Full text data of USP19
USP19
(KIAA0891, ZMYND9)
[Confidence: low (only semi-automatic identification from reviews)]
Ubiquitin carboxyl-terminal hydrolase 19; 3.4.19.12 (Deubiquitinating enzyme 19; Ubiquitin thioesterase 19; Ubiquitin-specific-processing protease 19; Zinc finger MYND domain-containing protein 9)
Ubiquitin carboxyl-terminal hydrolase 19; 3.4.19.12 (Deubiquitinating enzyme 19; Ubiquitin thioesterase 19; Ubiquitin-specific-processing protease 19; Zinc finger MYND domain-containing protein 9)
UniProt
O94966
ID UBP19_HUMAN Reviewed; 1318 AA.
AC O94966; A5PKX8; A6H8U2; B4DGT3; B4DTZ0; E7EN22; E7ETS0; E9PEG8;
read moreAC Q3KQW4; Q641Q9; Q6NZY8; Q86XV9;
DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 10-JUL-2007, sequence version 2.
DT 22-JAN-2014, entry version 125.
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;
DE AltName: Full=Zinc finger MYND domain-containing protein 9;
GN Name=USP19; Synonyms=KIAA0891, ZMYND9;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10048485; DOI=10.1093/dnares/5.6.355;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M.,
RA Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XII.
RT The complete sequences of 100 new cDNA clones from brain which code
RT for large proteins in vitro.";
RL DNA Res. 5:355-364(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 5 AND 7).
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 6),
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 846-1318 (ISOFORM 3), AND
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 90-1318 (ISOFORM 4).
RC TISSUE=Skin, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [6]
RP FUNCTION, TOPOLOGY, AND SUBCELLULAR LOCATION.
RX PubMed=19465887; DOI=10.1038/embor.2009.69;
RA Hassink G.C., Zhao B., Sompallae R., Altun M., Gastaldello S.,
RA Zinin N.V., Masucci M.G., Lindsten K.;
RT "The ER-resident ubiquitin-specific protease 19 participates in the
RT UPR and rescues ERAD substrates.";
RL EMBO Rep. 10:755-761(2009).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP FUNCTION, AND INTERACTION WITH BIRC2/C-IAP1; BIRC3/C-IAP2 AND
RP XIAP/BIRC4.
RX PubMed=21849505; DOI=10.1074/jbc.M111.282020;
RA Mei Y., Hahn A.A., Hu S., Yang X.;
RT "The USP19 deubiquitinase regulates the stability of c-IAP1 and c-
RT IAP2.";
RL J. Biol. Chem. 286:35380-35387(2011).
RN [10]
RP FUNCTION, AND LINKAGE SPECIFICITY.
RX PubMed=22689415; DOI=10.1002/cbic.201200261;
RA Iphofer A., Kummer A., Nimtz M., Ritter A., Arnold T., Frank R.,
RA van den Heuvel J., Kessler B.M., Jansch L., Franke R.;
RT "Profiling ubiquitin linkage specificities of deubiquitinating enzymes
RT with branched ubiquitin isopeptide probes.";
RL ChemBioChem 13:1416-1420(2012).
RN [11]
RP FUNCTION, AND INTERACTION WITH HIF1A.
RX PubMed=22128162; DOI=10.1074/jbc.M111.305615;
RA Altun M., Zhao B., Velasco K., Liu H., Hassink G., Paschke J.,
RA Pereira T., Lindsten K.;
RT "Ubiquitin-specific protease 19 (USP19) regulates hypoxia-inducible
RT factor 1alpha (HIF-1alpha) during hypoxia.";
RL J. Biol. Chem. 287:1962-1969(2012).
RN [12]
RP STRUCTURE BY NMR OF 273-393.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the CS domain of human USP19.";
RL Submitted (NOV-2004) to the PDB data bank.
CC -!- FUNCTION: Deubiquitinating enzyme that regulates the degradation
CC of various proteins. Deubiquitinates and prevents proteasomal
CC degradation of RNF123 which in turn stimulates CDKN1B ubiquitin-
CC dependent degradation thereby playing a role in cell
CC proliferation. Involved in decreased protein synthesis in
CC atrophying skeletal muscle. Modulates transcription of major
CC myofibrillar proteins. Also involved in turnover of endoplasmic-
CC reticulum-associated degradation (ERAD) substrates. Regulates the
CC stability of BIRC2/c-IAP1 and BIRC3/c-IAP2 by preventing their
CC 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
CC (E2)-inhibited myogenesis. Decreases the levels of ubiquitinated
CC proteins during skeletal muscle formation and acts to repress
CC myogenesis. Exhibits a preference towards 'Lys-63'-linked
CC Ubiquitin chains.
CC -!- CATALYTIC ACTIVITY: Thiol-dependent hydrolysis of ester,
CC thioester, amide, peptide and isopeptide bonds formed by the C-
CC terminal Gly of ubiquitin (a 76-residue protein attached to
CC proteins as an intracellular targeting signal).
CC -!- SUBUNIT: Interacts with RNF123 (By similarity). Interacts with
CC BIRC2/c-IAP1, BIRC3/c-IAP2 and XIAP/BIRC4. Interacts with HIF1A
CC (via N-terminus).
