Human Gene USP15 (ENST00000280377.10_7) from GENCODE V47lift37
  Description: ubiquitin specific peptidase 15, transcript variant 13 (from RefSeq NR_147079.2)
Gencode Transcript: ENST00000280377.10_7
Gencode Gene: ENSG00000135655.16_13
Transcript (Including UTRs)
   Position: hg19 chr12:62,654,185-62,810,169 Size: 155,985 Total Exon Count: 22 Strand: +
Coding Region
   Position: hg19 chr12:62,654,196-62,798,155 Size: 143,960 Coding Exon Count: 22 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr12:62,654,185-62,810,169)mRNA (may differ from genome)Protein (981 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
HGNCMalacardsMGIOMIMPubMedReactome
UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: UBP15_HUMAN
DESCRIPTION: RecName: Full=Ubiquitin carboxyl-terminal hydrolase 15; EC=3.4.19.12; AltName: Full=Deubiquitinating enzyme 15; AltName: Full=Ubiquitin thioesterase 15; AltName: Full=Ubiquitin-specific-processing protease 15; AltName: Full=Unph-2; AltName: Full=Unph4;
FUNCTION: Hydrolase that removes conjugated ubiquitin from target proteins and regulates various pathways such as the TGF-beta receptor signaling and NF-kappa-B pathways. Acts as a key regulator of TGF-beta receptor signaling pathway, but the precise mechanism is still unclear: according to a report, acts by promoting deubiquitination of monoubiquitinated R-SMADs (SMAD1, SMAD2 and/or SMAD3), thereby alleviating inhibition of R-SMADs and promoting activation of TGF-beta target genes (PubMed:21947082). According to another reports, regulates the TGF-beta receptor signaling pathway by mediating deubiquitination and stabilization of TGFBR1, leading to an enhanced TGF-beta signal (PubMed:22344298). Able to mediate deubiquitination of monoubiquitinated substrates as well as 'Lys-48'-linked polyubiquitin chains, protecting them against proteasomal degradation. Acts as an associated component of COP9 signalosome complex (CSN) and regulates different pathways via this association: regulates NF-kappa-B by mediating deubiquitination of NFKBIA and deubiquitinates substrates bound to VCP. Protects APC and human papillomavirus type 16 protein E6 against degradation via the ubiquitin proteasome pathway.
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: A homodimer structure has been reported; however it is unclear whether the protein form a homodimer in vivo (PubMed:22001210). Identified in a complex with the COP9 signalosome complex (CSN). Interacts with SMAD1, SMAD2 and SMAD3; the interaction is direct. Forms a complex with SMURF2 and SMAD7. Interacts with TGFBR1. Interacts with human papillomavirus type 16 protein E6.
SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
TISSUE SPECIFICITY: Expressed in skeletal muscle, kidney, heart, placenta, liver, thymus, lung, and ovary, with little or no expression in other tissues.
PTM: Phosphorylated. Phosphorylation protects against ubiquitination and subsequent degradation by the proteasome.
PTM: Ubiquitinated, leading to degradation by the proteasome.
SIMILARITY: Belongs to the peptidase C19 family.
SIMILARITY: Contains 1 DUSP domain.

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: USP15
Diseases sorted by gene-association score: microphthalmia, isolated 1 (6), speech and communication disorders (5)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 27.23 RPKM in Whole Blood
Total median expression: 396.85 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
3' UTR -3098.7012014-0.258 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR006615 - Pept_C19_DUSP
IPR018200 - Pept_C19ubi-hydrolase_C_CS
IPR001394 - Peptidase_C19
IPR013792 - RNA3'P_cycl/enolpyr_Trfase_a/b

Pfam Domains:
PF00443 - Ubiquitin carboxyl-terminal hydrolase
PF01473 - Putative cell wall binding repeat
PF06337 - DUSP domain
PF13423 - Ubiquitin carboxyl-terminal hydrolase
PF14533 - Ubiquitin-specific protease C-terminal
PF14836 - Ubiquitin-like domain

SCOP Domains:
54236 - Ubiquitin-like
54001 - Cysteine proteinases
143791 - DUSP-like
55205 - EPT/RTPC-like

