USPL1_HUMAN
ID USPL1_HUMAN Reviewed; 1092 AA.
AC Q5W0Q7; Q14109; Q6AI45; Q8IY30; Q8IYE8;
DT 06-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 07-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=SUMO-specific isopeptidase USPL1;
DE EC=3.4.22.-;
DE AltName: Full=Ubiquitin-specific peptidase-like protein 1;
DE Short=USP-like 1;
GN Name=USPL1; Synonyms=C13orf22, D13S106;
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).
RC TISSUE=Melanoma;
RA Wilton A.N., Zehavi-Feferman T., Fleming J., Baker E., Chen L.Z.,
RA Cooper D.W.;
RT "A unique intronless gene or gene segment on chromosome 13 specifying a
RT highly charged amino acid sequence.";
RL Cytogenet. Cell Genet. 58:1985-1985(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Semen;
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=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS GLY-173;
RP SER-531; ASN-950 AND SER-1043.
RC TISSUE=Testis;
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 FUNCTION IN PROTEIN DESUMOYLATION, NON-CATALYTIC FUNCTION, CATALYTIC
RP ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF TRP-229; CYS-236;
RP TRP-237; HIS-421; 340-LEU-LEU-341 AND 494-ILE-VAL-495.
RX PubMed=22878415; DOI=10.1038/embor.2012.125;
RA Schulz S., Chachami G., Kozaczkiewicz L., Winter U., Stankovic-Valentin N.,
RA Haas P., Hofmann K., Urlaub H., Ovaa H., Wittbrodt J., Meulmeester E.,
RA Melchior F.;
RT "Ubiquitin-specific protease-like 1 (USPL1) is a SUMO isopeptidase with
RT essential, non-catalytic functions.";
RL EMBO Rep. 13:930-938(2012).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-909, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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 [7]
RP FUNCTION IN RNAPII-MEDIATED SNRNA TRANSCRIPTION, SUBCELLULAR LOCATION, AND
RP INTERACTION WITH ELL.
RX PubMed=24413172; DOI=10.1242/jcs.141788;
RA Hutten S., Chachami G., Winter U., Melchior F., Lamond A.I.;
RT "A role for the Cajal-body-associated SUMO isopeptidase USPL1 in snRNA
RT transcription mediated by RNA polymerase II.";
RL J. Cell Sci. 127:1065-1078(2014).
CC -!- FUNCTION: SUMO-specific isopeptidase involved in protein desumoylation.
CC Specifically binds SUMO proteins with a higher affinity for SUMO2 and
CC SUMO3 which it cleaves more efficiently. Also able to process full-
CC length SUMO proteins to their mature forms (PubMed:22878415). Plays a
CC key role in RNA polymerase-II-mediated snRNA transcription in the Cajal
CC bodies (PubMed:24413172). Is a component of complexes that can bind to
CC U snRNA genes (PubMed:24413172). {ECO:0000269|PubMed:22878415,
CC ECO:0000269|PubMed:24413172}.
CC -!- SUBUNIT: Interacts with ELL. {ECO:0000269|PubMed:24413172}.
CC -!- INTERACTION:
CC Q5W0Q7; P63165: SUMO1; NbExp=5; IntAct=EBI-2513899, EBI-80140;
CC Q5W0Q7; P61956: SUMO2; NbExp=2; IntAct=EBI-2513899, EBI-473220;
CC Q5W0Q7; P55854: SUMO3; NbExp=16; IntAct=EBI-2513899, EBI-474067;
CC -!- SUBCELLULAR LOCATION: Nucleus, Cajal body {ECO:0000269|PubMed:22878415,
CC ECO:0000269|PubMed:24413172}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q5W0Q7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5W0Q7-2; Sequence=VSP_023479;
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; X59131; CAA41848.1; -; mRNA.
DR EMBL; CR627370; CAH10469.1; -; mRNA.
DR EMBL; AL138681; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC036027; AAH36027.1; -; mRNA.
DR EMBL; BC038103; AAH38103.1; -; mRNA.
DR CCDS; CCDS81760.1; -. [Q5W0Q7-2]
DR CCDS; CCDS9336.1; -. [Q5W0Q7-1]
DR PIR; I37273; I37273.
DR RefSeq; NP_001308461.1; NM_001321532.1.
DR RefSeq; NP_001308462.1; NM_001321533.1. [Q5W0Q7-2]
DR RefSeq; NP_001308463.1; NM_001321534.1. [Q5W0Q7-2]
DR RefSeq; NP_005791.3; NM_005800.4. [Q5W0Q7-1]
DR RefSeq; XP_005266270.1; XM_005266213.3.
DR PDB; 7P99; X-ray; 1.80 A; A=213-516.
DR PDBsum; 7P99; -.
DR AlphaFoldDB; Q5W0Q7; -.