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass
CC membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Name=1;
CC IsoId=O94966-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O94966-2; Sequence=VSP_026708, VSP_026709, VSP_026710,
CC VSP_026711;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=O94966-3; Sequence=VSP_026712, VSP_026713;
CC Note=No experimental confirmation available;
CC Name=4;
CC IsoId=O94966-4; Sequence=VSP_026708, VSP_045891, VSP_026712,
CC VSP_026713;
CC Note=No experimental confirmation available. Ref.4 (AAH82241)
CC sequence is in conflict in position: 1251:A->T;
CC Name=5;
CC IsoId=O94966-5; Sequence=VSP_026709;
CC Note=No experimental confirmation available;
CC Name=6;
CC IsoId=O94966-6; Sequence=VSP_026709, VSP_045891, VSP_026712,
CC VSP_026713;
CC Note=No experimental confirmation available;
CC Name=7;
CC IsoId=O94966-7; Sequence=VSP_047057, VSP_026712, VSP_026713;
CC Note=No experimental confirmation available;
CC -!- SIMILARITY: Belongs to the peptidase C19 family.
CC -!- SIMILARITY: Contains 2 CS domains.
CC -!- SIMILARITY: Contains 1 MYND-type zinc finger.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI06030.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=AAI06030.1; Type=Frameshift; Positions=572;
CC Sequence=AAI42661.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=BAA74914.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
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DR EMBL; AB020698; BAA74914.1; ALT_INIT; mRNA.
DR EMBL; AK294756; BAG57894.1; -; mRNA.
DR EMBL; AK300425; BAG62152.1; -; mRNA.
DR EMBL; AC135506; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC048269; AAH48269.1; -; mRNA.
DR EMBL; BC065909; AAH65909.1; -; mRNA.
DR EMBL; BC082241; AAH82241.1; -; mRNA.
DR EMBL; BC106029; AAI06030.1; ALT_SEQ; mRNA.
DR EMBL; BC142660; AAI42661.1; ALT_INIT; mRNA.
DR EMBL; BC146752; AAI46753.1; -; mRNA.
DR RefSeq; NP_001186089.1; NM_001199160.1.
DR RefSeq; NP_001186090.1; NM_001199161.1.
DR RefSeq; NP_001186091.1; NM_001199162.1.
DR RefSeq; NP_006668.1; NM_006677.2.
DR RefSeq; XP_005264888.1; XM_005264831.1.
DR UniGene; Hs.255596; -.
DR UniGene; Hs.734003; -.
DR PDB; 1WH0; NMR; -; A=273-393.
DR PDBsum; 1WH0; -.
DR ProteinModelPortal; O94966; -.
DR SMR; O94966; 273-402, 494-677, 996-1215.
DR IntAct; O94966; 35.
DR MINT; MINT-4658026; -.
DR STRING; 9606.ENSP00000381863; -.
DR MEROPS; C19.024; -.
DR PhosphoSite; O94966; -.
DR PaxDb; O94966; -.
DR PRIDE; O94966; -.
DR Ensembl; ENST00000398888; ENSP00000381863; ENSG00000172046.
DR Ensembl; ENST00000417901; ENSP00000395260; ENSG00000172046.
DR Ensembl; ENST00000434032; ENSP00000401197; ENSG00000172046.
DR Ensembl; ENST00000453664; ENSP00000400090; ENSG00000172046.
DR GeneID; 10869; -.
DR KEGG; hsa:10869; -.
DR UCSC; uc011bcg.2; human.
DR CTD; 10869; -.
DR GeneCards; GC03M049120; -.
DR HGNC; HGNC:12617; USP19.
DR MIM; 614471; gene.
DR neXtProt; NX_O94966; -.
DR PharmGKB; PA37243; -.
DR eggNOG; COG5560; -.
DR HOGENOM; HOG000074206; -.
DR HOVERGEN; HBG061889; -.
DR KO; K11847; -.
DR OMA; PQCKQHR; -.
DR ChiTaRS; USP19; human.
DR EvolutionaryTrace; O94966; -.
DR GenomeRNAi; 10869; -.
DR NextBio; 41271; -.
DR PRO; PR:O94966; -.
DR ArrayExpress; O94966; -.
DR Bgee; O94966; -.
DR CleanEx; HS_USP19; -.
DR Genevestigator; O94966; -.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0004843; F:deubiquitinase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004221; F:ubiquitin thiolesterase activity; IEA:InterPro.
DR GO; GO:0030433; P:ER-associated ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; ISS:UniProtKB.
DR GO; GO:1900037; P:regulation of cellular response to hypoxia; IMP:UniProtKB.
DR GO; GO:0031647; P:regulation of protein stability; ISS:UniProtKB.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IEP:UniProtKB.
DR GO; GO:0014732; P:skeletal muscle atrophy; ISS:UniProtKB.
DR InterPro; IPR007052; CS_dom.
DR InterPro; IPR008978; HSP20-like_chaperone.
DR InterPro; IPR018200; Pept_C19ubi-hydrolase_C_CS.
