to preferentially act as a SUMO E3 ligase at
CC physiological concentrations. Plays a role in the control of
CC mitochondrial morphology by promoting mitochondrial fragmentation, and
CC influences mitochondrial localization. Likely to promote mitochondrial
CC fission through negatively regulating the mitochondrial fusion proteins
CC MFN1 and MFN2, acting in a pathway that is parallel to the PRKN/PINK1
CC regulatory pathway. May also be involved in the sumoylation of the
CC membrane fission protein DNM1L. Inhibits cell growth. When
CC overexpressed, activates JNK through MAP3K7/TAK1 and induces caspase-
CC dependent apoptosis. Involved in the modulation of innate immune
CC defense against viruses by inhibiting DDX58-dependent antiviral
CC response (By similarity). Can mediate DDX58 sumoylation and disrupt its
CC polyubiquitination (By similarity). {ECO:0000250|UniProtKB:Q969V5}.
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 -!- 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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB168850; BAE00954.1; -; mRNA.
DR RefSeq; NP_001270010.1; NM_001283081.1.
DR AlphaFoldDB; Q4R7G8; -.
DR SMR; Q4R7G8; -.
DR STRING; 9541.XP_005544609.1; -.
DR GeneID; 101864962; -.
DR CTD; 79594; -.
DR eggNOG; KOG1571; Eukaryota.
DR OrthoDB; 926101at2759; -.
DR UniPathway; UPA00143; -.
DR UniPathway; UPA00886; -.
DR Proteomes; UP000233100; Unplaced.
DR GO; GO:0031307; C:integral component of mitochondrial outer membrane; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
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:0061630; F:ubiquitin protein ligase activity; ISS:UniProtKB.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
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: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:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; ISS:UniProtKB.
DR GO; GO:0016925; P:protein sumoylation; IEA:UniProtKB-UniPathway.
DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR GO; GO:1901028; P:regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway; ISS:UniProtKB.
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 2: Evidence at transcript level;
KW Isopeptide bond; Membrane; Metal-binding; Mitochondrion;
KW Mitochondrion outer membrane; Peroxisome; Reference proteome; Transferase;
KW Transmembrane; Transmembrane helix; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..352
FT /note="Mitochondrial ubiquitin ligase activator of NFKB 1"
FT /id="PRO_0000277661"
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 273
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"
SQ SEQUENCE 352 AA; 39827 MW; 4AB6245101E3B0D2 CRC64;
MENGGRPSLC QFILLGTTSV VTAALYSVYR QKAWVSQELK GAKKVHLGED LKSILSEAPG
KCVPYAVIEG AVRSVKETLN SQFVENCKGV IQRLTLQEHK MVWNRTTHLW NDCSKIIHQR
TNTVPFDLVP HEDGVDVAVR VLKPLDSVDL GLEAVYEKFH PSIQSFTDVI GHYISGERPK
GIQETEEMLK VGATLTGVGE LVLDNNSVRL QPPKQGMQYY LSSQDFDSLL QRQESSVRLW
KVLALVFGFA TCATLFFILR KQYLQRQERL RLKQMQEEFQ EHEAQLLSRA KPEDRESLKS
ACVVCLSSFK SCVFLECGHV CSCTECYRAL PEPKKCPICR QAITRVIPLY NS
