ID UBP14_BOVIN Reviewed; 494 AA. AC Q0IIF7; DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 02-SEP-2026, entry version 111. DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 14; DE EC=3.4.19.12; DE AltName: Full=Deubiquitinating enzyme 14; DE AltName: Full=Ubiquitin thioesterase 14; DE AltName: Full=Ubiquitin-specific-processing protease 14; GN Name=USP14; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Hereford; TISSUE=Fetal pons; RG NIH - Mammalian Gene Collection (MGC) project; RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases. RN [2] RP ASSOCIATION WITH THE 26S PROTEASOME. RX PubMed=18162577; DOI=10.1091/mbc.e07-10-1040; RA Koulich E., Li X., DeMartino G.N.; RT "Relative structural and functional roles of multiple deubiquitylating RT proteins associated with mammalian 26S proteasome."; RL Mol. Biol. Cell 19:1072-1082(2008). CC -!- FUNCTION: Proteasome-associated deubiquitinase which releases ubiquitin CC from the proteasome targeted ubiquitinated proteins. Ensures the CC regeneration of ubiquitin at the proteasome. Is a reversibly associated CC subunit of the proteasome and a large fraction of proteasome-free CC protein exists within the cell. Required for the degradation of the CC chemokine receptor CXCR4 which is critical for CXCL12-induced cell CC chemotaxis. Also serves as a physiological inhibitor of endoplasmic CC reticulum-associated degradation (ERAD) under the non-stressed CC condition by inhibiting the degradation of unfolded endoplasmic CC reticulum proteins via interaction with ERN1 (By similarity). CC Indispensable for synaptic development and function at neuromuscular CC junctions (NMJs) (By similarity). Plays a role in the innate immune CC defense against viruses by stabilizing the viral DNA sensor CGAS and CC thus inhibiting its autophagic degradation (By similarity). CC {ECO:0000250|UniProtKB:P54578, ECO:0000250|UniProtKB:Q9JMA1}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide CC and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76- CC residue protein attached to proteins as an intracellular targeting CC signal).; EC=3.4.19.12; CC -!- SUBUNIT: Homodimer (Potential). Associates with the 26S proteasome. CC Interacts with FANCC, CXCR4 and ERN1. Interacts with TRIM14; this CC interaction recruits USP14 to cleave ubiquitin chains of CGAS (By CC similarity). {ECO:0000250|UniProtKB:P54578}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane CC {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. CC -!- SIMILARITY: Belongs to the peptidase C19 family. USP14/UBP6 subfamily. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; BC122666; AAI22667.1; -; mRNA. DR RefSeq; NP_001068657.1; NM_001075189.1. DR AlphaFoldDB; Q0IIF7; -. DR BMRB; Q0IIF7; -. DR SMR; Q0IIF7; -. DR FunCoup; Q0IIF7; 4596. DR STRING; 9913.ENSBTAP00000063666; -. DR MEROPS; C19.015; -. DR GlyGen; Q0IIF7; 1 site. DR PaxDb; 9913-ENSBTAP00000063666; -. DR Ensembl; ENSBTAT00000025580.7; ENSBTAP00000025580.6; ENSBTAG00000019214.8. DR Ensembl; ENSBTAT00090051090; ENSBTAP00090026379; ENSBTAG00090024417. DR GeneID; 505106; -. DR KEGG; bta:505106; -. DR CTD; 9097; -. DR VEuPathDB; HostDB:ENSBTAG00000019214; -. DR VGNC; VGNC:36712; USP14. DR eggNOG; KOG1872; Eukaryota. DR GeneTree; ENSGT00390000009615; -. DR InParanoid; Q0IIF7; -. DR OMA; FKSDAEY; -. DR OrthoDB; 333239at2759; -. DR Reactome; R-BTA-5689880; Ub-specific processing proteases. DR Reactome; R-BTA-9758274; Regulation of NF-kappa B signaling. DR Proteomes; UP000009136; Chromosome 24. DR Bgee; ENSBTAG00000019214; Expressed in omental fat pad and 105 other cell types or tissues. DR ExpressionAtlas; Q0IIF7; baseline. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:UniProtKB. DR GO; GO:0070628; F:proteasome binding; IDA:UniProtKB. DR GO; GO:1904293; P:negative regulation of ERAD pathway; IBA:GO_Central. DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IEA:InterPro. DR GO; GO:0016579; P:protein deubiquitination; IEA:InterPro. DR CDD; cd02657; Peptidase_C19A; 1. DR CDD; cd16104; Ubl_USP14_like; 1. DR FunFam; 3.10.20.90:FF:000119; Ubiquitin carboxyl-terminal hydrolase 14; 1. DR FunFam; 3.90.70.10:FF:000032; Ubiquitin carboxyl-terminal hydrolase 14; 1. DR Gene3D; 3.90.70.10; Cysteine proteinases; 1. DR Gene3D; 3.10.20.90; Phosphatidylinositol 3-kinase Catalytic Subunit, Chain A, domain 1; 1. DR InterPro; IPR038765; Papain-like_cys_pep_sf. DR InterPro; IPR001394; Peptidase_C19_UCH. DR InterPro; IPR000626; Ubiquitin-like_dom. DR InterPro; IPR029071; Ubiquitin-like_domsf. DR InterPro; IPR019954; Ubiquitin_CS. DR InterPro; IPR044635; UBP14-like. DR InterPro; IPR028889; USP. DR InterPro; IPR018200; USP_CS. DR PANTHER; PTHR43982; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1. DR PANTHER; PTHR43982:SF1; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE 14; 1. DR Pfam; PF00443; UCH; 1. DR SMART; SM00213; UBQ; 1. DR SUPFAM; SSF54001; Cysteine proteinases; 1. DR SUPFAM; SSF54236; Ubiquitin-like; 1. DR PROSITE; PS00299; UBIQUITIN_1; 1. DR PROSITE; PS50053; UBIQUITIN_2; 1. DR PROSITE; PS00972; USP_1; 1. DR PROSITE; PS00973; USP_2; 1. DR PROSITE; PS50235; USP_3; 1. PE 2: Evidence at transcript level; KW Acetylation; Cell membrane; Cytoplasm; Hydrolase; Immunity; KW Innate immunity; Membrane; Phosphoprotein; Protease; Proteasome; KW Reference proteome; Thiol protease; Ubl conjugation pathway. FT CHAIN 1..494 FT /note="Ubiquitin carboxyl-terminal hydrolase 14" FT /id="PRO_0000268845" FT DOMAIN 4..80 FT /note="Ubiquitin-like" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214" FT DOMAIN 105..483 FT /note="USP" FT ACT_SITE 114 FT /note="Nucleophile" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092, FT ECO:0000255|PROSITE-ProRule:PRU10093" FT ACT_SITE 435 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092, FT ECO:0000255|PROSITE-ProRule:PRU10093" FT MOD_RES 52 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P54578" FT MOD_RES 143 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P54578" FT MOD_RES 148 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9JMA1" FT MOD_RES 235 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P54578" FT MOD_RES 237 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P54578" FT MOD_RES 302 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P54578" FT MOD_RES 432 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P54578" FT MOD_RES 449 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P54578" SQ SEQUENCE 494 AA; 56013 MW; 089AE0AC7790CCC5 CRC64; MPLYSVTVKW GKEKFEGVEL NTDEPPMVFK AQLFALTGVQ PARQKVMVKG GTLKDDDWGN IKMKNGMTVL MMGSADALPE EPSAKTVFVE DMTEEQLASA MELPCGLTNL GNTCYMNATV QCIRSVPELK DALKRYAGAL RASGEMASAQ YITAALRDLF DSMDKTSSSI PPIILLQFLH MAFPQFAEKG EQGQYLQQDA NECWVQMMRV LQQKLEAIED DTVKETDSSS ASAVTPSKKK SLIDQFFGVE FETTMKCTES EEEEVTKGKE SQLQLSCFIN QEVKYLFTGL KLRLQEEITK QSPTLQRNAL YIKSSKISRL PAYLTIQMVR FFYKEKESVN AKVLKDVKFP LMLDVYELCT PELQEKMVSF RSKFKDLEDK KVNQQPKTGD KDSSPQKEVK YEPFSFADDI GSNNCGYYDL QAVLTHQGRS SSSGHYVSWV KRKQDEWIKF DDDKVSIVTP EDILRLSGGG DWHIAYVLLY GPRRVEIMEE ESEQ //