DR InterPro; IPR001394; Peptidase_C19/C67.
DR InterPro; IPR002893; Znf_MYND.
DR Pfam; PF04969; CS; 2.
DR Pfam; PF00443; UCH; 1.
DR Pfam; PF01753; zf-MYND; 1.
DR SUPFAM; SSF49764; SSF49764; 2.
DR PROSITE; PS51203; CS; 2.
DR PROSITE; PS00972; UCH_2_1; 1.
DR PROSITE; PS00973; UCH_2_2; 1.
DR PROSITE; PS50235; UCH_2_3; 1.
DR PROSITE; PS01360; ZF_MYND_1; 1.
DR PROSITE; PS50865; ZF_MYND_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome;
KW Endoplasmic reticulum; Hydrolase; Membrane; Metal-binding;
KW Polymorphism; Protease; Reference proteome; Repeat; Thiol protease;
KW Transmembrane; Transmembrane helix; Ubl conjugation pathway; Zinc;
KW Zinc-finger.
FT CHAIN 1 1318 Ubiquitin carboxyl-terminal hydrolase 19.
FT /FTId=PRO_0000080646.
FT TOPO_DOM 1 1291 Cytoplasmic (Potential).
FT TRANSMEM 1292 1312 Helical; (Potential).
FT TOPO_DOM 1313 1318 Lumenal (Potential).
FT DOMAIN 113 202 CS 1.
FT DOMAIN 282 384 CS 2.
FT ZN_FING 791 833 MYND-type.
FT ACT_SITE 506 506 Nucleophile (By similarity).
FT ACT_SITE 1165 1165 Proton acceptor (By similarity).
FT VAR_SEQ 100 114 Missing (in isoform 2 and isoform 4).
FT /FTId=VSP_026708.
FT VAR_SEQ 193 202 VPMLTWPSLL -> KKPLGTQELVPGLRCQENGQELSPIAL
FT EPGPEPHRAKQEARNQKRAQGRGEVGAGAGPGAQAGPSAKR
FT AVHLCRGPEGDGSRDDPGPRGDAPPFVADPATQ (in
FT isoform 7).
FT /FTId=VSP_047057.
FT VAR_SEQ 202 202 L -> LKKPLGTQELVPGLRCQENGQELSPIALEPGPEPHR
FT AKQEARNQKRAQGRGEVGAGAGPGAQAGPSAKRAVHLCRGP
FT EGDGSRDDPGPRGDAPPFVADPATQ (in isoform 2,
FT isoform 5 and isoform 6).
FT /FTId=VSP_026709.
FT VAR_SEQ 389 389 R -> RGA (in isoform 4 and isoform 6).
FT /FTId=VSP_045891.
FT VAR_SEQ 573 574 IV -> RL (in isoform 2).
FT /FTId=VSP_026710.
FT VAR_SEQ 575 1318 Missing (in isoform 2).
FT /FTId=VSP_026711.
FT VAR_SEQ 1244 1298 ASRIWQELEAEEEPVPEGSGPLGPWGPQDWVGPLPRGPTTP
FT DEGCLRYFVLGTVA -> GLGPGQAPEVAPTRTAPERFAPP
FT VDRPAPTYSNMEEVD (in isoform 3, isoform 4,
FT isoform 6 and isoform 7).
FT /FTId=VSP_026712.
FT VAR_SEQ 1299 1318 Missing (in isoform 3, isoform 4, isoform
FT 6 and isoform 7).
FT /FTId=VSP_026713.
FT VARIANT 36 36 D -> H (in dbSNP:rs11552724).
FT /FTId=VAR_051528.
FT CONFLICT 942 942 S -> C (in Ref. 2; BAG57894).
FT CONFLICT 1041 1041 E -> G (in Ref. 2; BAG62152).
