<p>Provides any useful information about the protein, mostly biological knowledge.</p><p><a href='../manual/function_section' target='_top'>More...</a></p>Functionⁱ

<p>Describes the catalytic activity of an enzyme, i.e. the chemical reaction it catalyzes. This information usually correlates with the presence of an EC (Enzyme Commission) number in the ‘Names and taxonomy’ section.</p><p><a href='../manual/catalytic_activity' target='_top'>More...</a></p>Catalytic activityⁱ

Sites

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
<p>Is used for enzymes and indicates the residues directly involved in catalysis.</p><p><a href='../manual/act_site' target='_top'>More...</a></p>Active sitei	198 – 198	1	Charge relay system
<p>Is used for enzymes and indicates the residues directly involved in catalysis.</p><p><a href='../manual/act_site' target='_top'>More...</a></p>Active sitei	228 – 228	1	Charge relay system
<p>Is used for enzymes and indicates the residues directly involved in catalysis.</p><p><a href='../manual/act_site' target='_top'>More...</a></p>Active sitei	306 – 306	1	Charge relay system

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:</p><p><a href='../manual/gene_ontology' target='_top'>More...</a></p>GO - Molecular functionⁱ

1. peptidase activity Source: UniProtKB

   <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ

   • 11604410
   • 17266347
   • 20125124

2. serine-type endopeptidase activity Source: UniProtKB

   <p>Inferred from Mutant Phenotype</p> <p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypeⁱ

   • 10971580

3. serine-type peptidase activity Source: UniProtKB

   <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ

   • 11583623

4. unfolded protein binding Source: UniProtKB

   <p>Non-traceable Author Statement</p> <p>Used for statements in the abstract, introduction or discussion of a paper that cannot be traced back to another publication.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#nas">GO evidence code guide</a></p> Non-traceable author statementⁱ

   • 10644717

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:</p><p><a href='../manual/gene_ontology' target='_top'>More...</a></p>GO - Biological processⁱ

1. adult walking behavior Source: Ensembl
2. cellular protein catabolic process Source: ParkinsonsUK-UCL

   <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ

   • 17297443

3. cellular response to growth factor stimulus Source: UniProtKB

   <p>Inferred from Mutant Phenotype</p> <p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypeⁱ

   • 20125124

4. cellular response to heat Source: UniProtKB

   <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ

   • 10971580

5. cellular response to interferon-beta Source: ParkinsonsUK-UCL

   <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ

   • 17297443

6. cellular response to oxidative stress Source: ParkinsonsUK-UCL

   <p>Non-traceable Author Statement</p> <p>Used for statements in the abstract, introduction or discussion of a paper that cannot be traced back to another publication.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#nas">GO evidence code guide</a></p> Non-traceable author statementⁱ

   • 24522549

7. cellular response to retinoic acid Source: ParkinsonsUK-UCL

   <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ

   • 17297443

8. ceramide metabolic process Source: Ensembl
9. execution phase of apoptosis Source: UniProtKB

   <p>Traceable Author Statement</p> <p>Used for information from review articles where the original experiments are traceable through that article and also for information from text books or dictionaries.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#tas">GO evidence code guide</a></p> Traceable author statementⁱ

   • 18309324

10. forebrain development Source: Ensembl
11. intrinsic apoptotic signaling pathway in response to DNA damage Source: ParkinsonsUK-UCL

    <p>Inferred from Mutant Phenotype</p> <p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypeⁱ

    • 11602612

12. mitochondrion organization Source: Ensembl
13. negative regulation of cell cycle Source: UniProtKB

    <p>Traceable Author Statement</p> <p>Used for information from review articles where the original experiments are traceable through that article and also for information from text books or dictionaries.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#tas">GO evidence code guide</a></p> Traceable author statementⁱ

    • 18309324

14. negative regulation of neuron death Source: ParkinsonsUK-UCL

    <p>Traceable Author Statement</p> <p>Used for information from review articles where the original experiments are traceable through that article and also for information from text books or dictionaries.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#tas">GO evidence code guide</a></p> Traceable author statementⁱ

