UBP28_RAT
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 03-AUG-2022, entry version 74.
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.ENSRNOP00000060005; -.
DR MEROPS; C19.054; -.
DR PaxDb; D3ZJ96; -.
DR PeptideAtlas; D3ZJ96; -.
DR Ensembl; ENSRNOT00000067420; ENSRNOP00000060005; ENSRNOG00000007325. [D3ZJ96-1]
DR GeneID; 315639; -.
DR KEGG; rno:315639; -.
DR UCSC; RGD:1311555; rat. [D3ZJ96-1]
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 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 Genevisible; D3ZJ96; RN.
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: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:RGD.
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: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 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