FT HELIX 276 278
FT STRAND 279 283
FT STRAND 287 292
FT TURN 293 295
FT STRAND 296 302
FT STRAND 312 315
FT STRAND 317 324
FT HELIX 329 334
FT STRAND 344 352
FT TURN 356 358
FT STRAND 360 363
FT STRAND 365 377
SQ SEQUENCE 1318 AA; 145651 MW; EA9F318D03304AA1 CRC64;
MSGGASATGP RRGPPGLEDT TSKKKQKDRA NQESKDGDPR KETGSRYVAQ AGLEPLASGD
PSASASHAAG ITGSRHRTRL FFPSSSGSAS TPQEEQTKEG ACEDPHDLLA TPTPELLLDW
RQSAEEVIVK LRVGVGPLQL EDVDAAFTDT DCVVRFAGGQ QWGGVFYAEI KSSCAKVQTR
KGSLLHLTLP KKVPMLTWPS LLVEADEQLC IPPLNSQTCL LGSEENLAPL AGEKAVPPGN
DPVSPAMVRS RNPGKDDCAK EEMAVAADAA TLVDEPESMV NLAFVKNDSY EKGPDSVVVH
VYVKEICRDT SRVLFREQDF TLIFQTRDGN FLRLHPGCGP HTTFRWQVKL RNLIEPEQCT
FCFTASRIDI CLRKRQSQRW GGLEAPAARV GGAKVAVPTG PTPLDSTPPG GAPHPLTGQE
EARAVEKDKS KARSEDTGLD SVATRTPMEH VTPKPETHLA SPKPTCMVPP MPHSPVSGDS
VEEEEEEEKK VCLPGFTGLV NLGNTCFMNS VIQSLSNTRE LRDFFHDRSF EAEINYNNPL
GTGGRLAIGF AVLLRALWKG THHAFQPSKL KAIVASKASQ FTGYAQHDAQ EFMAFLLDGL
HEDLNRIQNK PYTETVDSDG RPDEVVAEEA WQRHKMRNDS FIVDLFQGQY KSKLVCPVCA
KVSITFDPFL YLPVPLPQKQ KVLPVFYFAR EPHSKPIKFL VSVSKENSTA SEVLDSLSQS
VHVKPENLRL AEVIKNRFHR VFLPSHSLDT VSPSDTLLCF ELLSSELAKE RVVVLEVQQR
PQVPSVPISK CAACQRKQQS EDEKLKRCTR CYRVGYCNQL CQKTHWPDHK GLCRPENIGY
PFLVSVPASR LTYARLAQLL EGYARYSVSV FQPPFQPGRM ALESQSPGCT TLLSTGSLEA
GDSERDPIQP PELQLVTPMA EGDTGLPRVW AAPDRGPVPS TSGISSEMLA SGPIEVGSLP
AGERVSRPEA AVPGYQHPSE AMNAHTPQFF IYKIDSSNRE QRLEDKGDTP LELGDDCSLA
LVWRNNERLQ EFVLVASKEL ECAEDPGSAG EAARAGHFTL DQCLNLFTRP EVLAPEEAWY
CPQCKQHREA SKQLLLWRLP NVLIVQLKRF SFRSFIWRDK INDLVEFPVR NLDLSKFCIG
QKEEQLPSYD LYAVINHYGG MIGGHYTACA RLPNDRSSQR SDVGWRLFDD STVTTVDESQ
VVTRYAYVLF YRRRNSPVER PPRAGHSEHH PDLGPAAEAA ASQASRIWQE LEAEEEPVPE
GSGPLGPWGP QDWVGPLPRG PTTPDEGCLR YFVLGTVAAL VALVLNVFYP LVSQSRWR
//
ID UBP19_HUMAN Reviewed; 1318 AA.
AC O94966; A5PKX8; A6H8U2; B4DGT3; B4DTZ0; E7EN22; E7ETS0; E9PEG8;
read moreAC Q3KQW4; Q641Q9; Q6NZY8; Q86XV9;
DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 10-JUL-2007, sequence version 2.
DT 22-JAN-2014, entry version 125.
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;
DE AltName: Full=Zinc finger MYND domain-containing protein 9;
GN Name=USP19; Synonyms=KIAA0891, ZMYND9;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10048485; DOI=10.1093/dnares/5.6.355;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M.,
RA Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XII.
RT The complete sequences of 100 new cDNA clones from brain which code
RT for large proteins in vitro.";
RL DNA Res. 5:355-364(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 5 AND 7).
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 6),
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 846-1318 (ISOFORM 3), AND
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 90-1318 (ISOFORM 4).
RC TISSUE=Skin, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [6]
RP FUNCTION, TOPOLOGY, AND SUBCELLULAR LOCATION.
RX PubMed=19465887; DOI=10.1038/embor.2009.69;
RA Hassink G.C., Zhao B., Sompallae R., Altun M., Gastaldello S.,
RA Zinin N.V., Masucci M.G., Lindsten K.;
RT "The ER-resident ubiquitin-specific protease 19 participates in the
RT UPR and rescues ERAD substrates.";
RL EMBO Rep. 10:755-761(2009).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP FUNCTION, AND INTERACTION WITH BIRC2/C-IAP1; BIRC3/C-IAP2 AND
RP XIAP/BIRC4.
RX PubMed=21849505; DOI=10.1074/jbc.M111.282020;
RA Mei Y., Hahn A.A., Hu S., Yang X.;
RT "The USP19 deubiquitinase regulates the stability of c-IAP1 and c-
RT IAP2.";
RL J. Biol. Chem. 286:35380-35387(2011).
RN [10]
RP FUNCTION, AND LINKAGE SPECIFICITY.
RX PubMed=22689415; DOI=10.1002/cbic.201200261;
RA Iphofer A., Kummer A., Nimtz M., Ritter A., Arnold T., Frank R.,
RA van den Heuvel J., Kessler B.M., Jansch L., Franke R.;
RT "Profiling ubiquitin linkage specificities of deubiquitinating enzymes
RT with branched ubiquitin isopeptide probes.";
RL ChemBioChem 13:1416-1420(2012).
RN [11]
RP FUNCTION, AND INTERACTION WITH HIF1A.
