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Protein

Ubiquitin carboxyl-terminal hydrolase 21

Gene

USP21

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Deubiquitinates histone H2A, a specific tag for epigenetic transcriptional repression, thereby acting as a coactivator. Deubiquitination of histone H2A releaves the repression of di- and trimethylation of histone H3 at 'Lys-4', resulting in regulation of transcriptional initiation. Regulates gene expression via histone H2A deubiquitination (By similarity). Also capable of removing NEDD8 from NEDD8 conjugates but has no effect on Sentrin-1 conjugates (PubMed:10799498). Deubiquitinates BAZ2A/TIP5 leading to its stabilization (PubMed:26100909).By similarity2 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 sitei221Nucleophile1
Metal bindingi384Zinc1
Metal bindingi387Zinc1
Metal bindingi437Zinc1
Metal bindingi440Zinc1
Active sitei518Proton acceptorPROSITE-ProRule annotation1

GO - Molecular functioni

  • cysteine-type peptidase activity Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • NEDD8-specific protease activity Source: UniProtKB
  • thiol-dependent ubiquitin-specific protease activity Source: UniProtKB
  • transcription coactivator activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator, Chromatin regulator, Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Transcription, Transcription regulation, Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:HS07017-MONOMER.
BRENDAi3.4.19.12. 2681.
ReactomeiR-HSA-5357786. TNFR1-induced proapoptotic signaling.
R-HSA-5357905. Regulation of TNFR1 signaling.
R-HSA-5357956. TNFR1-induced NFkappaB signaling pathway.
R-HSA-5689880. Ub-specific processing proteases.

Protein family/group databases

MEROPSiC19.034.

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin carboxyl-terminal hydrolase 21 (EC:3.4.19.12)
Alternative name(s):
Deubiquitinating enzyme 21
Ubiquitin thioesterase 21
Ubiquitin-specific-processing protease 21
Gene namesi
Name:USP21
Synonyms:USP23
ORF Names:PP1490
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:12620. USP21.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi221C → A: Abolishes ubiquitin thioesterase activity. 1 Publication1

Organism-specific databases

OpenTargetsiENSG00000143258.
PharmGKBiPA37246.

Chemistry databases

ChEMBLiCHEMBL2157852.

Polymorphism and mutation databases

BioMutaiUSP21.
DMDMi10720334.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000806481 – 565Ubiquitin carboxyl-terminal hydrolase 21Add BLAST565

Proteomic databases

PaxDbiQ9UK80.
PeptideAtlasiQ9UK80.
PRIDEiQ9UK80.

PTM databases

iPTMnetiQ9UK80.
PhosphoSitePlusiQ9UK80.

Miscellaneous databases

PMAP-CutDBQ9UK80.

Expressioni

Tissue specificityi

Highly expressed in heart, pancreas and skeletal muscle. Also expressed in brain, placenta, liver and kidney, and at very low level in lung.1 Publication

Gene expression databases

BgeeiENSG00000143258.
CleanExiHS_USP21.
ExpressionAtlasiQ9UK80. baseline and differential.
GenevisibleiQ9UK80. HS.

Organism-specific databases

HPAiHPA028397.

Interactioni

Subunit structurei

Interacts with BEND3 and BAZ2A/TIP5.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
KRT40Q6A1623EBI-373242,EBI-10171697

Protein-protein interaction databases

BioGridi117950. 74 interactors.
DIPiDIP-31255N.
IntActiQ9UK80. 23 interactors.
MINTiMINT-7970258.
STRINGi9606.ENSP00000289865.

Chemistry databases

BindingDBiQ9UK80.

Structurei

Secondary structure

1565
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi217 – 219Combined sources3
Helixi221 – 231Combined sources11
Helixi234 – 242Combined sources9
Helixi245 – 248Combined sources4
Helixi257 – 268Combined sources12
Helixi281 – 290Combined sources10
Helixi292 – 294Combined sources3
Helixi302 – 317Combined sources16
Helixi351 – 365Combined sources15
Helixi369 – 374Combined sources6
Beta strandi376 – 384Combined sources9
Turni385 – 387Combined sources3
Beta strandi390 – 402Combined sources13
Helixi416 – 424Combined sources9
Beta strandi427 – 429Combined sources3
Helixi431 – 433Combined sources3
Beta strandi438 – 440Combined sources3
Beta strandi446 – 454Combined sources9
Beta strandi457 – 463Combined sources7
Beta strandi466 – 471Combined sources6
Beta strandi473 – 475Combined sources3
Helixi490 – 492Combined sources3
Beta strandi501 – 513Combined sources13
Beta strandi516 – 525Combined sources10
Beta strandi528 – 533Combined sources6
Beta strandi536 – 540Combined sources5
Helixi542 – 546Combined sources5
Beta strandi551 – 557Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2Y5BX-ray2.70A/E196-565[»]
3I3TX-ray2.59A/C/E/G209-563[»]
3MTNX-ray2.70A/C209-562[»]
ProteinModelPortaliQ9UK80.
SMRiQ9UK80.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UK80.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini212 – 558USPAdd BLAST347

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi134 – 152Nuclear export signalAdd BLAST19

Sequence similaritiesi

Belongs to the peptidase C19 family. USP21 subfamily.Curated
Contains 1 USP domain.Curated

Phylogenomic databases

eggNOGiKOG1868. Eukaryota.
ENOG410XP8T. LUCA.
GeneTreeiENSGT00860000133682.
HOVERGENiHBG011164.
InParanoidiQ9UK80.
KOiK11833.
OMAiPSHGSFH.
OrthoDBiEOG091G0120.
PhylomeDBiQ9UK80.
TreeFamiTF106277.

