Overview
| Uniprot ID | Q9Y4E8 |
|---|
| Protein Name | Ubiquitin carboxyl-terminal hydrolase 15 |
|---|
| Gene Name | USP15 |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 259 |
NMNNRNVKNSNYCLP |
| 272 |
LPSYTAYKNYDYSEP |
Function
Hydrolase that removes conjugated ubiquitin from target proteins and regulates various pathways such as the TGF-beta receptor signaling, NF-kappa-B and RNF41/NRDP1-PRKN pathways (PubMed:16005295, PubMed:17318178, PubMed:19576224, PubMed:19826004, PubMed:21947082, PubMed:22344298, PubMed:24852371). Acts as a key regulator of TGF-beta receptor signaling pathway, but the precise mechanism is still unclear: according to a report, acts by promoting deubiquitination of monoubiquitinated R-SMADs (SMAD1, SMAD2 and/or SMAD3), thereby alleviating inhibition of R-SMADs and promoting activation of TGF-beta target genes (PubMed:21947082). According to another reports, regulates the TGF-beta receptor signaling pathway by mediating deubiquitination and stabilization of TGFBR1, leading to an enhanced TGF-beta signal (PubMed:22344298). Able to mediate deubiquitination of monoubiquitinated substrates, 'Lys-27'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains (PubMed:33093067). May also regulate gene expression and/or DNA repair through the deubiquitination of histone H2B (PubMed:24526689). Acts as an inhibitor of mitophagy by counteracting the action of parkin (PRKN): hydrolyzes cleavage of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains attached by parkin on target proteins such as MFN2, thereby reducing parkin's ability to drive mitophagy (PubMed:24852371). Acts as an associated component of COP9 signalosome complex (CSN) and regulates different pathways via this association: regulates NF-kappa-B by mediating deubiquitination of NFKBIA and deubiquitinates substrates bound to VCP (PubMed:16005295, PubMed:17318178, PubMed:19576224, PubMed:19826004). Involved in endosome organization by mediating deubiquitination of SQSTM1: ubiquitinated SQSTM1 forms a molecular bridge that restrains cognate vesicles in the perinuclear region and its deubiquitination releases target vesicles for fast transport into the cell periphery (PubMed:27368102). Acts as a negative regulator of antifungal immunity by mediating 'Lys-27'-linked deubiquitination of CARD9, thereby inactivating CARD9 (PubMed:33093067)
Protein Sequence
10
MAEGGAADLD
20
TQRSDIATLL
30
KTSLRKGDTW
40
YLVDSRWFKQ
50
WKKYVGFDSW
60
DKYQMGDQNV
70
YPGPIDNSGL
80
LKDGDAQSLK
90
EHLIDELDYI
100
LLPTEGWNKL
110
VSWYTLMEGQ
120
EPIARKVVEQ
130
GMFVKHCKVE
140
VYLTELKLCE
150
NGNMNNVVTR
160
RFSKADTIDT
170
IEKEIRKIFS
180
IPDEKETRLW
190
NKYMSNTFEP
200
LNKPDSTIQD
210
AGLYQGQVLV
220
IEQKNEDGTW
230
PRGPSTPKSP
240
GASNFSTLPK
250
ISPSSLSNNY
260
NNMNNRNVKN
270
SNYCLPSYTA
280
YKNYDYSEPG
290
RNNEQPGLCG
300
LSNLGNTCFM
310
NSAIQCLSNT
320
PPLTEYFLND
330
KYQEELNFDN
340
PLGMRGEIAK
350
SYAELIKQMW
360
SGKFSYVTPR
370
AFKTQVGRFA
380
PQFSGYQQQD
390
CQELLAFLLD
400
GLHEDLNRIR
410
KKPYIQLKDA
420
DGRPDKVVAE
430
EAWENHLKRN
440
DSIIVDIFHG
450
LFKSTLVCPE
460
CAKISVTFDP
470
FCYLTLPLPM
480
KKERTLEVYL
490
VRMDPLTKPM
500
QYKVVVPKIG
510
NILDLCTALS
520
ALSGIPADKM
530
IVTDIYNHRF
540
HRIFAMDENL
550
SSIMERDDIY
560
VFEININRTE
570
DTEHVIIPVC
580
LREKFRHSSY
590
THHTGSSLFG
600
QPFLMAVPRN
610
NTEDKLYNLL
620
LLRMCRYVKI
630
STETEETEGS
640
LHCCKDQNIN
650
GNGPNGIHEE
660
GSPSEMETDE
670
PDDESSQDQE
680
LPSENENSQS
690
EDSVGGDNDS
700
ENGLCTEDTC
710
KGQLTGHKKR
720
LFTFQFNNLG
730
NTDINYIKDD
740
TRHIRFDDRQ
750
LRLDERSFLA
760
LDWDPDLKKR
770
YFDENAAEDF
780
EKHESVEYKP
790
PKKPFVKLKD
800
CIELFTTKEK
810
LGAEDPWYCP
820
NCKEHQQATK
830
KLDLWSLPPV
840
LVVHLKRFSY
850
SRYMRDKLDT
860
LVDFPINDLD
870
MSEFLINPNA
880
GPCRYNLIAV
890
SNHYGGMGGG
900
HYTAFAKNKD
910
DGKWYYFDDS
920
SVSTASEDQI
930
VSKAAYVLFY
940
QRQDTFSGTG
950
FFPLDRETKG
960
ASAATGIPLE
970
SDEDSNDNDN
980
DIENENCMHT
N
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005737 |
cytoplasm |
| Cellular Component |
GO:0005829 |
cytosol |
| Cellular Component |
GO:0005739 |
mitochondrion |
| Cellular Component |
GO:0016604 |
nuclear body |
| Cellular Component |
GO:0005654 |
nucleoplasm |
| Cellular Component |
GO:0005634 |
nucleus |
| Molecular Function |
GO:0004843 |
cysteine-type deubiquitinase activity |
| Molecular Function |
GO:0004197 |
cysteine-type endopeptidase activity |
| Molecular Function |
GO:0101005 |
deubiquitinase activity |
| Molecular Function |
GO:1990380 |
K48-linked deubiquitinase activity |
| Molecular Function |
GO:0046332 |
SMAD binding |
| Molecular Function |
GO:0005160 |
transforming growth factor beta receptor binding |
| Molecular Function |
GO:0061649 |
ubiquitin-modified histone reader activity |
| Biological Process |
GO:0030509 |
BMP signaling pathway |
| Biological Process |
GO:0035520 |
monoubiquitinated protein deubiquitination |
| Biological Process |
GO:1905035 |
negative regulation of antifungal innate immune response |
| Biological Process |
GO:0030512 |
negative regulation of transforming growth factor beta receptor signaling pathway |
| Biological Process |
GO:1900246 |
positive regulation of RIG-I signaling pathway |
| Biological Process |
GO:0016579 |
protein deubiquitination |
| Biological Process |
GO:1990167 |
protein K27-linked deubiquitination |
| Biological Process |
GO:0006508 |
proteolysis |
| Biological Process |
GO:0051252 |
regulation of RNA metabolic process |
| Biological Process |
GO:0140673 |
transcription elongation-coupled chromatin remodeling |
| Biological Process |
GO:0007179 |
transforming growth factor beta receptor signaling pathway |
Reference
[1] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.