RX PubMed=22128162; DOI=10.1074/jbc.M111.305615;
RA Altun M., Zhao B., Velasco K., Liu H., Hassink G., Paschke J.,
RA Pereira T., Lindsten K.;
RT "Ubiquitin-specific protease 19 (USP19) regulates hypoxia-inducible
RT factor 1alpha (HIF-1alpha) during hypoxia.";
RL J. Biol. Chem. 287:1962-1969(2012).
RN [12]
RP STRUCTURE BY NMR OF 273-393.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the CS domain of human USP19.";
RL Submitted (NOV-2004) to the PDB data bank.
CC -!- FUNCTION: Deubiquitinating enzyme that regulates the degradation
CC of various proteins. Deubiquitinates and prevents proteasomal
CC degradation of RNF123 which in turn stimulates CDKN1B ubiquitin-
CC dependent degradation thereby playing a role in cell
CC proliferation. Involved in decreased protein synthesis in
CC atrophying skeletal muscle. Modulates transcription of major
CC myofibrillar proteins. Also involved in turnover of endoplasmic-
CC reticulum-associated degradation (ERAD) substrates. Regulates the
CC stability of BIRC2/c-IAP1 and BIRC3/c-IAP2 by preventing their
CC 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
CC (E2)-inhibited myogenesis. Decreases the levels of ubiquitinated
CC proteins during skeletal muscle formation and acts to repress
CC myogenesis. Exhibits a preference towards 'Lys-63'-linked
CC Ubiquitin chains.
CC -!- CATALYTIC ACTIVITY: Thiol-dependent hydrolysis of ester,
CC thioester, amide, peptide and isopeptide bonds formed by the C-
CC terminal Gly of ubiquitin (a 76-residue protein attached to
CC proteins as an intracellular targeting signal).
CC -!- SUBUNIT: Interacts with RNF123 (By similarity). Interacts with
CC BIRC2/c-IAP1, BIRC3/c-IAP2 and XIAP/BIRC4. Interacts with HIF1A
CC (via N-terminus).
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass
CC membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Name=1;
CC IsoId=O94966-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O94966-2; Sequence=VSP_026708, VSP_026709, VSP_026710,
CC VSP_026711;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=O94966-3; Sequence=VSP_026712, VSP_026713;
CC Note=No experimental confirmation available;
CC Name=4;
CC IsoId=O94966-4; Sequence=VSP_026708, VSP_045891, VSP_026712,
CC VSP_026713;
CC Note=No experimental confirmation available. Ref.4 (AAH82241)
CC sequence is in conflict in position: 1251:A->T;
CC Name=5;
CC IsoId=O94966-5; Sequence=VSP_026709;
CC Note=No experimental confirmation available;
CC Name=6;
CC IsoId=O94966-6; Sequence=VSP_026709, VSP_045891, VSP_026712,
CC VSP_026713;
CC Note=No experimental confirmation available;
CC Name=7;
CC IsoId=O94966-7; Sequence=VSP_047057, VSP_026712, VSP_026713;
CC Note=No experimental confirmation available;
CC -!- SIMILARITY: Belongs to the peptidase C19 family.
CC -!- SIMILARITY: Contains 2 CS domains.
CC -!- SIMILARITY: Contains 1 MYND-type zinc finger.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI06030.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=AAI06030.1; Type=Frameshift; Positions=572;
CC Sequence=AAI42661.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=BAA74914.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
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DR EMBL; AB020698; BAA74914.1; ALT_INIT; mRNA.
DR EMBL; AK294756; BAG57894.1; -; mRNA.
DR EMBL; AK300425; BAG62152.1; -; mRNA.
DR EMBL; AC135506; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC048269; AAH48269.1; -; mRNA.
DR EMBL; BC065909; AAH65909.1; -; mRNA.
DR EMBL; BC082241; AAH82241.1; -; mRNA.
DR EMBL; BC106029; AAI06030.1; ALT_SEQ; mRNA.
DR EMBL; BC142660; AAI42661.1; ALT_INIT; mRNA.
DR EMBL; BC146752; AAI46753.1; -; mRNA.
DR RefSeq; NP_001186089.1; NM_001199160.1.
DR RefSeq; NP_001186090.1; NM_001199161.1.
DR RefSeq; NP_001186091.1; NM_001199162.1.
DR RefSeq; NP_006668.1; NM_006677.2.
DR RefSeq; XP_005264888.1; XM_005264831.1.
DR UniGene; Hs.255596; -.
DR UniGene; Hs.734003; -.
DR PDB; 1WH0; NMR; -; A=273-393.
DR PDBsum; 1WH0; -.
DR ProteinModelPortal; O94966; -.
DR SMR; O94966; 273-402, 494-677, 996-1215.
DR IntAct; O94966; 35.
DR MINT; MINT-4658026; -.
DR STRING; 9606.ENSP00000381863; -.
DR MEROPS; C19.024; -.
DR PhosphoSite; O94966; -.
DR PaxDb; O94966; -.
DR PRIDE; O94966; -.
DR Ensembl; ENST00000398888; ENSP00000381863; ENSG00000172046.
DR Ensembl; ENST00000417901; ENSP00000395260; ENSG00000172046.
DR Ensembl; ENST00000434032; ENSP00000401197; ENSG00000172046.
