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Protein

Ubiquitin carboxyl-terminal hydrolase 36

Gene

USP36

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

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). Function 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 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).1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei131NucleophilePROSITE-ProRule annotation5 Publications1
Active sitei382Proton acceptorPROSITE-ProRule annotation1

GO - Molecular functioni

  • RNA binding Source: UniProtKB
  • thiol-dependent ubiquitin-specific protease activity Source: FlyBase

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processUbl conjugation pathway

Protein family/group databases

MEROPSiC19.042

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
Name:USP36Imported
Synonyms:KIAA1453
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000055483.19
HGNCiHGNC:20062 USP36
MIMi612543 gene
neXtProtiNX_Q9P275

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

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi131C → A or S: Abolishes deubiquitinase activity. No effect on NTRK1 ubiquitination levels. 5 Publications1

Organism-specific databases

DisGeNETi57602
OpenTargetsiENSG00000055483
PharmGKBiPA134949090

Polymorphism and mutation databases

BioMutaiUSP36
DMDMi124056592

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000806661 – 1123Ubiquitin carboxyl-terminal hydrolase 36Add BLAST1123

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei429PhosphoserineCombined sources1
Modified residuei464PhosphoserineCombined sources1
Modified residuei546PhosphoserineCombined sources1
Modified residuei582PhosphoserineCombined sources1
Modified residuei667PhosphoserineCombined sources1
Modified residuei682PhosphoserineCombined sources1
Modified residuei713PhosphoserineCombined sources1
Modified residuei742PhosphoserineCombined sources1
Modified residuei952PhosphoserineCombined sources1

Post-translational modificationi

Polyubiquitinated by NEDD4L, no effect on USP36 protein levels. Both proteins interact with and regulate each other's ubiquitination levels.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9P275
MaxQBiQ9P275
PaxDbiQ9P275
PeptideAtlasiQ9P275
PRIDEiQ9P275
ProteomicsDBi83743

2D gel databases

SWISS-2DPAGEiQ9P275

PTM databases

CarbonylDBiQ9P275
iPTMnetiQ9P275
PhosphoSitePlusiQ9P275

Miscellaneous databases

PMAP-CutDBiQ9P275

Expressioni

Tissue specificityi

Broadly expressed.1 Publication

Gene expression databases

BgeeiENSG00000055483 Expressed in 214 organ(s), highest expression level in adenohypophysis
CleanExiHS_USP36
ExpressionAtlasiQ9P275 baseline and differential
GenevisibleiQ9P275 HS

Organism-specific databases

HPAiHPA012082
HPA012395
HPA052860

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 Publications

Protein-protein interaction databases

BioGridi121651, 53 interactors
IntActiQ9P275, 29 interactors
STRINGi9606.ENSP00000310590

Structurei

3D structure databases

ProteinModelPortaliQ9P275
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini122 – 423USPAdd BLAST302

Sequence similaritiesi

Belongs to the peptidase C19 family.Curated

Phylogenomic databases

eggNOGiKOG1865 Eukaryota
ENOG410XQ92 LUCA
GeneTreeiENSGT00890000139343
HOGENOMiHOG000154759
HOVERGENiHBG061810
InParanoidiQ9P275
KOiK11855
OMAiKRNFNAF
OrthoDBiEOG091G02D8
PhylomeDBiQ9P275
TreeFamiTF315281

Family and domain databases

InterProiView protein in InterPro
IPR038765 Papain_like_cys_pep_sf
IPR001394 Peptidase_C19_UCH
IPR018200 USP_CS
IPR028889 USP_dom
PfamiView protein in Pfam
PF00443 UCH, 1 hit
SUPFAMiSSF54001 SSF54001, 1 hit
PROSITEiView protein in PROSITE
PS00972 USP_1, 1 hit
PS00973 USP_2, 1 hit
PS50235 USP_3, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

Q9P275-1 [UniParc]FASTAAdd to basket
« Hide
        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
Length:1,123
Mass (Da):122,908
Last modified:March 28, 2018 - v4
Checksum:i65CD93C1B8655319
GO

Sequence cautioni

The sequence AAH16487 differs from that shown. Contaminating sequence. Potential poly-A sequence.Curated
The sequence BAA95977 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti82R → G in AAH71582 (PubMed:15489334).Curated1
Sequence conflicti573D → G in BAA91825 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_037277271V → I1 PublicationCorresponds to variant dbSNP:rs3744793Ensembl.1
Natural variantiVAR_037278489I → M. Corresponds to variant dbSNP:rs3744795Ensembl.1
Natural variantiVAR_037279775R → Q. Corresponds to variant dbSNP:rs9889908Ensembl.1
Natural variantiVAR_037280806Q → R3 PublicationsCorresponds to variant dbSNP:rs3088040Ensembl.1
Natural variantiVAR_037281814K → N. Corresponds to variant dbSNP:rs3744797Ensembl.1
Natural variantiVAR_037282828R → C2 PublicationsCorresponds to variant dbSNP:rs1057040Ensembl.1
Natural variantiVAR_058034887R → P1 PublicationCorresponds to variant dbSNP:rs61760231Ensembl.1
Natural variantiVAR_080193959 – 960Missing 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
CCDSiCCDS32755.1
RefSeqiNP_001308220.1, NM_001321291.1
XP_005257599.1, XM_005257542.2
XP_005257600.1, XM_005257543.2
XP_016880389.1, XM_017024900.1
UniGeneiHs.464243

Genome annotation databases

EnsembliENST00000312010; ENSP00000310590; ENSG00000055483
ENST00000542802; ENSP00000441214; ENSG00000055483
ENST00000589225; ENSP00000467280; ENSG00000055483
GeneIDi57602
KEGGihsa:57602
UCSCiuc002jvz.2 human

Keywords - Coding sequence diversityi

Polymorphism

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
CCDSiCCDS32755.1
RefSeqiNP_001308220.1, NM_001321291.1
XP_005257599.1, XM_005257542.2
XP_005257600.1, XM_005257543.2
XP_016880389.1, XM_017024900.1
UniGeneiHs.464243

3D structure databases

ProteinModelPortaliQ9P275
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121651, 53 interactors
IntActiQ9P275, 29 interactors
STRINGi9606.ENSP00000310590

Protein family/group databases

MEROPSiC19.042

PTM databases

CarbonylDBiQ9P275
iPTMnetiQ9P275
PhosphoSitePlusiQ9P275

Polymorphism and mutation databases

BioMutaiUSP36
DMDMi124056592

2D gel databases

SWISS-2DPAGEiQ9P275

Proteomic databases

EPDiQ9P275
MaxQBiQ9P275
PaxDbiQ9P275
PeptideAtlasiQ9P275
PRIDEiQ9P275
ProteomicsDBi83743

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000312010; ENSP00000310590; ENSG00000055483
ENST00000542802; ENSP00000441214; ENSG00000055483
ENST00000589225; ENSP00000467280; ENSG00000055483
GeneIDi57602
KEGGihsa:57602
UCSCiuc002jvz.2 human

Organism-specific databases

CTDi57602
DisGeNETi57602
EuPathDBiHostDB:ENSG00000055483.19
GeneCardsiUSP36
H-InvDBiHIX0014226
HGNCiHGNC:20062 USP36
HPAiHPA012082
HPA012395
HPA052860
MIMi612543 gene
neXtProtiNX_Q9P275
OpenTargetsiENSG00000055483
PharmGKBiPA134949090
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1865 Eukaryota
ENOG410XQ92 LUCA
GeneTreeiENSGT00890000139343
HOGENOMiHOG000154759
HOVERGENiHBG061810
InParanoidiQ9P275
KOiK11855
OMAiKRNFNAF
OrthoDBiEOG091G02D8
PhylomeDBiQ9P275
TreeFamiTF315281

Miscellaneous databases

ChiTaRSiUSP36 human
GeneWikiiUSP36
GenomeRNAii57602
PMAP-CutDBiQ9P275
PROiPR:Q9P275
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000055483 Expressed in 214 organ(s), highest expression level in adenohypophysis
CleanExiHS_USP36
ExpressionAtlasiQ9P275 baseline and differential
GenevisibleiQ9P275 HS

Family and domain databases

InterProiView protein in InterPro
IPR038765 Papain_like_cys_pep_sf
IPR001394 Peptidase_C19_UCH
IPR018200 USP_CS
IPR028889 USP_dom
PfamiView protein in Pfam
PF00443 UCH, 1 hit
SUPFAMiSSF54001 SSF54001, 1 hit
PROSITEiView protein in PROSITE
PS00972 USP_1, 1 hit
PS00973 USP_2, 1 hit
PS50235 USP_3, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiUBP36_HUMAN
AccessioniPrimary (citable) accession number: Q9P275
Secondary accession number(s): Q05C98
, Q05DD0, Q6IQ38, Q8NDM8, Q9NVC8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 10, 2003
Last sequence update: March 28, 2018
Last modified: October 10, 2018
This is version 158 of the entry and version 4 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

Complete proteome, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families
  4. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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