Ubiquitin carboxy-terminal hydrolase L1

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Ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase)
Image:PBB Protein UCHL1 image.jpg
PDB rendering based on 2etl.
Available structures:
For the file format that describes the 3D structures of molecules found in the Protein Data Bank, see Protein Data Bank (file format).

The Protein Data Bank (PDB) is a repository for 3-D structural data of proteins and nucleic acids. These data, typically obtained by X-ray crystallography or NMR spectroscopy, are submitted by biologists and biochemists from around the world, are released into the public domain, and can be accessed for free.

History

Founded in 1971 by Drs. Edgar Meyer and Walter Hamilton Brookhaven National Laboratory, management of the Protein Data Bank was transferred in 1998 to members of the Research Collaboratory for Structural Bioinformatics (RCSB).

The Worldwide Protein Data Bank (wwPDB) consists of organizations that act as deposition, data processing and distribution centers for PDB data. The founding members are RCSB PDB (USA), MSD-EBI (Europe) and PDBj (Japan). The BMRB (USA) group joined the wwPDB in 2006. The mission of the wwPDB is to maintain a single Protein Data Bank Archive of macromolecular structural data that is freely and publicly available to the global community.

The PDB is a key resource in structural biology and is critical to more recent work in structural genomics.

Countless derived databases and projects have been developed to integrate and classify the PDB in terms of protein structure, protein function and protein evolution.

Growth

When the PDB was originally founded it contained just 7 protein structures. Since then it has undergone an approximate exponential growth in the number of structures, which does not show any sign of falling off.

The growth rate of the PDB has been the subject of fairly extensive analysis.

Contents

As of 26 September, 2006, the database contained 39,051 released atomic coordinate entries (or "structures"), 35,767 of that proteins, the rest being nucleic acids, nucleic acid-protein complexes, and a few other molecules. About 5,000 new structures are released each year. Data are stored in the mmCIF format specifically developed for the purpose.

Note that the database stores information about the exact location of all atoms in a large biomolecule (although, usually without the hydrogen atoms, as their positions are more of a statistical estimate); if one is only interested in sequence data, i.e. the list of amino acids making up a particular protein or the list of nucleotides making up a particular nucleic acid, the much larger databases from Swiss-Prot and the International Nucleotide Sequence Database Collaboration should be used.

Statistics

As of 11 September, 2007, the "PDB Holdings List" at RCSB reported the following statistics:

Proteins Nucleic Acids Protein/NA complexes Other Total
X-ray diffraction 36223 983 1684 24 38914
NMR 5665 781 134 7 6587
Electron microscopy 105 10 38 0 153
Other 80 4 4 2 90
Total 42073 1778 1860 33 45744

Note that theoretical models are no longer accepted in the PDB.

22461 structures in the PDB have a structure factor file. 3138 structures in the PDB have an NMR restraint file.

The current breakdown of holdings is updated weekly.

File format

Through the years the PDB file format has undergone many, many changes and revisions. Its original format was dictated by the width of computer punch cards.

This legacy format has caused many problems with the format, and consequently there are 'clean-up' projects;

The MMDB uses ASN.1 (and an XML conversion of this format). The wwPDB members RCSB PDB, MSD-EBI, and PDBj are working together to make the data uniform across the archive. Some believe this to be desirable; others argue that, without a universal repository of information (i.e., a common dictionary), it is not possible to draw comparisons.

Each structure published in PDB receives a four-character alphanumeric identifier, its PDB ID. This should not be used as an identifier for biomolecules, since often several structures for the same molecule (in different environments or conformations) are contained in PDB with different PDB IDs.

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Various funding agencies and scientific journals now require scientists to submit their structure data to PDB.

Viewing the data

The structural data can be used to visualize the biomolecules with appropriate software, such as VMD, RasMol, PyMOL, Jmol, MDL Chime, QuteMol, web browser VRML plugin or any web-based software designed to visualize and analyse the protein structures such as STING. A recent desktop software addition is Sirius. The RCSB PDB website also contains resources for education, structural genomics, and related software.

References

Printed

  • H.M. Berman, K. Henrick, H. Nakamura (2003): Announcing the worldwide Protein Data Bank. Nature Structural Biology 10 (12), p. 980 PMID 14634627.
  • H.M. Berman, J. Westbrook, Z. Feng, G. Gilliland, T.N. Bhat, H. Weissig, I.N. Shindyalov, P.E. Bourne: The Protein Data Bank. Nucleic Acids Research, 28 pp. 235-242 (2000). PMID 10592235
  • Bernstein FC, Koetzle TF, Williams GJ, Meyer Jr EF, Brice MD, Rodgers JR, Kennard O, Shimanouchi T, Tasumi M. The Protein Data Bank: a computer-based archival file for macromolecular structures. J Mol Biol 1977;112:535-542. PMID 875032.
  • E.F. Meyer “The First Years of the Protein Data Bank“, Protein Science 6:1591-1597 (1997)
  • Sussman, JL, Lin, D, Jiang, J, Manning, NO, Prilusky, J, Ritter, O & Abola, EE. Protein data bank (PDB): a database of 3D structural information of biological macromolecules. Acta Cryst 1998; D54:1078-1084. PMID 10089483.

