UBP45_DANRE
ID UBP45_DANRE Reviewed; 803 AA.
AC E9QG68;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 1.
DT 03-AUG-2022, entry version 81.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 45;
DE EC=3.4.19.12 {ECO:0000250|UniProtKB:Q70EL2};
DE AltName: Full=Ubiquitin specific peptidase 45 {ECO:0000312|ZFIN:ZDB-GENE-100211-2};
GN Name=usp45 {ECO:0000312|ZFIN:ZDB-GENE-100211-2};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=27613029; DOI=10.1007/978-1-4939-3756-1_3;
RA Toulis V., Garanto A., Marfany G.;
RT "Combining Zebrafish and Mouse Models to Test the Function of
RT Deubiquitinating Enzyme (Dubs) Genes in Development: Role of USP45 in the
RT Retina.";
RL Methods Mol. Biol. 1449:85-101(2016).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=30573563; DOI=10.1136/jmedgenet-2018-105709;
RA Yi Z., Ouyang J., Sun W., Xiao X., Li S., Jia X., Wang P., Zhang Q.;
RT "Biallelic mutations in USP45, encoding a deubiquitinating enzyme, are
RT associated with Leber congenital amaurosis.";
RL J. Med. Genet. 56:325-331(2019).
CC -!- FUNCTION: Catalyzes the deubiquitination of SPDL1 (By similarity).
CC Plays a role in the repair of UV-induced DNA damage via
CC deubiquitination of ERCC1, promoting its recruitment to DNA damage
CC sites (By similarity). May be involved in the maintenance of
CC photoreceptor function (PubMed:30573563). May play a role in normal
CC retinal development (PubMed:27613029). {ECO:0000250|UniProtKB:Q70EL2,
CC ECO:0000269|PubMed:27613029, ECO:0000269|PubMed:30573563}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide
CC and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-
CC residue protein attached to proteins as an intracellular targeting
CC signal).; EC=3.4.19.12; Evidence={ECO:0000250|UniProtKB:Q70EL2};
CC -!- SUBCELLULAR LOCATION: Photoreceptor inner segment
CC {ECO:0000269|PubMed:30573563}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q70EL2}. Nucleus {ECO:0000250|UniProtKB:Q70EL2}.
CC -!- TISSUE SPECIFICITY: Retina. {ECO:0000269|PubMed:27613029}.
CC -!- DISRUPTION PHENOTYPE: Morpholino-treated larvae show a reduction in eye
CC size and significantly fewers green cone photoreceptors compared to the
CC wild-type (PubMed:30573563). Moderate to severe eye morphological
CC defects, with a defective formation of the retinal structures
CC (PubMed:27613029). {ECO:0000269|PubMed:27613029,
CC ECO:0000269|PubMed:30573563}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000255|PROSITE-
CC ProRule:PRU01035}.
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; CR848729; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR848819; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_005158432.1; XM_005158375.3.
DR AlphaFoldDB; E9QG68; -.
DR Ensembl; ENSDART00000137232; ENSDARP00000118184; ENSDARG00000075013.
DR GeneID; 564004; -.
DR KEGG; dre:564004; -.
DR CTD; 85015; -.
DR ZFIN; ZDB-GENE-100211-2; usp45.
DR GeneTree; ENSGT00940000157719; -.
DR HOGENOM; CLU_007938_1_0_1; -.
DR OMA; RHHQAFH; -.
DR OrthoDB; 278083at2759; -.
DR PhylomeDB; E9QG68; -.
DR PRO; PR:E9QG68; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 16.
DR Bgee; ENSDARG00000075013; Expressed in early embryo and 21 other tissues.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0001917; C:photoreceptor inner segment; IDA:UniProtKB.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0016477; P:cell migration; ISS:UniProtKB.
DR GO; GO:0003407; P:neural retina development; IMP:UniProtKB.
DR GO; GO:0045494; P:photoreceptor cell maintenance; IMP:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; IEA:InterPro.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR001394; Peptidase_C19_UCH.
DR InterPro; IPR018200; USP_CS.
DR InterPro; IPR028889; USP_dom.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR001607; Znf_UBP.
DR Pfam; PF00443; UCH; 1.
DR Pfam; PF02148; zf-UBP; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS00972; USP_1; 1.
DR PROSITE; PS00973; USP_2; 1.
DR PROSITE; PS50235; USP_3; 1.
DR PROSITE; PS50271; ZF_UBP; 1.
PE 2: Evidence at transcript level;
KW Cytoplasm; Hydrolase; Metal-binding; Nucleus; Protease; Reference proteome;
KW Thiol protease; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..803
FT /note="Ubiquitin carboxyl-terminal hydrolase 45"
FT /id="PRO_0000448944"
FT DOMAIN 192..802
FT /note="USP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01035"
FT ZN_FING 36..153
FT /note="UBP-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT REGION 1..34
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 394..554
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..33
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 414..438
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 439..454
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 470..549
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 201
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01035"
FT ACT_SITE 739
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01035"
FT BINDING 38
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 40
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 62
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 65
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 85
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 88
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 93
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 100
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 104
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 113
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 126
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 129
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
SQ SEQUENCE 803 AA; 89221 MW; F751DCBEF7712C4B CRC64;
MRLKDPFSLK TADMTKRSNK PKKPRDEDSS DEVGGLTCQH VSRAVDLSSV KKAVTGSLWS
VCSDCLKERN VLEGETAGAH DILVCLKCGF QGCNQAEVQH STKHQQAHHS DSHCITISLT
TWKAWCFECK EELSTHCNKK ALAQTLDFLQ KQSAKATSGT SSKLIKLREE PAEYVDTQRG
KSPVNSTLIP VKGINNLGNT CFFNAVMQNL SQTHMLNDLI QDVKEKGHKM KISPSTETNL
GSLTVTLPSP EPLTSAMFLF LQSMKESGKG PVSPKILFNQ LCQKAPRFKG YQQQDSQELL
HYLLDSMRVE ETKRIKAGIL KAFNNPTEKT ADEETKRQVK AYGKEGVKLN FVDRIFVGEL
TSTIMCEECE HISTVKEAFI DISLPIIEER ISKPTNPARL GKSGREQDSL TSHDDSLAAH
SQANRNSRRL SGQKLQSRHS STSHDDRGPD TVSSRQEEDL CVAGRGLSSY RTDTMGSQSD
CSEKESNLQD SSNDADSEAS ESEWSPRIPS VSSHSSTSDK TSITTTLSTT THNPSLKSNP
SSTPLPSIRP QQGGAVEQLV SAVSKLGLVH TSTDTLPISH SQEELSETRD RDRQHHQGAF
QVLCHSYTPS SKECSVQSCL HQFTSIELLM GNNKLLCENC TDRRQRQMKR SDKKAEKVYT
SARKQMLISA LPPVVTLHLK RFHQAGMNLR KVNRHVDFPL LLDLAPFCSA TCKNLGSGER
VLYSLYGIVE HSGSMRGGHY AAYVKVRTPQ RKPEQRRNQS GSREACSAPQ GQWVYVSDTT
VQTVPESRVL NSQAYLLFYE ELL
