UBP45_MOUSE
ID UBP45_MOUSE Reviewed; 813 AA.
AC Q8K387; A2AJT1; Q8BU19; Q8BZ19;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 45;
DE EC=3.4.19.12 {ECO:0000250|UniProtKB:Q70EL2};
DE AltName: Full=Deubiquitinating enzyme 45;
DE AltName: Full=Ubiquitin thioesterase 45;
DE AltName: Full=Ubiquitin-specific-processing protease 45;
GN Name=Usp45;
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 [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Thymus, and Vagina;
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 [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-28; SER-29; SER-507 AND
RP SER-525, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
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 [5]
RP INTERACTION WITH ERCC1.
RX PubMed=25538220; DOI=10.15252/embj.201489184;
RA Perez-Oliva A.B., Lachaud C., Szyniarowski P., Munoz I., Macartney T.,
RA Hickson I., Rouse J., Alessi D.R.;
RT "USP45 deubiquitylase controls ERCC1-XPF endonuclease-mediated DNA damage
RT responses.";
RL EMBO J. 34:326-343(2015).
RN [6]
RP 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 [7]
RP FUNCTION, 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 (By similarity). Plays a role in cell migration (By
CC similarity). {ECO:0000250|UniProtKB:E9QG68,
CC ECO:0000250|UniProtKB:Q70EL2, 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 -!- SUBUNIT: Interacts with ERCC1 (PubMed:25538220). The catalytically
CC active form interacts with SPDL1 (By similarity).
CC {ECO:0000250|UniProtKB:Q70EL2, ECO:0000269|PubMed:25538220}.
CC -!- SUBCELLULAR LOCATION: Photoreceptor inner segment
CC {ECO:0000250|UniProtKB:Q70EL2}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q70EL2}. Nucleus {ECO:0000250|UniProtKB:Q70EL2}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8K387-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8K387-2; Sequence=VSP_023794;
CC -!- TISSUE SPECIFICITY: Retina. {ECO:0000269|PubMed:27613029}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice generated by CRISPR-Cas9-mediated
CC gene editing show severely reduced scotopic and photopic responses and
CC have significantly fewer green cone photoreceptors compared to wild-
CC type animals. {ECO:0000269|PubMed:30573563}.
CC -!- MISCELLANEOUS: [Isoform 1]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC29631.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK036903; BAC29631.1; ALT_INIT; mRNA.
DR EMBL; AK088073; BAC40129.1; -; mRNA.
DR EMBL; AL772187; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC027768; AAH27768.1; -; mRNA.
DR CCDS; CCDS38700.1; -. [Q8K387-1]
DR CCDS; CCDS71351.1; -. [Q8K387-2]
DR RefSeq; NP_001277354.1; NM_001290425.1. [Q8K387-2]
DR RefSeq; NP_690038.1; NM_152825.2. [Q8K387-1]
DR RefSeq; XP_006538424.1; XM_006538361.3. [Q8K387-1]
DR RefSeq; XP_011248434.1; XM_011250132.1. [Q8K387-1]
DR AlphaFoldDB; Q8K387; -.
DR BioGRID; 218782; 5.
DR STRING; 10090.ENSMUSP00000067109; -.
DR MEROPS; C19.064; -.
DR iPTMnet; Q8K387; -.
DR PhosphoSitePlus; Q8K387; -.
DR EPD; Q8K387; -.
DR MaxQB; Q8K387; -.
DR PaxDb; Q8K387; -.
DR PeptideAtlas; Q8K387; -.
DR PRIDE; Q8K387; -.
DR ProteomicsDB; 297707; -. [Q8K387-1]
DR ProteomicsDB; 297708; -. [Q8K387-2]
DR Antibodypedia; 32010; 181 antibodies from 25 providers.
DR DNASU; 77593; -.
DR Ensembl; ENSMUST00000040429; ENSMUSP00000048324; ENSMUSG00000040455. [Q8K387-2]
DR Ensembl; ENSMUST00000065111; ENSMUSP00000067109; ENSMUSG00000040455. [Q8K387-1]
DR Ensembl; ENSMUST00000108232; ENSMUSP00000103867; ENSMUSG00000040455. [Q8K387-1]
DR GeneID; 77593; -.
DR KEGG; mmu:77593; -.
DR UCSC; uc008sda.1; mouse. [Q8K387-1]
DR UCSC; uc008sdc.1; mouse. [Q8K387-2]
DR CTD; 85015; -.
