UBP27_MOUSE
ID UBP27_MOUSE Reviewed; 438 AA.
AC Q8CEG8; B1ATV2; Q8BSW2; Q9JIG5;
DT 24-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT 24-MAR-2009, sequence version 2.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 27;
DE EC=3.4.19.12 {ECO:0000269|PubMed:27013495};
DE AltName: Full=Deubiquitinating enzyme 27;
DE AltName: Full=Ubiquitin thioesterase 27;
DE AltName: Full=Ubiquitin-specific-processing protease 27;
DE AltName: Full=X-linked ubiquitin carboxyl-terminal hydrolase 27;
GN Name=Usp27x {ECO:0000312|MGI:MGI:1859645}; Synonyms=Usp27;
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 [MRNA].
RX PubMed=10857745; DOI=10.1006/geno.2000.6173;
RA Means G.D., Toy D.Y., Baum P.R., Derry J.M.J.;
RT "A transcript map of a 2-Mb BAC contig in the proximal portion of the mouse
RT X chromosome and regional mapping of the scurfy mutation.";
RL Genomics 65:213-223(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Head, and Pituitary;
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 [3]
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 [4]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH BCL2L11 ISOFORM BIMEL,
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-87.
RX PubMed=27013495; DOI=10.15252/embr.201541392;
RA Weber A., Heinlein M., Dengjel J., Alber C., Singh P.K., Haecker G.;
RT "The deubiquitinase Usp27x stabilizes the BH3-only protein Bim and enhances
RT apoptosis.";
RL EMBO Rep. 17:724-738(2016).
RN [5]
RP FUNCTION.
RX PubMed=31534008; DOI=10.4049/jimmunol.1900514;
RA Guo Y., Jiang F., Kong L., Li B., Yang Y., Zhang L., Liu B., Zheng Y.,
RA Gao C.;
RT "USP27X deubiquitinates and stabilizes the DNA sensor cGAS to regulate
RT cytosolic DNA-mediated signaling.";
RL J. Immunol. 203:2049-2054(2019).
CC -!- FUNCTION: Deubiquitinase involved in innate antiviral immunity by
CC mediating deubiquitination of CGAS and DDX58/RIG-I (PubMed:31534008).
CC Negatively regulates DDX58/RIG-I by mediating 'Lys-63'-linked
CC deubiquitination of DDX58/RIG-I, inhibiting type I interferon signaling
CC (By similarity). Also regulates 'Lys-63'-linked ubiquitination level of
CC MDA5/IFIH1 (By similarity). Acts as a positive regulator of the cGAS-
CC STING pathway by catalyzing 'Lys-48'-linked deubiquitination of CGAS,
CC thereby promoting its stabilization (PubMed:31534008). Can reduce the
CC levels of BCL2L11/BIM ubiquitination and stabilize BCL2L11 in response
CC to the RAF-MAPK-degradation signal (PubMed:27013495). By acting on
CC BCL2L11 levels, may counteract the anti-apoptotic effects of MAPK
CC activity (PubMed:27013495). {ECO:0000250|UniProtKB:A6NNY8,
CC ECO:0000269|PubMed:27013495, ECO:0000269|PubMed:31534008}.
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:27013495};
CC -!- SUBUNIT: Interacts with phosphorylated BCL2L11 isoform BIMEL; this
CC interaction leads to BCL2L11 deubiquitination and stabilization.
CC {ECO:0000269|PubMed:27013495}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:27013495}.
CC Nucleus {ECO:0000269|PubMed:27013495}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}.
CC -!- CAUTION: Although strongly related to USP22, which deubiquitinates
CC histones, lacks the N-terminal UBP-type zinc finger, suggesting it does
CC not have the ability to deubiquitinate histones. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF66953.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAC25840.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC25840.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAC26935.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF229643; AAF66953.1; ALT_INIT; mRNA.
DR EMBL; AK028249; BAC25840.1; ALT_SEQ; mRNA.
DR EMBL; AK030383; BAC26935.1; ALT_INIT; mRNA.
DR EMBL; AL663104; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS52983.1; -.
DR RefSeq; NP_062334.2; NM_019461.4.
DR AlphaFoldDB; Q8CEG8; -.
DR SMR; Q8CEG8; -.
DR STRING; 10090.ENSMUSP00000111409; -.
DR MEROPS; C19.075; -.
DR iPTMnet; Q8CEG8; -.
DR PhosphoSitePlus; Q8CEG8; -.
DR MaxQB; Q8CEG8; -.
