UBP19_RAT
ID UBP19_RAT Reviewed; 1357 AA.
AC Q6J1Y9;
DT 10-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 105.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 19;
DE EC=3.4.19.12;
DE AltName: Full=Deubiquitinating enzyme 19;
DE AltName: Full=Ubiquitin thioesterase 19;
DE AltName: Full=Ubiquitin-specific-processing protease 19;
GN Name=Usp19;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND INDUCTION.
RC STRAIN=Sprague-Dawley; TISSUE=Testis;
RX PubMed=15562254; DOI=10.1152/ajpendo.00281.2004;
RA Combaret L., Adegoke O.A.J., Bedard N., Baracos V., Attaix D., Wing S.S.;
RT "USP19 is a ubiquitin-specific protease regulated in rat skeletal muscle
RT during catabolic states.";
RL Am. J. Physiol. 288:E693-E700(2005).
RN [2]
RP PROTEIN SEQUENCE OF 2-11; 60-76 AND 837-845, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RA Lubec G., Kang S.U., Lubec S.;
RL Submitted (SEP-2007) to UniProtKB.
RN [3]
RP FUNCTION.
RX PubMed=19773579; DOI=10.1152/ajpendo.00409.2009;
RA Sundaram P., Pang Z., Miao M., Yu L., Wing S.S.;
RT "USP19-deubiquitinating enzyme regulates levels of major myofibrillar
RT proteins in L6 muscle cells.";
RL Am. J. Physiol. 297:E1283-E1290(2009).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH RNF123, AND MUTAGENESIS OF
RP CYS-545.
RX PubMed=19015242; DOI=10.1128/mcb.00329-08;
RA Lu Y., Adegoke O.A.J., Nepveu A., Nakayama K.I., Bedard N., Cheng D.,
RA Peng J., Wing S.S.;
RT "USP19 deubiquitinating enzyme supports cell proliferation by stabilizing
RT KPC1, a ubiquitin ligase for p27Kip1.";
RL Mol. Cell. Biol. 29:547-558(2009).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-283, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Deubiquitinating enzyme that regulates the degradation of
CC various proteins. Deubiquitinates and prevents proteasomal degradation
CC of RNF123 which in turn stimulates CDKN1B ubiquitin-dependent
CC degradation thereby playing a role in cell proliferation. Involved in
CC decreased protein synthesis in atrophying skeletal muscle. Modulates
CC transcription of major myofibrillar proteins. Also involved in turnover
CC of endoplasmic-reticulum-associated degradation (ERAD) substrates.
CC Regulates the stability of BIRC2/c-IAP1 and BIRC3/c-IAP2 by preventing
CC thier ubiquitination. Required for cells to mount an appropriate
CC response to hypoxia and rescues HIF1A from degradation in a non-
CC catalytic manner. Plays an important role in 17 beta-estradiol (E2)-
CC inhibited myogenesis. Decreases the levels of ubiquitinated proteins
CC during skeletal muscle formation and acts to repress myogenesis.
CC Exhibits a preference towards 'Lys-63'-linked ubiquitin chains (By
CC similarity). {ECO:0000250, ECO:0000269|PubMed:19015242,
CC ECO:0000269|PubMed:19773579}.
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: Interacts with and stabilizes RNF123. Interacts with BIRC2/c-
CC IAP1, BIRC3/c-IAP2 and XIAP/BIRC4. Interacts with HIF1A (via N-
CC terminus) (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:19015242}; Single-pass membrane protein
CC {ECO:0000269|PubMed:19015242}.
CC -!- TISSUE SPECIFICITY: Expressed in testis, heart, kidney and skeletal
CC muscle. Low levels of expression are detectable in all other tissues
CC screened. {ECO:0000269|PubMed:15562254}.
CC -!- INDUCTION: By streptozotocin and fasting in skeletal muscle.
CC {ECO:0000269|PubMed:15562254}.
