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Q9UK80 (UBP21_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 132. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:USP21
Synonyms:USP23
ORF Names:PP1490
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length565 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.2

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).

Subcellular location

Cytoplasm. Nucleus Ref.9.

Tissue specificity

Highly expressed in heart, pancreas and skeletal muscle. Also expressed in brain, placenta, liver and kidney, and at very low level in lung. Ref.2

Sequence similarities

Belongs to the peptidase C19 family. USP21 subfamily.

Contains 1 USP domain.

Sequence caution

The sequence AAF61308.1 differs from that shown. Reason: Frameshift at positions 90 and 132.

The sequence AAG17222.1 differs from that shown. Reason: Frameshift at positions 188, 214 and 228.

The sequence BAD92136.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
Ubl conjugation pathway
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandMetal-binding
Zinc
   Molecular functionActivator
Chromatin regulator
Hydrolase
Protease
Thiol protease
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processhistone deubiquitination

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

ubiquitin-dependent protein catabolic process

Inferred from electronic annotation. Source: InterPro

   Cellular_componentcytoplasm

Inferred from direct assay. Source: HPA

nucleus

Inferred from direct assay. Source: HPA

plasma membrane

Inferred from direct assay. Source: HPA

   Molecular_functionNEDD8-specific protease activity

Inferred from direct assay Ref.2. Source: UniProtKB

cysteine-type peptidase activity

Inferred from mutant phenotype Ref.2. Source: UniProtKB

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

transcription coactivator activity

Inferred from sequence or structural similarity. Source: UniProtKB

ubiquitin thiolesterase activity

Inferred from direct assay Ref.2. Source: UniProtKB

ubiquitin-specific protease activity

Inferred from direct assay Ref.2. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9UK80-1)

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.
Isoform 2 (identifier: Q9UK80-2)

The sequence of this isoform differs from the canonical sequence as follows:
     372-382: DLFVGQLKSCL → GMEWGKAMREN
     383-565: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q9UK80-3)

The sequence of this isoform differs from the canonical sequence as follows:
     498-511: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 565565Ubiquitin carboxyl-terminal hydrolase 21
PRO_0000080648

Regions

Domain212 – 558347USP
Motif134 – 15219Nuclear export signal

Sites

Active site2211Nucleophile
Active site5181Proton acceptor By similarity
Metal binding3841Zinc
Metal binding3871Zinc
Metal binding4371Zinc
Metal binding4401Zinc

Natural variations

Alternative sequence372 – 38211DLFVGQLKSCL → GMEWGKAMREN in isoform 2.
VSP_036717
Alternative sequence383 – 565183Missing in isoform 2.
VSP_036718
Alternative sequence498 – 51114Missing in isoform 3.
VSP_036719
Natural variant911P → S.
Corresponds to variant rs34779722 [ dbSNP | Ensembl ].
VAR_051531
Natural variant3211G → D.
Corresponds to variant rs17356051 [ dbSNP | Ensembl ].
VAR_051532
Natural variant3361P → T.
Corresponds to variant rs1127525 [ dbSNP | Ensembl ].
VAR_051533

Experimental info

Mutagenesis2211C → A: Abolishes ubiquitin thioesterase activity. Ref.2
Sequence conflict421A → G in AAH90946. Ref.8
Sequence conflict2721P → L in AAF61308. Ref.2
Sequence conflict4151S → F in AAF61308. Ref.2

Secondary structure

........................................................ 565
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: 8A13ED34C03B2330

FASTA56562,656
        10         20         30         40         50         60 
MPQASEHRLG RTREPPVNIQ PRVGSKLPFA PRARSKERRN PASGPNPMLR PLPPRPGLPD 

        70         80         90        100        110        120 
ERLKKLELGR GRTSGPRPRG PLRADHGVPL PGSPPPTVAL PLPSRTNLAR SKSVSSGDLR 

       130        140        150        160        170        180 
PMGIALGGHR GTGELGAALS RLALRPEPPT LRRSTSLRRL GGFPGPPTLF SIRTEPPASH 

       190        200        210        220        230        240 
GSFHMISARS SEPFYSDDKM AHHTLLLGSG HVGLRNLGNT CFLNAVLQCL SSTRPLRDFC 

       250        260        270        280        290        300 
LRRDFRQEVP GGGRAQELTE AFADVIGALW HPDSCEAVNP TRFRAVFQKY VPSFSGYSQQ 

       310        320        330        340        350        360 
DAQEFLKLLM ERLHLEINRR GRRAPPILAN GPVPSPPRRG GALLEEPELS DDDRANLMWK 

       370        380        390        400        410        420 
RYLEREDSKI VDLFVGQLKS CLKCQACGYR STTFEVFCDL SLPIPKKGFA GGKVSLRDCF 

       430        440        450        460        470        480 
NLFTKEEELE SENAPVCDRC RQKTRSTKKL TVQRFPRILV LHLNRFSASR GSIKKSSVGV 

       490        500        510        520        530        540 
DFPLQRLSLG DFASDKAGSP VYQLYALCNH SGSVHYGHYT ALCRCQTGWH VYNDSRVSPV 

       550        560 
SENQVASSEG YVLFYQLMQE PPRCL 

« Hide

Isoform 2 [UniParc].