DR Ensembl; ENST00000453664; ENSP00000400090; ENSG00000172046.
DR GeneID; 10869; -.
DR KEGG; hsa:10869; -.
DR UCSC; uc011bcg.2; human.
DR CTD; 10869; -.
DR GeneCards; GC03M049120; -.
DR HGNC; HGNC:12617; USP19.
DR MIM; 614471; gene.
DR neXtProt; NX_O94966; -.
DR PharmGKB; PA37243; -.
DR eggNOG; COG5560; -.
DR HOGENOM; HOG000074206; -.
DR HOVERGEN; HBG061889; -.
DR KO; K11847; -.
DR OMA; PQCKQHR; -.
DR ChiTaRS; USP19; human.
DR EvolutionaryTrace; O94966; -.
DR GenomeRNAi; 10869; -.
DR NextBio; 41271; -.
DR PRO; PR:O94966; -.
DR ArrayExpress; O94966; -.
DR Bgee; O94966; -.
DR CleanEx; HS_USP19; -.
DR Genevestigator; O94966; -.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0004843; F:deubiquitinase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004221; F:ubiquitin thiolesterase activity; IEA:InterPro.
DR GO; GO:0030433; P:ER-associated ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; ISS:UniProtKB.
DR GO; GO:1900037; P:regulation of cellular response to hypoxia; IMP:UniProtKB.
DR GO; GO:0031647; P:regulation of protein stability; ISS:UniProtKB.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IEP:UniProtKB.
DR GO; GO:0014732; P:skeletal muscle atrophy; ISS:UniProtKB.
DR InterPro; IPR007052; CS_dom.
DR InterPro; IPR008978; HSP20-like_chaperone.
DR InterPro; IPR018200; Pept_C19ubi-hydrolase_C_CS.
DR InterPro; IPR001394; Peptidase_C19/C67.
DR InterPro; IPR002893; Znf_MYND.
DR Pfam; PF04969; CS; 2.
DR Pfam; PF00443; UCH; 1.
DR Pfam; PF01753; zf-MYND; 1.
DR SUPFAM; SSF49764; SSF49764; 2.
DR PROSITE; PS51203; CS; 2.
DR PROSITE; PS00972; UCH_2_1; 1.
DR PROSITE; PS00973; UCH_2_2; 1.
DR PROSITE; PS50235; UCH_2_3; 1.
DR PROSITE; PS01360; ZF_MYND_1; 1.
DR PROSITE; PS50865; ZF_MYND_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome;
KW Endoplasmic reticulum; Hydrolase; Membrane; Metal-binding;
KW Polymorphism; Protease; Reference proteome; Repeat; Thiol protease;
KW Transmembrane; Transmembrane helix; Ubl conjugation pathway; Zinc;
KW Zinc-finger.
FT CHAIN 1 1318 Ubiquitin carboxyl-terminal hydrolase 19.
FT /FTId=PRO_0000080646.
FT TOPO_DOM 1 1291 Cytoplasmic (Potential).
FT TRANSMEM 1292 1312 Helical; (Potential).
FT TOPO_DOM 1313 1318 Lumenal (Potential).
FT DOMAIN 113 202 CS 1.
FT DOMAIN 282 384 CS 2.
FT ZN_FING 791 833 MYND-type.
FT ACT_SITE 506 506 Nucleophile (By similarity).
FT ACT_SITE 1165 1165 Proton acceptor (By similarity).
FT VAR_SEQ 100 114 Missing (in isoform 2 and isoform 4).
FT /FTId=VSP_026708.
FT VAR_SEQ 193 202 VPMLTWPSLL -> KKPLGTQELVPGLRCQENGQELSPIAL
FT EPGPEPHRAKQEARNQKRAQGRGEVGAGAGPGAQAGPSAKR
FT AVHLCRGPEGDGSRDDPGPRGDAPPFVADPATQ (in
FT isoform 7).
FT /FTId=VSP_047057.
FT VAR_SEQ 202 202 L -> LKKPLGTQELVPGLRCQENGQELSPIALEPGPEPHR
FT AKQEARNQKRAQGRGEVGAGAGPGAQAGPSAKRAVHLCRGP
FT EGDGSRDDPGPRGDAPPFVADPATQ (in isoform 2,
FT isoform 5 and isoform 6).
FT /FTId=VSP_026709.
FT VAR_SEQ 389 389 R -> RGA (in isoform 4 and isoform 6).
FT /FTId=VSP_045891.
FT VAR_SEQ 573 574 IV -> RL (in isoform 2).
FT /FTId=VSP_026710.
FT VAR_SEQ 575 1318 Missing (in isoform 2).
FT /FTId=VSP_026711.
FT VAR_SEQ 1244 1298 ASRIWQELEAEEEPVPEGSGPLGPWGPQDWVGPLPRGPTTP
FT DEGCLRYFVLGTVA -> GLGPGQAPEVAPTRTAPERFAPP
FT VDRPAPTYSNMEEVD (in isoform 3, isoform 4,
FT isoform 6 and isoform 7).
FT /FTId=VSP_026712.
FT VAR_SEQ 1299 1318 Missing (in isoform 3, isoform 4, isoform
FT 6 and isoform 7).
