UBP28_MOUSE
ID UBP28_MOUSE Reviewed; 1051 AA.
AC Q5I043; Q6NZP3; Q6ZPP1; Q8BWI1;
DT 13-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 28;
DE EC=3.4.19.12;
DE AltName: Full=Deubiquitinating enzyme 28;
DE AltName: Full=Ubiquitin thioesterase 28;
DE AltName: Full=Ubiquitin-specific-processing protease 28;
GN Name=Usp28; Synonyms=Kiaa1515;
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 [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Brain, and Embryonic germ cell;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 292-1051.
RC STRAIN=C57BL/6J; TISSUE=Lung;
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 MRNA] OF 392-1051.
RC TISSUE=Embryonic tail;
RX PubMed=14621295; DOI=10.1093/dnares/10.4.167;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: III.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:167-180(2003).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-555, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Deubiquitinase involved in DNA damage response checkpoint and
CC MYC proto-oncogene stability. Involved in DNA damage induced apoptosis
CC by specifically deubiquitinating proteins of the DNA damage pathway
CC such as CLSPN. Also involved in G2 DNA damage checkpoint, by
CC deubiquitinating CLSPN, and preventing its degradation by the anaphase
CC promoting complex/cyclosome (APC/C). In contrast, it does not
CC deubiquitinate PLK1. Specifically deubiquitinates MYC in the
CC nucleoplasm, leading to prevent MYC degradation by the proteasome: acts
CC by specifically interacting with FBXW7 (FBW7alpha) in the nucleoplasm
CC and counteracting ubiquitination of MYC by the SCF(FBXW7) complex.
CC Deubiquitinates ZNF304, hence preventing ZNF304 degradation by the
CC proteasome and leading to the activated KRAS-mediated promoter
CC hypermethylation and transcriptional silencing of tumor suppressor
CC genes (TSGs) in a subset of colorectal cancers (CRC) cells.
CC {ECO:0000250|UniProtKB:Q96RU2}.
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 ZNF304. Interacts with PRKD1. Interacts with
CC TP53BP1. Interacts with FBXW7; following DNA damage, dissociates from
CC FBXW7 leading to degradation of MYC. {ECO:0000250|UniProtKB:Q96RU2}.
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q5I043-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5I043-2; Sequence=VSP_015581;
CC -!- PTM: Degraded upon nickel ion level or hypoxia exposure. {ECO:0000250}.
CC -!- PTM: Phosphorylated upon DNA damage at Ser-67 and Ser-720, by ATM or
CC ATR. Phosphorylated by PRKD1. {ECO:0000250|UniProtKB:Q96RU2}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. USP28 subfamily.
CC {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; BC066033; AAH66033.1; -; mRNA.
DR EMBL; BC088733; AAH88733.1; -; mRNA.
DR EMBL; AK052442; BAC34993.1; -; mRNA.
DR EMBL; AK129380; BAC98190.1; -; mRNA.
DR CCDS; CCDS40613.1; -. [Q5I043-1]
DR RefSeq; NP_780691.2; NM_175482.3. [Q5I043-1]
DR AlphaFoldDB; Q5I043; -.
DR SMR; Q5I043; -.
DR BioGRID; 231641; 1.
DR IntAct; Q5I043; 2.
DR MINT; Q5I043; -.
DR STRING; 10090.ENSMUSP00000047467; -.
DR MEROPS; C19.054; -.
DR iPTMnet; Q5I043; -.
DR PhosphoSitePlus; Q5I043; -.
DR EPD; Q5I043; -.
DR MaxQB; Q5I043; -.
DR PaxDb; Q5I043; -.
DR PeptideAtlas; Q5I043; -.
DR PRIDE; Q5I043; -.
DR ProteomicsDB; 298099; -. [Q5I043-1]
DR ProteomicsDB; 298100; -. [Q5I043-2]
DR Antibodypedia; 1708; 309 antibodies from 38 providers.
DR DNASU; 235323; -.
DR Ensembl; ENSMUST00000047349; ENSMUSP00000047467; ENSMUSG00000032267. [Q5I043-1]
DR Ensembl; ENSMUST00000213874; ENSMUSP00000149207; ENSMUSG00000032267. [Q5I043-2]
DR GeneID; 235323; -.
DR KEGG; mmu:235323; -.
DR UCSC; uc009pir.1; mouse. [Q5I043-1]
DR UCSC; uc009pis.1; mouse. [Q5I043-2]
DR CTD; 57646; -.
DR MGI; MGI:2442293; Usp28.
DR VEuPathDB; HostDB:ENSMUSG00000032267; -.
DR eggNOG; KOG1863; Eukaryota.
DR GeneTree; ENSGT00940000157670; -.
DR HOGENOM; CLU_012188_0_0_1; -.
DR InParanoid; Q5I043; -.
DR OMA; DQQVLYK; -.
DR OrthoDB; 194025at2759; -.
DR PhylomeDB; Q5I043; -.
DR TreeFam; TF329035; -.
DR Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR BioGRID-ORCS; 235323; 3 hits in 112 CRISPR screens.
