UBP26_HUMAN
ID UBP26_HUMAN Reviewed; 913 AA.
AC Q9BXU7; B9WRT6; Q5H9H4;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 26;
DE EC=3.4.19.12;
DE AltName: Full=Deubiquitinating enzyme 26;
DE AltName: Full=Ubiquitin thioesterase 26;
DE AltName: Full=Ubiquitin-specific-processing protease 26;
GN Name=USP26;
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].
RC TISSUE=Testis;
RX PubMed=11279525; DOI=10.1038/86927;
RA Wang P.J., McCarrey J.R., Yang F., Page D.C.;
RT "An abundance of X-linked genes expressed in spermatogonia.";
RL Nat. Genet. 27:422-426(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-304, AND INTERACTION
RP WITH AR.
RX PubMed=20501646; DOI=10.1158/1541-7786.mcr-09-0424;
RA Dirac A.M., Bernards R.;
RT "The deubiquitinating enzyme USP26 is a regulator of androgen receptor
RT signaling.";
RL Mol. Cancer Res. 8:844-854(2010).
RN [5]
RP VARIANTS PHE-364 AND TYR-475.
RX PubMed=15970005; DOI=10.1016/s1472-6483(10)61119-4;
RA Paduch D.A., Mielnik A., Schlegel P.N.;
RT "Novel mutations in testis-specific ubiquitin protease 26 gene may cause
RT male infertility and hypogonadism.";
RL Reprod. BioMed. Online 10:747-754(2005).
RN [6]
RP VARIANTS PHE-364 AND PHE-517.
RX PubMed=18377898; DOI=10.1016/j.fertnstert.2007.06.096;
RA Christensen G.L., Griffin J., Carrell D.T.;
RT "Sequence analysis of the X-linked USP26 gene in severe male factor
RT infertility patients and fertile controls.";
RL Fertil. Steril. 90:851-852(2008).
RN [7]
RP VARIANTS THR-123 INS; SER-165; PHE-364; TYR-475 AND ILE-579.
RX PubMed=18927127; DOI=10.1093/humrep/den374;
RA Ribarski I., Lehavi O., Yogev L., Hauser R., Bar-Shira Maymon B.,
RA Botchan A., Paz G., Yavetz H., Kleiman S.E.;
RT "USP26 gene variations in fertile and infertile men.";
RL Hum. Reprod. 24:477-484(2009).
CC -!- FUNCTION: Involved in the ubiquitin-dependent proteolytic pathway in
CC conjunction with the 26S proteasome (By similarity). Deubiquitinates
CC the androgen receptor and regulates the androgen receptor signaling
CC pathway. {ECO:0000250, ECO:0000269|PubMed:20501646}.
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;
CC -!- SUBUNIT: Interacts with AR. {ECO:0000269|PubMed:20501646}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20501646}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}.
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DR EMBL; AF285593; AAK31972.1; -; mRNA.
DR EMBL; Z81365; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC069073; AAH69073.1; -; mRNA.
DR EMBL; BC101190; AAI01191.1; -; mRNA.
DR EMBL; BC101191; AAI01192.1; -; mRNA.
DR CCDS; CCDS14635.1; -.
DR RefSeq; NP_114113.1; NM_031907.1.
DR RefSeq; XP_016885381.1; XM_017029892.1.
DR AlphaFoldDB; Q9BXU7; -.
DR SMR; Q9BXU7; -.
DR BioGRID; 123764; 17.
DR IntAct; Q9BXU7; 3.
DR STRING; 9606.ENSP00000423390; -.
DR MEROPS; C19.046; -.
DR iPTMnet; Q9BXU7; -.
DR PhosphoSitePlus; Q9BXU7; -.
DR BioMuta; USP26; -.
DR DMDM; 18202739; -.
DR PaxDb; Q9BXU7; -.
DR PeptideAtlas; Q9BXU7; -.
DR PRIDE; Q9BXU7; -.
DR ProteomicsDB; 79521; -.
DR Antibodypedia; 30257; 111 antibodies from 22 providers.
DR DNASU; 83844; -.
DR Ensembl; ENST00000370832.1; ENSP00000359869.1; ENSG00000134588.13.
DR Ensembl; ENST00000511190.6; ENSP00000423390.1; ENSG00000134588.13.
DR GeneID; 83844; -.
DR KEGG; hsa:83844; -.
DR MANE-Select; ENST00000511190.6; ENSP00000423390.1; NM_031907.3; NP_114113.1.
DR UCSC; uc010nrm.1; human.
DR CTD; 83844; -.
DR DisGeNET; 83844; -.
DR GeneCards; USP26; -.
DR HGNC; HGNC:13485; USP26.
DR HPA; ENSG00000134588; Not detected.
DR MIM; 300309; gene.
DR neXtProt; NX_Q9BXU7; -.
DR OpenTargets; ENSG00000134588; -.
DR PharmGKB; PA37782; -.
DR VEuPathDB; HostDB:ENSG00000134588; -.
DR eggNOG; KOG1868; Eukaryota.
DR GeneTree; ENSGT00940000166393; -.
DR HOGENOM; CLU_012557_0_0_1; -.
DR InParanoid; Q9BXU7; -.
DR OMA; DAYDFER; -.
DR OrthoDB; 129045at2759; -.
DR PhylomeDB; Q9BXU7; -.
DR TreeFam; TF323032; -.