Checksum: 750D5FE7DBA5F9BF
Show »

FASTA38242,171
Isoform 3 [UniParc].

Checksum: 9F04C052E111F030
Show »

FASTA55161,122

References

« Hide 'large scale' references
[1]"Sequencing, tissue distribution and chromosomal assignment of a novel ubiquitin-specific protease USP23."
Smith T.S., Southan C.
Biochim. Biophys. Acta 1490:184-188(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Identification of a novel isopeptidase with dual specificity for ubiquitin- and NEDD8-conjugated proteins."
Gong L., Kamitani T., Millas S., Yeh E.T.H.
J. Biol. Chem. 275:14212-14216(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, MUTAGENESIS OF CYS-221.
Tissue: Placenta.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Testis.
[4]"Large-scale cDNA transfection screening for genes related to cancer development and progression."
Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X. expand/collapse author list , Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.
Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
[5]Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F.
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Brain.
[6]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Kidney, Lung and Testis.
[9]"A global survey of CRM1-dependent nuclear export sequences in the human deubiquitinase family."
Garcia-Santisteban I., Banuelos S., Rodriguez J.A.
Biochem. J. 441:209-217(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, NUCLEAR EXPORT SIGNAL.
[10]"Polyubiquitin binding and cross-reactivity in the USP domain deubiquitinase USP21."
Ye Y., Akutsu M., Reyes-Turcu F., Enchev R.I., Wilkinson K.D., Komander D.
EMBO Rep. 12:350-357(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.59 ANGSTROMS) OF 1-75 IN COMPLEX WITH USP21.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS30920.1. [Q9UK80-1]
RefSeqNP_001014443.1. NM_001014443.2. [Q9UK80-1]
NP_036607.3. NM_012475.4. [Q9UK80-1]
UniGeneHs.8015.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2Y5BX-ray2.70A/E196-565[»]
3I3TX-ray2.59A/C/E/G209-563[»]
3MTNX-ray2.70A/C209-562[»]
ProteinModelPortalQ9UK80.
SMRQ9UK80. Positions 202-559.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117950. 69 interactions.
DIPDIP-31255N.
IntActQ9UK80. 19 interactions.
MINTMINT-7970258.
STRING9606.ENSP00000289865.

Chemistry

ChEMBLCHEMBL2157852.

Protein family/group databases

MEROPSC19.034.

PTM databases

PhosphoSiteQ9UK80.

Polymorphism databases

DMDM10720334.

Proteomic databases

PaxDbQ9UK80.
PRIDEQ9UK80.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000289865; ENSP00000289865; ENSG00000143258. [Q9UK80-1]
ENST00000368001; ENSP00000356980; ENSG00000143258. [Q9UK80-3]
ENST00000368002; ENSP00000356981; ENSG00000143258. [Q9UK80-1]
GeneID27005.
KEGGhsa:27005.
UCSCuc010pkc.2. human. [Q9UK80-1]

Organism-specific databases

CTD27005.
GeneCardsGC01P161129.
HGNCHGNC:12620. USP21.
HPAHPA028397.
MIM604729. gene.
neXtProtNX_Q9UK80.
PharmGKBPA37246.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5533.
HOVERGENHBG011164.
KOK11833.
OMANVQPRVG.
OrthoDBEOG7FR7GN.
PhylomeDBQ9UK80.
TreeFamTF106277.

Enzyme and pathway databases

BRENDA3.1.2.15. 2681.

Gene expression databases

BgeeQ9UK80.
CleanExHS_USP21.
GenevestigatorQ9UK80.

Family and domain databases

InterProIPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19_UCH.
IPR028889. UCH/PAN2.
[Graphical view]
PfamPF00443. UCH. 1 hit.
[Graphical view]
PROSITEPS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9UK80.
GenomeRNAi27005.
NextBio49506.
PMAP-CutDBQ9UK80.
PROQ9UK80.
SOURCESearch...

Entry information

Entry nameUBP21_HUMAN
AccessionPrimary (citable) accession number: Q9UK80
Secondary accession number(s): Q59H60 expand/collapse secondary AC list , Q5BKT5, Q5VTW9, Q5VTX0, Q9BTV1, Q9HBS2, Q9NYN4
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 1, 2000
Last modified: July 9, 2014
This is version 132 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM