Overview
| Uniprot ID | Q92995 |
|---|
| Protein Name | Ubiquitin carboxyl-terminal hydrolase 13 |
|---|
| Gene Name | USP13 |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 110 |
ASGGALPKRRNSKIF |
Function
Deubiquitinase that mediates deubiquitination of target proteins such as BECN1, MITF, SKP2 and USP10 and is involved in various processes such as autophagy, endoplasmic reticulum-associated degradation (ERAD), cell cycle progression or DNA damage response (PubMed:21571647, PubMed:32772043, PubMed:33592542). Component of a regulatory loop that controls autophagy and p53/TP53 levels: mediates deubiquitination of BECN1, a key regulator of autophagy, leading to stabilize the PIK3C3/VPS34-containing complexes. Alternatively, forms with NEDD4 a deubiquitination complex, which subsequently stabilizes VPS34 to promote autophagy (PubMed:32101753). Also deubiquitinates USP10, an essential regulator of p53/TP53 stability. In turn, PIK3C3/VPS34-containing complexes regulate USP13 stability, suggesting the existence of a regulatory system by which PIK3C3/VPS34-containing complexes regulate p53/TP53 protein levels via USP10 and USP13. Recruited by nuclear UFD1 and mediates deubiquitination of SKP2, thereby regulating endoplasmic reticulum-associated degradation (ERAD). Also regulates ERAD through the deubiquitination of UBL4A a component of the BAG6/BAT3 complex. Mediates stabilization of SIAH2 independently of deubiquitinase activity: binds ubiquitinated SIAH2 and acts by impairing SIAH2 autoubiquitination. Regulates the cell cycle progression by stabilizing cell cycle proteins such as SKP2 and AURKB (PubMed:32772043). In addition, plays an important role in maintaining genomic stability and in DNA replication checkpoint activation via regulation of RAP80 and TOPBP1 (PubMed:33592542). Deubiquitinates the multifunctional protein HMGB1 and subsequently drives its nucleocytoplasmic localization and its secretion (PubMed:36585612). Positively regulates type I and type II interferon signalings by deubiquitinating STAT1 but negatively regulates antiviral response by deubiquitinating STING1 (PubMed:23940278, PubMed:28534493)
Protein Sequence
10
MQRRGALFGM
20
PGGSGGRKMA
30
AGDIGELLVP
40
HMPTIRVPRS
50
GDRVYKNECA
60
FSYDSPNSEG
70
GLYVCMNTFL
80
AFGREHVERH
90
FRKTGQSVYM
100
HLKRHVREKV
110
RGASGGALPK
120
RRNSKIFLDL
130
DTDDDLNSDD
140
YEYEDEAKLV
150
IFPDHYEIAL
160
PNIEELPALV
170
TIACDAVLSS
180
KSPYRKQDPD
190
TWENELPVSK
200
YANNLTQLDN
210
GVRIPPSGWK
220
CARCDLRENL
230
WLNLTDGSVL
240
CGKWFFDSSG
250
GNGHALEHYR
260
DMGYPLAVKL
270
GTITPDGADV
280
YSFQEEEPVL
290
DPHLAKHLAH
300
FGIDMLHMHG
310
TENGLQDNDI
320
KLRVSEWEVI
330
QESGTKLKPM
340
YGPGYTGLKN
350
LGNSCYLSSV
360
MQAIFSIPEF
370
QRAYVGNLPR
380
IFDYSPLDPT
390
QDFNTQMTKL
400
GHGLLSGQYS
410
KPPVKSELIE
420
QVMKEEHKPQ
430
QNGISPRMFK
440
AFVSKSHPEF
450
SSNRQQDAQE
460
FFLHLVNLVE
470
RNRIGSENPS
480
DVFRFLVEER
490
IQCCQTRKVR
500
YTERVDYLMQ
510
LPVAMEAATN
520
KDELIAYELT
530
RREAEANRRP
540
LPELVRAKIP
550
FSACLQAFSE
560
PENVDDFWSS
570
ALQAKSAGVK
580
TSRFASFPEY
590
LVVQIKKFTF
600
GLDWVPKKFD
610
VSIDMPDLLD
620
INHLRARGLQ
630
PGEEELPDIS
640
PPIVIPDDSK
650
DRLMNQLIDP
660
SDIDESSVMQ
670
LAEMGFPLEA
680
CRKAVYFTGN
690
MGAEVAFNWI
700
IVHMEEPDFA
710
EPLTMPGYGG
720
AASAGASVFG
730
ASGLDNQPPE
740
EIVAIITSMG
750
FQRNQAIQAL
760
RATNNNLERA
770
LDWIFSHPEF
780
EEDSDFVIEM
790
ENNANANIIS
800
EAKPEGPRVK
810
DGSGTYELFA
820
FISHMGTSTM
830
SGHYICHIKK
840
EGRWVIYNDH
850
KVCASERPPK
860
DLGYMYFYRR
IPS
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005829 |
cytosol |
| Cellular Component |
GO:0005654 |
nucleoplasm |
| Cellular Component |
GO:0005634 |
nucleus |
| Molecular Function |
GO:1904288 |
BAT3 complex binding |
| Molecular Function |
GO:0004843 |
cysteine-type deubiquitinase activity |
| Molecular Function |
GO:0004197 |
cysteine-type endopeptidase activity |
| Molecular Function |
GO:1990380 |
K48-linked deubiquitinase activity |
| Molecular Function |
GO:0070628 |
proteasome binding |
| Molecular Function |
GO:0051087 |
protein-folding chaperone binding |
| Molecular Function |
GO:0043130 |
ubiquitin binding |
| Molecular Function |
GO:0031625 |
ubiquitin protein ligase binding |
| Molecular Function |
GO:0044389 |
ubiquitin-like protein ligase binding |
| Molecular Function |
GO:0008270 |
zinc ion binding |
| Biological Process |
GO:0006914 |
autophagy |
| Biological Process |
GO:0008283 |
cell population proliferation |
| Biological Process |
GO:0036506 |
maintenance of unfolded protein |
| Biological Process |
GO:0030318 |
melanocyte differentiation |
| Biological Process |
GO:1904294 |
positive regulation of ERAD pathway |
| Biological Process |
GO:0016579 |
protein deubiquitination |
| Biological Process |
GO:0035523 |
protein K29-linked deubiquitination |
| Biological Process |
GO:0044313 |
protein K6-linked deubiquitination |
| Biological Process |
GO:0070536 |
protein K63-linked deubiquitination |
| Biological Process |
GO:0050821 |
protein stabilization |
| Biological Process |
GO:0006508 |
proteolysis |
| Biological Process |
GO:0010506 |
regulation of autophagy |
| Biological Process |
GO:0006355 |
regulation of DNA-templated transcription |
| Biological Process |
GO:0031647 |
regulation of protein stability |
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.