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P15374 (UCHL3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 145. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ubiquitin carboxyl-terminal hydrolase isozyme L3

Short name=UCH-L3
EC=3.4.19.12
Alternative name(s):
Ubiquitin thioesterase L3
Gene names
Name:UCHL3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length230 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Deubiquitinating enzyme (DUB) that controls levels of cellular ubiquitin through processing of ubiquitin precursors and ubiquitinated proteins. Thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of either ubiquitin or NEDD8. Has a 10-fold preference for Arg and Lys at position P3", and exhibits a preference towards 'Lys-48'-linked Ubiquitin chains. Deubiquitinates ENAC in apical compartments, thereby regulating apical membrane recycling. Indirectly increases the phosphorylation of IGFIR, AKT and FOXO1 and promotes insulin-signaling and insulin-induced adipogenesis. Required for stress-response retinal, skeletal muscle and germ cell maintenance. May be involved in working memory. Can hydrolyze UBB(+1), a mutated form of ubiquitin which is not effectively degraded by the proteasome and is associated with neurogenerative disorders. Ref.1 Ref.8 Ref.13 Ref.16 Ref.17

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). Ref.8 Ref.14 Ref.19

Enzyme regulation

Inhibited by monoubiquitin and diubiquitin. Ref.13

Subunit structure

Preferentially binds diubiquitin; the interaction does not hydrolyze diubiquitin but, in vitro, inhibits the hydrolyzing activity on other substrates.

Subcellular location

Cytoplasm.

Tissue specificity

Highly expressed in heart, skeletal muscle, and testis. Ref.8

Miscellaneous

Identified as a tumor-specific antigen in colon cancer.

Sequence similarities

Belongs to the peptidase C12 family.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

SMAD1Q157972EBI-954554,EBI-1567153

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 230230Ubiquitin carboxyl-terminal hydrolase isozyme L3
PRO_0000211061

Regions

Region8 – 136Interaction with ubiquitin
Region152 – 1598Interaction with ubiquitin
Region219 – 2246Interaction with ubiquitin

Sites

Active site951Nucleophile
Active site1691Proton donor Probable
Site1841Important for enzyme activity By similarity

Amino acid modifications

Modified residue1301Phosphoserine Ref.12

Experimental info

Mutagenesis331D → A: Decreased interaction with diubiquitin. No accumulation of free diubiquitin. Decreased levels of polyubiquitinated lysozyme. Ref.13 Ref.14
Mutagenesis951C → A: Increased interaction with diubiquitin. Ref.8 Ref.13 Ref.14
Mutagenesis951C → S: Abolishes enzymatic activity. Increased interaction with diubiquitin. Ref.8 Ref.13 Ref.14

Secondary structure

.................................... 230
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P15374 [UniParc].

Last modified April 1, 1990. Version 1.
Checksum: 8ACACE6E1D86FD55

FASTA23026,183
        10         20         30         40         50         60 
MEGQRWLPLE ANPEVTNQFL KQLGLHPNWQ FVDVYGMDPE LLSMVPRPVC AVLLLFPITE 

        70         80         90        100        110        120 
KYEVFRTEEE EKIKSQGQDV TSSVYFMKQT ISNACGTIGL IHAIANNKDK MHFESGSTLK 

       130        140        150        160        170        180 
KFLEESVSMS PEERARYLEN YDAIRVTHET SAHEGQTEAP SIDEKVDLHF IALVHVDGHL 

