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Basic Information Integrated Annotations
Tag Content
iUUCD ID IUUC-Hsa-046277
UUCD1 version UUC-HoS-01147
Ensembl Protein ID ENSP00000003302.4
UniProt Accession Q96RU2; B0YJC0; B0YJC1; Q6NZX9; Q9P213; UBP28_HUMAN
Genbank Protein ID AAK58565.1; ACA06098.1; ACA06099.1; EAW67232.1; AAH65928.1; BAA96039.1
Protein Name Ubiquitin carboxyl-terminal hydrolase 28; Deubiquitinating enzyme 28; Ubiquitin thioesterase 28; Ubiquitin-specific-processing protease 28
Genbank Nucleotide ID AF266283; EF445045; EF445045; AP001874; BC065928; AB040948
Gene Name USP28; KIAA1515
Ensembl Information
Ensembl Gene ID Ensembl Transcript ID Ensembl Protein ID
ENSG00000048028.11 ENST00000003302.8 ENSP00000003302.4
ENSG00000048028.11 ENST00000544967.5 ENSP00000442431.1
ENSG00000048028.11 ENST00000545540.5 ENSP00000444991.1
ENSG00000048028.11 ENST00000540438.5 ENSP00000441513.1
ENSG00000048028.11 ENST00000538224.1 ENSP00000440260.1
ENSG00000048028.11 ENST00000538475.5 ENSP00000442257.1
ENSG00000048028.11 ENST00000537706.5 ENSP00000445743.1
ENSG00000048028.11 ENST00000545608.5 ENSP00000438050.1
ENSG00000048028.11 ENST00000535607.5 ENSP00000437688.1
ENSG00000048028.11 ENST00000537490.1 ENSP00000445722.1
ENSG00000048028.11 ENST00000537642.1 ENSP00000440799.1
ENSG00000048028.11 ENST00000540925.5 ENSP00000446284.1
Annotation
Cancer Mutation
TCGAICGCCOSMICCGAP
IntOGen
Single Nucleotide Polymorphisms (SNP)
dbSNP
mRNA Expression
GEOArrayExpressTCGAICGC
COSMICTHPAHPM
DNA & RNA Element
UTRdbAREsitecircBasecircRNADb
CircNetmiRTarBasemicroRNATRANSFAC
TargetScanRepTarmiRNAMapSomamiR
miRcodeRAID2
Protein-protein Interaction
IIDiRefIndexPINAHINT
MenthaInWeb_IM
Protein 3D Structure
PDB
Disease-associated Information
ClinVarGWASdbOMIM
Post-translational Modifications (PTMs)
CPLMdbPAFPhosphositePlusdbPTM
HPRDPhospho.ELMUniProtBioGRID
mUbiSiDa
DNA Methylation
TCGAICGCCOSMIC
Protein Expression/Proteomics
THPAHPMGPMDB
Status Reviewed
Details
Family Domain References (PMIDs)
DUB/USP USP 16901786; 12401499
UBD/Alpha-Helix/UIM UIM 26268556
Classification
Family E-value Score Start End
DUB/USP 2.70e-58 199.5 162 648
UBD/Alpha-Helix/UIM 0.16 13.8 100 113
Active Site
Position(s) Description Evidence
171 Nucleophile
600 Proton acceptor ECO:0000255|PROSITE-ProRule:PRU10092,
ECO:0000255|PROSITE-ProRule:PRU10093}
Domain Profile