    • 18221368

15. negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway Source: ParkinsonsUK-UCL

    <p>Non-traceable Author Statement</p> <p>Used for statements in the abstract, introduction or discussion of a paper that cannot be traced back to another publication.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#nas">GO evidence code guide</a></p> Non-traceable author statementⁱ

    • 18221368

16. neuron development Source: Ensembl
17. pentacyclic triterpenoid metabolic process Source: Ensembl
18. positive regulation of apoptotic process Source: UniProtKB

    <p>Inferred from Mutant Phenotype</p> <p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypeⁱ

    • 20125124

19. positive regulation of cell death Source: UniProtKB

    <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ

    • 11583623

20. positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB

    <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ

    • 11583623
    • 11604410

21. positive regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway Source: ParkinsonsUK-UCL

    <p>Inferred from Mutant Phenotype</p> <p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypeⁱ

    • 11602612

22. positive regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: UniProtKB

    <p>Inferred from Mutant Phenotype</p> <p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypeⁱ

    • 20125124

23. protein autoprocessing Source: ParkinsonsUK-UCL

    <p>Traceable Author Statement</p> <p>Used for information from review articles where the original experiments are traceable through that article and also for information from text books or dictionaries.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#tas">GO evidence code guide</a></p> Traceable author statementⁱ

    • 11602612

24. proteolysis Source: UniProtKB

    <p>Inferred from Mutant Phenotype</p> <p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypeⁱ

    • 10971580

25. regulation of mitochondrion degradation Source: ParkinsonsUK-UCL

    <p>Traceable Author Statement</p> <p>Used for information from review articles where the original experiments are traceable through that article and also for information from text books or dictionaries.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#tas">GO evidence code guide</a></p> Traceable author statementⁱ

    • 24522549

26. regulation of multicellular organism growth Source: Ensembl
27. response to herbicide Source: Ensembl

<p>UniProtKB Keywords constitute a <a target="_top" href="/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='../help/keywords' target='_top'>More...</a></p>Keywords - Molecular functionⁱ

<p>UniProtKB Keywords constitute a <a target="_top" href="/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='../help/keywords' target='_top'>More...</a></p>Keywords - Biological processⁱ

Enzyme and pathway databases

Protein family/group databases

<p>Provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.</p><p><a href='../manual/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyⁱ

Organism-specific databases

<p>Provides information on the location and the topology of the mature protein in the cell.</p><p><a href='../manual/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationⁱ

Topology

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
<p>Describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.</p><p><a href='../manual/transmem' target='_top'>More...</a></p>Transmembranei	105 – 125	21	HelicalSequence Analysis			Add BLAST

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:</p><p><a href='../manual/gene_ontology' target='_top'>More...</a></p>GO - Cellular componentⁱ

1. CD40 receptor complex Source: BHF-UCL
2. chromatin Source: ParkinsonsUK-UCL

   <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ

   • 24798695

3. cytoplasmic side of plasma membrane Source: BHF-UCL
4. cytoskeleton Source: ParkinsonsUK-UCL

   <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ

   • 24798695

5. cytosol Source: ParkinsonsUK-UCL

   <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ

   • 11602612

6. endoplasmic reticulum Source: UniProtKB

   <p>Non-traceable Author Statement</p> <p>Used for statements in the abstract, introduction or discussion of a paper that cannot be traced back to another publication.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#nas">GO evidence code guide</a></p> Non-traceable author statementⁱ

   • 10995577

7. endoplasmic reticulum membrane Source: UniProtKB

   <p>Traceable Author Statement</p> <p>Used for information from review articles where the original experiments are traceable through that article and also for information from text books or dictionaries.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#tas">GO evidence code guide</a></p> Traceable author statementⁱ