Online

Other external links

Links to enzyme database data

  • [1] The best mapping is provided by Kim Henrick's group at EBI as part of the MSD SIFTS initiative.
  • [2] PDB provide a mapping on their beta site, but it is at the whole PDB level not chain level.
  • [3] Search at BRENDA enzyme database portal.
  • [4] PDBSProtEC:

Molecular graphic visualisation tools

Identifiers
Symbol(s) UCHL1; PARK5; PGP9.5; Uch-L1
External IDs OMIM: 191342 MGI: 103149 Homologene: 37894
EC number 3.1.2.15
RNA expression pattern

Image:PBB GE UCHL1 201387 s at tn.png

More reference expression data

Orthologs
Human Mouse
Entrez 7345 22223
Ensembl ENSG00000154277 ENSMUSG00000029223
Uniprot P09936 Q3TCH2
Refseq NM_004181 (mRNA)
NP_004172 (protein) 		NM_011670 (mRNA)
NP_035800 (protein)
Location Chr 4: 40.95 - 40.97 Mb Chr 5: 66.96 - 66.97 Mb
Pubmed search [5] [6]

Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) (EC 3.1.2.15) is a deubiqutinating enzyme.

UCHL1 is a member of a gene family whose products hydrolyze small C-terminal adducts of ubiquitin to generate the ubiquitin monomer. Expression of UCHL1 is highly specific to neurons and to cells of the diffuse neuroendocrine system and their tumors. It is present in all neurons (Doran et al., 1983).[supplied by OMIM][1]

Pathology

A point mutation (I93M) in the gene encoding this protein is implicated as the cause of Parkinson's disease in one kindred.

Furthermore, a polymorphism (S18Y) in this gene has been found to be associated with a reduced risk for Parkinson's disease.

The gene is also associated with the Alzheimer's disease, and required for normal synaptic and cognitive function. (Gong. et al 2006)[1]