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DR EMBL; AY605065; AAT35219.1; -; mRNA.
DR RefSeq; NP_001001516.1; NM_001001516.2.
DR AlphaFoldDB; Q6J1Y9; -.
DR SMR; Q6J1Y9; -.
DR STRING; 10116.ENSRNOP00000067744; -.
DR MEROPS; C19.024; -.
DR iPTMnet; Q6J1Y9; -.
DR PhosphoSitePlus; Q6J1Y9; -.
DR jPOST; Q6J1Y9; -.
DR PaxDb; Q6J1Y9; -.
DR PRIDE; Q6J1Y9; -.
DR GeneID; 361190; -.
DR KEGG; rno:361190; -.
DR CTD; 10869; -.
DR RGD; 1303276; Usp19.
DR eggNOG; KOG1870; Eukaryota.
DR InParanoid; Q6J1Y9; -.
DR OrthoDB; 1283205at2759; -.
DR PhylomeDB; Q6J1Y9; -.
DR BRENDA; 3.4.19.12; 5301.
DR Reactome; R-RNO-5689880; Ub-specific processing proteases.
DR PRO; PR:Q6J1Y9; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISS:UniProtKB.
DR GO; GO:0051879; F:Hsp90 protein binding; ISO:RGD.
DR GO; GO:1990380; F:Lys48-specific deubiquitinase activity; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:1901799; P:negative regulation of proteasomal protein catabolic process; ISO:RGD.
DR GO; GO:0048642; P:negative regulation of skeletal muscle tissue development; ISS:UniProtKB.
DR GO; GO:0090068; P:positive regulation of cell cycle process; IMP:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; IMP:UniProtKB.
DR GO; GO:0071108; P:protein K48-linked deubiquitination; ISO:RGD.
DR GO; GO:0050821; P:protein stabilization; ISO:RGD.
DR GO; GO:1900037; P:regulation of cellular response to hypoxia; ISS:UniProtKB.
DR GO; GO:1904292; P:regulation of ERAD pathway; ISO:RGD.
DR GO; GO:0031647; P:regulation of protein stability; IDA:UniProtKB.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; ISS:UniProtKB.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; ISS:UniProtKB.
DR Gene3D; 2.60.40.790; -; 2.
DR InterPro; IPR007052; CS_dom.
DR InterPro; IPR008978; HSP20-like_chaperone.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR001394; Peptidase_C19_UCH.
DR InterPro; IPR018200; USP_CS.
DR InterPro; IPR028889; USP_dom.
DR InterPro; IPR002893; Znf_MYND.
DR Pfam; PF04969; CS; 1.
DR Pfam; PF00443; UCH; 1.
DR Pfam; PF01753; zf-MYND; 1.
DR SUPFAM; SSF49764; SSF49764; 2.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS51203; CS; 2.
DR PROSITE; PS00972; USP_1; 1.
DR PROSITE; PS00973; USP_2; 1.
DR PROSITE; PS50235; USP_3; 1.
DR PROSITE; PS01360; ZF_MYND_1; 1.
DR PROSITE; PS50865; ZF_MYND_2; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Endoplasmic reticulum; Hydrolase; Membrane;
KW Metal-binding; Phosphoprotein; Protease; Reference proteome; Repeat;
KW Thiol protease; Transmembrane; Transmembrane helix;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..1357
FT /note="Ubiquitin carboxyl-terminal hydrolase 19"
FT /id="PRO_0000295158"
FT TOPO_DOM 1..1330
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1331..1351
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1352..1357
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT DOMAIN 51..140
FT /note="CS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00547"
FT DOMAIN 321..423
FT /note="CS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00547"
FT DOMAIN 536..1253
FT /note="USP"
FT ZN_FING 830..872
FT /note="MYND-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT REGION 1..52
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 162..239
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 275..296
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 432..479
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 962..981
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1259..1278
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1292..1320
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 17..52
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 172..186
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 460..477
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1302..1316
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 545
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT ACT_SITE 1204
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT BINDING 830
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 833
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 847
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 850
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 856
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 860
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 868
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 872
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT MOD_RES 221
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UJD6"
FT MOD_RES 283
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MUTAGEN 545
FT /note="C->A: Has a destabilizing effect on RNF123."
