Q6J1Y9 (UBP19_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ubiquitin carboxyl-terminal hydrolase 19
EC=3.4.19.12

Alternative name(s):
Deubiquitinating enzyme 19
Ubiquitin thioesterase 19
Ubiquitin-specific-processing protease 19

Gene names

Name:

Usp19

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	1357 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Deubiquitinating enzyme that regulates the degradation of various proteins. Deubiquitinates and prevents proteasomal degradation of RNF123 which in turn stimulates CDKN1B ubiquitin-dependent degradation thereby playing a role in cell proliferation. Involved in decreased protein synthesis in atrophying skeletal muscle. Modulates transcription of major myofibrillar proteins. Also involved in turnover of endoplasmic-reticulum-associated degradation (ERAD) substrates. Regulates the stability of BIRC2/c-IAP1 and BIRC3/c-IAP2 by preventing thier ubiquitination. Required for cells to mount an appropriate response to hypoxia and rescues HIF1A from degradation in a non-catalytic manner. Plays an important role in 17 beta-estradiol (E2)-inhibited myogenesis. Decreases the levels of ubiquitinated proteins during skeletal muscle formation and acts to repress myogenesis. Exhibits a preference towards 'Lys-63'-linked Ubiquitin chains By similarity. Ref.3 Ref.4
Catalytic activity	Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).
Subunit structure	Interacts with and stabilizes RNF123. Interacts with BIRC2/c-IAP1, BIRC3/c-IAP2 and XIAP/BIRC4. Interacts with HIF1A (via N-terminus) By similarity. Ref.4
Subcellular location	Endoplasmic reticulum membrane; Single-pass membrane protein Ref.4.
Tissue specificity	Expressed in testis, heart, kidney and skeletal muscle. Low levels of expression are detectable in all other tissues screened. Ref.1
Induction	By streptozotocin and fasting in skeletal muscle. Ref.1
Sequence similarities	Contains 2 CS domains. Contains 1 MYND-type zinc finger.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Endoplasmic reticulum Membrane
Domain	Repeat Transmembrane Transmembrane helix Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Protease Thiol protease
PTM	Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	ER-associated protein catabolic process Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of skeletal muscle tissue development Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cell cycle process Inferred from mutant phenotype Ref.4. Source: UniProtKB protein deubiquitination Inferred from mutant phenotype Ref.1. Source: UniProtKB regulation of cellular response to hypoxia Inferred from sequence or structural similarity. Source: UniProtKB regulation of protein stability Inferred from direct assay Ref.4. Source: UniProtKB response to endoplasmic reticulum stress Inferred from sequence or structural similarity. Source: UniProtKB skeletal muscle atrophy Inferred from expression pattern Ref.3. Source: UniProtKB
Cellular_component	endoplasmic reticulum membrane Inferred from sequence or structural similarity. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	ubiquitin thiolesterase activity Inferred from electronic annotation. Source: InterPro ubiquitin-specific protease activity Inferred from sequence or structural similarity. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1357	1357	Ubiquitin carboxyl-terminal hydrolase 19		PRO_0000295158
Regions
	Topological domain	1 – 1330	1330	Cytoplasmic Potential
	Transmembrane	1331 – 1351	21	Helical; Potential
	Topological domain	1352 – 1357	6	Lumenal Potential
	Domain	51 – 140	90	CS 1
	Domain	321 – 423	103	CS 2
	Zinc finger	830 – 872	43	MYND-type
Sites
	Active site	545	1	Nucleophile By similarity
	Active site	1204	1	Proton acceptor By similarity
Experimental info
	Mutagenesis	545	1	C → A: Has a destabilizing effect on RNF123. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Q6J1Y9 [UniParc]. Last modified July 5, 2004. Version 1. Checksum: E2CE888D61EC3C81	FASTA	1,357	150,302
	10 20 30 40 50 60 MSAGTSATGP RRGPPGLEEA TSKKKQKDRA NQESKDGDPR RVSMPRKEPT KDELLLDWRQ 70 80 90 100 110 120 SSDKVVVKLR VGTGPICLEE VDAAFTDTDC VVRLPDGRQW GGVFFAKIQS SCTKVQTRKG 130 140 150 160 170 180 GLLQLALPKK VPLLTWPSLL KKPLGTQELV PGLRCQENGQ ELSPIALEPG SEPRRAKQEA 190 200 210 220 230 240 RNQKRAQGRG EVGSGASPGA QAGPSAKRAV HLCRGPEGEG SMDGPGPQGD APSFLSDSAT 250 260 270 280 290 300 QVEAEEQLHV PPVNPQTSLL GSEKNLALLT VEKTVSPRSD SVSPVMIRNR DPEKDDHFKE 310 320 330 340 350 360 EMAVGADPAA LADEPESMVN LAFVKNDSYE KGPDSVVVHV YVKESRRDTS RVLFREQDFT 370 380 390 400 410 420 LIFQTRDGNF LRLHPGCGPH TIFRWQVKLR NLIEPEQCTF CFTASRIDIC LRKRQSQRWG 430 440 450 460 470 480 GLEAPATRVG GAKVAVPTGP TPLDSTPPGG GPLPLTGQEE ARAVEKEKPK ARSEDSGLDG 490 500 510 520 530 540 VVARTPLEHV TPKPEPHLAS PKPTCMVPPM PHSPVSGDSV EEDEEEEKKV CLPGFTGLVN 550 560 570 580 590 600 LGNTCFMNSV IQSLSNTREL RDFFHDRSFE AEINYNNPLG TGGRLAIGFA VLLRALWKGT 610 620 630 640 650 660 HQAFQPSKLK AIVASKASQF TGYAQHDAQE FMAFLLDGLH EDLNRIQNKP YTETVDSDGR 670 680 690 700 710 720 PDEVVAEEAW QRHKMRNDSF IVDLFQGQYK SKLVCPVCAK VSITFDPFLY LPVPLPQKQK 730 740 750 760 770 780 VLPIYYFARE PHSKPIKFLV SVSKENSSAS EVLESLSQSV HVKPESLRLA EVIKNRFHRV 790 800 810 820 830 840 FLPSHSLDAV SPTDVLLCFE LLSPELAKER VVVLEVQQRP QVPSIPISKC AACQRKQQSE 850 860 870 880 890 900 DEKLKRCTRC YRVGYCNQFC QKTHWPDHKG LCRPENIGYP FLVSVPASRL TYARLAQLLE 910 920 930 940 950 960 GYARYSVSVF QPPFQPGRMA LESQSPGCTT LLSTSSLEAG DSEREPIQPS ELQLVTPVAE 970 980 990 1000 1010 1020 GDTGAHRMWP PADRGPVPST SGISSEMLAS GPMEGCSLLA GERVSRPEAA VPGYQHSRES 1030 1040 1050 1060 1070 1080 VSAHTPQFFI YKIDASSREQ RLEDKGDTPL ELGDDCSLAL VWRNNERLQE FVLVASKELE 1090 1100 1110 1120 1130 1140 CAEDPGSAGE AARAGHFTLD QCLNLFTRPE VLAPEEAWYC PQCKQHREAS KQLLLWRLPN 1150 1160 1170 1180 1190 1200 VLIVQLKRFS FRSFIWRDKI NDLVEFPVRN LDLSKFCIGQ KEEQLPSYDL YAVINHYGGM 1210 1220 1230 1240 1250 1260 IGGHYTACAR LPSDRSSQRS DVGWRLFDDS TVTTVDESQV VTRYAYVLFY RRRNSPVERP 1270 1280 1290 1300 1310 1320 PRAAHAEHHP DLGPAAEAAA SQASRIWQEL EAEEEMVPEG PGPLGPWGPQ DWVGPPPRGP 1330 1340 1350 TTSDEGCLRY FVLGTVAALV ALVLNVFYPL VSQSRWR

