UniProtKB - Q9P275 (UBP36_HUMAN)
Ubiquitin carboxyl-terminal hydrolase 36
USP36
Functioni
Deubiquitinase essential for the regulation of nucleolar structure and function. Required for cell and organism viability. Plays an important role in ribosomal RNA processing and protein synthesis, which is mediated, at least in part, through deubiquitination of DHX33, NPM1 and FBL, regulating their protein stability (PubMed:29273634, PubMed:19208757, PubMed:22902402).
Functions as a transcriptional repressor by deubiquiting histone H2B at the promoters of genes critical for cellular differentiation, such as CDKN1A, thereby preventing histone H3 'Lys-4' trimethylation (H3K4) (PubMed:29274341).
Specifically deubiquitinates MYC in the nucleolus, leading to prevent MYC degradation by the proteasome: acts by specifically interacting with isoform 3 of FBXW7 (FBW7gamma) in the nucleolus and counteracting ubiquitination of MYC by the SCF(FBW7) complex. In contrast, it does not interact with isoform 1 of FBXW7 (FBW7alpha) in the nucleoplasm (PubMed:25775507).
Interacts to and regulates the actions of E3 ubiquitin-protein ligase NEDD4L over substrates such as NTRK1, KCNQ2 and KCNQ3, affecting their expression an functions (PubMed:27445338).
Deubiquitinates SOD2, regulates SOD2 protein stability (PubMed:21268071).
Deubiquitinase activity is required to control selective autophagy activation by ubiquitinated proteins (PubMed:22622177).
8 PublicationsCatalytic 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).1 Publication EC:3.4.19.12
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 131 | NucleophilePROSITE-ProRule annotation5 Publications | 1 | |
Active sitei | 382 | Proton acceptorPROSITE-ProRule annotation | 1 |
GO - Molecular functioni
- cysteine-type endopeptidase activity Source: GO_Central
- RNA binding Source: UniProtKB
- thiol-dependent deubiquitinase Source: FlyBase
GO - Biological processi
- histone deubiquitination Source: UniProtKB
- negative regulation of macroautophagy Source: UniProtKB
- nucleolus organization Source: UniProtKB
- positive regulation of protein targeting to mitochondrion Source: ParkinsonsUK-UCL
- protein deubiquitination Source: UniProtKB
- protein stabilization Source: UniProtKB
- regulation of apoptotic process Source: GO_Central
- regulation of autophagy of mitochondrion Source: ParkinsonsUK-UCL
- regulation of protein stability Source: UniProtKB
- regulation of rRNA processing Source: UniProtKB
- ubiquitin-dependent protein catabolic process Source: InterPro
Keywordsi
Molecular function | Hydrolase, Protease, Thiol protease |
Biological process | Ubl conjugation pathway |
Enzyme and pathway databases
PathwayCommonsi | Q9P275 |
SignaLinki | Q9P275 |
Protein family/group databases
MEROPSi | C19.042 |
Names & Taxonomyi
Protein namesi | Recommended name: Ubiquitin carboxyl-terminal hydrolase 36Curated (EC:3.4.19.12)Alternative name(s): Deubiquitinating enzyme 36 Ubiquitin thioesterase 36 Ubiquitin-specific-processing protease 36 |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:20062, USP36 |
MIMi | 612543, gene |
neXtProti | NX_Q9P275 |
VEuPathDBi | HostDB:ENSG00000055483 |
Subcellular locationi
Cytosol
- cytosol Source: GO_Central
