Search by BoMiProt ID - Bomi10221


Primary Information

BoMiProt ID Bomi10221
Protein Name Ubiquitin carboxyl-terminal hydrolase 4/Deubiquitinating enzyme 4/Ubiquitin thioesterase 4/Ubiquitin-specific-processing protease 4
Organism Bos taurus
Uniprot IdA6QR55
Milk FractionWhey
Aminoacid Length 963
Molecular Weight 108510
Fasta Sequence https://www.uniprot.org/uniprot/A6QR55.fasta
Gene Name USP4
Gene Id 508042
Protein Existence Status reviewed

Secondary Information

Protein Function cysteine protease.removes monoubiquitinated and polyubiquitinated chains K48 and K63 conjugated ubiquitin chains from targets.Deubiquitinates PDPK1 and TRIM21.also involved in the regulation of p53, TGF-β, Wnt/β-catenin, and nuclear factor κB (NF-κB) signaling pathways.
Biochemical Properties Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin .USP4 ontains a DUSP (domain in USP)-UBL (ubiquitin-like) domain and a UBL-insert catalytic domain.Both domains 1 and 2 contain the active site.Domain 1 contains Cys box (residues 303–320) and QQD box (residues 390–403) of the active site.Domain 2 completes the active site with the His box (residues 864–885, 894–903, and 915–922).Cataltic action starts with His residue,which deprotonates the thiol group of the Cys residue.Cys residue launches a nucleophilic attack on the isopeptide bond, releasing the ε-amine of the target Lys residue and producing a covalent acylenzyme intermediate with ubiquitin.Then,with the help of water molecules, USP4 undergoes diacylation. Consequently, free ubiquitin is released.The aspartic acid (Asp) residue is required to polarize the His residue to stabilize the enzyme’s catalytic activity.
PTMs phosphorylation,ubl conjugation
Site(s) of PTM(s)

N-glycosylation, O-glycosylation,
Phosphorylation
>sp|A6QR55|UBP4_BOVIN Ubiquitin carboxyl-terminal hydrolase 4 OS=Bos taurus OX=9913 GN=USP4 PE=2 SV=1 MAEGGGYRERPDAETQKSELGALMRTTLQRGAQWYLIDSRWFKQWKKYVGFDSWDMYNVG EHNLYPGPIDNSGLFSDPESQTLKEHLIDELDYVLVPAEAWNKLLNWYGCVEGQQPIVRK VVEHGLFVKHCKVEVYLLELKLCENSDPTNVLSCHFSKADTIATIEKEMRKLFNIPAERE TRLWNKYMSNTYEQLSKLDNTVQDAGLYQGQVLVIEPQNEDGTWPRQTQQSKSSTAPSRN FTTSPKSSASPYSSVSASPIANGDSTNTSGMHSSGVSRGGSGFSASYNCQESPLTHVQPG LCGLGNLGNTCFMNSALQCLSNTAPLTDYFLKDEYEAEINRDNPLGMKGEIAEAYAELIK QMWSGRDAHVAPRMFKTQVGRFAPQFSGYQQQDSQELLAFLLDGLHEDLNRVKKKPYLEL KDANGRPDAVVAKEAWENHRLRNDSVIVDTFHGLFKSTLVCPECAKVSVTFDPFCYLTLP LPLKKDRVMEIFLVPADPRCRPTQYRVVVPLMGAVSDLCEALSKLSGIAAENMVVTDVYN HRFHKIFQMDEGLNHIMPRDDIFVYEVCSTSPDGSECVTLPVYFRERKSRPSSTSTGAVL YGQPLLVSVPKHKLTLESLYQAVCERISRYIKQPLPDESGSSPLELGACNGSRSGCAGED EEEMEHQEEGREQLS*675ETEGS*680GDDEPGSDHGEATQKKNKGRPCPRRLFTFSLVNSYGTADI NSLATDGKLLKLNSRSTLAIDWDSETRSCYYNEQESETYEKHVSMLQPQKKKKTAVALRD CIELFTTMETLGEHDPWYCPNCKKHQQATKKFDLWSLPKILVVHLKRFSYNRYWRDKLDT VVEFPVRGLNMSEFVCDPSARPYVYDLIAVSNHYGAMGVGHYTAYAKNKLNGKWYYFDDS NVSLACEDQIVTKAAYVLFYQRRDDEFHKTPSLSFPGSSDGGARPSSSQQGTGDDETYSM DTN
Predicted Disorder Regions 219-290, 635-697, 929-963
DisProt Annotation
TM Helix Prediction No TM helices
Significance of PTMs AKT directly phosphorylates USP4 at Ser445, relocating nuclear USP4 to the cytoplasm and membrane with the help of 14-3-3 protein, as well as enhancing its stability and deubiquitinating activity.Phosphorylation of USP4 at Thr149 and Thr219, is mediated by cyclin-dependent kinases and exerts a negative role in pre-mRNA splicing through blocking USP4 interactions with squamous cell carcinoma antigen recognized by T cells 3 (SART3).Cys-461, Cys-464, Cys-799, and Cys-802 are ubiquitination sites, ubiquitinated by the ubiquitin ligase Ro52.phosphorylation and ubiquitination are involved in USP4-mediated deubiquitinating processes by acting as a positive or negative regulator.
Additional Comments Loss of UPS4 leads to the activation of several p53-directed pathways, including upregulation of apoptosis, premature cell senescence, and reduced oncogene-associated transformation
Bibliography Hu B, Zhang D, Zhao K, Wang Y, Pei L, Fu Q, Ma X. Spotlight on USP4: Structure, Function, and Regulation. Front Cell Dev Biol. 2021 Feb 18;9:595159. doi: 10.3389/fcell.2021.595159. PMID: 33681193; PMCID: PMC7935551.