DR SMR; Q5W0Q7; -.
DR BioGRID; 115503; 29.
DR DIP; DIP-47278N; -.
DR IntAct; Q5W0Q7; 22.
DR MINT; Q5W0Q7; -.
DR STRING; 9606.ENSP00000255304; -.
DR MEROPS; C98.001; -.
DR iPTMnet; Q5W0Q7; -.
DR PhosphoSitePlus; Q5W0Q7; -.
DR BioMuta; USPL1; -.
DR DMDM; 74747969; -.
DR EPD; Q5W0Q7; -.
DR jPOST; Q5W0Q7; -.
DR MassIVE; Q5W0Q7; -.
DR MaxQB; Q5W0Q7; -.
DR PaxDb; Q5W0Q7; -.
DR PeptideAtlas; Q5W0Q7; -.
DR PRIDE; Q5W0Q7; -.
DR ProteomicsDB; 65772; -. [Q5W0Q7-1]
DR ProteomicsDB; 65773; -. [Q5W0Q7-2]
DR Antibodypedia; 22766; 21 antibodies from 10 providers.
DR DNASU; 10208; -.
DR Ensembl; ENST00000255304.9; ENSP00000255304.4; ENSG00000132952.12. [Q5W0Q7-1]
DR Ensembl; ENST00000614860.1; ENSP00000480656.1; ENSG00000132952.12. [Q5W0Q7-2]
DR GeneID; 10208; -.
DR KEGG; hsa:10208; -.
DR MANE-Select; ENST00000255304.9; ENSP00000255304.4; NM_005800.5; NP_005791.3.
DR UCSC; uc001utc.3; human. [Q5W0Q7-1]
DR CTD; 10208; -.
DR DisGeNET; 10208; -.
DR GeneCards; USPL1; -.
DR HGNC; HGNC:20294; USPL1.
DR HPA; ENSG00000132952; Low tissue specificity.
DR MIM; 617470; gene.
DR neXtProt; NX_Q5W0Q7; -.
DR OpenTargets; ENSG00000132952; -.
DR PharmGKB; PA134872379; -.
DR VEuPathDB; HostDB:ENSG00000132952; -.
DR eggNOG; ENOG502QRFM; Eukaryota.
DR GeneTree; ENSGT00390000002316; -.
DR HOGENOM; CLU_009764_0_0_1; -.
DR InParanoid; Q5W0Q7; -.
DR OMA; NANALCW; -.
DR PhylomeDB; Q5W0Q7; -.
DR TreeFam; TF350670; -.
DR BRENDA; 3.4.22.B70; 2681.
DR PathwayCommons; Q5W0Q7; -.
DR SignaLink; Q5W0Q7; -.
DR BioGRID-ORCS; 10208; 746 hits in 1084 CRISPR screens.
DR ChiTaRS; USPL1; human.
DR GenomeRNAi; 10208; -.
DR Pharos; Q5W0Q7; Tbio.
DR PRO; PR:Q5W0Q7; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; Q5W0Q7; protein.
DR Bgee; ENSG00000132952; Expressed in sperm and 198 other tissues.
DR Genevisible; Q5W0Q7; HS.
DR GO; GO:0015030; C:Cajal body; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0016929; F:deSUMOylase activity; IDA:UniProtKB.
DR GO; GO:0032183; F:SUMO binding; IDA:UniProtKB.
DR GO; GO:0030576; P:Cajal body organization; IMP:UniProtKB.
DR GO; GO:0008283; P:cell population proliferation; IMP:UniProtKB.
DR GO; GO:0016926; P:protein desumoylation; IDA:UniProtKB.
DR GO; GO:0009301; P:snRNA transcription; IMP:UniProtKB.
DR InterPro; IPR029388; DUF4650.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR028890; Peptidase_C98.
DR InterPro; IPR028889; USP_dom.
DR InterPro; IPR033505; USPL1.
DR PANTHER; PTHR15294; PTHR15294; 1.
DR Pfam; PF15509; DUF4650; 1.
DR Pfam; PF15499; Peptidase_C98; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS50235; USP_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Hydrolase; Nucleus; Phosphoprotein;
KW Protease; Reference proteome; Thiol protease.
