Hydrolase that deubiquitinates target proteins such as FOXO4, KAT5, p53/TP53, MDM2, ERCC6, DNMT1, UHRF1, PTEN, KMT2E/MLL5 and DAXX. Together with DAXX, prevents MDM2 self-ubiquitination and enhances theE3 ligase activity of MDM2 towards p53/TP53, thereby promoting p53/TP53ubiquitination and proteasomal degradation. Deubiquitinatesp53/TP53, preventing degradation of p53/TP53, and enhances p53/TP53-dependent transcription regulation, cell growth repression andapoptosis. Deubiquitinates p53/TP53 and MDM2 andstrongly stabilizes p53/TP53 even in the presence of excess MDM2, andalso induces p53/TP53-dependent cell growth repression and apoptosis. Deubiquitination of FOXO4 in presence of hydrogenperoxide is not dependent on p53/TP53 and inhibits FOXO4-inducedtranscriptional activity. In association with DAXX, is involved in the deubiquitination and translocation of PTEN from thenucleus to the cytoplasm, both processes that are counteracted by PML. Deubiquitinates KMT2E/MLL5 preventing KMT2E/MLL5proteasomal-mediated degradation. Involved in cellproliferation during early embryonic development. Involved intranscription-coupled nucleotide excision repair (TC-NER) in responseto UV damage: recruited to DNA damage sites following interaction withKIAA1530/UVSSA and promotes deubiquitination of ERCC6, preventing UV-induced degradation of ERCC6. Involved in maintenance of DNA methylation via its interaction withUHRF1 and DNMT1: acts by mediating deubiquitination of UHRF1 and DNMT1, preventing their degradation and promoting DNA methylation by DNMT1. Deubiquitinates alkylation repairenzyme ALKBH3. OTUD4 recruits USP7 and USP9X to stabilize ALKBH3, thereby promoting the repair of alkylated DNA lesions. Acts as a chromatin regulator via its associationwith the Polycomb group (PcG) multiprotein PRC1-like complex; may actby deubiquitinating components of the PRC1-like complex. Able to mediate deubiquitination of histone H2B; itis however unsure whether this activity takes place in vivo. Exhibits a preference towards 'Lys-48'-linkedubiquitin chains. Increases regulatory T-cells (Treg) suppressive capacity by deubiquitinating and stabilizing thetranscription factor FOXP3 which is crucial for Treg cell function. Plays a role in the maintenance of the circadianclock periodicity via deubiquitination and stabilization of the CRY1and CRY2 proteins. Deubiquitinates REST, therebystabilizing REST and promoting the maintenance of neural progenitorcells. Deubiquitinates SIRT7, inhibiting SIRT7histone deacetylase activity and regulating gluconeogenesis. [1-11]

MNHQQQQQQQKAGEQQLSEPEDMEMEAGDTDDPPRITQNPVINGNVALSDGHNTAEEDMEDDTSWRSEATFQFTVERFSRLSESVLSPPCFVRNLPWKIMVMPRFYPDRPHQKSVGFFLQCNAESDSTSWSCHAQAVLKIINYRDDEKSFSRRISHLFFHKENDWGFSNFMAWSEVTDPEKGFIDDDKVTFEVFVQADAPHGVAWDSKKHTGYVGLKNQGATCYMNSLLQTLFFTNQLRKAVYMMPTEGDDSSKSVPLALQRVFYELQHSDKPVGTKKLTKSFGWETLDSFMQHDVQELCRVLLDNVENKMKGTCVEGTIPKLFRGKMVSYIQCKEVDYRSDRREDYYDIQLSIKGKKNIFESFVDYVAVEQLDGDNKYDAGEHGLQEAEKGVKFLTLPPVLHLQLMRFMYDPQTDQNIKINDRFEFPEQLPLDEFLQKTDPKDPANYILHAVLVHSGDNHGGHYVVYLNPKGDGKWCKFDDDVVSRCTKEEAIEHNYGGHDDDLSVRHCTNAYMLVYIRESKLSEVLQAVTDHDIPQQLVERLQEEKRIEAQKRKERQEAHLYMQVQIVAEDQFCGHQGNDMYDEEKVKYTVFKVLKNSSLAEFVQSLSQTMGFPQDQIRLWPMQARSNGTKRPAMLDNEADGNKTMIELSDNENPWTIFLETVDPELAASGATLPKFDKDHDVMLFLKMYDPKTRSLNYCGHIYTPISCKIRDLLPVMCDRAGFIQDTSLILYEEVKPNLTERIQDYDVSLDKALDELMDGDIIVFQKDDPENDNSELPTAKEYFRDLYHRVDVIFCDKTIPNDPGFVVTLSNRMNYFQVAKTVAQRLNTDPMLLQFFKSQGYRDGPGNPLRHNYEGTLRDLLQFFKPRQPKKLYYQQLKMKITDFENRRSFKCIWLNSQFREEEITLYPDKHGCVRDLLEECKKAVELGEKASGKLRLLEIVSYKIIGVHQEDELLECLSPATSRTFRIEEIPLDQVDIDKENEMLVTVAHFHKEVFGTFGIPFLLRIHQGEHFREVMKRIQSLLDIQEKEFEKFKFAIVMMGRHQYINEDEYEVNLKDFEPQPGNMSHPRPWLGLDHFNKAPKRSRYTYLEKAIKIHN