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Protein

Ubiquitin carboxyl-terminal hydrolase 19

Gene

USP19

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 their 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.4 Publications

Catalytic activityi

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).

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei506NucleophilePROSITE-ProRule annotation1
Active sitei1165Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri791 – 833MYND-typePROSITE-ProRule annotationAdd BLAST43

GO - Molecular functioni

GO - Biological processi

  • negative regulation of proteasomal protein catabolic process Source: Ensembl
  • negative regulation of skeletal muscle tissue development Source: UniProtKB
  • positive regulation of cell cycle process Source: UniProtKB
  • protein deubiquitination Source: ParkinsonsUK-UCL
  • protein stabilization Source: ParkinsonsUK-UCL
  • regulation of cellular response to hypoxia Source: UniProtKB
  • regulation of ERAD pathway Source: ParkinsonsUK-UCL
  • regulation of protein stability Source: UniProtKB
  • response to endoplasmic reticulum stress Source: UniProtKB
  • ubiquitin-dependent ERAD pathway Source: UniProtKB

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processUbl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-5689880 Ub-specific processing proteases

Protein family/group databases

MEROPSiC19.024

Names & Taxonomyi

Protein namesi
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
Zinc finger MYND domain-containing protein 9
Gene namesi
Name:USP19
Synonyms:KIAA0891, ZMYND9
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000172046.18
HGNCiHGNC:12617 USP19
MIMi614471 gene
neXtProtiNX_O94966

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 1291CytoplasmicSequence analysisAdd BLAST1291
Transmembranei1292 – 1312HelicalSequence analysisAdd BLAST21
Topological domaini1313 – 1318LumenalSequence analysis6

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi10869
OpenTargetsiENSG00000172046
PharmGKBiPA37243

Polymorphism and mutation databases

BioMutaiUSP19

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000806461 – 1318Ubiquitin carboxyl-terminal hydrolase 19Add BLAST1318

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei244PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO94966
MaxQBiO94966
PaxDbiO94966
PeptideAtlasiO94966
PRIDEiO94966
ProteomicsDBi50583
50584 [O94966-2]
50585 [O94966-3]
50586 [O94966-4]

PTM databases

iPTMnetiO94966
PhosphoSitePlusiO94966

Expressioni

Gene expression databases

BgeeiENSG00000172046
CleanExiHS_USP19
ExpressionAtlasiO94966 baseline and differential
GenevisibleiO94966 HS

Interactioni

Subunit structurei

Interacts with RNF123 (By similarity). Interacts with BIRC2/c-IAP1, BIRC3/c-IAP2 and XIAP/BIRC4. Interacts with HIF1A (via N-terminus).By similarity2 Publications

GO - Molecular functioni

  • Hsp90 protein binding Source: ParkinsonsUK-UCL
  • ubiquitin protein ligase binding Source: Ensembl

Protein-protein interaction databases

BioGridi116078, 82 interactors
IntActiO94966, 50 interactors
MINTiO94966
STRINGi9606.ENSP00000401197

Structurei

Secondary structure

11318
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi276 – 278Combined sources3
Beta strandi279 – 283Combined sources5
Beta strandi287 – 292Combined sources6
Turni293 – 295Combined sources3
Beta strandi296 – 302Combined sources7
Beta strandi312 – 315Combined sources4
Beta strandi317 – 324Combined sources8
Helixi329 – 334Combined sources6
Beta strandi344 – 352Combined sources9
Turni356 – 358Combined sources3
Beta strandi360 – 363Combined sources4
Beta strandi365 – 377Combined sources13
Beta strandi465 – 468Combined sources4

3D structure databases

ProteinModelPortaliO94966
SMRiO94966
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO94966

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini113 – 202CS 1PROSITE-ProRule annotationAdd BLAST90
Domaini282 – 384CS 2PROSITE-ProRule annotationAdd BLAST103
Domaini497 – 1214USPAdd BLAST718

Sequence similaritiesi

Belongs to the peptidase C19 family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri791 – 833MYND-typePROSITE-ProRule annotationAdd BLAST43