   DUB/USP
   S: 1    tGlkNlgNtCYmNSvLQcLsnipelrellle.....kkkeklneenpkepkgellkslqklfeelwkskkkavsprellkalkkeaeefsgy 87
           +GlkN+gNtC++ +v+Q+L+++pe+r+l+l+     +  e+++    ++++  ++++lq lf+ ++ s++k v+p++ l+ lk + ++ s+ 
   Q: 162  VGLKNVGNTCWFSAVIQSLFQLPEFRRLVLSyslpqNVLENCRSH-TEKRNIMFMQELQYLFALMMGSNRKFVDPSAALDLLKGAFRS-SEE 251
           6******************************97665555555543.478888*******************************99987.99* PP
   S: 88   eqqDaqEflaflldqleeelkkeknkpkeeeeeedkselsdeaeekkkkknkslisdlFqgqlksqikclecdnvssreepfldlslpvpgk 179
           +qqD++Ef++ lld le++++                     + +++ +k+++++++lF g++ ++ + +        +e+f +++l+v+g 
   Q: 252  QQQDVSEFTHKLLDWLEDAFQL------------------AVNVNSPRNKSENPMVQLFYGTFLTEGVREGKPFC--NNETFGQYPLQVNGY 323
           ********************22..................23467899****************99998665555..5899*********** PP
   S: 180  eetkkeslqdcLesftkeeelegenkyycekckkkqeaekklklkklPevLilhLkRfsfseeqksrekinkkvefpleLdlspfcts.... 267
           +     +l++cLe  + e  +e    +  +   ++++  ++ +++klP+vL+++L+Rf+f+++ +++eki++k+efp+ + +++++ +    
   Q: 324  R-----NLDECLEGAMVEGDVE----LLPSD--HSVKYGQERWFTKLPPVLTFELSRFEFNQSLGQPEKIHNKLEFPQIIYMDRYMYRskel 404
           *.....99****7665555555....55554..556778899******************************************99997788 PP
   S: 268  ...................................................................................peekqke.. 274
                                                                                              +     +  
   Q: 405  irnkrecirklkeeikilqqkleryvkygsgparfplpdmlkyviefastkpasescppesdthmtlplssvhcsvsdqtskeS-----Tst 491
           888888888888777777777777777777777777777777777777777777777777777777777776666666555550.....055 PP
   S: 275  .........................................................................................kkk 277
                                                                                                    ++ 
   Q: 492  esssqdvestfsspedslpkskpltssrssmempsqpaprtvtdeeinfvktclqrwrseieqdiqdlktciasttqtieqmycdpllrQVP 583
           55566666777777777777777777888888888888888888888888889999999999999999999999999999999*****9*** PP
   S: 278  YeLiavvvHsGslssGHYvayvknekgk.WllfdDskVtevkeeevleetg.....staYvlfYk 336
           Y+L+av+vH+G+++ GHY+ay++n+ ++ Wl+++D +Vte+++eev++++       +aY+l+Y 
   Q: 584  YRLHAVLVHEGQANAGHYWAYIYNQPRQsWLKYNDISVTESSWEEVERDSYgglrnVSAYCLMYI 648
           ************************88888*******************8879************6 PP
   

   UBD/Alpha-Helix/UIM
   S: 4    eeLqlAlalSlqEe 17
           ++Lq A+alSl E 
   Q: 100  DDLQAAIALSLLES 113
           89*********996 PP
   
Organism Homo sapiens
Functional Description
(View)

Functional Description


     Deubiquitinase involved in DNA damage response checkpoint and MYC proto-oncogene stability. Involved in DNA damage induced apoptosis by specifically deubiquitinating proteins of the DNA damage pathway such as CLSPN. Also involved in G2 DNA damage checkpoint, by deubiquitinating CLSPN, and preventing its degradation by the anaphase promoting complex/cyclosome (APC/C). In contrast, it does not deubiquitinate PLK1. Specifically deubiquitinates MYC in the nucleoplasm, leading to prevent MYC degradation by the proteasome: acts by specifically interacting with isoform 1 of FBXW7 (FBW7alpha) in the nucleoplasm and counteracting ubiquitination of MYC by the SCF(FBW7) complex. In contrast, it does not interact with isoform 4 of FBXW7 (FBW7gamma) in the nucleolus, allowing MYC degradation and explaining the selective MYC degradation in the nucleolus. Deubiquitinates ZNF304, hence preventing ZNF304 degradation by the proteasome and leading to the activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) in a subset of colorectal cancers (CRC) cells (PubMed:24623306).
 Deubiquitinase involved in DNA damage response checkpoint and MYC proto-oncogene stability. Involved in DNA damage induced apoptosis by specifically deubiquitinating proteins of the DNA damage pathway such as CLSPN. Also involved in G2 DNA damage checkpoint, by deubiquitinating CLSPN, and preventing its degradation by the anaphase promoting complex/cyclosome (APC/C). In contrast, it does not deubiquitinate PLK1. Specifically deubiquitinates MYC in the nucleoplasm, leading to prevent MYC degradation by the proteasome: acts by specifically interacting with isoform 1 of FBXW7 (FBW7alpha) in the nucleoplasm and counteracting ubiquitination of MYC by the SCF(FBW7) complex. In contrast, it does not interact with isoform 4 of FBXW7 (FBW7gamma) in the nucleolus, allowing MYC degradation and explaining the selective MYC degradation in the nucleolus. Deubiquitinates ZNF304, hence preventing ZNF304 degradation by the proteasome and leading to the activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) in a subset of colorectal cancers (CRC) cells (PubMed:24623306).
Protein Sequence
(Fasta)
MTAELQQDDA AGAADGHGSS CQMLLNQLRE ITGIQDPSFL HEALKASNGD ITQAVSLLTD 60
ERVKEPSQDT VATEPSEVEG SAANKEVLAK VIDLTHDNKD DLQAAIALSL LESPKIQADG 120
It may take some time, please wait.

