Overview
| Uniprot ID | P45974 |
|---|
| Protein Name | Ubiquitin carboxyl-terminal hydrolase 5 |
|---|
| Gene Name | USP5 |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 163 |
SADSASRKQEVQAWD |
Function
Deubiquitinating enzyme that participates in a wide range of cellular processes by specifically cleaving isopeptide bonds between ubiquitin and substrate proteins or ubiquitin itself. Affects thereby important cellular signaling pathways such as NF-kappa-B, Wnt/beta-catenin, and cytokine production by regulating ubiquitin-dependent protein degradation. Participates in the activation of the Wnt signaling pathway by promoting FOXM1 deubiquitination and stabilization that induces the recruitment of beta-catenin to Wnt target gene promoter (PubMed:26912724). Regulates the assembly and disassembly of heat-induced stress granules by mediating the hydrolysis of unanchored ubiquitin chains (PubMed:29567855). Promotes lipopolysaccharide-induced apoptosis and inflammatory response by stabilizing the TXNIP protein (PubMed:37534934). Affects T-cell biology by stabilizing the inhibitory receptor on T-cells PDC1 (PubMed:37208329). Acts as a negative regulator of autophagy by regulating ULK1 at both protein and mRNA levels (PubMed:37607937). Acts also as a negative regulator of type I interferon production by simultaneously removing both 'Lys-48'-linked unanchored and 'Lys-63'-linked anchored polyubiquitin chains on the transcription factor IRF3 (PubMed:39761299). Modulates the stability of DNA mismatch repair protein MLH1 and counteracts the effect of the ubiquitin ligase UBR4 (PubMed:39032648). Upon activation by insulin, it gets phosphorylated through mTORC1-mediated phosphorylation to enhance YTHDF1 stability by removing 'Lys-11'-linked polyubiquitination (PubMed:39900921). May also deubiquitinate other substrates such as the calcium channel CACNA1H (By similarity)
Protein Sequence
10
MAELSEEALL
20
SVLPTIRVPK
30
AGDRVHKDEC
40
AFSFDTPESE
50
GGLYICMNTF
60
LGFGKQYVER
70
HFNKTGQRVY
80
LHLRRTRRPK
90
EEDPATGTGD
100
PPRKKPTRLA
110
IGVEGGFDLS
120
EEKFELDEDV
130
KIVILPDYLE
140
IARDGLGGLP
150
DIVRDRVTSA
160
VEALLSADSA
170
SRKQEVQAWD
180
GEVRQVSKHA
190
FSLKQLDNPA
200
RIPPCGWKCS
210
KCDMRENLWL
220
NLTDGSILCG
230
RRYFDGSGGN
240
NHAVEHYRET
250
GYPLAVKLGT
260
ITPDGADVYS
270
YDEDDMVLDP
280
SLAEHLSHFG
290
IDMLKMQKTD
300
KTMTELEIDM
310
NQRIGEWELI
320
QESGVPLKPL
330
FGPGYTGIRN
340
LGNSCYLNSV
350
VQVLFSIPDF
360
QRKYVDKLEK
370
IFQNAPTDPT
380
QDFSTQVAKL
390
GHGLLSGEYS
400
KPVPESGDGE
410
RVPEQKEVQD
420
GIAPRMFKAL
430
IGKGHPEFST
440
NRQQDAQEFF
450
LHLINMVERN
460
CRSSENPNEV
470
FRFLVEEKIK
480
CLATEKVKYT
490
QRVDYIMQLP
500
VPMDAALNKE
510
ELLEYEEKKR
520
QAEEEKMALP
530
ELVRAQVPFS
540
SCLEAYGAPE
550
QVDDFWSTAL
560
QAKSVAVKTT
570
RFASFPDYLV
580
IQIKKFTFGL
590
DWVPKKLDVS
600
IEMPEELDIS
610
QLRGTGLQPG
620
EEELPDIAPP
630
LVTPDEPKGS
640
LGFYGNEDED
650
SFCSPHFSSP
660
TSPMLDESVI
670
IQLVEMGFPM
680
DACRKAVYYT
690
GNSGAEAAMN
700
WVMSHMDDPD
710
FANPLILPGS
720
SGPGSTSAAA
730
DPPPEDCVTT
740
IVSMGFSRDQ
750
ALKALRATNN
760
SLERAVDWIF
770
SHIDDLDAEA
780
AMDISEGRSA
790
ADSISESVPV
800
GPKVRDGPGK
810
YQLFAFISHM
820
GTSTMCGHYV
830
CHIKKEGRWV
840
IYNDQKVCAS
850
EKPPKDLGYI
YFYQRVAS
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005737 |
cytoplasm |
| Cellular Component |
GO:0010494 |
cytoplasmic stress granule |
| Cellular Component |
GO:0005829 |
cytosol |
| Cellular Component |
GO:0005764 |
lysosome |
| Cellular Component |
GO:0005634 |
nucleus |
| Cellular Component |
GO:0098793 |
presynapse |
| 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:0043130 |
ubiquitin binding |
| Molecular Function |
GO:0008270 |
zinc ion binding |
| Biological Process |
GO:0032435 |
negative regulation of proteasomal ubiquitin-dependent protein catabolic process |
| Biological Process |
GO:0002841 |
negative regulation of T cell mediated immune response to tumor cell |
| Biological Process |
GO:2000059 |
negative regulation of ubiquitin-dependent protein catabolic process |
| Biological Process |
GO:0032436 |
positive regulation of proteasomal ubiquitin-dependent protein catabolic process |
| Biological Process |
GO:0016579 |
protein deubiquitination |
| Biological Process |
GO:0071108 |
protein K48-linked deubiquitination |
| Biological Process |
GO:0016567 |
protein ubiquitination |
| Biological Process |
GO:0006508 |
proteolysis |
| Biological Process |
GO:0031647 |
regulation of protein stability |
| Biological Process |
GO:0140251 |
regulation protein catabolic process at presynapse |
Reference
[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.