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1W6V - NMR MuPIT 3LMN - X-ray MuPIT 3PPA - X-ray MuPIT 3PV1 - X-ray MuPIT 3T9L - X-ray MuPIT 4A3O - X-ray MuPIT 4A3P - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q9Y4E8
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGD    
      
      

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003824 catalytic activity
GO:0004197 cysteine-type endopeptidase activity
GO:0004843 thiol-dependent ubiquitin-specific protease activity
GO:0005160 transforming growth factor beta receptor binding
GO:0005515 protein binding
GO:0008233 peptidase activity
GO:0008234 cysteine-type peptidase activity
GO:0016787 hydrolase activity
GO:0036459 thiol-dependent ubiquitinyl hydrolase activity
GO:0042802 identical protein binding
GO:0046332 SMAD binding
GO:0061649 ubiquitinated histone binding

Biological Process:
GO:0006508 proteolysis
GO:0006511 ubiquitin-dependent protein catabolic process
GO:0007179 transforming growth factor beta receptor signaling pathway
GO:0016579 protein deubiquitination
GO:0030509 BMP signaling pathway
GO:0035520 monoubiquitinated protein deubiquitination
GO:0035616 histone H2B conserved C-terminal lysine deubiquitination
GO:0060389 pathway-restricted SMAD protein phosphorylation

Cellular Component:
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005829 cytosol