DR PathwayCommons; Q9BXU7; -.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR SignaLink; Q9BXU7; -.
DR BioGRID-ORCS; 83844; 15 hits in 739 CRISPR screens.
DR GenomeRNAi; 83844; -.
DR Pharos; Q9BXU7; Tbio.
DR PRO; PR:Q9BXU7; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q9BXU7; protein.
DR Bgee; ENSG00000134588; Expressed in hindlimb stylopod muscle and 59 other tissues.
DR Genevisible; Q9BXU7; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IBA:GO_Central.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0016579; P:protein deubiquitination; IDA:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR CDD; cd13312; PH_USP37_like; 1.
DR Gene3D; 2.30.29.180; -; 1.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR001394; Peptidase_C19_UCH.
DR InterPro; IPR032069; USP37-like_PH.
DR InterPro; IPR038093; USP37-like_PH_sf.
DR InterPro; IPR018200; USP_CS.
DR InterPro; IPR028889; USP_dom.
DR Pfam; PF00443; UCH; 1.
DR Pfam; PF16674; UCH_N; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS00972; USP_1; 1.
DR PROSITE; PS00973; USP_2; 1.
DR PROSITE; PS50235; USP_3; 1.
PE 1: Evidence at protein level;
KW Hydrolase; Nucleus; Protease; Reference proteome; Thiol protease;
KW Ubl conjugation pathway.
FT CHAIN 1..913
FT /note="Ubiquitin carboxyl-terminal hydrolase 26"
FT /id="PRO_0000080655"
FT DOMAIN 295..886
FT /note="USP"
FT REGION 601..636
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 753..772
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 614..636
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 304
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT ACT_SITE 841
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT VARIANT 123
FT /note="T -> TT"
FT /evidence="ECO:0000269|PubMed:18927127"
FT /id="VAR_063413"
FT VARIANT 165
FT /note="L -> S (in dbSNP:rs61741870)"
FT /evidence="ECO:0000269|PubMed:18927127"
FT /id="VAR_063414"
FT VARIANT 364
FT /note="L -> F (in dbSNP:rs35397110)"
FT /evidence="ECO:0000269|PubMed:15970005,
FT ECO:0000269|PubMed:18377898, ECO:0000269|PubMed:18927127"
FT /id="VAR_063415"
FT VARIANT 475
FT /note="H -> Y (in dbSNP:rs41299088)"
FT /evidence="ECO:0000269|PubMed:15970005,
FT ECO:0000269|PubMed:18927127"
FT /id="VAR_063416"
FT VARIANT 517
FT /note="L -> F (in dbSNP:rs1323347016)"
FT /evidence="ECO:0000269|PubMed:18377898"
FT /id="VAR_063417"
FT VARIANT 579
FT /note="M -> I (in dbSNP:rs138385391)"
FT /evidence="ECO:0000269|PubMed:18927127"
FT /id="VAR_063418"
FT MUTAGEN 304
FT /note="C->S: Results in increased AR signaling."
FT /evidence="ECO:0000269|PubMed:20501646"
SQ SEQUENCE 913 AA; 104047 MW; BB70B09CDCBA3C48 CRC64;
MAALFLRGFV QIGNCKTGIS KSKEAFIEAV ERKKKDRLVL YFKSGKYSTF RLSDNIQNVV
LKSYRGNQNH LHLTLQNNNG LFIEGLSSTD AEQLKIFLDR VHQNEVQPPV RPGKGGSVFS
STTQKEINKT SFHKVDEKSS SKSFEIAKGS GTGVLQRMPL LTSKLTLTCG ELSENQHKKR
KRMLSSSSEM NEEFLKENNS VEYKKSKADC SRCVSYNREK QLKLKELEEN KKLECESSCI
MNATGNPYLD DIGLLQALTE KMVLVFLLQQ GYSDGYTKWD KLKLFFELFP EKICHGLPNL
GNTCYMNAVL QSLLSIPSFA DDLLNQSFPW GKIPLNALTM CLARLLFFKD TYNIEIKEML
LLNLKKAISA AAEIFHGNAQ NDAHEFLAHC LDQLKDNMEK LNTIWKPKSE FGEDNFPKQV
FADDPDTSGF SCPVITNFEL ELLHSIACKA CGQVILKTEL NNYLSINLPQ RIKAHPSSIQ
STFDLFFGAE ELEYKCAKCE HKTSVGVHSF SRLPRILIVH LKRYSLNEFC ALKKNDQEVI
ISKYLKVSSH CNEGTRPPLP LSEDGEITDF QLLKVIRKMT SGNISVSWPA TKESKDILAP
HIGSDKESEQ KKGQTVFKGA SRRQQQKYLG KNSKPNELES VYSGDRAFIE KEPLAHLMTY
LEDTSLCQFH KAGGKPASSP GTPLSKVDFQ TVPENPKRKK YVKTSKFVAF DRIINPTKDL
YEDKNIRIPE RFQKVSEQTQ QCDGMRICEQ APQQALPQSF PKPGTQGHTK NLLRPTKLNL
QKSNRNSLLA LGSNKNPRNK DILDKIKSKA KETKRNDDKG DHTYRLISVV SHLGKTLKSG
HYICDAYDFE KQIWFTYDDM RVLGIQEAQM QEDRRCTGYI FFYMHNEIFE EMLKREENAQ
LNSKEVEETL QKE
