ID UBP45_HUMAN Reviewed; 814 AA. AC Q70EL2; B2RXG0; Q5T062; Q86T44; Q86TC0; Q9BRU1; DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot. DT 18-MAY-2010, sequence version 3. DT 27-MAR-2024, entry version 155. DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 45; DE EC=3.4.19.12 {ECO:0000269|PubMed:25538220, ECO:0000269|PubMed:30258100}; DE AltName: Full=Deubiquitinating enzyme 45; DE AltName: Full=Ubiquitin thioesterase 45; DE AltName: Full=Ubiquitin-specific-processing protease 45; GN Name=USP45; 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] (ISOFORM 1), CATALYTIC ACTIVITY, AND TISSUE RP SPECIFICITY. RX PubMed=14715245; DOI=10.1016/j.bbrc.2003.12.050; RA Quesada V., Diaz-Perales A., Gutierrez-Fernandez A., Garabaya C., Cal S., RA Lopez-Otin C.; RT "Cloning and enzymatic analysis of 22 novel human ubiquitin-specific RT proteases."; RL Biochem. Biophys. Res. Commun. 314:54-62(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 248-814 (ISOFORM 1), AND VARIANT SER-778. RC TISSUE=Skeletal muscle; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANTS RP GLU-67; THR-521 AND SER-778. RC TISSUE=Bone marrow, and Brain cortex; 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 [5] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [6] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH ERCC1, RP AND MUTAGENESIS OF ASP-25; GLU-26; ASP-27; THR-37 AND CYS-199. 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 [7] RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH SPDL1, AND MUTAGENESIS OF RP CYS-199. RX PubMed=30258100; DOI=10.1038/s41598-018-32685-8; RA Conte C., Griffis E.R., Hickson I., Perez-Oliva A.B.; RT "USP45 and Spindly are part of the same complex implicated in cell RT migration."; RL Sci. Rep. 8:14375-14375(2018). RN [8] RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INVOLVEMENT IN LCA19, RP AND VARIANTS LCA19 GLN-312 AND 546-LYS--LEU-814 DEL. 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 (PubMed:30258100). 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 (PubMed:25538220). 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 CC (PubMed:30258100). {ECO:0000250|UniProtKB:E9QG68, CC ECO:0000269|PubMed:25538220, ECO:0000269|PubMed:30258100, CC 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:0000269|PubMed:14715245, CC ECO:0000269|PubMed:25538220, ECO:0000269|PubMed:30258100}; CC -!- SUBUNIT: Interacts with ERCC1 (PubMed:25538220). The catalytically CC active form interacts with SPDL1 (PubMed:30258100). CC {ECO:0000269|PubMed:25538220, ECO:0000269|PubMed:30258100}. CC -!- SUBCELLULAR LOCATION: Photoreceptor inner segment CC {ECO:0000269|PubMed:30573563}. Cytoplasm {ECO:0000269|PubMed:25538220}. CC Nucleus {ECO:0000269|PubMed:25538220}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q70EL2-1; Sequence=Displayed; CC Name=2; CC IsoId=Q70EL2-2; Sequence=VSP_023791, VSP_023792; CC Name=3; CC IsoId=Q70EL2-3; Sequence=VSP_023789, VSP_023790, VSP_023793; CC -!- TISSUE SPECIFICITY: Widely expressed. High expression is detected in CC the cerebellum. In the eye, it is expressed at high levels in the optic CC nerve, sclera and retina, with relatively low levels in the choroid, CC lens and retinal pigment epithelium (PubMed:30573563). CC {ECO:0000269|PubMed:14715245, ECO:0000269|PubMed:30573563}. CC -!- DISEASE: Leber congenital amaurosis 19 (LCA19) [MIM:618513]: A form of CC Leber congenital amaurosis, a severe dystrophy of the retina, typically CC becoming evident in the first years of life. Visual function is usually CC poor and often accompanied by nystagmus, sluggish or near-absent CC pupillary responses, photophobia, high hyperopia and keratoconus. LCA19 CC is an autosomal recessive form characterized by reduced vision in early CC childhood and severely reduced responses of both rods and cones. CC {ECO:0000269|PubMed:30573563}. Note=The disease may be caused by CC variants affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform 3]: May be produced at very low levels due to a CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA CC decay. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}. 