DR ChiTaRS; Usp28; mouse.
DR PRO; PR:Q5I043; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q5I043; protein.
DR Bgee; ENSMUSG00000032267; Expressed in interventricular septum and 224 other tissues.
DR ExpressionAtlas; Q5I043; baseline and differential.
DR Genevisible; Q5I043; MM.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISS:UniProtKB.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0008283; P:cell population proliferation; ISS:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISO:MGI.
DR GO; GO:0034644; P:cellular response to UV; ISO:MGI.
DR GO; GO:0000077; P:DNA damage checkpoint signaling; ISS:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; ISS:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; ISS:UniProtKB.
DR GO; GO:0007265; P:Ras protein signal transduction; ISS:UniProtKB.
DR GO; GO:0031647; P:regulation of protein stability; ISS:UniProtKB.
DR GO; GO:0010212; P:response to ionizing radiation; ISS: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; IPR009060; UBA-like_sf.
DR InterPro; IPR018200; USP_CS.
DR InterPro; IPR028889; USP_dom.
DR Pfam; PF00443; UCH; 1.
DR SUPFAM; SSF46934; SSF46934; 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 Alternative splicing; DNA damage; DNA repair; Hydrolase; Isopeptide bond;
KW Nucleus; Phosphoprotein; Protease; Reference proteome; Thiol protease;
KW Ubl conjugation; Ubl conjugation pathway.
FT CHAIN 1..1051
FT /note="Ubiquitin carboxyl-terminal hydrolase 28"
FT /id="PRO_0000080658"
FT DOMAIN 97..116
FT /note="UIM"
FT /evidence="ECO:0000305"
FT DOMAIN 162..655
FT /note="USP"
FT REGION 60..82
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 121..140
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 483..538
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 703..735
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 62..82
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 483..527
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 708..735
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 171
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT ACT_SITE 605
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT MOD_RES 67
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96RU2"
FT MOD_RES 376
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96RU2"
FT MOD_RES 555
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 720
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96RU2"
FT MOD_RES 1022
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q96RU2"
FT CROSSLNK 99
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q96RU2"
FT VAR_SEQ 429..453
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_015581"
FT CONFLICT 523
FT /note="P -> L (in Ref. 3; BAC98190)"
FT /evidence="ECO:0000305"
FT CONFLICT 617
FT /note="T -> I (in Ref. 3; BAC98190)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1051 AA; 119318 MW; 72623C4668860749 CRC64;
MTAELQQDDS AGAADGHGSS CQMLLNQLRE ITGIQDPSFL HEALKASNGD ITQAVSLLTD
QRVKEPSHDT TAAEPSEVEE SATSKDLLAK VIDLTHDNKD DLQAAIALSL LESPNIQADN
RDLNRAHEAN SAETKRSKRK RCEVWGENHN PNNWRRVDGW PVGLKNVGNT CWFSAVIQSL
FQLPEFRRLV LSYNLPQNIL ENCRSHTEKR NIMFMQELQY LFALLLGSNR KFVDPSAALD
LLKGAFRSSE EQQQDVSEFT HKLLDWLEDA FQLAVNVNSH LRNKSENPMV QLFYGTFLTE
GVREGKPFCN NETFGQYPLQ VNGYHNLDEC LEGAMVEGDI ALLPSDRSVK YGQERWFTKL
PPVLTFELSR FEFNQSLGQP EKIHNKLEFP QIIYMDRYMY KSKELIRSKR ESVRKLKEEI
QVLQQKLERY VKYGSGPSRF PLPDMLKYVI EFASTKPASE SCLSGSAEHV TLPLPSVHCP
ISDLTPKESS SPESCSQNAG STFSSPEDAL PSSEGMNGPF TSPHSSLETP APPAPRTVTD
EEMNFVKTCL QRWRSEIEQD IQDLKNCISS STKAIEQMYC DPLLRQVPYR LHAVLVHEGQ
ASAGHYWAYI YNQPRQTWLK YNDISVTESS WEELERDSYG GLRNVSAYCL MYINDNLPHF
SAEASSNESD ETAGEVEALS VELRQYIQED NWRFQQEVEE WEEEQSCKIP QMESSPNSSS
QDFSTSQESP AVSSHEVRCL SSEHAVIAKE QTAQAIANTA HAYEKSGVEA ALSEAFHEEY
SRLYQLAKET PTSHSDPRLQ HVLVYFFQNE APKRVVERTL LEQFADRNLS YDERSISIMK
VAQAKLMEIG PDDMNMEEYK RWHEDYSLFR KVSVYLLTGL ELFQKGKYQE ALSYLVYAYQ
SNAGLLVKGP RRGVKESVIA LYRRKCLLEL NAKAASLFET NDDHSVTEGI NVMNELIIPC
IHLIINNDIS KDDLDAIEVM RNHWCSYLGK DIAENLQLCL GEFLPRLLDP SAEIIVLKEP
PTIRPNSPYD LCNRFAAVME SIQGVSTVTV K