Protein Fasta Sequence


>IUUC-Hsa-046277|DUB,USP;UBD,UIM|Homo sapiens
Please wait for a moment...
Nucleotide Sequence
(Fasta)
AGTCCTGAGA GGCTGGGCCG GCGGCGGCTG CGGCGGGAGA CCGGTGACCC GCGGCTGGGC 60
GCCTCGGCCA TGACTGCGGA GCTGCAGCAG GACGACGCGG CCGGCGCGGC AGACGGCCAC 120
It may take some time, please wait.

Nucleotide Fasta Sequence


>IUUC-Hsa-046277|DUB,USP;UBD,UIM|Homo sapiens
Please wait for a moment...
Sequence Source Ensembl
Keyword

KW-0002--3D-structure
KW-0025--Alternative splicing
KW-0181--Complete proteome
KW-0227--DNA damage
KW-0234--DNA repair
KW-0378--Hydrolase
KW-0539--Nucleus
KW-0597--Phosphoprotein
KW-0645--Protease
KW-1185--Reference proteome
KW-0788--Thiol protease
KW-0833--Ubl conjugation pathway
Interpro

IPR001394--Peptidase_C19_UCH
IPR009060--UBA-like
IPR018200--USP_CS
IPR028889--USP_dom
PROSITE

PS00972--USP_1
PS00973--USP_2
PS50235--USP_3
Pfam

PF00443--UCH
Gene Ontology

GO:0016604--C:nuclear body
GO:0005654--C:nucleoplasm
GO:0043234--C:protein complex
GO:0004843--F:thiol-dependent ubiquitin-specific protease activity
GO:0036459--F:thiol-dependent ubiquitinyl hydrolase activity
GO:0008283--P:cell proliferation
GO:0006974--P:cellular response to DNA damage stimulus
GO:0034644--P:cellular response to UV
GO:0000077--P:DNA damage checkpoint
GO:0006281--P:DNA repair
GO:0042771--P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
GO:0016579--P:protein deubiquitination
GO:0007265--P:Ras protein signal transduction
GO:0031647--P:regulation of protein stability
GO:0010212--P:response to ionizing radiation
GO:0006511--P:ubiquitin-dependent protein catabolic process
KEGG hsa:57646
Orthology
iUUCD ID Species Identity E-value Score
IUUC-Aml-001836 Ailuropoda melanoleuca 94.54 0.00e+00 2026.00
IUUC-Apl-004010 Anas platyrhynchos 70.36 0.00e+00 1479.00
IUUC-Aca-004741 Anolis carolinensis 58.57 0.00e+00 846.00
IUUC-Ang-009577 Aspergillus niger 35.35 1.00e-10 62.80
IUUC-Ate-010275 Aspergillus terreus 35.24 4.00e-11 64.30
IUUC-Bta-013377 Bos taurus 93.07 0.00e+00 1960.00
IUUC-Cja-019977 Callithrix jacchus 98.52 0.00e+00 2076.00
IUUC-Cfa-020378 Canis familiaris 93.33 0.00e+00 1390.00
IUUC-Cpo-021817 Cavia porcellus 91.17 0.00e+00 1945.00
IUUC-Csa-023446 Chlorocebus sabaeus 98.70 0.00e+00 1458.00
IUUC-Cho-024717 Choloepus hoffmanni 84.45 0.00e+00 1222.00
IUUC-Csv-025911 Ciona savignyi 35.90 2.00e-143 503.00
IUUC-Cme-027167 Cyanidioschyzon merolae 33.00 9.00e-16 79.70
IUUC-Dre-028105 Danio rerio 56.59 0.00e+00 713.00
IUUC-Dno-029559 Dasypus novemcinctus 91.02 0.00e+00 1505.00
IUUC-Dor-030955 Dipodomys ordii 90.92 0.00e+00 1937.00