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; AJ583819; CAE47746.2; -; mRNA. DR EMBL; AL713747; CAD89915.1; -; mRNA. DR EMBL; AL832030; CAD91148.1; -; mRNA. DR EMBL; AL137784; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL513550; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC005991; AAH05991.1; -; mRNA. DR EMBL; BC150648; AAI50649.1; -; mRNA. DR EMBL; BC157838; AAI57839.1; -; mRNA. DR CCDS; CCDS34501.1; -. [Q70EL2-1] DR CCDS; CCDS87419.1; -. [Q70EL2-2] DR RefSeq; NP_001073950.1; NM_001080481.1. [Q70EL2-1] DR RefSeq; NP_001332950.1; NM_001346021.1. [Q70EL2-1] DR RefSeq; NP_001332951.1; NM_001346022.1. [Q70EL2-1] DR RefSeq; XP_005267227.1; XM_005267170.4. [Q70EL2-1] DR AlphaFoldDB; Q70EL2; -. DR BioGRID; 124430; 37. DR IntAct; Q70EL2; 30. DR STRING; 9606.ENSP00000333376; -. DR BindingDB; Q70EL2; -. DR ChEMBL; CHEMBL4630841; -. DR MEROPS; C19.064; -. DR GlyGen; Q70EL2; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q70EL2; -. DR PhosphoSitePlus; Q70EL2; -. DR BioMuta; USP45; -. DR DMDM; 296453002; -. DR EPD; Q70EL2; -. DR jPOST; Q70EL2; -. DR MassIVE; Q70EL2; -. DR MaxQB; Q70EL2; -. DR PaxDb; 9606-ENSP00000333376; -. DR PeptideAtlas; Q70EL2; -. DR ProteomicsDB; 68545; -. [Q70EL2-1] DR ProteomicsDB; 68546; -. [Q70EL2-2] DR ProteomicsDB; 68547; -. [Q70EL2-3] DR Antibodypedia; 32010; 191 antibodies from 25 providers. DR DNASU; 85015; -. DR Ensembl; ENST00000327681.10; ENSP00000333376.6; ENSG00000123552.18. [Q70EL2-1] DR Ensembl; ENST00000500704.7; ENSP00000424372.1; ENSG00000123552.18. [Q70EL2-1] DR GeneID; 85015; -. DR KEGG; hsa:85015; -. DR MANE-Select; ENST00000500704.7; ENSP00000424372.1; NM_001346022.3; NP_001332951.1. DR UCSC; uc003ppx.4; human. [Q70EL2-1] DR AGR; HGNC:20080; -. DR CTD; 85015; -. DR DisGeNET; 85015; -. DR GeneCards; USP45; -. DR HGNC; HGNC:20080; USP45. DR HPA; ENSG00000123552; Low tissue specificity. DR MalaCards; USP45; -. DR MIM; 618439; gene. DR MIM; 618513; phenotype. DR neXtProt; NX_Q70EL2; -. DR OpenTargets; ENSG00000123552; -. DR Orphanet; 65; Leber congenital amaurosis. DR PharmGKB; PA134889604; -. DR VEuPathDB; HostDB:ENSG00000123552; -. DR eggNOG; KOG1873; Eukaryota. DR GeneTree; ENSGT00940000157719; -. DR InParanoid; Q70EL2; -. DR OMA; STWIVWC; -. DR OrthoDB; 227085at2759; -. DR PhylomeDB; Q70EL2; -. DR TreeFam; TF326075; -. DR PathwayCommons; Q70EL2; -. DR Reactome; R-HSA-5696395; Formation of Incision Complex in GG-NER. DR SignaLink; Q70EL2; -. DR SIGNOR; Q70EL2; -. DR BioGRID-ORCS; 85015; 15 hits in 1203 CRISPR screens. DR ChiTaRS; USP45; human. DR GenomeRNAi; 85015; -. DR Pharos; Q70EL2; Tbio. DR PRO; PR:Q70EL2; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; Q70EL2; Protein. DR Bgee; ENSG00000123552; Expressed in calcaneal tendon and 155 other cell types or tissues. DR ExpressionAtlas; Q70EL2; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:MGI. DR GO; GO:0001917; C:photoreceptor inner segment; IDA:UniProtKB. DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:FlyBase. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0016477; P:cell migration; IMP:UniProtKB. DR GO; GO:0006281; P:DNA repair; IMP:MGI. DR GO; GO:0070911; P:global genome nucleotide-excision repair; TAS:Reactome. DR GO; GO:0003407; P:neural retina development; ISS:UniProtKB. DR GO; GO:0045494; P:photoreceptor cell maintenance; ISS:UniProtKB. DR GO; GO:0016579; P:protein deubiquitination; IDA:FlyBase. DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW. DR CDD; cd02667; Peptidase_C19K; 1. DR Gene3D; 3.90.70.10; Cysteine proteinases; 2. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 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 PANTHER; PTHR21646; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1. DR PANTHER; PTHR21646:SF34; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE 45; 1. DR Pfam; PF00443; UCH; 1. DR Pfam; PF02148; zf-UBP; 1. DR SUPFAM; SSF54001; Cysteine proteinases; 1. DR SUPFAM; SSF57850; RING/U-box; 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. DR Genevisible; Q70EL2; HS. PE 1: Evidence at protein level; KW Alternative splicing; Cytoplasm; Disease variant; Hydrolase; KW Leber congenital amaurosis; Metal-binding; Nucleus; Phosphoprotein; KW Protease; Reference proteome; Thiol protease; Ubl conjugation pathway; KW Zinc; Zinc-finger. FT CHAIN 1..814 FT /note="Ubiquitin carboxyl-terminal