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix, Zinc-finger

Phylogenomic databases

eggNOGiKOG1870 Eukaryota
COG5560 LUCA
GeneTreeiENSGT00670000097750
HOGENOMiHOG000074206
HOVERGENiHBG061889
InParanoidiO94966
KOiK11847
OMAiAMNAHTP
OrthoDBiEOG091G021E
PhylomeDBiO94966
TreeFamiTF106276

Family and domain databases

Gene3Di2.60.40.790, 2 hits
InterProiView protein in InterPro
IPR007052 CS_dom
IPR008978 HSP20-like_chaperone
IPR038765 Papain_like_cys_pep_sf
IPR001394 Peptidase_C19_UCH
IPR018200 USP_CS
IPR028889 USP_dom
IPR002893 Znf_MYND
PfamiView protein in Pfam
PF04969 CS, 2 hits
PF00443 UCH, 1 hit
PF01753 zf-MYND, 1 hit
SUPFAMiSSF49764 SSF49764, 2 hits
SSF54001 SSF54001, 2 hits
PROSITEiView protein in PROSITE
PS51203 CS, 2 hits
PS00972 USP_1, 1 hit
PS00973 USP_2, 1 hit
PS50235 USP_3, 1 hit
PS01360 ZF_MYND_1, 1 hit
PS50865 ZF_MYND_2, 1 hit

Sequences (7)i

Sequence statusi: Complete.

This entry describes 7 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O94966-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSGGASATGP RRGPPGLEDT TSKKKQKDRA NQESKDGDPR KETGSRYVAQ
60 70 80 90 100
AGLEPLASGD PSASASHAAG ITGSRHRTRL FFPSSSGSAS TPQEEQTKEG
110 120 130 140 150
ACEDPHDLLA TPTPELLLDW RQSAEEVIVK LRVGVGPLQL EDVDAAFTDT
160 170 180 190 200
DCVVRFAGGQ QWGGVFYAEI KSSCAKVQTR KGSLLHLTLP KKVPMLTWPS
210 220 230 240 250
LLVEADEQLC IPPLNSQTCL LGSEENLAPL AGEKAVPPGN DPVSPAMVRS
260 270 280 290 300
RNPGKDDCAK EEMAVAADAA TLVDEPESMV NLAFVKNDSY EKGPDSVVVH
310 320 330 340 350
VYVKEICRDT SRVLFREQDF TLIFQTRDGN FLRLHPGCGP HTTFRWQVKL
360 370 380 390 400
RNLIEPEQCT FCFTASRIDI CLRKRQSQRW GGLEAPAARV GGAKVAVPTG
410 420 430 440 450
PTPLDSTPPG GAPHPLTGQE EARAVEKDKS KARSEDTGLD SVATRTPMEH
460 470 480 490 500
VTPKPETHLA SPKPTCMVPP MPHSPVSGDS VEEEEEEEKK VCLPGFTGLV
510 520 530 540 550
NLGNTCFMNS VIQSLSNTRE LRDFFHDRSF EAEINYNNPL GTGGRLAIGF
560 570 580 590 600
AVLLRALWKG THHAFQPSKL KAIVASKASQ FTGYAQHDAQ EFMAFLLDGL
610 620 630 640 650
HEDLNRIQNK PYTETVDSDG RPDEVVAEEA WQRHKMRNDS FIVDLFQGQY
660 670 680 690 700
KSKLVCPVCA KVSITFDPFL YLPVPLPQKQ KVLPVFYFAR EPHSKPIKFL
710 720 730 740 750
VSVSKENSTA SEVLDSLSQS VHVKPENLRL AEVIKNRFHR VFLPSHSLDT
760 770 780 790 800
VSPSDTLLCF ELLSSELAKE RVVVLEVQQR PQVPSVPISK CAACQRKQQS
810 820 830 840 850
EDEKLKRCTR CYRVGYCNQL CQKTHWPDHK GLCRPENIGY PFLVSVPASR
860 870 880 890 900
LTYARLAQLL EGYARYSVSV FQPPFQPGRM ALESQSPGCT TLLSTGSLEA
910 920 930 940 950
GDSERDPIQP PELQLVTPMA EGDTGLPRVW AAPDRGPVPS TSGISSEMLA
960 970 980 990 1000
SGPIEVGSLP AGERVSRPEA AVPGYQHPSE AMNAHTPQFF IYKIDSSNRE
1010 1020 1030 1040 1050
QRLEDKGDTP LELGDDCSLA LVWRNNERLQ EFVLVASKEL ECAEDPGSAG
1060 1070 1080 1090 1100
EAARAGHFTL DQCLNLFTRP EVLAPEEAWY CPQCKQHREA SKQLLLWRLP
1110 1120 1130 1140 1150
NVLIVQLKRF SFRSFIWRDK INDLVEFPVR NLDLSKFCIG QKEEQLPSYD
1160 1170 1180 1190 1200
LYAVINHYGG MIGGHYTACA RLPNDRSSQR SDVGWRLFDD STVTTVDESQ
1210 1220 1230 1240 1250
VVTRYAYVLF YRRRNSPVER PPRAGHSEHH PDLGPAAEAA ASQASRIWQE
1260 1270 1280 1290 1300
LEAEEEPVPE GSGPLGPWGP QDWVGPLPRG PTTPDEGCLR YFVLGTVAAL
1310
VALVLNVFYP LVSQSRWR
Length:1,318
Mass (Da):145,651
Last modified:July 10, 2007 - v2
Checksum:iEA9F318D03304AA1
GO
Isoform 2 (identifier: O94966-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     100-114: Missing.
     202-202: L → LKKPLGTQEL...PPFVADPATQ
     573-574: IV → RL
     575-1318: Missing.