DR MGI; MGI:101850; Usp45.
DR VEuPathDB; HostDB:ENSMUSG00000040455; -.
DR eggNOG; KOG1873; Eukaryota.
DR GeneTree; ENSGT00940000157719; -.
DR HOGENOM; CLU_007938_1_0_1; -.
DR InParanoid; Q8K387; -.
DR OMA; DNMFACE; -.
DR OrthoDB; 278083at2759; -.
DR PhylomeDB; Q8K387; -.
DR TreeFam; TF326075; -.
DR Reactome; R-MMU-5696395; Formation of Incision Complex in GG-NER.
DR BioGRID-ORCS; 77593; 2 hits in 108 CRISPR screens.
DR ChiTaRS; Usp45; mouse.
DR PRO; PR:Q8K387; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q8K387; protein.
DR Bgee; ENSMUSG00000040455; Expressed in CA1 field of hippocampus and 250 other tissues.
DR ExpressionAtlas; Q8K387; baseline and differential.
DR Genevisible; Q8K387; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0001917; C:photoreceptor inner segment; ISS: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:0006281; P:DNA repair; ISO:MGI.
DR GO; GO:0003407; P:neural retina development; ISS:UniProtKB.
DR GO; GO:0045494; P:photoreceptor cell maintenance; IMP:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; ISO:MGI.
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 SMART; SM00290; ZnF_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 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Hydrolase; Metal-binding; Nucleus;
KW Phosphoprotein; Protease; Reference proteome; Thiol protease;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..813
FT /note="Ubiquitin carboxyl-terminal hydrolase 45"
FT /id="PRO_0000280562"
FT DOMAIN 191..812
FT /note="USP"
FT ZN_FING 36..153
FT /note="UBP-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT REGION 1..62
FT /note="Interaction with ERCC1"
FT /evidence="ECO:0000305|PubMed:25538220"
FT REGION 1..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 405..552
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 411..428
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 429..462
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 463..489
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 200
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT ACT_SITE 745
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
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 101
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 105
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 114
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 127
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 130
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT MOD_RES 28
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 29
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 507
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 525
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 390..437
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_023794"
FT CONFLICT 595
FT /note="R -> G (in Ref. 1; BAC40129)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 813 AA; 90361 MW; ED1DD9B9F007B178 CRC64;
MRVKDPSKDL PEKGKRNKRP LLPHDEDSSD DIAVGLTCQH VSYAVSVNHV KKAVAESLWS
VCSECLKERR FCDGQPVLPA DVWLCLKCGL QGCGKNSESQ HSLRHFKSSG TESHCVVISL
STWVIWCYEC NEKLSTHCNK KVLAQIVDFL QKHAFKTQTG AFSRIIKLCE EKREAGEIKK
GKKGCTVPSV KGITNLGNTC FFNAVIQNLA QTYILFELMN EIKEDGTKFK ISLSSAPQLE
PLVVELSSPG PLTSALFLFL HSMKEAEKGP LSPKVLFNQL CQKAPRFKGF QQQDSQELLH
HLLDAVRTEE TKRIQASILK AFNNPTTKTA DDETRKKVKA YGKEGVKMNF IDRIFIGELT
STVMCEECAN ISTMKDPFID ISLPIIEERV SKPVLLGKMS KCRSLQETDQ DHNKGTVTVG
NAHQPRASRK HSSPNDKNQL SHDRKHLRKW PSEEEKTVVT HPKNDNLEAS PPASTLSTEA
SLNESLTDGS ERDASLESSV DADSEASEPE IASKQPVLLR SRGDSCGHAE QHPHLPLASE
LPQAKETHGG EEEMAEAIAE LHLSGTVTGN RDFHREKQPL NVPNNLCFSE GKHTRLHSAQ
NAFQTLSQSY VTTSKECSVQ SCLYQFTSME LLMGNNKLLC EDCTEKRRKC HKETSSAEKK
AGGVYTNARK QLLISAVPAI LILHLKRFHQ AGLSLRKVNR HVDFPLTLDL APFCAATCKN
ISVGEKVLYG LYGIVEHSGS MRGGHYTAYV KVRVPSRKLS ECITGRKTAA GLKEPDGELG
GHWVHVSDTY VQVVPESRAL SAQAYLLFYE RIL