-  Descriptions from all associated GenBank mRNAs
  LF208915 - JP 2014500723-A/16418: Polycomb-Associated Non-Coding RNAs.
AF153604 - Homo sapiens ubiquitin-specific protease homolog (UPH) mRNA, complete cds.
LP895249 - Sequence 113 from Patent EP3253886.
BC125123 - Homo sapiens ubiquitin specific peptidase 15, mRNA (cDNA clone MGC:149838 IMAGE:40118994), complete cds.
AF106069 - Homo sapiens deubiquitinating enzyme (UNPH4) mRNA, complete cds.
LF385461 - JP 2014500723-A/192964: Polycomb-Associated Non-Coding RNAs.
KJ898126 - Synthetic construct Homo sapiens clone ccsbBroadEn_07520 USP15 gene, encodes complete protein.
AB383899 - Synthetic construct DNA, clone: pF1KSDA0529, Homo sapiens USP15 gene for ubiquitin carboxyl-terminal hydrolase 15, complete cds, without stop codon, in Flexi system.
AB011101 - Homo sapiens KIAA0529 mRNA for KIAA0529 protein.
AF013990 - Homo sapiens ubiquitin C-terminal hydrolase (Unph-2) mRNA, complete cds.
MA621038 - JP 2018138019-A/192964: Polycomb-Associated Non-Coding RNAs.
MA444492 - JP 2018138019-A/16418: Polycomb-Associated Non-Coding RNAs.
HZ459466 - WO 2015182781-A/169: Kit or device and method for detecting pancreatic cancer.
HZ460188 - WO 2015190542-A/194: Kit or device and method for detecting biliary tract cancer.
HZ460708 - WO 2015190584-A/205: Kit or device and method for detecting prostate cancer.
HZ461410 - WO 2015190586-A/223: Kit and method for detecting colon cancer.
HZ462354 - WO 2015190591-A/509: Kit and method for detecting breast cancer.
HZ463180 - WO 2015194535-A/274: Kit and method for detecting stomach cancer.
HZ463882 - WO 2015194610-A/318: Kit and method for detecting lung cancer.
HZ464467 - WO 2015194615-A/285: Kit or device and method for detecting hepatic cancer.
HZ465191 - WO 2015194627-A/244: Kit and method for detecting esophageal cancer.
LY480906 - KR 1020170010856-A/169: PANCREATIC CANCER DETECTION KIT, DEVICE, AND DETECTION METHOD.
LY495815 - KR 1020170015509-A/194: DETECTION KIT OR DEVICE AND DETECTION METHOD FOR BILIARY TRACT CANCER.
LY496374 - KR 1020170018406-A/244: ESOPHAGEAL CANCER DETECTION KIT OR DEVICE, AND DETECTION METHOD.
LY497053 - KR 1020170016485-A/223: COLORECTAL CANCER DETECTION KIT OR DEVICE, AND DETECTION METHOD.
LY497783 - KR 1020170018409-A/318: KIT OR DEVICE FOR DETECTING LUNG CANCER, AND LUNG CANCER DETECTION METHOD.
LY498368 - KR 1020170018411-A/285: LIVER CANCER DETECTION KIT OR DEVICE, AND DETECTION METHOD.
LY499357 - KR 1020170018412-A/509: BREAST CANCER DETECTION KIT OR DEVICE, AND METHOD FOR DETECTING BREAST CANCER.
LY499993 - KR 1020170019425-A/274: STOMACH CANCER DETECTION KIT OR DEVICE, AND DETECTION METHOD.
LY500581 - KR 1020170016490-A/205: PROSTATE CANCER DETECTION KIT OR DEVICE, AND DETECTION METHOD.
LZ238679 - WO 2017171048-A/340: Kit, device and method for detecting early pancreatic cancer or precancerous lesion of pancreas.
MS868980 - Sequence 194 from Patent EP3156500.
MS869500 - Sequence 205 from Patent EP3156483.
MS880672 - Sequence 509 from Patent EP3156498.
MS884240 - Sequence 223 from Patent EP3156499.
MS885112 - Sequence 274 from Patent EP3156503.
MS994382 - Sequence 244 from Patent EP3159406.
MS996849 - Sequence 318 from Patent EP3159416.
AK292337 - Homo sapiens cDNA FLJ77181 complete cds, highly similar to Homo sapiens ubiquitin specific peptidase 15, mRNA.
AK023703 - Homo sapiens cDNA FLJ13641 fis, clone PLACE1011229, highly similar to Homo sapiens ubiquitin-specific protease homolog (UPH) mRNA.
BC063454 - Homo sapiens ubiquitin specific peptidase 15, mRNA (cDNA clone IMAGE:5169196), complete cds.
HZ460332 - WO 2015190542-A/338: Kit or device and method for detecting biliary tract cancer.
HZ460897 - WO 2015190584-A/394: Kit or device and method for detecting prostate cancer.
HZ461597 - WO 2015190586-A/410: Kit and method for detecting colon cancer.
HZ462642 - WO 2015190591-A/797: Kit and method for detecting breast cancer.
HZ463381 - WO 2015194535-A/475: Kit and method for detecting stomach cancer.
HZ464071 - WO 2015194610-A/507: Kit and method for detecting lung cancer.
HZ464682 - WO 2015194615-A/500: Kit or device and method for detecting hepatic cancer.
HZ465395 - WO 2015194627-A/448: Kit and method for detecting esophageal cancer.
LY495959 - KR 1020170015509-A/338: DETECTION KIT OR DEVICE AND DETECTION METHOD FOR BILIARY TRACT CANCER.
LY496578 - KR 1020170018406-A/448: ESOPHAGEAL CANCER DETECTION KIT OR DEVICE, AND DETECTION METHOD.
LY497240 - KR 1020170016485-A/410: COLORECTAL CANCER DETECTION KIT OR DEVICE, AND DETECTION METHOD.
LY497972 - KR 1020170018409-A/507: KIT OR DEVICE FOR DETECTING LUNG CANCER, AND LUNG CANCER DETECTION METHOD.
LY498583 - KR 1020170018411-A/500: LIVER CANCER DETECTION KIT OR DEVICE, AND DETECTION METHOD.
LY499645 - KR 1020170018412-A/797: BREAST CANCER DETECTION KIT OR DEVICE, AND METHOD FOR DETECTING BREAST CANCER.
LY500194 - KR 1020170019425-A/475: STOMACH CANCER DETECTION KIT OR DEVICE, AND DETECTION METHOD.
LY500770 - KR 1020170016490-A/394: PROSTATE CANCER DETECTION KIT OR DEVICE, AND DETECTION METHOD.
LZ238954 - WO 2017171048-A/615: Kit, device and method for detecting early pancreatic cancer or precancerous lesion of pancreas.
MS869124 - Sequence 338 from Patent EP3156500.
MS869689 - Sequence 394 from Patent EP3156483.
MS880960 - Sequence 797 from Patent EP3156498.
