dbPTM

UBP28_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	UBP28_HUMAN
UniProt AC	Q96RU2
Protein Name	Ubiquitin carboxyl-terminal hydrolase 28
Gene Name	USP28
Organism	Homo sapiens (Human).
Sequence Length	1077
Subcellular Localization	Nucleus, nucleoplasm .
Protein Description	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	MTAELQQDDAAGAADGHGSSCQMLLNQLREITGIQDPSFLHEALKASNGDITQAVSLLTDERVKEPSQDTVATEPSEVEGSAANKEVLAKVIDLTHDNKDDLQAAIALSLLESPKIQADGRDLNRMHEATSAETKRSKRKRCEVWGENPNPNDWRRVDGWPVGLKNVGNTCWFSAVIQSLFQLPEFRRLVLSYSLPQNVLENCRSHTEKRNIMFMQELQYLFALMMGSNRKFVDPSAALDLLKGAFRSSEEQQQDVSEFTHKLLDWLEDAFQLAVNVNSPRNKSENPMVQLFYGTFLTEGVREGKPFCNNETFGQYPLQVNGYRNLDECLEGAMVEGDVELLPSDHSVKYGQERWFTKLPPVLTFELSRFEFNQSLGQPEKIHNKLEFPQIIYMDRYMYRSKELIRNKRECIRKLKEEIKILQQKLERYVKYGSGPARFPLPDMLKYVIEFASTKPASESCPPESDTHMTLPLSSVHCSVSDQTSKESTSTESSSQDVESTFSSPEDSLPKSKPLTSSRSSMEMPSQPAPRTVTDEEINFVKTCLQRWRSEIEQDIQDLKTCIASTTQTIEQMYCDPLLRQVPYRLHAVLVHEGQANAGHYWAYIYNQPRQSWLKYNDISVTESSWEEVERDSYGGLRNVSAYCLMYINDKLPYFNAEAAPTESDQMSEVEALSVELKHYIQEDNWRFEQEVEEWEEEQSCKIPQMESSTNSSSQDYSTSQEPSVASSHGVRCLSSEHAVIVKEQTAQAIANTARAYEKSGVEAALSEVMLSPAMQGVILAIAKARQTFDRDGSEAGLIKAFHEEYSRLYQLAKETPTSHSDPRLQHVLVYFFQNEAPKRVVERTLLEQFADKNLSYDERSISIMKVAQAKLKEIGPDDMNMEEYKKWHEDYSLFRKVSVYLLTGLELYQKGKYQEALSYLVYAYQSNAALLMKGPRRGVKESVIALYRRKCLLELNAKAASLFETNDDHSVTEGINVMNELIIPCIHLIINNDISKDDLDAIEVMRNHWCSYLGQDIAENLQLCLGEFLPRLLDPSAEIIVLKEPPTIRPNSPYDLCSRFAAVMESIQGVSTVTVK