FT /FTId=VSP_026713.
FT VARIANT 36 36 D -> H (in dbSNP:rs11552724).
FT /FTId=VAR_051528.
FT CONFLICT 942 942 S -> C (in Ref. 2; BAG57894).
FT CONFLICT 1041 1041 E -> G (in Ref. 2; BAG62152).
FT HELIX 276 278
FT STRAND 279 283
FT STRAND 287 292
FT TURN 293 295
FT STRAND 296 302
FT STRAND 312 315
FT STRAND 317 324
FT HELIX 329 334
FT STRAND 344 352
FT TURN 356 358
FT STRAND 360 363
FT STRAND 365 377
SQ SEQUENCE 1318 AA; 145651 MW; EA9F318D03304AA1 CRC64;
MSGGASATGP RRGPPGLEDT TSKKKQKDRA NQESKDGDPR KETGSRYVAQ AGLEPLASGD
PSASASHAAG ITGSRHRTRL FFPSSSGSAS TPQEEQTKEG ACEDPHDLLA TPTPELLLDW
RQSAEEVIVK LRVGVGPLQL EDVDAAFTDT DCVVRFAGGQ QWGGVFYAEI KSSCAKVQTR
KGSLLHLTLP KKVPMLTWPS LLVEADEQLC IPPLNSQTCL LGSEENLAPL AGEKAVPPGN
DPVSPAMVRS RNPGKDDCAK EEMAVAADAA TLVDEPESMV NLAFVKNDSY EKGPDSVVVH
VYVKEICRDT SRVLFREQDF TLIFQTRDGN FLRLHPGCGP HTTFRWQVKL RNLIEPEQCT
FCFTASRIDI CLRKRQSQRW GGLEAPAARV GGAKVAVPTG PTPLDSTPPG GAPHPLTGQE
EARAVEKDKS KARSEDTGLD SVATRTPMEH VTPKPETHLA SPKPTCMVPP MPHSPVSGDS
VEEEEEEEKK VCLPGFTGLV NLGNTCFMNS VIQSLSNTRE LRDFFHDRSF EAEINYNNPL
GTGGRLAIGF AVLLRALWKG THHAFQPSKL KAIVASKASQ FTGYAQHDAQ EFMAFLLDGL
HEDLNRIQNK PYTETVDSDG RPDEVVAEEA WQRHKMRNDS FIVDLFQGQY KSKLVCPVCA
KVSITFDPFL YLPVPLPQKQ KVLPVFYFAR EPHSKPIKFL VSVSKENSTA SEVLDSLSQS
VHVKPENLRL AEVIKNRFHR VFLPSHSLDT VSPSDTLLCF ELLSSELAKE RVVVLEVQQR
PQVPSVPISK CAACQRKQQS EDEKLKRCTR CYRVGYCNQL CQKTHWPDHK GLCRPENIGY
PFLVSVPASR LTYARLAQLL EGYARYSVSV FQPPFQPGRM ALESQSPGCT TLLSTGSLEA
GDSERDPIQP PELQLVTPMA EGDTGLPRVW AAPDRGPVPS TSGISSEMLA SGPIEVGSLP
AGERVSRPEA AVPGYQHPSE AMNAHTPQFF IYKIDSSNRE QRLEDKGDTP LELGDDCSLA
LVWRNNERLQ EFVLVASKEL ECAEDPGSAG EAARAGHFTL DQCLNLFTRP EVLAPEEAWY
CPQCKQHREA SKQLLLWRLP NVLIVQLKRF SFRSFIWRDK INDLVEFPVR NLDLSKFCIG
QKEEQLPSYD LYAVINHYGG MIGGHYTACA RLPNDRSSQR SDVGWRLFDD STVTTVDESQ
VVTRYAYVLF YRRRNSPVER PPRAGHSEHH PDLGPAAEAA ASQASRIWQE LEAEEEPVPE
GSGPLGPWGP QDWVGPLPRG PTTPDEGCLR YFVLGTVAAL VALVLNVFYP LVSQSRWR
//
MIM
614471
*RECORD*
*FIELD* NO
614471
*FIELD* TI
*614471 UBIQUITIN-SPECIFIC PROTEASE 19; USP19
;;KIAA0891
*FIELD* TX
DESCRIPTION
USP19 is a ubiquitin protein ligase (EC 3.4.19.12) with a role in
read moreregulating cell cycle progression (Lu et al., 2009).
CLONING
By sequencing clones obtained from a size-fractionated adult brain cDNA
library, Nagase et al. (1998) cloned USP19, which they designated
KIAA0891. The deduced 1,371-amino acid protein shares significant
similarity with the ubiquitin protease UNPH (USP4; 603486). RT-PCR ELISA
detected highest expression in fetal liver, followed by adult spinal
cord. All other tissues, including adult and fetal brain, showed much
lower expression, and no expression was detected in spleen.