       190        200        210        220        230 
YELDGRKPFP INHGETSDET LLEDAIEVCK KFMERDPDEL RFNAIALSAA 

« Hide

References

« Hide 'large scale' references
[1]"The neuron-specific protein PGP 9.5 is a ubiquitin carboxyl-terminal hydrolase."
Wilkinson K.D., Lee K., Deshpande S., Duerksen-Hughes P., Boss J.M., Pohl J.
Science 246:670-673(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
[2]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]"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].
Tissue: Brain.
[5]"The DNA sequence and analysis of human chromosome 13."
Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T.
Nature 428:522-528(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]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 (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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].
Tissue: Lung.
[8]"Cleavage of the C-terminus of NEDD8 by UCH-L3."
Wada H., Kito K., Caskey L.S., Yeh E.T.H., Kamitani T.
Biochem. Biophys. Res. Commun. 251:688-692(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME ACTIVITY, TISSUE SPECIFICITY, MUTAGENESIS OF CYS-95.
[9]"Molecular profiling of the immune response in colon cancer using protein microarrays: occurrence of autoantibodies to ubiquitin C-terminal hydrolase L3."
Nam M.J., Madoz-Gurpide J., Wang H., Lescure P., Schmalbach C.E., Zhao R., Misek D.E., Kuick R., Brenner D.E., Hanash S.M.
Proteomics 3:2108-2115(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION AS TUMOR-ASSOCIATED ANTIGEN BY MASS SPECTROMETRY.
[10]"Substrate profiling of deubiquitin hydrolases with a positional scanning library and mass spectrometry."
Mason D.E., Ek J., Peters E.C., Harris J.L.
Biochemistry 43:6535-6544(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBSTRATE SPECIFICITY.
[11]"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage."
Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.
Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic kidney.
[12]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-130, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[13]"Ubiquitin dimers control the hydrolase activity of UCH-L3."
Setsuie R., Sakurai M., Sakaguchi Y., Wada K.
Neurochem. Int. 54:314-321(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH UBIQUITIN, FUNCTION, ENZYME REGULATION, MUTAGENESIS OF ASP-33 AND CYS-95.
[14]"Skeletal muscles of Uchl3 knockout mice show polyubiquitinated protein accumulation and stress responses."
Setsuie R., Suzuki M., Tsuchiya Y., Wada K.
Neurochem. Int. 56:911-918(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME ACTIVITY, MUTAGENESIS OF ASP-33 AND CYS-95.
[15]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]"Mutant ubiquitin (UBB(+1)) associated with neurodegenerative disorders is hydrolyzed by ubiquitin C-terminal hydrolase L3 (UCH-L3)."
Dennissen F.J., Kholod N., Hermes D.J., Kemmerling N., Steinbusch H.W., Dantuma N.P., van Leeuwen F.W.
FEBS Lett. 585:2568-2574(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[17]"Profiling ubiquitin linkage specificities of deubiquitinating enzymes with branched ubiquitin isopeptide probes."
Iphofer A., Kummer A., Nimtz M., Ritter A., Arnold T., Frank R., van den Heuvel J., Kessler B.M., Jansch L., Franke R.
ChemBioChem 13:1416-1420(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, LINKAGE SPECIFICITY.
[18]"Crystal structure of a deubiquitinating enzyme (human UCH-L3) at 1.8-A resolution."
Johnston S.C., Larsen C.N., Cook W.J., Wilkinson K.D., Hill C.P.
EMBO J. 16:3787-3796(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
[19]"Structure of the ubiquitin hydrolase UCH-L3 complexed with a suicide substrate."
Misaghi S., Galardy P.J., Meester W.J.N., Ovaa H., Ploegh H.L., Gaudet R.
J. Biol. Chem. 280:1512-1520(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) IN COMPLEX WITH UBIQUITIN VINYLMETHYLESTER, ENZYME ACTIVITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M30496 mRNA. Translation: AAA36791.1.
BT019359 mRNA. Translation: AAV38166.1.
CR456855 mRNA. Translation: CAG33136.1.
AK313665 mRNA. Translation: BAG36417.1.
AL137244 Genomic DNA. Translation: CAI12419.1.
CH471093 Genomic DNA. Translation: EAW80542.1.
BC018125 mRNA. Translation: AAH18125.1.
CCDSCCDS9453.1.
PIRA40085.
RefSeqNP_001257881.1. NM_001270952.1.
NP_005993.1. NM_006002.4.
UniGeneHs.162241.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1UCHX-ray1.80A1-230[»]
1XD3X-ray1.45A/C1-230[»]
ProteinModelPortalP15374.
SMRP15374. Positions 2-230.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113194. 56 interactions.
DIPDIP-29135N.
IntActP15374. 10 interactions.
MINTMINT-2863935.
STRING9606.ENSP00000366819.

Chemistry

BindingDBP15374.
ChEMBLCHEMBL6195.

Protein family/group databases

MEROPSC12.003.

PTM databases

PhosphoSiteP15374.

Polymorphism databases

DMDM136682.

2D gel databases

OGPP15374.
REPRODUCTION-2DPAGEIPI00011250.

Proteomic databases

MaxQBP15374.
PaxDbP15374.
PeptideAtlasP15374.
PRIDEP15374.

Protocols and materials databases

DNASU7347.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000377595; ENSP00000366819; ENSG00000118939.
GeneID7347.
KEGGhsa:7347.
UCSCuc001vjq.4. human.

Organism-specific databases

CTD7347.
GeneCardsGC13P076123.
HGNCHGNC:12515. UCHL3.
HPAHPA019678.
MIM603090. gene.
neXtProtNX_P15374.
PharmGKBPA37162.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG327708.
HOGENOMHOG000182400.
HOVERGENHBG075483.
KOK05609.
OMAYETFRTE.
OrthoDBEOG7S7SFK.
PhylomeDBP15374.
TreeFamTF316166.

Enzyme and pathway databases

SABIO-RKP15374.

Gene expression databases

BgeeP15374.
CleanExHS_UCHL3.
GenevestigatorP15374.

Family and domain databases

Gene3D3.40.532.10. 1 hit.
InterProIPR001578. Peptidase_C12_UCH.
[Graphical view]
PANTHERPTHR10589. PTHR10589. 1 hit.
PfamPF01088. Peptidase_C12. 1 hit.
[Graphical view]
PRINTSPR00707. UBCTHYDRLASE.
PROSITEPS00140. UCH_1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSUCHL3. human.
EvolutionaryTraceP15374.
GeneWikiUCHL3.
GenomeRNAi7347.
NextBio28762.
PROP15374.
SOURCESearch...

Entry information

Entry nameUCHL3_HUMAN
AccessionPrimary (citable) accession number: P15374
Secondary accession number(s): B2R970, Q5TBK8, Q6IBE9
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: July 9, 2014
This is version 145 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 chromosome 13

Human chromosome 13: entries, gene names and cross-references to MIM