FT CHAIN 1..1092
FT /note="SUMO-specific isopeptidase USPL1"
FT /id="PRO_0000279526"
FT DOMAIN 227..500
FT /note="USP"
FT REGION 145..168
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 185..207
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 236..495
FT /note="SUMO-binding"
FT REGION 713..749
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 797..859
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 904..930
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 145..167
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 189..207
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 907..929
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 236
FT /note="Nucleophile"
FT ACT_SITE 456
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT MOD_RES 909
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..329
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_023479"
FT VARIANT 173
FT /note="E -> G (in dbSNP:rs17853512)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_030916"
FT VARIANT 384
FT /note="P -> S (in dbSNP:rs3742303)"
FT /id="VAR_030917"
FT VARIANT 522
FT /note="A -> P (in dbSNP:rs17609459)"
FT /id="VAR_030918"
FT VARIANT 531
FT /note="L -> S (in dbSNP:rs7984952)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_030919"
FT VARIANT 583
FT /note="I -> V (in dbSNP:rs41412648)"
FT /id="VAR_051542"
FT VARIANT 739
FT /note="S -> C (in dbSNP:rs9578190)"
FT /id="VAR_030920"
FT VARIANT 786
FT /note="L -> I (in dbSNP:rs35371042)"
FT /id="VAR_051543"
FT VARIANT 950
FT /note="S -> N (in dbSNP:rs3742302)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_030921"
FT VARIANT 1043
FT /note="T -> S (in dbSNP:rs17857086)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_030922"
FT MUTAGEN 229
FT /note="W->L: Altered SUMO-binding and SUMO-specific
FT isopeptidase activity."
FT /evidence="ECO:0000269|PubMed:22878415"
FT MUTAGEN 236
FT /note="C->S: Abolishes the SUMO-specific isopeptidase
FT activity."
FT /evidence="ECO:0000269|PubMed:22878415"
FT MUTAGEN 237
FT /note="W->F: Altered SUMO-binding and SUMO-specific
FT isopeptidase activity."
FT /evidence="ECO:0000269|PubMed:22878415"
FT MUTAGEN 340..341
FT /note="LL->AA: Altered SUMO-binding and SUMO-specific
FT isopeptidase activity."
FT /evidence="ECO:0000269|PubMed:22878415"
FT MUTAGEN 421
FT /note="H->A: Altered SUMO-binding and SUMO-specific
FT isopeptidase activity."
FT /evidence="ECO:0000269|PubMed:22878415"
FT MUTAGEN 494..495
FT /note="IV->AA: Loss of SUMO-binding and catalytic
FT activity."
FT /evidence="ECO:0000269|PubMed:22878415"
SQ SEQUENCE 1092 AA; 120440 MW; FBE4626FC311E706 CRC64;
MMDSPKIGNG LPVIGPGTDI GISSLHMVGY LGKNFDSAKV PSDEYCPACR EKGKLKALKT
YRISFQESIF LCEDLQCIYP LGSKSLNNLI SPDLEECHTP HKPQKRKSLE SSYKDSLLLA
NSKKTRNYIA IDGGKVLNSK HNGEVYDETS SNLPDSSGQQ NPIRTADSLE RNEILEADTV
DMATTKDPAT VDVSGTGRPS PQNEGCTSKL EMPLESKCTS FPQALCVQWK NAYALCWLDC
ILSALVHSEE LKNTVTGLCS KEESIFWRLL TKYNQANTLL YTSQLSGVKD GDCKKLTSEI
FAEIETCLNE VRDEIFISLQ PQLRCTLGDM ESPVFAFPLL LKLETHIEKL FLYSFSWDFE
CSQCGHQYQN RHMKSLVTFT NVIPEWHPLN AAHFGPCNNC NSKSQIRKMV LEKVSPIFML
HFVEGLPQND LQHYAFHFEG CLYQITSVIQ YRANNHFITW ILDADGSWLE CDDLKGPCSE
RHKKFEVPAS EIHIVIWERK ISQVTDKEAA CLPLKKTNDQ HALSNEKPVS LTSCSVGDAA
SAETASVTHP KDISVAPRTL SQDTAVTHGD HLLSGPKGLV DNILPLTLEE TIQKTASVSQ
LNSEAFLLEN KPVAENTGIL KTNTLLSQES LMASSVSAPC NEKLIQDQFV DISFPSQVVN
TNMQSVQLNT EDTVNTKSVN NTDATGLIQG VKSVEIEKDA QLKQFLTPKT EQLKPERVTS
QVSNLKKKET TADSQTTTSK SLQNQSLKEN QKKPFVGSWV KGLISRGASF MPLCVSAHNR
NTITDLQPSV KGVNNFGGFK TKGINQKASH VSKKARKSAS KPPPISKPPA GPPSSNGTAA
HPHAHAASEV LEKSGSTSCG AQLNHSSYGN GISSANHEDL VEGQIHKLRL KLRKKLKAEK
KKLAALMSSP QSRTVRSENL EQVPQDGSPN DCESIEDLLN ELPYPIDIAS ESACTTVPGV
SLYSSQTHEE ILAELLSPTP VSTELSENGE GDFRYLGMGD SHIPPPVPSE FNDVSQNTHL
RQDHNYCSPT KKNPCEVQPD SLTNNACVRT LNLESPMKTD IFDEFFSSSA LNALANDTLD
LPHFDEYLFE NY
