UBP45_HUMAN
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 03-AUG-2022, entry version 146.
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}.
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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; 36.
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; Q70EL2; -.
DR PeptideAtlas; Q70EL2; -.
DR PRIDE; Q70EL2; -.
DR ProteomicsDB; 68545; -. [Q70EL2-1]
DR ProteomicsDB; 68546; -. [Q70EL2-2]
DR ProteomicsDB; 68547; -. [Q70EL2-3]
DR Antibodypedia; 32010; 181 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 CTD; 85015; -.
DR DisGeNET; 85015; -.
DR GeneCards; USP45; -.
DR HGNC; HGNC:20080; USP45.
DR HPA; ENSG00000123552; Tissue enriched (brain).
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; RHHQAFH; -.
DR OrthoDB; 278083at2759; -.
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; 14 hits in 1125 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 153 other tissues.
DR ExpressionAtlas; Q70EL2; baseline and differential.
DR Genevisible; Q70EL2; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
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: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 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; unknown pathological
FT 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; unknown pathological
FT 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