Nucleus
- nuclear speck Source: HPA
- nucleolus Source: UniProtKB
- nucleoplasm Source: HPA
- nucleus Source: GO_Central
Other locations
- cytoplasm Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 131 | C → A or S: Abolishes deubiquitinase activity. No effect on NTRK1 ubiquitination levels. 5 Publications | 1 |
Organism-specific databases
DisGeNETi | 57602 |
OpenTargetsi | ENSG00000055483 |
PharmGKBi | PA134949090 |
Miscellaneous databases
Pharosi | Q9P275, Tbio |
Chemistry databases
ChEMBLi | CHEMBL4630861 |
Genetic variation databases
BioMutai | USP36 |
DMDMi | 124056592 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000080666 | 1 – 1123 | Ubiquitin carboxyl-terminal hydrolase 36Add BLAST | 1123 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 429 | PhosphoserineCombined sources | 1 | |
Modified residuei | 464 | PhosphoserineCombined sources | 1 | |
Modified residuei | 546 | PhosphoserineCombined sources | 1 | |
Modified residuei | 582 | PhosphoserineCombined sources | 1 | |
Modified residuei | 667 | PhosphoserineCombined sources | 1 | |
Modified residuei | 682 | PhosphoserineCombined sources | 1 | |
Modified residuei | 713 | PhosphoserineCombined sources | 1 | |
Modified residuei | 742 | PhosphoserineCombined sources | 1 | |
Modified residuei | 952 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Keywords - PTMi
Phosphoprotein, Ubl conjugationProteomic databases
EPDi | Q9P275 |
jPOSTi | Q9P275 |
MassIVEi | Q9P275 |
MaxQBi | Q9P275 |
PaxDbi | Q9P275 |
PeptideAtlasi | Q9P275 |
PRIDEi | Q9P275 |
2D gel databases
SWISS-2DPAGEi | Q9P275 |
PTM databases
CarbonylDBi | Q9P275 |
iPTMneti | Q9P275 |
PhosphoSitePlusi | Q9P275 |
SwissPalmi | Q9P275 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000055483, Expressed in adenohypophysis and 226 other tissues |
ExpressionAtlasi | Q9P275, baseline and differential |
Genevisiblei | Q9P275, HS |
Organism-specific databases
HPAi | ENSG00000055483, Low tissue specificity |
Interactioni
Subunit structurei
Interacts with isoform 3 of FBXW7; the interaction inhibits MYC degradation induced by SCF(FBW7) complex (PubMed:25775507).
Interacts with NTRK1; USP36 does not deubiquitinate NTRK1 (PubMed:27445338).
Interacts with NEDD4L (via domains WW1, 3 and 4); the interaction inhibits ubiquitination of, at least, NTRK1, KCNQ2 and KCNQ3 by NEDD4L (PubMed:27445338).
2 PublicationsProtein-protein interaction databases
BioGRIDi | 121651, 121 interactors |
IntActi | Q9P275, 35 interactors |
STRINGi | 9606.ENSP00000441214 |
Chemistry databases
BindingDBi | Q9P275 |
Miscellaneous databases
RNActi | Q9P275, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 122 – 423 | USPAdd BLAST | 302 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 22 | DisorderedSequence analysisAdd BLAST | 22 | |
Regioni | 67 – 95 | DisorderedSequence analysisAdd BLAST | 29 | |
Regioni | 430 – 577 | DisorderedSequence analysisAdd BLAST | 148 | |
Regioni | 589 – 999 | DisorderedSequence analysisAdd BLAST | 411 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 70 – 89 | Basic and acidic residuesSequence analysisAdd BLAST | 20 | |
Compositional biasi | 432 – 446 | Polar residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 457 – 471 | Polar residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 487 – 501 | Polar residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 549 – 577 | Polar residuesSequence analysisAdd BLAST | 29 | |
Compositional biasi | 605 – 681 | Polar residuesSequence analysisAdd BLAST | 77 | |
Compositional biasi | 742 – 758 | Polar residuesSequence analysisAdd BLAST | 17 | |
Compositional biasi | 765 – 788 | Polar residuesSequence analysisAdd BLAST | 24 | |
Compositional biasi | 858 – 872 | Polar residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 886 – 906 | Polar residuesSequence analysisAdd BLAST | 21 | |
Compositional biasi | 917 – 932 | Basic and acidic residuesSequence analysisAdd BLAST | 16 | |
Compositional biasi | 964 – 979 | Basic and acidic residuesSequence analysisAdd BLAST | 16 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG1865, Eukaryota |
GeneTreei | ENSGT00940000157948 |
InParanoidi | Q9P275 |
OMAi | SETCLPQ |
OrthoDBi | 929408at2759 |
PhylomeDBi | Q9P275 |
TreeFami | TF315281 |
Family and domain databases
InterProi | View protein in InterPro IPR038765, Papain-like_cys_pep_sf IPR001394, Peptidase_C19_UCH IPR018200, USP_CS IPR028889, USP_dom |
Pfami | View protein in Pfam PF00443, UCH, 1 hit |
SUPFAMi | SSF54001, SSF54001, 1 hit |
PROSITEi | View protein in PROSITE PS00972, USP_1, 1 hit PS00973, USP_2, 1 hit PS50235, USP_3, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 16 potential isoforms that are computationally mapped.Show allAlign All
10 20 30 40 50
MPIVDKLKEA LKPGRKDSAD DGELGKLLAS SAKKVLLQKI EFEPASKSFS
60 70 80 90 100
YQLEALKSKY VLLNPKTEGA SRHKSGDDPP ARRQGSEHTY ESCGDGVPAP
110 120 130 140 150
QKVLFPTERL SLRWERVFRV GAGLHNLGNT CFLNATIQCL TYTPPLANYL
160 170 180 190 200
LSKEHARSCH QGSFCMLCVM QNHIVQAFAN SGNAIKPVSF IRDLKKIARH
210 220 230 240 250
FRFGNQEDAH EFLRYTIDAM QKACLNGCAK LDRQTQATTL VHQIFGGYLR
260 270 280 290 300
SRVKCSVCKS VSDTYDPYLD VALEIRQAAN IVRALELFVK ADVLSGENAY
310 320 330 340 350
MCAKCKKKVP ASKRFTIHRT SNVLTLSLKR FANFSGGKIT KDVGYPEFLN
360 370 380 390 400
IRPYMSQNNG DPVMYGLYAV LVHSGYSCHA GHYYCYVKAS NGQWYQMNDS
410 420 430 440 450
LVHSSNVKVV LNQQAYVLFY LRIPGSKKSP EGLISRTGSS SLPGRPSVIP
460 470 480 490 500
DHSKKNIGNG IISSPLTGKR QDSGTMKKPH TTEEIGVPIS RNGSTLGLKS
510 520 530 540 550
QNGCIPPKLP SGSPSPKLSQ TPTHMPTILD DPGKKVKKPA PPQHFSPRTA
560 570 580 590 600
QGLPGTSNSN SSRSGSQRQG SWDSRDVVLS TSPKLLATAT ANGHGLKGND
610 620 630 640 650
ESAGLDRRGS SSSSPEHSAS SDSTKAPQTP RSGAAHLCDS QETNCSTAGH
660 670 680 690 700
SKTPPSGADS KTVKLKSPVL SNTTTEPAST MSPPPAKKLA LSAKKASTLW
710 720 730 740 750
RATGNDLRPP PPSPSSDLTH PMKTSHPVVA STWPVHRARA VSPAPQSSSR
760 770 780 790 800
LQPPFSPHPT LLSSTPKPPG TSEPRSCSSI STALPQVNED LVSLPHQLPE
810 820 830 840 850
ASEPPQSPSE KRKKTFVGEP QRLGSETRLP QHIREATAAP HGKRKRKKKK
860 870 880 890 900
RPEDTAASAL QEGQTQRQPG SPMYRREGQA QLPAVRRQED GTQPQVNGQQ
910 920 930 940 950
VGCVTDGHHA SSRKRRRKGA EGLGEEGGLH QDPLRHSCSP MGDGDPEAME
960 970 980 990 1000
ESPRKKKKKK RKQETQRAVE EDGHLKCPRS AKPQDAVVPE SSSCAPSANG
1010 1020 1030 1040 1050
WCPGDRMGLS QAPPVSWNGE RESDVVQELL KYSSDKAYGR KVLTWDGKMS
1060 1070 1080 1090 1100
AVSQDAIEDS RQARTETVVD DWDEEFDRGK EKKIKKFKRE KRRNFNAFQK
1110 1120
LQTRRNFWSV THPAKAASLS YRR
Computationally mapped potential isoform sequencesi