Note: No experimental confirmation available.
Show »
Length:660
Mass (Da):71,090
Checksum:i3DEF7C14294E7E92
GO
Isoform 3 (identifier: O94966-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1244-1298: ASRIWQELEA...LRYFVLGTVA → GLGPGQAPEV...PTYSNMEEVD
     1299-1318: Missing.

Note: No experimental confirmation available.
Show »
Length:1,281
Mass (Da):141,413
Checksum:i442FF7C6DE59AE94
GO
Isoform 4 (identifier: O94966-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     100-114: Missing.
     389-389: R → RGA
     1244-1298: ASRIWQELEA...LRYFVLGTVA → GLGPGQAPEV...PTYSNMEEVD
     1299-1318: Missing.

Note: No experimental confirmation available.Curated
Show »
Length:1,268
Mass (Da):140,022
Checksum:iCD9BFE22C20EB03E
GO
Isoform 5 (identifier: O94966-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     202-202: L → LKKPLGTQEL...PPFVADPATQ

Note: No experimental confirmation available.
Show »
Length:1,419
Mass (Da):156,035
Checksum:i0FCD06C7B0C80C4E
GO
Isoform 6 (identifier: O94966-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     202-202: L → LKKPLGTQEL...PPFVADPATQ
     389-389: R → RGA
     1244-1298: ASRIWQELEA...LRYFVLGTVA → GLGPGQAPEV...PTYSNMEEVD
     1299-1318: Missing.

Note: No experimental confirmation available.
Show »
Length:1,384
Mass (Da):151,925
Checksum:iCC8F00B6C0033058
GO
Isoform 7 (identifier: O94966-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     193-202: VPMLTWPSLL → KKPLGTQELV...PPFVADPATQ
     1244-1298: ASRIWQELEA...LRYFVLGTVA → GLGPGQAPEV...PTYSNMEEVD
     1299-1318: Missing.

Note: No experimental confirmation available.
Show »
Length:1,372
Mass (Da):150,659
Checksum:i982B811383529FEE
GO

Sequence cautioni

The sequence AAI06030 differs from that shown. Reason: Frameshift at position 572.Curated
The sequence AAI06030 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAI42661 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence BAA74914 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti942S → C in BAG57894 (PubMed:14702039).Curated1
Sequence conflicti1041E → G in BAG62152 (PubMed:14702039).Curated1
Isoform 4 (identifier: O94966-4)
Sequence conflicti1251A → T in AAH82241 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05152836D → H. Corresponds to variant dbSNP:rs11552724Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_026708100 – 114Missing in isoform 2 and isoform 4. 1 PublicationAdd BLAST15
Alternative sequenceiVSP_047057193 – 202VPMLTWPSLL → KKPLGTQELVPGLRCQENGQ ELSPIALEPGPEPHRAKQEA RNQKRAQGRGEVGAGAGPGA QAGPSAKRAVHLCRGPEGDG SRDDPGPRGDAPPFVADPAT Q in isoform 7. 1 Publication10
Alternative sequenceiVSP_026709202L → LKKPLGTQELVPGLRCQENG QELSPIALEPGPEPHRAKQE ARNQKRAQGRGEVGAGAGPG AQAGPSAKRAVHLCRGPEGD GSRDDPGPRGDAPPFVADPA TQ in isoform 2, isoform 5 and isoform 6. 2 Publications1
Alternative sequenceiVSP_045891389R → RGA in isoform 4 and isoform 6. 1 Publication1
Alternative sequenceiVSP_026710573 – 574IV → RL in isoform 2. 1 Publication2
Alternative sequenceiVSP_026711575 – 1318Missing in isoform 2. 1 PublicationAdd BLAST744
Alternative sequenceiVSP_0267121244 – 1298ASRIW…LGTVA → GLGPGQAPEVAPTRTAPERF APPVDRPAPTYSNMEEVD in isoform 3, isoform 4, isoform 6 and isoform 7. 2 PublicationsAdd BLAST55
Alternative sequenceiVSP_0267131299 – 1318Missing in isoform 3, isoform 4, isoform 6 and isoform 7. 2 PublicationsAdd BLAST20

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB020698 mRNA Translation: BAA74914.1 Different initiation.
AK294756 mRNA Translation: BAG57894.1
AK300425 mRNA Translation: BAG62152.1
AC135506 Genomic DNA No translation available.
BC048269 mRNA Translation: AAH48269.1
BC065909 mRNA Translation: AAH65909.1
BC082241 mRNA Translation: AAH82241.1
BC106029 mRNA Translation: AAI06030.1 Sequence problems.
BC142660 mRNA Translation: AAI42661.1 Different initiation.
BC146752 mRNA Translation: AAI46753.1
CCDSiCCDS43090.1 [O94966-1]
CCDS56254.1 [O94966-5]
CCDS56255.1 [O94966-6]
CCDS56256.1 [O94966-7]
RefSeqiNP_001186089.1, NM_001199160.1 [O94966-5]
NP_001186090.1, NM_001199161.1 [O94966-6]
NP_001186091.1, NM_001199162.1 [O94966-7]
NP_006668.1, NM_006677.2 [O94966-1]
XP_005264888.1, XM_005264831.2
XP_016861115.1, XM_017005626.1 [O94966-1]
XP_016861122.1, XM_017005633.1 [O94966-3]
UniGeneiHs.255596
Hs.734003

Genome annotation databases

EnsembliENST00000398888; ENSP00000381863; ENSG00000172046 [O94966-1]
ENST00000417901; ENSP00000395260; ENSG00000172046 [O94966-6]
ENST00000434032; ENSP00000401197; ENSG00000172046 [O94966-5]
ENST00000453664; ENSP00000400090; ENSG00000172046 [O94966-7]
GeneIDi10869
KEGGihsa:10869
UCSCiuc003cvz.5 human [O94966-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiUBP19_HUMAN
AccessioniPrimary (citable) accession number: O94966
Secondary accession number(s): A5PKX8
, A6H8U2, B4DGT3, B4DTZ0, E7EN22, E7ETS0, E9PEG8, Q3KQW4, Q641Q9, Q6NZY8, Q86XV9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: July 10, 2007
Last modified: June 20, 2018
This is version 169 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

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