hydrolase 45" FT /id="PRO_0000280561" FT DOMAIN 190..813 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:0000269|PubMed:25538220" FT REGION 1..28 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 418..443 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 479..533 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 423..443 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 484..503 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 506..529 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 199 FT /note="Nucleophile" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092, FT ECO:0000255|PROSITE-ProRule:PRU10093" FT ACT_SITE 746 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:0000250|UniProtKB:Q8K387" FT MOD_RES 29 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8K387" FT MOD_RES 508 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8K387" FT MOD_RES 526 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8K387" FT VAR_SEQ 1..262 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_023789" FT VAR_SEQ 263..282 FT /note="KETEKGPLSPKVLFNQLCQK -> MRSKKVVQNSRFFLPQTLSW (in FT isoform 3)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_023790" FT VAR_SEQ 283..289 FT /note="APRFKDF -> RVHLHLI (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_023791" FT VAR_SEQ 290..814 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_023792" FT VAR_SEQ 312..369 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_023793" FT VARIANT 67 FT /note="K -> E (in dbSNP:rs7744845)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_031167" FT VARIANT 312 FT /note="R -> Q (in LCA19; uncertain significance)" FT /evidence="ECO:0000269|PubMed:30573563" FT /id="VAR_083031" FT VARIANT 521 FT /note="R -> T (in dbSNP:rs41288947)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_060663" FT VARIANT 546..814 FT /note="Missing (in LCA19; uncertain significance)" FT /evidence="ECO:0000269|PubMed:30573563" FT /id="VAR_083032" FT VARIANT 778 FT /note="N -> S (in dbSNP:rs6570065)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:17974005" FT /id="VAR_031168" FT MUTAGEN 25 FT /note="D->A: Significant reduction in interaction with FT ERCC1. Complete loss of ability to interact with and FT deubiquitinate ERCC1; when associated with A-26." FT /evidence="ECO:0000269|PubMed:25538220" FT MUTAGEN 26 FT /note="E->A: Significant reduction in interaction with FT ERCC1. Complete loss of ability to interact with and FT deubiquitinate ERCC1; when associated with A-25." FT /evidence="ECO:0000269|PubMed:25538220" FT MUTAGEN 27 FT /note="D->A: Significant reduction in interaction with FT ERCC1." FT /evidence="ECO:0000269|PubMed:25538220" FT MUTAGEN 37 FT /note="T->A: Loss of protein expression." FT /evidence="ECO:0000269|PubMed:25538220" FT MUTAGEN 199 FT /note="C->A: Catalytically inactive. Loss of ability to FT deubiquitinate ERCC1. Loss of interaction with SPDL1 and FT ability to deubiquitinate SPDL1." FT /evidence="ECO:0000269|PubMed:25538220, FT ECO:0000269|PubMed:30258100" FT CONFLICT 603 FT /note="A -> V (in Ref. 2; CAD91148)" FT /evidence="ECO:0000305" FT CONFLICT 691 FT /note="Q -> K (in Ref. 1; CAE47746)" FT /evidence="ECO:0000305" FT CONFLICT 726 FT /note="D -> G (in Ref. 2; CAD89915)" FT /evidence="ECO:0000305" SQ SEQUENCE 814 AA; 91733 MW; DE4FCC0AD7AD6499 CRC64; MRVKDPTKAL PEKAKRSKRP TVPHDEDSSD DIAVGLTCQH VSHAISVNHV KRAIAENLWS VCSECLKERR FYDGQLVLTS DIWLCLKCGF QGCGKNSESQ HSLKHFKSSR TEPHCIIINL STWIIWCYEC DEKLSTHCNK KVLAQIVDFL QKHASKTQTS AFSRIMKLCE EKCETDEIQK GGKCRNLSVR GITNLGNTCF FNAVMQNLAQ TYTLTDLMNE IKESSTKLKI FPSSDSQLDP LVVELSRPGP LTSALFLFLH SMKETEKGPL SPKVLFNQLC QKAPRFKDFQ QQDSQELLHY LLDAVRTEET KRIQASILKA FNNPTTKTAD DETRKKVKAY GKEGVKMNFI DRIFIGELTS TVMCEECANI STVKDPFIDI SLPIIEERVS KPLLWGRMNK YRSLRETDHD RYSGNVTIEN IHQPRAAKKH SSSKDKSQLI HDRKCIRKLS SGETVTYQKN ENLEMNGDSL MFASLMNSES RLNESPTDDS EKEASHSESN VDADSEPSES ESASKQTGLF RSSSGSGVQP DGPLYPLSAG KLLYTKETDS GDKEMAEAIS ELRLSSTVTG DQDFDRENQP LNISNNLCFL EGKHLRSYSP QNAFQTLSQS YITTSKECSI QSCLYQFTSM ELLMGNNKLL CENCTKNKQK YQEETSFAEK KVEGVYTNAR KQLLISAVPA VLILHLKRFH QAGLSLRKVN RHVDFPLMLD LAPFCSATCK NASVGDKVLY GLYGIVEHSG SMREGHYTAY VKVRTPSRKL SEHNTKKKNV PGLKAADNES AGQWVHVSDT YLQVVPESRA LSAQAYLLFY ERVL //