ULP4_CAEEL
ID ULP4_CAEEL Reviewed; 382 AA.
AC Q09275;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 22-SEP-2009, sequence version 2.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Ubiquitin-like protease 4;
DE EC=3.4.22.- {ECO:0000305|PubMed:30642431};
GN Name=ulp-4 {ECO:0000312|WormBase:C41C4.6};
GN ORFNames=C41C4.6 {ECO:0000312|WormBase:C41C4.6};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=25475837; DOI=10.1038/ncomms6485;
RA Pelisch F., Sonneville R., Pourkarimi E., Agostinho A., Blow J.J.,
RA Gartner A., Hay R.T.;
RT "Dynamic SUMO modification regulates mitotic chromosome assembly and cell
RT cycle progression in Caenorhabditis elegans.";
RL Nat. Commun. 5:5485-5485(2014).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=25187565; DOI=10.1073/pnas.1414748111;
RA Sapir A., Tsur A., Koorman T., Ching K., Mishra P., Bardenheier A.,
RA Podolsky L., Bening-Abu-Shach U., Boxem M., Chou T.F., Broday L.,
RA Sternberg P.W.;
RT "Controlled sumoylation of the mevalonate pathway enzyme HMGS-1 regulates
RT metabolism during aging.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:E3880-E3889(2014).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=30642431; DOI=10.7554/elife.41792;
RA Gao K., Li Y., Hu S., Liu Y.;
RT "SUMO peptidase ULP-4 regulates mitochondrial UPR-mediated innate immunity
RT and lifespan extension.";
RL Elife 8:0-0(2019).
CC -!- FUNCTION: Protease required for deconjugation of smo-1 conjugates from
CC target proteins which is necessary for cell cycle progression
CC (PubMed:25475837) (Probable). Required for respiration and the
CC maintenance of normal mitochondrial homeostasis (PubMed:25187565). In
CC response to mitochondrial stress, required for the removal of smo-1
CC conjugates from the transcription factor dve-1, which promotes the
CC translocation of dve-1 from the cytosol to the nucleus to initiate the
CC mitochondrial unfolded protein response (PubMed:30642431). Furthermore,
CC removes the smo-1 conjugates from the transcription factor atfs-1 to
CC promote its stability and activate the mitochondrial unfolded protein
CC response (PubMed:30642431). Also plays a role in promoting
CC mitochondrial unfolded protein response-mediated innate immunity
CC following infection with P.aeruginosa (PubMed:30642431).
CC {ECO:0000269|PubMed:25187565, ECO:0000269|PubMed:25475837,
CC ECO:0000269|PubMed:30642431, ECO:0000305|PubMed:30642431}.
CC -!- PATHWAY: Protein modification; protein sumoylation.
CC {ECO:0000269|PubMed:30642431}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing
CC center, centrosome {ECO:0000269|PubMed:25475837}. Nucleus
CC {ECO:0000269|PubMed:25187565}. Cytoplasm {ECO:0000269|PubMed:25187565}.
CC Mitochondrion matrix {ECO:0000269|PubMed:25187565}. Note=Localizes
CC around the metaphase plate and the pericentriolar region and in the
CC surroundings of the central spindle (PubMed:25475837). Translocates
CC from cytoplasm to mitochondrion at late developmental stages
CC (PubMed:25187565). {ECO:0000269|PubMed:25187565,
CC ECO:0000269|PubMed:25475837}.
CC -!- TISSUE SPECIFICITY: Expressed in hermaphrodite-specific neurons, head
CC muscles, body wall muscles and pharyngeal cells.
CC {ECO:0000269|PubMed:25187565}.
CC -!- DEVELOPMENTAL STAGE: First expressed in body wall muscles and
CC hypodermal cells during embryonic development to adulthood. Expressed
CC in the pharynx and hypodermis from larval stages L1 to L3. Expressed in
CC hermaphrodite-specific neurons from the L4 stage of larval development.
CC {ECO:0000269|PubMed:25187565}.
CC -!- INDUCTION: Up-regulated in response to mitochondrial stress induced by
CC antimycin A. {ECO:0000269|PubMed:30642431}.
