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Overview

Uniprot IDQ96RU2
Protein NameUbiquitin carboxyl-terminal hydrolase 28
Gene NameUSP28
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
135 EATSAETKRSKRKRC

Function

Deubiquitinase involved in DNA damage response checkpoint and MYC proto-oncogene stability. Involved in DNA damage induced apoptosis by specifically deubiquitinating proteins of the DNA damage pathway such as CLSPN. Also involved in G2 DNA damage checkpoint, by deubiquitinating CLSPN, and preventing its degradation by the anaphase promoting complex/cyclosome (APC/C). In contrast, it does not deubiquitinate PLK1. Specifically deubiquitinates MYC in the nucleoplasm, leading to prevent MYC degradation by the proteasome: acts by specifically interacting with isoform 1 of FBXW7 (FBW7alpha) in the nucleoplasm and counteracting ubiquitination of MYC by the SCF(FBW7) complex. In contrast, it does not interact with isoform 4 of FBXW7 (FBW7gamma) in the nucleolus, allowing MYC degradation and explaining the selective MYC degradation in the nucleolus. Deubiquitinates ZNF304, hence preventing ZNF304 degradation by the proteasome and leading to the activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) in a subset of colorectal cancers (CRC) cells (PubMed:24623306)

Protein Sequence

10 MTAELQQDDA 20 AGAADGHGSS 30 CQMLLNQLRE 40 ITGIQDPSFL 50 HEALKASNGD 60 ITQAVSLLTD 70 ERVKEPSQDT 80 VATEPSEVEG 90 SAANKEVLAK 100 VIDLTHDNKD 110 DLQAAIALSL 120 LESPKIQADG 130 RDLNRMHEAT 140 SAETKRSKRK 150 RCEVWGENPN 160 PNDWRRVDGW 170 PVGLKNVGNT 180 CWFSAVIQSL 190 FQLPEFRRLV 200 LSYSLPQNVL 210 ENCRSHTEKR 220 NIMFMQELQY 230 LFALMMGSNR 240 KFVDPSAALD 250 LLKGAFRSSE 260 EQQQDVSEFT 270 HKLLDWLEDA 280 FQLAVNVNSP 290 RNKSENPMVQ 300 LFYGTFLTEG 310 VREGKPFCNN 320 ETFGQYPLQV 330 NGYRNLDECL 340 EGAMVEGDVE 350 LLPSDHSVKY 360 GQERWFTKLP 370 PVLTFELSRF 380 EFNQSLGQPE 390 KIHNKLEFPQ 400 IIYMDRYMYR 410 SKELIRNKRE 420 CIRKLKEEIK 430 ILQQKLERYV 440 KYGSGPARFP 450 LPDMLKYVIE 460 FASTKPASES 470 CPPESDTHMT 480 LPLSSVHCSV 490 SDQTSKESTS 500 TESSSQDVES 510 TFSSPEDSLP 520 KSKPLTSSRS 530 SMEMPSQPAP 540 RTVTDEEINF 550 VKTCLQRWRS 560 EIEQDIQDLK 570 TCIASTTQTI 580 EQMYCDPLLR 590 QVPYRLHAVL 600 VHEGQANAGH 610 YWAYIYNQPR 620 QSWLKYNDIS 630 VTESSWEEVE 640 RDSYGGLRNV 650 SAYCLMYIND 660 KLPYFNAEAA 670 PTESDQMSEV 680 EALSVELKHY 690 IQEDNWRFEQ 700 EVEEWEEEQS 710 CKIPQMESST 720 NSSSQDYSTS 730 QEPSVASSHG 740 VRCLSSEHAV 750 IVKEQTAQAI 760 ANTARAYEKS 770 GVEAALSEVM 780 LSPAMQGVIL 790 AIAKARQTFD 800 RDGSEAGLIK 810 AFHEEYSRLY 820 QLAKETPTSH 830 SDPRLQHVLV 840 YFFQNEAPKR 850 VVERTLLEQF 860 ADKNLSYDER 870 SISIMKVAQA 880 KLKEIGPDDM 890 NMEEYKKWHE 900 DYSLFRKVSV 910 YLLTGLELYQ 920 KGKYQEALSY 930 LVYAYQSNAA 940 LLMKGPRRGV 950 KESVIALYRR 960 KCLLELNAKA 970 ASLFETNDDH 980 SVTEGINVMN 990 ELIIPCIHLI 1000 INNDISKDDL 1010 DAIEVMRNHW 1020 CSYLGQDIAE 1030 NLQLCLGEFL 1040 PRLLDPSAEI 1050 IVLKEPPTIR 1060 PNSPYDLCSR 1070 FAAVMESIQG VSTVTVK

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005829 cytosol
Cellular Component GO:0016604 nuclear body
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0032991 protein-containing complex
Molecular Function GO:0004843 cysteine-type deubiquitinase activity
Molecular Function GO:0101005 deubiquitinase activity
Biological Process GO:0008283 cell population proliferation
Biological Process GO:0034644 cellular response to UV
Biological Process GO:0000077 DNA damage checkpoint signaling
Biological Process GO:0006974 DNA damage response
Biological Process GO:0006281 DNA repair
Biological Process GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
Biological Process GO:0016579 protein deubiquitination
Biological Process GO:0071947 protein deubiquitination involved in ubiquitin-dependent protein catabolic process
Biological Process GO:0031647 regulation of protein stability
Biological Process GO:0010212 response to ionizing radiation

Reference

PMID: N/A