References

[1]	"USP19 is a ubiquitin-specific protease regulated in rat skeletal muscle during catabolic states." Combaret L., Adegoke O.A.J., Bedard N., Baracos V., Attaix D., Wing S.S. Am. J. Physiol. 288:E693-E700(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, INDUCTION. Strain: Sprague-Dawley. Tissue: Testis.
[2]	Lubec G., Kang S.U., Lubec S. Submitted (SEP-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-11; 60-76 AND 837-845, MASS SPECTROMETRY. Strain: Sprague-Dawley. Tissue: Brain.
[3]	"USP19-deubiquitinating enzyme regulates levels of major myofibrillar proteins in L6 muscle cells." Sundaram P., Pang Z., Miao M., Yu L., Wing S.S. Am. J. Physiol. 297:E1283-E1290(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[4]	"USP19 deubiquitinating enzyme supports cell proliferation by stabilizing KPC1, a ubiquitin ligase for p27Kip1." Lu Y., Adegoke O.A.J., Nepveu A., Nakayama K.I., Bedard N., Cheng D., Peng J., Wing S.S. Mol. Cell. Biol. 29:547-558(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH RNF123, MUTAGENESIS OF CYS-545.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY605065 mRNA. Translation: AAT35219.1.
IPI	IPI00421941.
RefSeq	NP_001001516.1. NM_001001516.2.
UniGene	Rn.13484.
3D structure databases
HSSP	HSSP built from PDB template 1WH0 based on UniProtKB O94966.
ProteinModelPortal	Q6J1Y9.
SMR	Q6J1Y9. Positions 305-441.
ModBase	Search...
Protein family/group databases
MEROPS	C19.024.
PTM databases
PhosphoSite	Q6J1Y9.
Proteomic databases
PRIDE	Q6J1Y9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	361190.
KEGG	rno:361190.
Organism-specific databases
CTD	10869.
RGD	1303276. Usp19.
Phylogenomic databases
HOVERGEN	HBG061889.
KO	K11847.
Gene expression databases
Genevestigator	Q6J1Y9.
Family and domain databases
InterPro	IPR007052. CS-like_domain. IPR017447. CS_domain. IPR015054. DUF1872. IPR008978. HSP20-like_chaperone. IPR018200. Pept_C19ubi-hydrolase_C_CS. IPR001394. Peptidase_C19. IPR002893. Znf_MYND. [Graphical view]
Pfam	PF04969. CS. 1 hit. PF08959. DUF1872. 1 hit. PF00443. UCH. 1 hit. PF01753. zf-MYND. 1 hit. [Graphical view]
SUPFAM	SSF49764. HSP20_chap. 2 hits.
PROSITE	PS51203. CS. 2 hits. PS00972. UCH_2_1. 1 hit. PS00973. UCH_2_2. 1 hit. PS50235. UCH_2_3. 1 hit. PS01360. ZF_MYND_1. 1 hit. PS50865. ZF_MYND_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	675485.

Entry information

Entry name

UBP19_RAT

Accession

Primary (citable) accession number: Q6J1Y9

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 10, 2007
Last sequence update:	July 5, 2004
Last modified:	May 1, 2013
This is version 59 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program