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
38	Phosphorylation	ITGIQDPSFLHEALK HHCCCCHHHHHHHHH	49.05	28555341
45	Ubiquitination	SFLHEALKASNGDIT HHHHHHHHHCCCCHH	57.74	-
64	Ubiquitination	LLTDERVKEPSQDTV HHCCCCCCCCCCCCC	70.86	21906983
64 (in isoform 1)	Ubiquitination	-	70.86	21890473
64 (in isoform 2)	Ubiquitination	-	70.86	21890473
67	Phosphorylation	DERVKEPSQDTVATE CCCCCCCCCCCCCCC	41.60	17525332
70	Phosphorylation	VKEPSQDTVATEPSE CCCCCCCCCCCCHHH	12.38	25159151
73	Phosphorylation	PSQDTVATEPSEVEG CCCCCCCCCHHHCCC	44.06	27732954
85	Ubiquitination	VEGSAANKEVLAKVI CCCCHHCHHHHHHHH	44.46	-
90	Ubiquitination	ANKEVLAKVIDLTHD HCHHHHHHHHHCCCC	35.25	-
95	Phosphorylation	LAKVIDLTHDNKDDL HHHHHHCCCCCHHHH	24.36	28674419
99	Sumoylation	IDLTHDNKDDLQAAI HHCCCCCHHHHHHHH	59.69	28112733
99	Sumoylation	IDLTHDNKDDLQAAI HHCCCCCHHHHHHHH	59.69	-
109	Phosphorylation	LQAAIALSLLESPKI HHHHHHHHHHHCCCC	23.14	27080861
113	Phosphorylation	IALSLLESPKIQADG HHHHHHHCCCCCCCC	31.31	29496963
130	Phosphorylation	LNRMHEATSAETKRS HHHHHHHCCHHHHHH	26.03	25159151
131	Phosphorylation	NRMHEATSAETKRSK HHHHHHCCHHHHHHH	31.02	20068231
134	Phosphorylation	HEATSAETKRSKRKR HHHCCHHHHHHHHHC	31.32	29396449
220	Phosphorylation	MFMQELQYLFALMMG HHHHHHHHHHHHHHC	19.19	24043423
228	Phosphorylation	LFALMMGSNRKFVDP HHHHHHCCCCCCCCH	18.63	24043423
243 (in isoform 2)	Ubiquitination	-	56.33	21890473
243 (in isoform 1)	Ubiquitination	-	56.33	21890473
243	Ubiquitination	SAALDLLKGAFRSSE HHHHHHHHHHHCCCH	56.33	21890473
243	Ubiquitination	SAALDLLKGAFRSSE HHHHHHHHHHHCCCH	56.33	21890473
248	Phosphorylation	LLKGAFRSSEEQQQD HHHHHHCCCHHHHHC	35.33	29214152
249	Phosphorylation	LKGAFRSSEEQQQDV HHHHHCCCHHHHHCH	40.68	29214152
279	Phosphorylation	QLAVNVNSPRNKSEN HHHHHCCCCCCCCCC	22.43	27422710
375	Phosphorylation	SRFEFNQSLGQPEKI EEHHCCHHCCCCHHH	35.26	25159151
381	Ubiquitination	QSLGQPEKIHNKLEF HHCCCCHHHHCCCCC	56.82	-
420	Ubiquitination	RKLKEEIKILQQKLE HHHHHHHHHHHHHHH	40.41	-
425	Ubiquitination	EIKILQQKLERYVKY HHHHHHHHHHHHHHH	39.08	-
431	Ubiquitination	QKLERYVKYGSGPAR HHHHHHHHHCCCCCC	34.65	-
447	Phosphorylation	PLPDMLKYVIEFAST CCCHHHHHHHHHHCC	11.60	-
488	Phosphorylation	SDQTSKESTSTESSS CCCCCCCCCCCCCCC	31.24	20873877
489	Phosphorylation	DQTSKESTSTESSSQ CCCCCCCCCCCCCCC	40.54	20873877
490	Phosphorylation	QTSKESTSTESSSQD CCCCCCCCCCCCCCC	39.18	20873877
491	Phosphorylation	TSKESTSTESSSQDV CCCCCCCCCCCCCCH	39.72	20873877
493	Phosphorylation	KESTSTESSSQDVES CCCCCCCCCCCCHHH	35.06	25159151
494	Phosphorylation	ESTSTESSSQDVEST CCCCCCCCCCCHHHH	26.28	20873877
495	Phosphorylation	STSTESSSQDVESTF CCCCCCCCCCHHHHC	39.41	17478428
500	Phosphorylation	SSSQDVESTFSSPED CCCCCHHHHCCCCCC	34.30	20873877
501	Phosphorylation	SSQDVESTFSSPEDS CCCCHHHHCCCCCCC	17.65	20873877
503	Phosphorylation	QDVESTFSSPEDSLP CCHHHHCCCCCCCCC	45.10	25159151
504	Phosphorylation	DVESTFSSPEDSLPK CHHHHCCCCCCCCCC	28.28	28985074
508	Phosphorylation	TFSSPEDSLPKSKPL HCCCCCCCCCCCCCC	44.93	27251275
512	Phosphorylation	PEDSLPKSKPLTSSR CCCCCCCCCCCCCCC	37.25	24719451
513	Ubiquitination	EDSLPKSKPLTSSRS CCCCCCCCCCCCCCC	50.61	-
516	Phosphorylation	LPKSKPLTSSRSSME CCCCCCCCCCCCCCC	32.93	26330541