CC -!- DISRUPTION PHENOTYPE: Animals are viable, but sterile and display
CC phenotypes including an increased lifespan, age-dependent decline in
CC their pharyngeal pumping rate and locomotion, reduced body fat and
CC decreased oxygen consumption and an impaired ability to maintain
CC mitochondrial membrane potential (PubMed:25187565). RNAi-mediated
CC knockdown causes a number of defects during the first embryonic mitotic
CC division including delayed spindle rotation, diminished spindle pole
CC separation, two-fold faster chromosomal segregation, increased distance
CC between chromosomes after anaphase onset, delayed mitotic exit, less
CC efficient removal of smo-1 from chromatin after anaphase onset and
CC prevention of air-2 from localizing to the spindle midzone
CC (PubMed:25475837). RNAi-mediated knockdown results in increased
CC sumoylation of hmgs-1 (PubMed:25187565). RNAi-mediated knockdown
CC prevents dve-1 translocation to the nucleus in response to
CC mitochondrial stress (PubMed:30642431). RNAi-mediated knockdown reduces
CC the levels of afts-1, but levels are restored following inhibition of
CC the proteasome (PubMed:30642431). RNAi-mediated knockdown reduces the
CC survival of animals and results in impaired activation of the
CC mitochondrial unfolded protein response following the inhibition of
CC respiration induced by antimycin A (PubMed:30642431). RNAi-mediated
CC knockdown impairs development and survival, and reduces the expression
CC of immune response genes lys-2, zip-2, clec-4, clec-65 and ugt-61
CC following infection with P.aeruginosa (PubMed:30642431).
CC {ECO:0000269|PubMed:25187565, ECO:0000269|PubMed:25475837,
CC ECO:0000269|PubMed:30642431}.
CC -!- SIMILARITY: Belongs to the peptidase C48 family. {ECO:0000305}.
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DR EMBL; BX284602; CAA88104.2; -; Genomic_DNA.
DR PIR; T19877; T19877.
DR RefSeq; NP_495703.2; NM_063302.4.
DR AlphaFoldDB; Q09275; -.
DR SMR; Q09275; -.
DR BioGRID; 39636; 4.
DR STRING; 6239.C41C4.6; -.
DR MEROPS; C48.A16; -.
DR PaxDb; Q09275; -.
DR EnsemblMetazoa; C41C4.6.1; C41C4.6.1; WBGene00006739.
DR GeneID; 174307; -.
DR KEGG; cel:CELE_C41C4.6; -.
DR UCSC; C41C4.6; c. elegans.
DR CTD; 174307; -.
DR WormBase; C41C4.6; CE43329; WBGene00006739; ulp-4.
DR eggNOG; KOG0779; Eukaryota.
DR GeneTree; ENSGT00940000172065; -.
DR HOGENOM; CLU_724090_0_0_1; -.
DR InParanoid; Q09275; -.
DR OMA; NHIRCHL; -.
DR OrthoDB; 800332at2759; -.
DR PhylomeDB; Q09275; -.
DR UniPathway; UPA00886; -.
DR PRO; PR:Q09275; -.
DR Proteomes; UP000001940; Chromosome II.
DR Bgee; WBGene00006739; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:WormBase.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0016929; F:deSUMOylase activity; IMP:UniProtKB.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IMP:UniProtKB.
DR GO; GO:0034514; P:mitochondrial unfolded protein response; IMP:UniProtKB.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IMP:UniProtKB.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; IMP:UniProtKB.
DR GO; GO:0016926; P:protein desumoylation; IMP:UniProtKB.
DR GO; GO:0016925; P:protein sumoylation; IEA:UniProtKB-UniPathway.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR003653; Peptidase_C48_C.
DR Pfam; PF02902; Peptidase_C48; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS50600; ULP_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Cytoskeleton; Hydrolase; Mitochondrion; Nucleus; Protease;
KW Reference proteome; Thiol protease; Ubl conjugation pathway.
FT CHAIN 1..382
FT /note="Ubiquitin-like protease 4"
FT /id="PRO_0000101737"
FT REGION 46..106
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 50..68
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 69..99
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 382 AA; 44290 MW; F96B54F281F96CF6 CRC64;
MEVSTSYCTP AVNFKYGSFQ DSDVSMREDD LFRMGSYNSQ GYYADGTHLD GSIGEEDETS
SGSNDQHMDF EEDDFDMESS MTEDLVDEDE EEEDEEDNDE WTNQKRTDNQ NSVAYYAAME
MLRIRFPFQS IAIRISDFCC LQEKDLLNDT MIDFYLNHIV EHVLPDSNGS NVTVLPSIFW
HNLSLRQHAF DSEDEKMMSD EQKMDLKFGD LHDFVADFDL QDFDYIVVPV NEWEHWSLAV
ICHPFTAQAR TVIFDSQLTA DLNNLQNMAT LIESFMKYSY EKRTGNAMPF PLPCILPQRM
PQQTNNFDCG IFIAEFARRF LLSPPKDLDN FDFAREYPDF STATKRTEMQ RVVLSLSTNR
ARWRPLVELL NGYSTAAPHR AL