FT /evidence="ECO:0000269|PubMed:19015242"
SQ SEQUENCE 1357 AA; 150302 MW; E2CE888D61EC3C81 CRC64;
MSAGTSATGP RRGPPGLEEA TSKKKQKDRA NQESKDGDPR RVSMPRKEPT KDELLLDWRQ
SSDKVVVKLR VGTGPICLEE VDAAFTDTDC VVRLPDGRQW GGVFFAKIQS SCTKVQTRKG
GLLQLALPKK VPLLTWPSLL KKPLGTQELV PGLRCQENGQ ELSPIALEPG SEPRRAKQEA
RNQKRAQGRG EVGSGASPGA QAGPSAKRAV HLCRGPEGEG SMDGPGPQGD APSFLSDSAT
QVEAEEQLHV PPVNPQTSLL GSEKNLALLT VEKTVSPRSD SVSPVMIRNR DPEKDDHFKE
EMAVGADPAA LADEPESMVN LAFVKNDSYE KGPDSVVVHV YVKESRRDTS RVLFREQDFT
LIFQTRDGNF LRLHPGCGPH TIFRWQVKLR NLIEPEQCTF CFTASRIDIC LRKRQSQRWG
GLEAPATRVG GAKVAVPTGP TPLDSTPPGG GPLPLTGQEE ARAVEKEKPK ARSEDSGLDG
VVARTPLEHV TPKPEPHLAS PKPTCMVPPM PHSPVSGDSV EEDEEEEKKV CLPGFTGLVN
LGNTCFMNSV IQSLSNTREL RDFFHDRSFE AEINYNNPLG TGGRLAIGFA VLLRALWKGT
HQAFQPSKLK AIVASKASQF TGYAQHDAQE FMAFLLDGLH EDLNRIQNKP YTETVDSDGR
PDEVVAEEAW QRHKMRNDSF IVDLFQGQYK SKLVCPVCAK VSITFDPFLY LPVPLPQKQK
VLPIYYFARE PHSKPIKFLV SVSKENSSAS EVLESLSQSV HVKPESLRLA EVIKNRFHRV
FLPSHSLDAV SPTDVLLCFE LLSPELAKER VVVLEVQQRP QVPSIPISKC AACQRKQQSE
DEKLKRCTRC YRVGYCNQFC QKTHWPDHKG LCRPENIGYP FLVSVPASRL TYARLAQLLE
GYARYSVSVF QPPFQPGRMA LESQSPGCTT LLSTSSLEAG DSEREPIQPS ELQLVTPVAE
GDTGAHRMWP PADRGPVPST SGISSEMLAS GPMEGCSLLA GERVSRPEAA VPGYQHSRES
VSAHTPQFFI YKIDASSREQ RLEDKGDTPL ELGDDCSLAL VWRNNERLQE FVLVASKELE
CAEDPGSAGE AARAGHFTLD QCLNLFTRPE VLAPEEAWYC PQCKQHREAS KQLLLWRLPN
VLIVQLKRFS FRSFIWRDKI NDLVEFPVRN LDLSKFCIGQ KEEQLPSYDL YAVINHYGGM
IGGHYTACAR LPSDRSSQRS DVGWRLFDDS TVTTVDESQV VTRYAYVLFY RRRNSPVERP
PRAAHAEHHP DLGPAAEAAA SQASRIWQEL EAEEEMVPEG PGPLGPWGPQ DWVGPPPRGP
TTSDEGCLRY FVLGTVAALV ALVLNVFYPL VSQSRWR