IUUC-Ete-032828 Echinops telfairi 81.82 0.00e+00 1170.00
IUUC-Eca-034300 Equus caballus 94.35 0.00e+00 1944.00
IUUC-Eeu-034458 Erinaceus europaeus 89.41 0.00e+00 1721.00
IUUC-Fca-035753 Felis catus 94.26 0.00e+00 2016.00
IUUC-Fal-037062 Ficedula albicollis 64.15 0.00e+00 882.00
IUUC-Gmo-039593 Gadus morhua 52.14 0.00e+00 1038.00
IUUC-Gga-040878 Gallus gallus 65.10 0.00e+00 1323.00
IUUC-Gac-041867 Gasterosteus aculeatus 54.55 0.00e+00 1109.00
IUUC-Ggo-045384 Gorilla gorilla 99.63 0.00e+00 2092.00
IUUC-Itr-048276 Ictidomys tridecemlineatus 87.74 0.00e+00 1152.00
IUUC-Lch-049692 Latimeria chalumnae 67.07 0.00e+00 1404.00
IUUC-Laf-053808 Loxodonta africana 88.89 0.00e+00 1838.00
IUUC-Mcc-055473 Macaca mulatta 98.70 0.00e+00 1457.00
IUUC-Meu-056416 Macropus eugenii 75.49 0.00e+00 1521.00
IUUC-Mla-058944 Melampsora laricipopulina 22.66 4.00e-10 61.20
IUUC-Mga-060011 Meleagris gallopavo 67.85 0.00e+00 1405.00
IUUC-Mmr-060720 Microcebus murinus 93.19 0.00e+00 1934.00
IUUC-Mdo-061955 Monodelphis domestica 85.31 0.00e+00 1313.00
IUUC-Mmu-063870 Mus musculus 87.53 0.00e+00 1887.00
IUUC-Mpu-066454 Mustela putorius furo 91.60 0.00e+00 1336.00
IUUC-Mlu-067487 Myotis lucifugus 88.53 0.00e+00 1858.00
IUUC-Nle-070044 Nomascus leucogenys 99.16 0.00e+00 2086.00
IUUC-Opr-070888 Ochotona princeps 98.19 5.00e-162 565.00
IUUC-Ocu-074523 Oryctolagus cuniculus 91.24 0.00e+00 1939.00
IUUC-Ola-086393 Oryzias latipes 54.37 0.00e+00 1108.00
IUUC-Oga-088618 Otolemur garnettii 94.80 0.00e+00 1991.00
IUUC-Oar-089848 Ovis aries 84.67 0.00e+00 1828.00
IUUC-Ptr-091630 Pan troglodytes 99.76 0.00e+00 1595.00
IUUC-Psi-093422 Pelodiscus sinensis 65.43 0.00e+00 1395.00
IUUC-Pma-094250 Petromyzon marinus 52.27 5.00e-73 267.00
IUUC-Pfo-096466 Poecilia formosa 56.53 0.00e+00 748.00
IUUC-Pab-098337 Pongo abelii 99.26 0.00e+00 2088.00
IUUC-Pca-100901 Procavia capensis 78.33 0.00e+00 1617.00
IUUC-Pva-102226 Pteropus vampyrus 88.81 0.00e+00 1735.00
IUUC-Rno-105735 Rattus norvegicus 84.78 0.00e+00 1877.00
IUUC-Sha-107489 Sarcophilus harrisii 87.99 0.00e+00 1870.00
IUUC-Tgu-116609 Taeniopygia guttata 69.47 0.00e+00 1425.00
IUUC-Tru-117807 Takifugu rubripes 53.85 0.00e+00 1090.00
IUUC-Tsy-118971 Tarsius syrichta 88.97 0.00e+00 1251.00
IUUC-Tni-119983 Tetraodon nigroviridis 54.57 0.00e+00 1110.00
IUUC-Ttr-128887 Tursiops truncatus 88.63 0.00e+00 1852.00
IUUC-Vpa-130614 Vicugna pacos 92.29 0.00e+00 1497.00
IUUC-Xtr-132436 Xenopus tropicalis 63.68 0.00e+00 1301.00
Created Date 25-Jun-2017

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