Search Results

Overview

Uniprot IDQ93009
Protein NameUbiquitin C-terminal hydrolase 7
Gene NameUSP7
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
1084 LGLDHFNKAPKRSRY
1096 SRYTYLEKAIKIHN*
490 DVVSRCTKEEAIEHN
884 YYQQLKMKITDFENR

Function

Hydrolase that deubiquitinates target proteins such as ARMC5, FOXO4, DEPTOR, KAT5, p53/TP53, MDM2, ERCC6, DNMT1, UHRF1, PTEN, KMT2E/MLL5 and DAXX (PubMed:11923872, PubMed:15053880, PubMed:16964248, PubMed:18716620, PubMed:25283148, PubMed:25865756, PubMed:26678539, PubMed:28655758, PubMed:33544460, PubMed:35216969). Together with DAXX, prevents MDM2 self-ubiquitination and enhances the E3 ligase activity of MDM2 towards p53/TP53, thereby promoting p53/TP53 ubiquitination and proteasomal degradation (PubMed:15053880, PubMed:16845383, PubMed:18566590, PubMed:20153724). Deubiquitinates p53/TP53, preventing degradation of p53/TP53, and enhances p53/TP53-dependent transcription regulation, cell growth repression and apoptosis (PubMed:25283148). Deubiquitinates p53/TP53 and MDM2 and strongly stabilizes p53/TP53 even in the presence of excess MDM2, and also induces p53/TP53-dependent cell growth repression and apoptosis (PubMed:11923872, PubMed:26786098). Deubiquitination of FOXO4 in presence of hydrogen peroxide is not dependent on p53/TP53 and inhibits FOXO4-induced transcriptional activity (PubMed:16964248). In association with DAXX, is involved in the deubiquitination and translocation of PTEN from the nucleus to the cytoplasm, both processes that are counteracted by PML (PubMed:18716620). Deubiquitinates KMT2E/MLL5 preventing KMT2E/MLL5 proteasomal-mediated degradation (PubMed:26678539). Involved in cell proliferation during early embryonic development. Involved in transcription-coupled nucleotide excision repair (TC-NER) in response to UV damage: recruited to DNA damage sites following interaction with KIAA1530/UVSSA and promotes deubiquitination of ERCC6, preventing UV-induced degradation of ERCC6 (PubMed:22466611, PubMed:22466612). Involved in maintenance of DNA methylation via its interaction with UHRF1 and DNMT1: acts by mediating deubiquitination of UHRF1 and DNMT1, preventing their degradation and promoting DNA methylation by DNMT1 (PubMed:21745816, PubMed:22411829). Deubiquitinates alkylation repair enzyme ALKBH3. OTUD4 recruits USP7 and USP9X to stabilize ALKBH3, thereby promoting the repair of alkylated DNA lesions (PubMed:25944111). Acts as a chromatin regulator via its association with the Polycomb group (PcG) multiprotein PRC1-like complex; may act by deubiquitinating components of the PRC1-like complex (PubMed:20601937). Able to mediate deubiquitination of histone H2B; it is however unsure whether this activity takes place in vivo (PubMed:20601937). Exhibits a preference towards 'Lys-48'-linked ubiquitin chains (PubMed:22689415). Increases regulatory T-cells (Treg) suppressive capacity by deubiquitinating and stabilizing the transcription factor FOXP3 which is crucial for Treg cell function (PubMed:23973222). Plays a role in the maintenance of the circadian clock periodicity via deubiquitination and stabilization of the CRY1 and CRY2 proteins (PubMed:27123980). Deubiquitinates REST, thereby stabilizing REST and promoting the maintenance of neural progenitor cells (PubMed:21258371). Deubiquitinates SIRT7, inhibiting SIRT7 histone deacetylase activity and regulating gluconeogenesis (PubMed:28655758). Involved in the regulation of WASH-dependent actin polymerization at the surface of endosomes and the regulation of endosomal protein recycling (PubMed:26365382). It maintains optimal WASH complex activity and precise F-actin levels via deubiquitination of TRIM27 and WASHC1 (PubMed:26365382). Mediates the deubiquitination of phosphorylated DEPTOR, promoting its stability and leading to decreased mTORC1 signaling (PubMed:35216969). Deubiquitinates H2AB1, H2BC4 and H2BC22 (By similarity)

