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   24-JAN-2024, entry version 145.
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}.
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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; 3.
DR   MINT; Q5I043; -.
DR   STRING; 10090.ENSMUSP00000047467; -.
DR   MEROPS; C19.054; -.
DR   iPTMnet; Q5I043; -.
DR   PhosphoSitePlus; Q5I043; -.
DR   SwissPalm; Q5I043; -.
DR   EPD; Q5I043; -.
DR   MaxQB; Q5I043; -.
DR   PaxDb; 10090-ENSMUSP00000047467; -.
DR   PeptideAtlas; Q5I043; -.
DR   ProteomicsDB; 298099; -. [Q5I043-1]
DR   ProteomicsDB; 298100; -. [Q5I043-2]
DR   Pumba; Q5I043; -.
DR   Antibodypedia; 1708; 352 antibodies from 38 providers.
DR   DNASU; 235323; -.
DR   Ensembl; ENSMUST00000047349.8; ENSMUSP00000047467.6; ENSMUSG00000032267.9. [Q5I043-1]
DR   Ensembl; ENSMUST00000213874.2; ENSMUSP00000149207.2; ENSMUSG00000032267.9. [Q5I043-2]
DR   GeneID; 235323; -.
DR   KEGG; mmu:235323; -.
DR   UCSC; uc009pir.1; mouse. [Q5I043-1]
DR   UCSC; uc009pis.1; mouse. [Q5I043-2]
DR   AGR; MGI:2442293; -.
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; 1423057at2759; -.
DR   PhylomeDB; Q5I043; -.
DR   TreeFam; TF329035; -.
DR   Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR   BioGRID-ORCS; 235323; 3 hits in 117 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 226 other cell types or tissues.
DR   ExpressionAtlas; Q5I043; baseline and differential.
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:0101005; F:deubiquitinase activity; ISO:MGI.
DR   GO; GO:0008283; P:cell population proliferation; ISS:UniProtKB.
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:0006974; P:DNA damage response; ISO:MGI.
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:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   GO; GO:0031647; P:regulation of protein stability; ISS:UniProtKB.
DR   GO; GO:0010212; P:response to ionizing radiation; ISS:UniProtKB.
DR   CDD; cd02665; Peptidase_C19I; 1.
DR   CDD; cd14355; UBA_UBP28; 1.
DR   CDD; cd20487; USP28_C; 1.
DR   Gene3D; 6.10.250.1720; -; 1.
DR   Gene3D; 3.90.70.10; Cysteine proteinases; 1.
DR   Gene3D; 1.10.8.10; DNA helicase RuvA subunit, C-terminal domain; 1.
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   PANTHER; PTHR24006; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1.
DR   PANTHER; PTHR24006:SF678; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE 28; 1.
DR   Pfam; PF00443; UCH; 1.
DR   SUPFAM; SSF54001; Cysteine proteinases; 1.
DR   SUPFAM; SSF46934; UBA-like; 1.
DR   PROSITE; PS00972; USP_1; 1.
DR   PROSITE; PS00973; USP_2; 1.
DR   PROSITE; PS50235; USP_3; 1.
DR   Genevisible; Q5I043; MM.
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
//