Family and domain databases

InterProiIPR001394. Peptidase_C19_UCH.
IPR018200. USP_CS.
IPR028889. USP_dom.
[Graphical view]
PfamiPF00443. UCH. 1 hit.
[Graphical view]
PROSITEiPS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9UK80-1) [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
MPQASEHRLG RTREPPVNIQ PRVGSKLPFA PRARSKERRN PASGPNPMLR
60 70 80 90 100
PLPPRPGLPD ERLKKLELGR GRTSGPRPRG PLRADHGVPL PGSPPPTVAL
110 120 130 140 150
PLPSRTNLAR SKSVSSGDLR PMGIALGGHR GTGELGAALS RLALRPEPPT
160 170 180 190 200
LRRSTSLRRL GGFPGPPTLF SIRTEPPASH GSFHMISARS SEPFYSDDKM
210 220 230 240 250
AHHTLLLGSG HVGLRNLGNT CFLNAVLQCL SSTRPLRDFC LRRDFRQEVP
260 270 280 290 300
GGGRAQELTE AFADVIGALW HPDSCEAVNP TRFRAVFQKY VPSFSGYSQQ
310 320 330 340 350
DAQEFLKLLM ERLHLEINRR GRRAPPILAN GPVPSPPRRG GALLEEPELS
360 370 380 390 400
DDDRANLMWK RYLEREDSKI VDLFVGQLKS CLKCQACGYR STTFEVFCDL
410 420 430 440 450
SLPIPKKGFA GGKVSLRDCF NLFTKEEELE SENAPVCDRC RQKTRSTKKL
460 470 480 490 500
TVQRFPRILV LHLNRFSASR GSIKKSSVGV DFPLQRLSLG DFASDKAGSP
510 520 530 540 550
VYQLYALCNH SGSVHYGHYT ALCRCQTGWH VYNDSRVSPV SENQVASSEG
560
YVLFYQLMQE PPRCL
Length:565
Mass (Da):62,656
Last modified:May 1, 2000 - v1
Checksum:i8A13ED34C03B2330
GO
Isoform 2 (identifier: Q9UK80-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     372-382: DLFVGQLKSCL → GMEWGKAMREN
     383-565: Missing.

Note: No experimental confirmation available.
Show »
Length:382
Mass (Da):42,171
Checksum:i750D5FE7DBA5F9BF
GO
Isoform 3 (identifier: Q9UK80-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     498-511: Missing.

Note: No experimental confirmation available.
Show »
Length:551
Mass (Da):61,122
Checksum:i9F04C052E111F030
GO

Sequence cautioni

The sequence AAF61308 differs from that shown. Reason: Frameshift at positions 90 and 132.Curated
The sequence AAG17222 differs from that shown. Reason: Frameshift at positions 188, 214 and 228.Curated
The sequence BAD92136 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti42A → G in AAH90946 (PubMed:15489334).Curated1
Sequence conflicti272P → L in AAF61308 (PubMed:10799498).Curated1
Sequence conflicti415S → F in AAF61308 (PubMed:10799498).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05153191P → S.Corresponds to variant rs34779722dbSNPEnsembl.1
Natural variantiVAR_051532321G → D.Corresponds to variant rs17356051dbSNPEnsembl.1
Natural variantiVAR_051533336P → T.Corresponds to variant rs1127525dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_036717372 – 382DLFVGQLKSCL → GMEWGKAMREN in isoform 2. 1 PublicationAdd BLAST11
Alternative sequenceiVSP_036718383 – 565Missing in isoform 2. 1 PublicationAdd BLAST183
Alternative sequenceiVSP_036719498 – 511Missing in isoform 3. 1 PublicationAdd BLAST14

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF177758 mRNA. Translation: AAD54321.1.
AF233442 mRNA. Translation: AAF61308.1. Frameshift.
AK292319 mRNA. Translation: BAF85008.1.
AF217979 mRNA. Translation: AAG17222.1. Frameshift.
AB208899 mRNA. Translation: BAD92136.1. Different initiation.
AL590714 Genomic DNA. Translation: CAH72142.1.
AL590714 Genomic DNA. Translation: CAH72143.1.
CH471121 Genomic DNA. Translation: EAW52644.1.
BC003130 mRNA. Translation: AAH03130.2.
BC090946 mRNA. Translation: AAH90946.1.
BC136291 mRNA. Translation: AAI36292.1.
CCDSiCCDS30920.1. [Q9UK80-1]
CCDS81392.1. [Q9UK80-3]
RefSeqiNP_001014443.1. NM_001014443.2. [Q9UK80-1]
NP_001306777.1. NM_001319848.1. [Q9UK80-3]
NP_036607.3. NM_012475.4. [Q9UK80-1]
UniGeneiHs.8015.

