Overview
| Uniprot ID | Q8R5H1 |
|---|
| Protein Name | Ubiquitin carboxyl-terminal hydrolase 15 |
|---|
| Gene Name | Usp15 |
|---|
| Organism | Mus musculus |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 175 |
IFNIPDEKEARLWNK |
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. 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. 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. Able to mediate deubiquitination of monoubiquitinated substrates, 'Lys-27'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains. May also regulate gene expression and/or DNA repair through the deubiquitination of histone H2B. 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. 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. 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. Acts as a negative regulator of antifungal immunity by mediating 'Lys-27'-linked deubiquitination of CARD9, thereby inactivating CARD9
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
IEKEIRKIFN
180
IPDEKEARLW
190
NKYMSNTFEP
200
LNKPDSTIQD
210
AGLYQGQVLV
220
IEQKNEDGTW
230
PRGPSTPKSP
240
GASNFSTLPK
250
ISPSSLSNNY
260
NNINNRNVKN
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
KKERSLEVYL
490
VRMDPLAKPM
500
QYKVIVPKIG
510
NILDLCTALS
520
ALSGVPADKM
530
IVTDIYNHRF
540
HRIFAVDENL
550
SSIMERDDIY
560
VFEININRAE
570
DTEHVVIPVC
580
LREKFRHSSY
590
THHTGSSLFG
600
QPFLMAIPRN
610
NTEDKLYNLL
620
LLRMCRYVKM
630
STETEETDGH
640
LRCCEDQNIN
650
GNGPNGLHEE
660
GSPSEMETDE
670
PDDESSQDQE
680
LPSENENSQS
690
EDSVGGDNDS
700
ENGLCTEETC
710
KGQLTGHKKR
720
LFTFQFNNLG
730
NNDINYIKDD
740
TSHIRFDDRQ
750
LRLDERSFLA
760
LDWDPDLKKR
770
YFDENAAEDF
780
EKHESVEYKP
790
PKRPFVKLKD
800
CIELFTTKEK
810
LGAEDPWYCP
820
NCKEHQQATK
830
KLDLWSLPPV
840
LVVHLKRFSY
850
SRYMRDKLDT
860
LVDFPISDLD
870
MSEFLINPNA
880
GPCRYNLIAV
890
SNHYGGMGGG
900
HYTAFAKNKD
910
DGKWYYFDDS
920
SVSTASEDQI
930
VSKAAYVLFY
940
QRQDTFSGTG
950
FFPLDRETKG
960
ASAATGIPLE
970
SDEDSNDNDN
980
DLENENCMHT
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:0042802 |
identical protein binding |
| 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:0043123 |
positive regulation of canonical NF-kappaB signal transduction |
| 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:1902238 |
regulation of intrinsic apoptotic signaling pathway in response to osmotic stress by p53 class mediator |
| 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] Wu D, Tang Y, Li X, Xiong S, Zhang Z et al.. Characterization of protein lactylation in healthy and ischemic mouse hearts.. Front Cardiovasc Med 12:1644886. 2025. PMID: 41089239.