See also

References

Further reading

  • Healy DG, Abou-Sleiman PM, Wood NW (2005). "Genetic causes of Parkinson's disease: UCHL-1.". Cell Tissue Res. 318 (1): 189-94. doi:10.1007/s00441-004-0917-3. PMID 15221445.
  • Rasmussen HH, van Damme J, Puype M, et al. (1993). "Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes.". Electrophoresis 13 (12): 960-9. PMID 1286667.
  • Edwards YH, Fox MF, Povey S, et al. (1992). "The gene for human neurone specific ubiquitin C-terminal hydrolase (UCHL1, PGP9.5) maps to chromosome 4p14.". Ann. Hum. Genet. 55 (Pt 4): 273-8. PMID 1840236.
  • Honoré B, Rasmussen HH, Vandekerckhove J, Celis JE (1991). "Neuronal protein gene product 9.5 (IEF SSP 6104) is expressed in cultured human MRC-5 fibroblasts of normal origin and is strongly down-regulated in their SV40 transformed counterparts.". FEBS Lett. 280 (2): 235-40. doi:10.1016/0014-5793(91)80300-R. PMID 1849484.
  • Day IN, Hinks LJ, Thompson RJ (1990). "The structure of the human gene encoding protein gene product 9.5 (PGP9.5), a neuron-specific ubiquitin C-terminal hydrolase.". Biochem. J. 268 (2): 521-4. PMID 2163617.
  • Day IN, Thompson RJ (1987). "Molecular cloning of cDNA coding for human PGP 9.5 protein. A novel cytoplasmic marker for neurones and neuroendocrine cells.". FEBS Lett. 210 (2): 157-60. doi:10.1016/0014-5793(87)81327-3. PMID 2947814.
  • Doran JF, Jackson P, Kynoch PA, Thompson RJ (1983). "Isolation of PGP 9.5, a new human neurone-specific protein detected by high-resolution two-dimensional electrophoresis.". J. Neurochem. 40 (6): 1542-7. doi:10.1111/j.1471-4159.1983.tb08124.x. PMID 6343558.
  • Onno M, Nakamura T, Mariage-Samson R, et al. (1993). "Human TRE17 oncogene is generated from a family of homologous polymorphic sequences by single-base changes.". DNA Cell Biol. 12 (2): 107-18. PMID 8471161.
  • Larsen CN, Price JS, Wilkinson KD (1996). "Substrate binding and catalysis by ubiquitin C-terminal hydrolases: identification of two active site residues.". Biochemistry 35 (21): 6735-44. doi:10.1021/bi960099f. PMID 8639624.
  • Best CL, Pudney J, Welch WR, et al. (1996). "Localization and characterization of white blood cell populations within the human ovary throughout the menstrual cycle and menopause.". Hum. Reprod. 11 (4): 790-7. PMID 8671330.
  • D'Andrea V, Malinovsky L, Berni A, et al. (1998). "The immunolocalization of PGP 9.5 in normal human kidney and renal cell carcinoma.". Il Giornale di chirurgia 18 (10): 521-4. PMID 9435142.
  • Larsen CN, Krantz BA, Wilkinson KD (1998). "Substrate specificity of deubiquitinating enzymes: ubiquitin C-terminal hydrolases.". Biochemistry 37 (10): 3358-68. doi:10.1021/bi972274d. PMID 9521656.
  • Leroy E, Boyer R, Auburger G, et al. (1998). "The ubiquitin pathway in Parkinson's disease.". Nature 395 (6701): 451-2. doi:10.1038/26652. PMID 9774100.
  • Wada H, Kito K, Caskey LS, et al. (1998). "Cleavage of the C-terminus of NEDD8 by UCH-L3.". Biochem. Biophys. Res. Commun. 251 (3): 688-92. doi:10.1006/bbrc.1998.9532. PMID 9790970.
  • Leroy E, Boyer R, Polymeropoulos MH (1999). "Intron-exon structure of ubiquitin c-terminal hydrolase-L1.". DNA Res. 5 (6): 397-400. PMID 10048490.
  • Lincoln S, Vaughan J, Wood N, et al. (1999). "Low frequency of pathogenic mutations in the ubiquitin carboxy-terminal hydrolase gene in familial Parkinson's disease.". Neuroreport 10 (2): 427-9. doi:10.1097/00001756-199902050-00040. PMID 10203348.
  • Harhangi BS, Farrer MJ, Lincoln S, et al. (1999). "The Ile93Met mutation in the ubiquitin carboxy-terminal-hydrolase-L1 gene is not observed in European cases with familial Parkinson's disease.". Neurosci. Lett. 270 (1): 1-4. doi:10.1016/S0304-3940(99)00465-6. PMID 10454131.
  • Saigoh K, Wang YL, Suh JG, et al. (1999). "Intragenic deletion in the gene encoding ubiquitin carboxy-terminal hydrolase in gad mice.". Nat. Genet. 23 (1): 47-51. doi:10.1038/12647. PMID 10471497.
  • Mellick GD, Silburn PA (2000). "The ubiquitin carboxy-terminal hydrolase-L1 gene S18Y polymorphism does not confer protection against idiopathic Parkinson's disease.". Neurosci. Lett. 293 (2): 127-30. doi:10.1016/S0304-3940(00)01510-X. PMID 11027850.
  • Sharma N, McLean PJ, Kawamata H, et al. (2002). "Alpha-synuclein has an altered conformation and shows a tight intermolecular interaction with ubiquitin in Lewy bodies.". Acta Neuropathol. 102 (4): 329-34. PMID 11603807.

External links

 This hydrolase article is a stub. You can help WikiDoc by expanding it.
v • d • e
Hydrolase: esterases (EC 3.1)
3.1.1: Carboxylic ester hydrolasesCholinesterase - Pectinesterase - 6-phosphogluconolactonase - PAF acetylhydrolase

Lipase (Gastric/Lingual, Pancreatic, Lysosomal, Hormone-sensitive, Endothelial, Hepatic, Lipoprotein, Monoacylglycerol, Diacylglycerol)

Phospholipase (A1, A2, B)
3.1.2: ThioesterasePalmitoyl thioesterase - Ubiquitin carboxy-terminal hydrolase L1
3.1.3: PhosphataseAlkaline phosphatase - Acid phosphatase (Prostatic)/Tartrate resistant acid phosphatase/Purple acid phosphatases - Nucleotidase - Glucose 6-phosphatase - Fructose 1,6-bisphosphatase - Calcineurin - Phosphoprotein phosphatase (PP2A) - OCRL - Pyruvate dehydrogenase phosphatase - Fructose 2,6-bisphosphatase - Protein tyrosine phosphatase - PTEN
3.1.4: PhosphodiesteraseAutotaxin - Phospholipase (C, D) - Sphingomyelin phosphodiesterase - PDE1 - PDE2 - PDE3 - PDE5
3.1.6: SulfataseArylsulfatase B - Steroid sulfatase - Galactosamine-6 sulfatase - Arylsulfatase A - Iduronate-2-sulfatase - N-acetylglucosamine-6-sulfatase
otherNuclease

Acknowledgement and Attribution Regarding Sources of Content

Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .

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