517	Phosphorylation	PKSKPLTSSRSSMEM CCCCCCCCCCCCCCC	31.28	25159151
518	Phosphorylation	KSKPLTSSRSSMEMP CCCCCCCCCCCCCCC	30.83	25627689
520	Phosphorylation	KPLTSSRSSMEMPSQ CCCCCCCCCCCCCCC	35.66	25159151
521	Phosphorylation	PLTSSRSSMEMPSQP CCCCCCCCCCCCCCC	20.04	25159151
542	Ubiquitination	DEEINFVKTCLQRWR HHHHHHHHHHHHHHH	29.41	-
543	Phosphorylation	EEINFVKTCLQRWRS HHHHHHHHHHHHHHH	17.10	-
550	Phosphorylation	TCLQRWRSEIEQDIQ HHHHHHHHHHHHHHH	35.65	25159151
654	Phosphorylation	YINDKLPYFNAEAAP HHCCCCCCCCCCCCC	21.65	-
708	Phosphorylation	CKIPQMESSTNSSSQ CCCCCCCCCCCCCCC	36.80	24043423
709	Phosphorylation	KIPQMESSTNSSSQD CCCCCCCCCCCCCCC	20.50	24043423
710	Phosphorylation	IPQMESSTNSSSQDY CCCCCCCCCCCCCCC	48.69	28348404
712	Phosphorylation	QMESSTNSSSQDYST CCCCCCCCCCCCCCC	31.30	29116813
713	Phosphorylation	MESSTNSSSQDYSTS CCCCCCCCCCCCCCC	33.80	29116813
714	Phosphorylation	ESSTNSSSQDYSTSQ CCCCCCCCCCCCCCC	27.22	17525332
717	Phosphorylation	TNSSSQDYSTSQEPS CCCCCCCCCCCCCCC	13.25	24043423
718	Phosphorylation	NSSSQDYSTSQEPSV CCCCCCCCCCCCCCH	29.85	23312004
719	Phosphorylation	SSSQDYSTSQEPSVA CCCCCCCCCCCCCHH	28.35	23312004
720	Phosphorylation	SSQDYSTSQEPSVAS CCCCCCCCCCCCHHH	26.97	17478428
735	Phosphorylation	SHGVRCLSSEHAVIV HCCCEECCCCCEEEE	36.99	24719451
736	Phosphorylation	HGVRCLSSEHAVIVK CCCEECCCCCEEEEE	22.06	28348404
753	Phosphorylation	TAQAIANTARAYEKS HHHHHHHHHHHHHHH	14.43	21712546
788	Phosphorylation	AIAKARQTFDRDGSE HHHHHHHHCCCCCCH	23.19	23312004
794	Phosphorylation	QTFDRDGSEAGLIKA HHCCCCCCHHHHHHH	28.67	29970186
807 (in isoform 2)	Ubiquitination	-	21.06	21890473
839	Ubiquitination	FFQNEAPKRVVERTL HHCCCCCHHHHHHHH	65.94	2190698
839 (in isoform 1)	Ubiquitination	-	65.94	21890473
853	Ubiquitination	LLEQFADKNLSYDER HHHHHHCCCCCCCHH	57.25	-
856	Phosphorylation	QFADKNLSYDERSIS HHHCCCCCCCHHHHH	39.67	22210691
857	Phosphorylation	FADKNLSYDERSISI HHCCCCCCCHHHHHH	25.62	22210691
861	Phosphorylation	NLSYDERSISIMKVA CCCCCHHHHHHHHHH	20.74	22210691
897	Ubiquitination	EDYSLFRKVSVYLLT HHHHHHHHHHHHHHH	31.37	-
901	Phosphorylation	LFRKVSVYLLTGLEL HHHHHHHHHHHCHHH	6.62	21955146
914	Phosphorylation	ELYQKGKYQEALSYL HHHHCCCHHHHHHHH	21.91	29978859
919	Phosphorylation	GKYQEALSYLVYAYQ CCHHHHHHHHHHHHH	24.38	29978859
920	Phosphorylation	KYQEALSYLVYAYQS CHHHHHHHHHHHHHC	10.88	22210691
923	Phosphorylation	EALSYLVYAYQSNAA HHHHHHHHHHHCCHH	9.30	29978859
925	Phosphorylation	LSYLVYAYQSNAALL HHHHHHHHHCCHHHH	8.52	29978859
927	Phosphorylation	YLVYAYQSNAALLMK HHHHHHHCCHHHHCC	18.76	29978859
943	Phosphorylation	PRRGVKESVIALYRR CCCCHHHHHHHHHHH	17.07	23403867
948	Phosphorylation	KESVIALYRRKCLLE HHHHHHHHHHHHHHH	10.19	23403867
1037	Phosphorylation	LPRLLDPSAEIIVLK HHHHHCCCCEEEEEC	37.89	27080861
1048	Phosphorylation	IVLKEPPTIRPNSPY EEECCCCCCCCCCHH	40.09	24623306
1053	Phosphorylation	PPTIRPNSPYDLCSR CCCCCCCCHHHHHHH	27.76	23401153
1055	Phosphorylation	TIRPNSPYDLCSRFA CCCCCCHHHHHHHHH	22.74	22617229
1059	Phosphorylation	NSPYDLCSRFAAVME CCHHHHHHHHHHHHH	37.42	28450419
1067	Phosphorylation	RFAAVMESIQGVSTV HHHHHHHHCCCCEEE	11.34	20860994
1075	Phosphorylation	IQGVSTVTVK----- CCCCEEEEEC-----	23.75	20860994