There are 16 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketE9PEW0 | E9PEW0_HUMAN | Ubiquitin carboxyl-terminal hydrola... | USP36 | 548 | Annotation score: | ||
A0A075B784 | A0A075B784_HUMAN | Ubiquitin carboxyl-terminal hydrola... | USP36 | 961 | Annotation score: | ||
K7EMM6 | K7EMM6_HUMAN | Ubiquitin carboxyl-terminal hydrola... | USP36 | 259 | Annotation score: | ||
K7EQS0 | K7EQS0_HUMAN | Ubiquitin carboxyl-terminal hydrola... | USP36 | 159 | Annotation score: | ||
K7ELR5 | K7ELR5_HUMAN | Ubiquitin carboxyl-terminal hydrola... | USP36 | 234 | Annotation score: | ||
K7EPT1 | K7EPT1_HUMAN | Ubiquitin carboxyl-terminal hydrola... | USP36 | 179 | Annotation score: | ||
Q8IXW9 | Q8IXW9_HUMAN | USP36 protein | USP36 | 285 | Annotation score: | ||
K7ELT3 | K7ELT3_HUMAN | Ubiquitin carboxyl-terminal hydrola... | USP36 | 80 | Annotation score: | ||
U3KQ92 | U3KQ92_HUMAN | Ubiquitin carboxyl-terminal hydrola... | USP36 | 61 | Annotation score: | ||
K7EIH0 | K7EIH0_HUMAN | Ubiquitin carboxyl-terminal hydrola... | USP36 | 101 | Annotation score: | ||
There are more potential isoformsShow all |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 82 | R → G in AAH71582 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 573 | D → G in BAA91825 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_037277 | 271 | V → I1 PublicationCorresponds to variant dbSNP:rs3744793Ensembl. | 1 | |
Natural variantiVAR_037278 | 489 | I → M. Corresponds to variant dbSNP:rs3744795Ensembl. | 1 | |
Natural variantiVAR_037279 | 775 | R → Q. Corresponds to variant dbSNP:rs9889908Ensembl. | 1 | |
Natural variantiVAR_037280 | 806 | Q → R3 PublicationsCorresponds to variant dbSNP:rs3088040Ensembl. | 1 | |
Natural variantiVAR_037281 | 814 | K → N. Corresponds to variant dbSNP:rs3744797Ensembl. | 1 | |
Natural variantiVAR_037282 | 828 | R → C2 PublicationsCorresponds to variant dbSNP:rs1057040Ensembl. | 1 | |
Natural variantiVAR_058034 | 887 | R → P1 PublicationCorresponds to variant dbSNP:rs61760231EnsemblClinVar. | 1 | |
Natural variantiVAR_080193 | 959 – 960 | Missing 1 PublicationCorresponds to variant dbSNP:rs866027510Ensembl. | 2 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB040886 mRNA Translation: BAA95977.1 Different initiation. BC016487 mRNA Translation: AAH16487.1 Sequence problems. BC027992 mRNA Translation: AAH27992.1 BC071582 mRNA Translation: AAH71582.1 AK001671 mRNA Translation: BAA91825.1 AL833835 mRNA Translation: CAD38695.1 |
CCDSi | CCDS32755.1 |
RefSeqi | NP_001308220.1, NM_001321291.1 XP_005257599.1, XM_005257542.2 XP_005257600.1, XM_005257543.2 XP_016880389.1, XM_017024900.1 |
Genome annotation databases
Ensembli | ENST00000312010; ENSP00000310590; ENSG00000055483 ENST00000542802; ENSP00000441214; ENSG00000055483 ENST00000589225; ENSP00000467280; ENSG00000055483 |
GeneIDi | 57602 |
KEGGi | hsa:57602 |
UCSCi | uc002jvz.2, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB040886 mRNA Translation: BAA95977.1 Different initiation. BC016487 mRNA Translation: AAH16487.1 Sequence problems. BC027992 mRNA Translation: AAH27992.1 BC071582 mRNA Translation: AAH71582.1 AK001671 mRNA Translation: BAA91825.1 AL833835 mRNA Translation: CAD38695.1 |
