ID   UBP28_RAT               Reviewed;        1083 AA.
AC   D3ZJ96; D2Y8W6;
DT   13-JUL-2010, integrated into UniProtKB/Swiss-Prot.
DT   13-JUL-2010, sequence version 2.
DT   24-JAN-2024, entry version 81.
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;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Testis;
RA   Haraguchi C.M., Mabuchi T., Yokota S.;
RT   "Expression of deubiquitination enzyme (USP28) in rat spermatogenic cell.
RT   Immunocytochemical analysis.";
RL   Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway;
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
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=D3ZJ96-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=D3ZJ96-2; Sequence=VSP_039547;
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; AB240643; BAF97608.1; -; mRNA.
DR   EMBL; CH473975; EDL95433.1; -; Genomic_DNA.
DR   RefSeq; NP_001101614.1; NM_001108144.1.
DR   RefSeq; XP_006243070.1; XM_006243008.3. [D3ZJ96-1]
DR   RefSeq; XP_006243073.1; XM_006243011.3. [D3ZJ96-2]
DR   AlphaFoldDB; D3ZJ96; -.
DR   SMR; D3ZJ96; -.
DR   STRING; 10116.ENSRNOP00000009724; -.
DR   MEROPS; C19.054; -.
DR   PhosphoSitePlus; D3ZJ96; -.
DR   PaxDb; 10116-ENSRNOP00000060005; -.
DR   PeptideAtlas; D3ZJ96; -.
DR   Ensembl; ENSRNOT00000067420.5; ENSRNOP00000060005.4; ENSRNOG00000007325.9. [D3ZJ96-1]
DR   Ensembl; ENSRNOT00055053897; ENSRNOP00055044616; ENSRNOG00055030891. [D3ZJ96-1]
DR   Ensembl; ENSRNOT00060023950; ENSRNOP00060019075; ENSRNOG00060013905. [D3ZJ96-1]
DR   Ensembl; ENSRNOT00065029117; ENSRNOP00065023078; ENSRNOG00065017368. [D3ZJ96-1]
DR   GeneID; 315639; -.
DR   KEGG; rno:315639; -.
DR   UCSC; RGD:1311555; rat. [D3ZJ96-1]
DR   AGR; RGD:1311555; -.
DR   CTD; 57646; -.
DR   RGD; 1311555; Usp28.
DR   eggNOG; KOG1863; Eukaryota.
DR   GeneTree; ENSGT00940000157670; -.
DR   HOGENOM; CLU_012188_0_0_1; -.
DR   InParanoid; D3ZJ96; -.
DR   OrthoDB; 1423057at2759; -.
DR   PhylomeDB; D3ZJ96; -.
DR   TreeFam; TF329035; -.
DR   Reactome; R-RNO-5689880; Ub-specific processing proteases.
DR   PRO; PR:D3ZJ96; -.
DR   Proteomes; UP000002494; Chromosome 8.
DR   Proteomes; UP000234681; Chromosome 8.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
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:RGD.
DR   GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISS:UniProtKB.
DR   GO; GO:0101005; F:deubiquitinase activity; ISO:RGD.
DR   GO; GO:0008283; P:cell population proliferation; ISS:UniProtKB.
DR   GO; GO:0034644; P:cellular response to UV; ISO:RGD.
DR   GO; GO:0000077; P:DNA damage checkpoint signaling; ISS:UniProtKB.
DR   GO; GO:0006974; P:DNA damage response; ISO:RGD.
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; D3ZJ96; RN.
PE   2: Evidence at transcript 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..1083
FT                   /note="Ubiquitin carboxyl-terminal hydrolase 28"
FT                   /id="PRO_0000395809"
FT   DOMAIN          97..116
FT                   /note="UIM"
FT                   /evidence="ECO:0000305"
FT   DOMAIN          162..656
FT                   /note="USP"
FT   REGION          60..82
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          483..539
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          703..728
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..524
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        708..728
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        606
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         556
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q5I043"
FT   MOD_RES         720
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q96RU2"
FT   MOD_RES         1054
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         775..806
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_039547"
FT   CONFLICT        73
FT                   /note="T -> S (in Ref. 1; BAF97608)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1083 AA;  122688 MW;  A0E69DE733BB921E CRC64;
     MTAELQQDDA AGAADGHGSS CQMLLNQLRE ITGIQDPSFL HEALKASNGD ITQAVSLLTD
     QRVKEPSHDT AATEPSEVEE SATSKDLLAK VIDLTHDNKD DLQAAIALSL LESPNIQTDS
     RDLNRIHEAN SAETKRSKRK RCEVWGENHN PNNWRRVDGW PVGLKNVGNT CWFSAVIQSL
     FQLPEFRRLV LSYSLPQNIL ENCRSHTEKR NIMFMQELQY LFALLLGSNR KFVDPSAALD
     LLKGAFRSSE EQQQDVSEFT HKLLDWLEDA FQLAVNVNSN PRTKSENPMV QLFYGTFLTE
     GVREGKPFCN NETFGQYPLQ VNGYHNLDEC LEGAMVEGDI ALLPSDRSVK YGQERWFTKL
     PPVLTFELSR FEFNQSLGQP EKIHNKLEFP QVIYMDRYMY KSKELIRSKR ESIRKLKEEI
     QVLQQKLERY VKYGSGPSRF PLPDMLKYVI EFASTKPASE SCLSGSVEHM TLPLPSVHCP
     ISDLTAKESS SPKSCSQNAE GSFSSPEDAL PNSEVMNGPF TSPHSSLEMP APPPAPRTVT
     DEEMNFVKTC LQRWRSEIEQ DIQDLKNCIS STTQAIEQMY CDPLLRQVPY RLHAVLVHEG
     QASAGHYWAY IYNQPRQIWL KYNDISVTES SWEELERDSY GGLRNVSAYC LMYINDKLPH
     CSAEAAHGES DQTAEVEALS VELRQYIQED NWRFEQEVEE WEEEQSCKIP QMESSPNSSS
     QDFSTSQESS AASSHGVRCL SSEHAVIAKE QTAQAIANTA HAYEKSGVEA ALSEVMLSPA
     MQGVLLAIAK ARQTFDRDGS EAGLIKAFHE EYSRLYQLAK ETPTSHSDPR LQHVLVYFFQ
     NEAPKRVVER TLLEQFADRN LSYDERSISI MKVAQAKLME IGPEDMNMEE YKRWHEDYSL
     FRKVSVYLLT GLELFQKGKY QEALSYLVYA YQSNAGLLVK GPRRGVKESV IALYRRKCLL
     ELNAKAASLF ETNDDHSVTE GINVMNELII PCIHLIINND ISKDDLDAIE VMRNHWCSYL
     GKDIAENLQL CLGEFLPRLL DPSAEIIVLK EPPTIRPNSP YDLCSRFAAV MESIQGVSTV
     TVK
//