MS884427 - Sequence 410 from Patent EP3156499.
MS885313 - Sequence 475 from Patent EP3156503.
MS994586 - Sequence 448 from Patent EP3159406.
MS997038 - Sequence 507 from Patent EP3159416.
AK297759 - Homo sapiens cDNA FLJ58918 complete cds, highly similar to Ubiquitin carboxyl-terminal hydrolase 15 (EC 3.1.2.15).
BC020688 - Homo sapiens ubiquitin specific peptidase 15, mRNA (cDNA clone IMAGE:4689787), complete cds.
BC110908 - Homo sapiens ubiquitin specific peptidase 15, mRNA (cDNA clone IMAGE:5176281), complete cds.
AK295947 - Homo sapiens cDNA FLJ55073 complete cds, highly similar to Ubiquitin carboxyl-terminal hydrolase 15 (EC 3.1.2.15).
KJ906016 - Synthetic construct Homo sapiens clone ccsbBroadEn_15686 USP15 gene, encodes complete protein.
JC515096 - Sequence 5349 from Patent WO2014113089.
LP951599 - Sequence 105 from Patent WO2017157650.
LQ072684 - Sequence 3008 from Patent EP2964234.
LQ724890 - Sequence 523 from Patent WO2018096084.
MS868830 - Sequence 44 from Patent EP3156500.
MS869314 - Sequence 19 from Patent EP3156483.
MS880395 - Sequence 232 from Patent EP3156498.
MS884045 - Sequence 28 from Patent EP3156499.
MS884913 - Sequence 75 from Patent EP3156503.
MS994168 - Sequence 30 from Patent EP3159406.
MS996669 - Sequence 138 from Patent EP3159416.
LF324058 - JP 2014500723-A/131561: Polycomb-Associated Non-Coding RNAs.
LF324057 - JP 2014500723-A/131560: Polycomb-Associated Non-Coding RNAs.
LF324056 - JP 2014500723-A/131559: Polycomb-Associated Non-Coding RNAs.
LF324055 - JP 2014500723-A/131558: Polycomb-Associated Non-Coding RNAs.
LF324040 - JP 2014500723-A/131543: Polycomb-Associated Non-Coding RNAs.
JD024091 - Sequence 5115 from Patent EP1572962.
JD034747 - Sequence 15771 from Patent EP1572962.
LF324037 - JP 2014500723-A/131540: Polycomb-Associated Non-Coding RNAs.
MA559635 - JP 2018138019-A/131561: Polycomb-Associated Non-Coding RNAs.
MA559634 - JP 2018138019-A/131560: Polycomb-Associated Non-Coding RNAs.
MA559633 - JP 2018138019-A/131559: Polycomb-Associated Non-Coding RNAs.
MA559632 - JP 2018138019-A/131558: Polycomb-Associated Non-Coding RNAs.
MA559617 - JP 2018138019-A/131543: Polycomb-Associated Non-Coding RNAs.
MA559614 - JP 2018138019-A/131540: Polycomb-Associated Non-Coding RNAs.
MP015128 - Sequence 331 from Patent WO2019016252.
MA806254 - WO 2018199275-A/514: Kit, device and method for detection of ovary tumor.
MA806529 - WO 2018199275-A/789: Kit, device and method for detection of ovary tumor.
MA822779 - WO 2019004436-A/592: Kit, device, and method for detection of lung cancer.
MA823122 - WO 2019004436-A/935: Kit, device, and method for detection of lung cancer.
LY616443 - KR 1020180129785-A/340: KIT OR DEVICE FOR DETECTING EARLY STAGE PANCREATIC CANCER OR PANCREATIC CANCER PRECURSOR LESIONS AND DETECTION METHOD THEREFOR.
LY616718 - KR 1020180129785-A/615: KIT OR DEVICE FOR DETECTING EARLY STAGE PANCREATIC CANCER OR PANCREATIC CANCER PRECURSOR LESIONS AND DETECTION METHOD THEREFOR.
LF324036 - JP 2014500723-A/131539: Polycomb-Associated Non-Coding RNAs.
LF324035 - JP 2014500723-A/131538: Polycomb-Associated Non-Coding RNAs.
LF324034 - JP 2014500723-A/131537: Polycomb-Associated Non-Coding RNAs.
LF324032 - JP 2014500723-A/131535: Polycomb-Associated Non-Coding RNAs.
LF324031 - JP 2014500723-A/131534: Polycomb-Associated Non-Coding RNAs.
LF324028 - JP 2014500723-A/131531: Polycomb-Associated Non-Coding RNAs.
LF324024 - JP 2014500723-A/131527: Polycomb-Associated Non-Coding RNAs.
LF324023 - JP 2014500723-A/131526: Polycomb-Associated Non-Coding RNAs.
LF324022 - JP 2014500723-A/131525: Polycomb-Associated Non-Coding RNAs.
JD455830 - Sequence 436854 from Patent EP1572962.
LF324021 - JP 2014500723-A/131524: Polycomb-Associated Non-Coding RNAs.
JD037610 - Sequence 18634 from Patent EP1572962.
JD560355 - Sequence 541379 from Patent EP1572962.
JD313213 - Sequence 294237 from Patent EP1572962.
JD563504 - Sequence 544528 from Patent EP1572962.
JD404063 - Sequence 385087 from Patent EP1572962.
JD491144 - Sequence 472168 from Patent EP1572962.
JD236813 - Sequence 217837 from Patent EP1572962.
JD549729 - Sequence 530753 from Patent EP1572962.
JD113230 - Sequence 94254 from Patent EP1572962.
JD279978 - Sequence 261002 from Patent EP1572962.
JD241193 - Sequence 222217 from Patent EP1572962.
JD301132 - Sequence 282156 from Patent EP1572962.
JD101572 - Sequence 82596 from Patent EP1572962.
LF324020 - JP 2014500723-A/131523: Polycomb-Associated Non-Coding RNAs.
MA559613 - JP 2018138019-A/131539: Polycomb-Associated Non-Coding RNAs.
MA559612 - JP 2018138019-A/131538: Polycomb-Associated Non-Coding RNAs.
MA559611 - JP 2018138019-A/131537: Polycomb-Associated Non-Coding RNAs.
MA559609 - JP 2018138019-A/131535: Polycomb-Associated Non-Coding RNAs.
MA559608 - JP 2018138019-A/131534: Polycomb-Associated Non-Coding RNAs.
MA559605 - JP 2018138019-A/131531: Polycomb-Associated Non-Coding RNAs.
MA559601 - JP 2018138019-A/131527: Polycomb-Associated Non-Coding RNAs.
MA559600 - JP 2018138019-A/131526: Polycomb-Associated Non-Coding RNAs.
MA559599 - JP 2018138019-A/131525: Polycomb-Associated Non-Coding RNAs.
MA559598 - JP 2018138019-A/131524: Polycomb-Associated Non-Coding RNAs.
MA559597 - JP 2018138019-A/131523: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q9Y4E8 (Reactome details) participates in the following event(s):