GENE FUNCTION
p27(KIP1) (CDKN1B; 600778) is a cyclin-dependent kinase inhibitor that
regulates the G1/S transition. Using rat myoblast and fibroblast cell
lines, Lu et al. (2009) showed that Usp19 regulated p27(KIP1) levels by
deubiquitinating and stabilizing Kpc1 (RNF123; 614472), an E3 ubiquitin
ligase that ubiquitinates cytosolic p27(KIP1) and targets it for
proteasomal degradation at G1 phase. Immunoprecipitation analysis
revealed that Usp19 interacted directly with Kpc1. Knockdown of Usp19
resulted in loss of Kpc1, accumulation of p27(KIP1), inhibition of cell
proliferation, and slower progression from G0/G1 to S phase.
MAPPING
By radiation hybrid analysis, Nagase et al. (1998) mapped the USP19 gene
to chromosome 3.
Hartz (2011) mapped the USP19 gene to chromosome 3p21.31 based on an
alignment of the USP19 sequence (GenBank GENBANK AB020698) with the
genomic sequence (GRCh37).
*FIELD* RF
1. Hartz, P. A.: Personal Communication. Baltimore, Md. 10/24/2011.
2. Lu, Y.; Adegoke, O. A. J.; Nepveu, A.; Nakayama, K. I.; Bedard,
N.; Cheng, D.; Peng, J.; Wing, S. S.: USP19 deubiquitinating enzyme
supports cell proliferation by stabilizing KPC1, a ubiquitin ligase
for p27(Kip1). Molec. Cell. Biol. 29: 547-558, 2009. Note: Erratum:
Molec. Cell. Biol. 29: 3241 only, 2009.
3. Nagase, T.; Ishikawa, K.; Suyama, M.; Kikuno, R.; Hirosawa, M.;
Miyajima, N.; Tanaka, A.; Kotani, H.; Nomura, N.; Oharo, O.: Prediction
of the coding sequences of unidentified human genes. XII. The complete
sequences of 100 new cDNA clones from brain which code for large proteins
in vitro. DNA Res. 5: 355-364, 1998.
*FIELD* CD
Patricia A. Hartz: 2/6/2012
*FIELD* ED
terry: 11/28/2012
mgross: 2/6/2012
*RECORD*
*FIELD* NO
614471
*FIELD* TI
*614471 UBIQUITIN-SPECIFIC PROTEASE 19; USP19
;;KIAA0891
*FIELD* TX
DESCRIPTION
USP19 is a ubiquitin protein ligase (EC 3.4.19.12) with a role in
read moreregulating cell cycle progression (Lu et al., 2009).
CLONING
By sequencing clones obtained from a size-fractionated adult brain cDNA
library, Nagase et al. (1998) cloned USP19, which they designated
KIAA0891. The deduced 1,371-amino acid protein shares significant
similarity with the ubiquitin protease UNPH (USP4; 603486). RT-PCR ELISA
detected highest expression in fetal liver, followed by adult spinal
cord. All other tissues, including adult and fetal brain, showed much
lower expression, and no expression was detected in spleen.
GENE FUNCTION
p27(KIP1) (CDKN1B; 600778) is a cyclin-dependent kinase inhibitor that
regulates the G1/S transition. Using rat myoblast and fibroblast cell
lines, Lu et al. (2009) showed that Usp19 regulated p27(KIP1) levels by
deubiquitinating and stabilizing Kpc1 (RNF123; 614472), an E3 ubiquitin
ligase that ubiquitinates cytosolic p27(KIP1) and targets it for
proteasomal degradation at G1 phase. Immunoprecipitation analysis
revealed that Usp19 interacted directly with Kpc1. Knockdown of Usp19
resulted in loss of Kpc1, accumulation of p27(KIP1), inhibition of cell
proliferation, and slower progression from G0/G1 to S phase.
MAPPING
By radiation hybrid analysis, Nagase et al. (1998) mapped the USP19 gene
to chromosome 3.
Hartz (2011) mapped the USP19 gene to chromosome 3p21.31 based on an
alignment of the USP19 sequence (GenBank GENBANK AB020698) with the
genomic sequence (GRCh37).
*FIELD* RF
1. Hartz, P. A.: Personal Communication. Baltimore, Md. 10/24/2011.
2. Lu, Y.; Adegoke, O. A. J.; Nepveu, A.; Nakayama, K. I.; Bedard,
N.; Cheng, D.; Peng, J.; Wing, S. S.: USP19 deubiquitinating enzyme
supports cell proliferation by stabilizing KPC1, a ubiquitin ligase
for p27(Kip1). Molec. Cell. Biol. 29: 547-558, 2009. Note: Erratum:
Molec. Cell. Biol. 29: 3241 only, 2009.
3. Nagase, T.; Ishikawa, K.; Suyama, M.; Kikuno, R.; Hirosawa, M.;
Miyajima, N.; Tanaka, A.; Kotani, H.; Nomura, N.; Oharo, O.: Prediction
of the coding sequences of unidentified human genes. XII. The complete
sequences of 100 new cDNA clones from brain which code for large proteins
in vitro. DNA Res. 5: 355-364, 1998.
*FIELD* CD
Patricia A. Hartz: 2/6/2012
*FIELD* ED
terry: 11/28/2012
mgross: 2/6/2012