Protein Sequence

10 MNHQQQQQQQ 20 KAGEQQLSEP 30 EDMEMEAGDT 40 DDPPRITQNP 50 VINGNVALSD 60 GHNTAEEDME 70 DDTSWRSEAT 80 FQFTVERFSR 90 LSESVLSPPC 100 FVRNLPWKIM 110 VMPRFYPDRP 120 HQKSVGFFLQ 130 CNAESDSTSW 140 SCHAQAVLKI 150 INYRDDEKSF 160 SRRISHLFFH 170 KENDWGFSNF 180 MAWSEVTDPE 190 KGFIDDDKVT 200 FEVFVQADAP 210 HGVAWDSKKH 220 TGYVGLKNQG 230 ATCYMNSLLQ 240 TLFFTNQLRK 250 AVYMMPTEGD 260 DSSKSVPLAL 270 QRVFYELQHS 280 DKPVGTKKLT 290 KSFGWETLDS 300 FMQHDVQELC 310 RVLLDNVENK 320 MKGTCVEGTI 330 PKLFRGKMVS 340 YIQCKEVDYR 350 SDRREDYYDI 360 QLSIKGKKNI 370 FESFVDYVAV 380 EQLDGDNKYD 390 AGEHGLQEAE 400 KGVKFLTLPP 410 VLHLQLMRFM 420 YDPQTDQNIK 430 INDRFEFPEQ 440 LPLDEFLQKT 450 DPKDPANYIL 460 HAVLVHSGDN 470 HGGHYVVYLN 480 PKGDGKWCKF 490 DDDVVSRCTK 500 EEAIEHNYGG 510 HDDDLSVRHC 520 TNAYMLVYIR 530 ESKLSEVLQA 540 VTDHDIPQQL 550 VERLQEEKRI 560 EAQKRKERQE 570 AHLYMQVQIV 580 AEDQFCGHQG 590 NDMYDEEKVK 600 YTVFKVLKNS 610 SLAEFVQSLS 620 QTMGFPQDQI 630 RLWPMQARSN 640 GTKRPAMLDN 650 EADGNKTMIE 660 LSDNENPWTI 670 FLETVDPELA 680 ASGATLPKFD 690 KDHDVMLFLK 700 MYDPKTRSLN 710 YCGHIYTPIS 720 CKIRDLLPVM 730 CDRAGFIQDT 740 SLILYEEVKP 750 NLTERIQDYD 760 VSLDKALDEL 770 MDGDIIVFQK 780 DDPENDNSEL 790 PTAKEYFRDL 800 YHRVDVIFCD 810 KTIPNDPGFV 820 VTLSNRMNYF 830 QVAKTVAQRL 840 NTDPMLLQFF 850 KSQGYRDGPG 860 NPLRHNYEGT 870 LRDLLQFFKP 880 RQPKKLYYQQ 890 LKMKITDFEN 900 RRSFKCIWLN 910 SQFREEEITL 920 YPDKHGCVRD 930 LLEECKKAVE 940 LGEKASGKLR 950 LLEIVSYKII 960 GVHQEDELLE 970 CLSPATSRTF 980 RIEEIPLDQV 990 DIDKENEMLV 1000 TVAHFHKEVF 1010 GTFGIPFLLR 1020 IHQGEHFREV 1030 MKRIQSLLDI 1040 QEKEFEKFKF 1050 AIVMMGRHQY 1060 INEDEYEVNL 1070 KDFEPQPGNM 1080 SHPRPWLGLD 1090 HFNKAPKRSR 1100 YTYLEKAIKI HN

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005694 chromosome
Molecular Function GO:1990380 K48-linked deubiquitinase activity
Molecular Function GO:0002039 p53 binding
Biological Process GO:0140374 antiviral innate immune response
Biological Process GO:0006307 DNA alkylation repair
Biological Process GO:0035520 monoubiquitinated protein deubiquitination
Biological Process GO:0044027 negative regulation of gene expression via chromosomal CpG island methylation
Biological Process GO:0045721 negative regulation of gluconeogenesis
Biological Process GO:0032435 negative regulation of proteasomal ubiquitin-dependent protein catabolic process
Biological Process GO:1904262 negative regulation of TORC1 signaling
Biological Process GO:0016579 protein deubiquitination
Biological Process GO:0050821 protein stabilization
Biological Process GO:0016567 protein ubiquitination
Biological Process GO:0006508 proteolysis
Biological Process GO:0042752 regulation of circadian rhythm
Biological Process GO:0070203 regulation of establishment of protein localization to telomere
Biological Process GO:0031647 regulation of protein stability
Biological Process GO:1905279 regulation of retrograde transport, endosome to Golgi
Biological Process GO:1901796 regulation of signal transduction by p53 class mediator
Biological Process GO:1904353 regulation of telomere capping
Biological Process GO:0010803 regulation of tumor necrosis factor-mediated signaling pathway
Biological Process GO:0048511 rhythmic process
Biological Process GO:0075342 symbiont-mediated disruption of host cell PML body
Biological Process GO:0006283 transcription-coupled nucleotide-excision repair
Cellular Component GO:0005829 cytosol
Cellular Component GO:0016604 nuclear body
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0016605 PML body
Cellular Component GO:0032991 protein-containing complex
Molecular Function GO:0004843 cysteine-type deubiquitinase activity
Molecular Function GO:0004197 cysteine-type endopeptidase activity
Molecular Function GO:0101005 deubiquitinase activity

Reference

[1] Yang D, Yin J, Shan L, Yi X, Zhang W et al.. Identification of lysine-lactylated substrates in gastric cancer cells.. iScience 25(7):104630. 2022 Jul 15. PMID: 35800753.

[2] 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.

[3] Lin Y, Chen M, Wang D, Yu Y, Chen R et al.. Multi-Proteomic Analysis Reveals the Effect of Protein Lactylation on Matrix and Cholesterol Metabolism in Tendinopathy.. J Proteome Res 22(6):1712-1722. 2023 Jun 2. PMID: 37159428.

[4] Yang YH, Wang QC, Kong J, Yang JT, Liu JF. Global profiling of lysine lactylation in human lungs.. Proteomics 23(15):e2200437. 2023 Aug. PMID: 37170646.

[5] Cheng Z, Huang H, Li M, Chen Y. Proteomic analysis identifies PFKP lactylation in SW480 colon cancer cells.. iScience 27(1):108645. 2024 Jan 19. PMID: 38155775.

[6] 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.

[7] Shi CM, Wang QC, Li XL, Yang YH, Tang XY et al.. Global Profiling of Protein Lactylation in Human Hippocampi.. Proteomics Clin Appl 19(2):e202400061. 2025 Mar. PMID: 39610256.

[8] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.

[9] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.