Genome annotation databases

EnsembliENST00000289865; ENSP00000289865; ENSG00000143258. [Q9UK80-1]
ENST00000368001; ENSP00000356980; ENSG00000143258. [Q9UK80-3]
ENST00000368002; ENSP00000356981; ENSG00000143258. [Q9UK80-1]
GeneIDi27005.
KEGGihsa:27005.
UCSCiuc031vci.2. human. [Q9UK80-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF177758 mRNA. Translation: AAD54321.1.
AF233442 mRNA. Translation: AAF61308.1. Frameshift.
AK292319 mRNA. Translation: BAF85008.1.
AF217979 mRNA. Translation: AAG17222.1. Frameshift.
AB208899 mRNA. Translation: BAD92136.1. Different initiation.
AL590714 Genomic DNA. Translation: CAH72142.1.
AL590714 Genomic DNA. Translation: CAH72143.1.
CH471121 Genomic DNA. Translation: EAW52644.1.
BC003130 mRNA. Translation: AAH03130.2.
BC090946 mRNA. Translation: AAH90946.1.
BC136291 mRNA. Translation: AAI36292.1.
CCDSiCCDS30920.1. [Q9UK80-1]
CCDS81392.1. [Q9UK80-3]
RefSeqiNP_001014443.1. NM_001014443.2. [Q9UK80-1]
NP_001306777.1. NM_001319848.1. [Q9UK80-3]
NP_036607.3. NM_012475.4. [Q9UK80-1]
UniGeneiHs.8015.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2Y5BX-ray2.70A/E196-565[»]
3I3TX-ray2.59A/C/E/G209-563[»]
3MTNX-ray2.70A/C209-562[»]
ProteinModelPortaliQ9UK80.
SMRiQ9UK80.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117950. 74 interactors.
DIPiDIP-31255N.
IntActiQ9UK80. 23 interactors.
MINTiMINT-7970258.
STRINGi9606.ENSP00000289865.

Chemistry databases

BindingDBiQ9UK80.
ChEMBLiCHEMBL2157852.

Protein family/group databases

MEROPSiC19.034.

PTM databases

iPTMnetiQ9UK80.
PhosphoSitePlusiQ9UK80.

Polymorphism and mutation databases

BioMutaiUSP21.
DMDMi10720334.

Proteomic databases

PaxDbiQ9UK80.
PeptideAtlasiQ9UK80.
PRIDEiQ9UK80.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000289865; ENSP00000289865; ENSG00000143258. [Q9UK80-1]
ENST00000368001; ENSP00000356980; ENSG00000143258. [Q9UK80-3]
ENST00000368002; ENSP00000356981; ENSG00000143258. [Q9UK80-1]
GeneIDi27005.
KEGGihsa:27005.
UCSCiuc031vci.2. human. [Q9UK80-1]

Organism-specific databases

CTDi27005.
GeneCardsiUSP21.
HGNCiHGNC:12620. USP21.
HPAiHPA028397.
MIMi604729. gene.
neXtProtiNX_Q9UK80.
OpenTargetsiENSG00000143258.
PharmGKBiPA37246.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1868. Eukaryota.
ENOG410XP8T. LUCA.
GeneTreeiENSGT00860000133682.
HOVERGENiHBG011164.
InParanoidiQ9UK80.
KOiK11833.
OMAiPSHGSFH.
OrthoDBiEOG091G0120.
PhylomeDBiQ9UK80.
TreeFamiTF106277.

Enzyme and pathway databases

BioCyciZFISH:HS07017-MONOMER.
BRENDAi3.4.19.12. 2681.
ReactomeiR-HSA-5357786. TNFR1-induced proapoptotic signaling.
R-HSA-5357905. Regulation of TNFR1 signaling.
R-HSA-5357956. TNFR1-induced NFkappaB signaling pathway.
R-HSA-5689880. Ub-specific processing proteases.

Miscellaneous databases

EvolutionaryTraceiQ9UK80.
GenomeRNAii27005.
PMAP-CutDBQ9UK80.
PROiQ9UK80.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000143258.
CleanExiHS_USP21.
ExpressionAtlasiQ9UK80. baseline and differential.
GenevisibleiQ9UK80. HS.

Family and domain databases

InterProiIPR001394. Peptidase_C19_UCH.
IPR018200. USP_CS.
IPR028889. USP_dom.
[Graphical view]
PfamiPF00443. UCH. 1 hit.
[Graphical view]
PROSITEiPS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiUBP21_HUMAN
AccessioniPrimary (citable) accession number: Q9UK80
Secondary accession number(s): Q59H60
, Q5BKT5, Q5VTW9, Q5VTX0, Q9BTV1, Q9HBS2, Q9NYN4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 1, 2000
Last modified: November 30, 2016
This is version 158 of the entry and version 1 of the sequence. [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 1
    Human chromosome 1: 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.