DR PaxDb; Q8CEG8; -.
DR PRIDE; Q8CEG8; -.
DR ProteomicsDB; 298410; -.
DR Antibodypedia; 73225; 69 antibodies from 14 providers.
DR DNASU; 54651; -.
DR Ensembl; ENSMUST00000115744; ENSMUSP00000111409; ENSMUSG00000046269.
DR Ensembl; ENSMUST00000178293; ENSMUSP00000137509; ENSMUSG00000046269.
DR Ensembl; ENSMUST00000191497; ENSMUSP00000139402; ENSMUSG00000046269.
DR GeneID; 54651; -.
DR KEGG; mmu:54651; -.
DR UCSC; uc012hee.1; mouse.
DR CTD; 389856; -.
DR MGI; MGI:1859645; Usp27x.
DR VEuPathDB; HostDB:ENSMUSG00000046269; -.
DR eggNOG; KOG1867; Eukaryota.
DR GeneTree; ENSGT00940000162674; -.
DR HOGENOM; CLU_008279_11_0_1; -.
DR InParanoid; Q8CEG8; -.
DR OMA; QCSMPGL; -.
DR OrthoDB; 929408at2759; -.
DR PhylomeDB; Q8CEG8; -.
DR TreeFam; TF323554; -.
DR BioGRID-ORCS; 54651; 3 hits in 72 CRISPR screens.
DR PRO; PR:Q8CEG8; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q8CEG8; protein.
DR Bgee; ENSMUSG00000046269; Expressed in supraoptic nucleus and 174 other tissues.
DR Genevisible; Q8CEG8; MM.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:UniProtKB.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; ISS:UniProtKB.
DR GO; GO:1990380; F:Lys48-specific deubiquitinase activity; IDA:UniProtKB.
DR GO; GO:0061578; F:Lys63-specific deubiquitinase activity; IDA:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; ISS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0060340; P:positive regulation of type I interferon-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; IDA:UniProtKB.
DR GO; GO:0071108; P:protein K48-linked deubiquitination; IDA:UniProtKB.
DR GO; GO:0070536; P:protein K63-linked deubiquitination; IDA:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IDA:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
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 Pfam; PF00443; UCH; 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 Cytoplasm; Hydrolase; Immunity; Innate immunity; Nucleus; Protease;
KW Reference proteome; Thiol protease; Ubl conjugation pathway.
FT CHAIN 1..438
FT /note="Ubiquitin carboxyl-terminal hydrolase 27"
FT /id="PRO_0000367515"
FT DOMAIN 78..421
FT /note="USP"
FT ACT_SITE 87
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT ACT_SITE 380
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT MUTAGEN 87
FT /note="C->A: Loss of catalytic activity. No effect on
FT BCL2L11-binding, BCL2L11 stabilization, nor on apoptosis."
FT /evidence="ECO:0000269|PubMed:27013495"
FT CONFLICT 74
FT /note="T -> A (in Ref. 1; AAF66953)"
FT /evidence="ECO:0000305"
FT CONFLICT 192
FT /note="P -> H (in Ref. 1; AAF66953)"
FT /evidence="ECO:0000305"
FT CONFLICT 251..252
FT /note="LN -> VD (in Ref. 1; AAF66953)"
FT /evidence="ECO:0000305"
FT CONFLICT 324
FT /note="T -> A (in Ref. 1; AAF66953)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 438 AA; 49599 MW; 159B156E0E00FEB9 CRC64;
MCKDYVYDID IEQIAKEEQG EALKLQASTS TEVSQQQCSV PGLGEKYPTW ETTKPELELL
GHNPRRRRIA SSFTIGLRGL INLGNTCFMN CIVQALTHTP ILRDFFLSDR HRCEMPSPEL
CLVCEMSSLF RELYSGNPSP HVPYKLLHLV WIHARHLAGY RQQDAHEFLI AALDVLHRHC
KGDDVGKVAS NPNHCNCIID QIFTGGLQSD VTCQACHGVS TTIDPCWDIS LDLPGSCTSF
WPMSPGRESS LNGESHIPGI TTLTDCLRRF TRPEHLGSSA KIKCGSCQSY QESTKQLTMK
KLPVVACFHF KRFEHSAKQR RKITTYISFP LELDMTPFMA SSKETRVNGQ LQLPTNSANN
ENKYSLFAVV NHQGTLESGH YTSFIRHHRD QWFKCDDAVI TKASIKDVLD SEGYLLFYHK
QVLEPEPEKV KEMTPQAY