R-HSA-6781764 USP15 deubiquitinates SMAD1,SMAD2,SMAD3, SMAD7:SMURF,KEAP1
R-HSA-2179293 UCHL5 binds SMAD7 in complex with ubiquitinated TGFBR1
R-HSA-2179291 UCHL5, USP15 deubiquitinate TGFBR1
R-HSA-5689880 Ub-specific processing proteases
R-HSA-2173788 Downregulation of TGF-beta receptor signaling
R-HSA-5689603 UCH proteinases
R-HSA-5688426 Deubiquitination
R-HSA-2173789 TGF-beta receptor signaling activates SMADs
R-HSA-597592 Post-translational protein modification
R-HSA-170834 Signaling by TGF-beta Receptor Complex
R-HSA-392499 Metabolism of proteins
R-HSA-9006936 Signaling by TGF-beta family members
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: ENST00000280377.1, ENST00000280377.2, ENST00000280377.3, ENST00000280377.4, ENST00000280377.5, ENST00000280377.6, ENST00000280377.7, ENST00000280377.8, ENST00000280377.9, KIAA0529 , NR_147079, Q08AL5, Q9H8G9, Q9HCA6, Q9UNP0, Q9Y4E8, Q9Y5B5, UBP15_HUMAN, uc317jtu.1, uc317jtu.2, USP15
UCSC ID: ENST00000280377.10_7
RefSeq Accession: NM_001252078.2
Protein: Q9Y4E8 (aka UBP15_HUMAN or UB15_HUMAN)

-  Gene Model Information
  Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.