CCDSi | CCDS32755.1 |
RefSeqi | NP_001308220.1, NM_001321291.1 XP_005257599.1, XM_005257542.2 XP_005257600.1, XM_005257543.2 XP_016880389.1, XM_017024900.1 |
3D structure databases
SMRi | Q9P275 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 121651, 121 interactors |
IntActi | Q9P275, 35 interactors |
STRINGi | 9606.ENSP00000441214 |
Chemistry databases
BindingDBi | Q9P275 |
ChEMBLi | CHEMBL4630861 |
Protein family/group databases
MEROPSi | C19.042 |
PTM databases
CarbonylDBi | Q9P275 |
iPTMneti | Q9P275 |
PhosphoSitePlusi | Q9P275 |
SwissPalmi | Q9P275 |
Genetic variation databases
BioMutai | USP36 |
DMDMi | 124056592 |
2D gel databases
SWISS-2DPAGEi | Q9P275 |
Proteomic databases
EPDi | Q9P275 |
jPOSTi | Q9P275 |
MassIVEi | Q9P275 |
MaxQBi | Q9P275 |
PaxDbi | Q9P275 |
PeptideAtlasi | Q9P275 |
PRIDEi | Q9P275 |
Protocols and materials databases
Antibodypediai | 1709, 239 antibodies from 29 providers |
DNASUi | 57602 |
Genome annotation databases
Ensembli | ENST00000312010; ENSP00000310590; ENSG00000055483 ENST00000542802; ENSP00000441214; ENSG00000055483 ENST00000589225; ENSP00000467280; ENSG00000055483 |
GeneIDi | 57602 |
KEGGi | hsa:57602 |
UCSCi | uc002jvz.2, human |
Organism-specific databases
CTDi | 57602 |
DisGeNETi | 57602 |
GeneCardsi | USP36 |
HGNCi | HGNC:20062, USP36 |
HPAi | ENSG00000055483, Low tissue specificity |
MIMi | 612543, gene |
neXtProti | NX_Q9P275 |
OpenTargetsi | ENSG00000055483 |
PharmGKBi | PA134949090 |
VEuPathDBi | HostDB:ENSG00000055483 |
HUGEi | Search... |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1865, Eukaryota |
GeneTreei | ENSGT00940000157948 |
InParanoidi | Q9P275 |
OMAi | SETCLPQ |
OrthoDBi | 929408at2759 |
PhylomeDBi | Q9P275 |
TreeFami | TF315281 |
Enzyme and pathway databases
PathwayCommonsi | Q9P275 |
SignaLinki | Q9P275 |
Miscellaneous databases
BioGRID-ORCSi | 57602, 560 hits in 1063 CRISPR screens |
ChiTaRSi | USP36, human |
GeneWikii | USP36 |
GenomeRNAii | 57602 |
Pharosi | Q9P275, Tbio |
PROi | PR:Q9P275 |
RNActi | Q9P275, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000055483, Expressed in adenohypophysis and 226 other tissues |
ExpressionAtlasi | Q9P275, baseline and differential |
Genevisiblei | Q9P275, HS |
Family and domain databases
InterProi | View protein in InterPro IPR038765, Papain-like_cys_pep_sf IPR001394, Peptidase_C19_UCH IPR018200, USP_CS IPR028889, USP_dom |
Pfami | View protein in Pfam PF00443, UCH, 1 hit |
SUPFAMi | SSF54001, SSF54001, 1 hit |
PROSITEi | View protein in PROSITE PS00972, USP_1, 1 hit PS00973, USP_2, 1 hit PS50235, USP_3, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | UBP36_HUMAN | |
Accessioni | Q9P275Primary (citable) accession number: Q9P275 Secondary accession number(s): Q05C98 Q9NVC8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 10, 2003 |
Last sequence update: | March 28, 2018 | |
Last modified: | February 23, 2022 | |
This is version 180 of the entry and version 4 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Reference proteomeDocuments
- Peptidase families
Classification of peptidase families and list of entries - Human chromosome 17
Human chromosome 17: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families