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
67	S	Phosphorylation	Kinase	ATM	Q13315	PSP
495	S	Phosphorylation	Kinase	ATM	Q13315	PSP
714	S	Phosphorylation	Kinase	ATM	Q13315	PSP
720	S	Phosphorylation	Kinase	ATM	Q13315	PSP

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
67	S	Phosphorylation	16901786
Phosphorylated upon DNA damage at Ser-67 and Ser-714, by ATM or ATR.
714	S	Phosphorylation	16901786
Phosphorylated upon DNA damage at Ser-67 and Ser-714, by ATM or ATR.

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of UBP28_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
SUMO2_HUMAN	SUMO2	physical	19615732
TP53B_HUMAN	TP53BP1	physical	19615732
AQR_HUMAN	AQR	physical	19615732
TP53B_HUMAN	TP53BP1	physical	16901786
CLSPN_HUMAN	CLSPN	physical	16901786
MDC1_HUMAN	MDC1	physical	16901786
MYC_HUMAN	MYC	physical	17558397
FBXW7_HUMAN	FBXW7	physical	17558397
UBP20_HUMAN	USP20	physical	22626734
UBP51_HUMAN	USP51	physical	22626734
UBP5_HUMAN	USP5	physical	22626734
UBP7_HUMAN	USP7	physical	22626734
STABP_HUMAN	STAMBP	physical	22626734
OTUB1_HUMAN	OTUB1	physical	22626734
JOS1_HUMAN	JOSD1	physical	22626734
UCHL3_HUMAN	UCHL3	physical	22626734
UBP8_HUMAN	USP8	physical	22626734
UCHL5_HUMAN	UCHL5	physical	22626734
OTUB2_HUMAN	OTUB2	physical	22626734
ATX3L_HUMAN	ATXN3L	physical	22626734
UBP33_HUMAN	USP33	physical	22626734
UBP15_HUMAN	USP15	physical	22626734
UBP28_HUMAN	USP28	physical	22626734
ESPL1_HUMAN	ESPL1	physical	22626734
SENP8_HUMAN	SENP8	physical	22626734
UBP14_HUMAN	USP14	physical	22626734
STAM1_HUMAN	STAM	physical	22626734
BAP1_HUMAN	BAP1	physical	22626734
UCHL1_HUMAN	UCHL1	physical	22626734
UBP21_HUMAN	USP21	physical	22626734
UBC_HUMAN	UBC	physical	22626734
UBP4_HUMAN	USP4	physical	22626734
ZC3H4_HUMAN	ZC3H4	physical	22939629
USO1_HUMAN	USO1	physical	22939629
ZCHC8_HUMAN	ZCCHC8	physical	22939629
MYC_HUMAN	MYC	physical	23389829
PA2GA_HUMAN	PLA2G2A	physical	22118674
UBC_HUMAN	UBC	physical	25359778
KDM1A_HUMAN	KDM1A	physical	24075993
MYC_HUMAN	MYC	physical	25716680
UBC_HUMAN	UBC	physical	26268556
SUMO2_HUMAN	SUMO2	physical	26268556
ZN304_HUMAN	ZNF304	physical	24623306
KPCD1_HUMAN	PRKD1	physical	24623306
UBC_HUMAN	UBC	physical	29131570

Drug and Disease Associations

Kegg Disease
OMIM Disease
There are no disease associations of PTM sites.
Kegg Drug
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of UBP28_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"A role for the deubiquitinating enzyme USP28 in control of the DNA-damage response."; Zhang D., Zaugg K., Mak T.W., Elledge S.J.; Cell 126:529-542(2006). Cited for: FUNCTION, INTERACTION WITH TP53BP1, PHOSPHORYLATION AT SER-67 ANDSER-714, AND MUTAGENESIS OF CYS-171.	16901786 [Abstract]
"ATM and ATR substrate analysis reveals extensive protein networksresponsive to DNA damage."; Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.; Science 316:1160-1166(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-67 AND SER-714, AND MASSSPECTROMETRY.	17525332 [Abstract]

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