Primary Information |
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| BoMiProt ID | Bomi10221 |
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| Protein Name | Ubiquitin carboxyl-terminal hydrolase 4/Deubiquitinating enzyme 4/Ubiquitin thioesterase 4/Ubiquitin-specific-processing protease 4 |
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| Organism | Bos taurus |
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| Uniprot ID | A6QR55 |
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| Milk Fraction | Whey |
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| Aminoacid Length | 963 |
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| Molecular Weight | 108510 |
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| FASTA Sequence |
Download |
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| Gene Name | USP4 |
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| Gene ID | 508042 |
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| Protein Existence Status | reviewed |
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Secondary Information |
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| 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. |
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| 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. |
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| PTMs | phosphorylation,ubl conjugation |
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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
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| Predicted Disorder Regions | 219-290, 635-697, 929-963 |
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| DisProt Annotation | |
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| TM Helix Prediction | No TM helices |
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| 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. |
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| 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 |
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| 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. |
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