   • 10644717

8. membrane Source: ParkinsonsUK-UCL

   <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ

   • 24798695

9. mitochondrial intermembrane space Source: MGI

   <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ

   • 15044455

10. mitochondrial membrane Source: UniProtKB-SubCell
11. mitochondrion Source: UniProtKB

    <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ

    • 11583623

12. nucleus Source: UniProtKB

    <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ

    • 10971580

<p>UniProtKB Keywords constitute a <a target="_top" href="/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='../help/keywords' target='_top'>More...</a></p>Keywords - Cellular componentⁱ

<p>Provides information on the disease(s) and phenotype(s) associated with the deficiency of a protein.</p><p><a href='../manual/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechⁱ

<p>Provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim"><span class="caps">OMIM</span></a> database are represented with a <a href="/diseases">controlled vocabulary</a> in the following way:</p><p><a href='../manual/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseaseⁱ

Parkinson disease 13 (PARK13)

[MIM:610297]: A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain.1 Publication

<p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment inⁱ

• Ref.12

  "Loss of function mutations in the gene encoding Omi/HtrA2 in Parkinson's disease."
  Strauss K.M., Martins L.M., Plun-Favreau H., Marx F.P., Kautzmann S., Berg D., Gasser T., Wszolek Z., Mueller T., Bornemann A., Wolburg H., Downward J., Riess O., Schulz J.B., Krueger R.
  Hum. Mol. Genet. 14:2099-2111(2005) [PubMed] [Europe PMC] [Abstract]

  Cited for: VARIANT PARK13 SER-399, VARIANT SER-141, CHARACTERIZATION OF VARIANTS SER-141 AND SER-399.

Note: The disease is caused by mutations affecting the gene represented in this entry.

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	399 – 399	1	G → S in PARK13; reduced protease activity. 1 Publication <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.12 "Loss of function mutations in the gene encoding Omi/HtrA2 in Parkinson's disease." Strauss K.M., Martins L.M., Plun-Favreau H., Marx F.P., Kautzmann S., Berg D., Gasser T., Wszolek Z., Mueller T., Bornemann A., Wolburg H., Downward J., Riess O., Schulz J.B., Krueger R. Hum. Mol. Genet. 14:2099-2111(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PARK13 SER-399, VARIANT SER-141, CHARACTERIZATION OF VARIANTS SER-141 AND SER-399. Corresponds to variant rs72470545 [ dbSNP | Ensembl ].		VAR_027350

Mutagenesis

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
<p>Describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.</p><p><a href='../manual/mutagen' target='_top'>More...</a></p>Mutagenesisi	134 – 134	1	A → M: Loss of interaction with XIAP. Loss of inhibition of XIAP activity. 1 Publication <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.6 "A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death." Suzuki Y., Imai Y., Nakayama H., Takahashi K., Takio K., Takahashi R. Mol. Cell 8:613-621(2001) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 134-458, INTERACTION WITH XIAP, MUTAGENESIS OF ALA-134.
<p>Describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.</p><p><a href='../manual/mutagen' target='_top'>More...</a></p>Mutagenesisi	306 – 306	1	S → A: Loss of protease activity. 1 Publication <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.1 "Characterization of a novel human serine protease that has extensive homology to bacterial heat shock endoprotease HtrA and is regulated by kidney ischemia." Faccio L., Fusco C., Chen A., Martinotti S., Bonventre J.V., Zervos A.S. J. Biol. Chem. 275:2581-2588(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), MUTAGENESIS OF SER-306.

<p>UniProtKB Keywords constitute a <a target="_top" href="/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='../help/keywords' target='_top'>More...</a></p>Keywords - Diseaseⁱ

Organism-specific databases

<p>Describes post-translational modifications (PTMs) and/or processing events.</p><p><a href='../manual/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
<p>Describes the extent of a transit peptide.</p><p><a href='../manual/transit' target='_top'>More...</a></p>Transit peptidei	1 – 31	31	Mitochondrion			Add BLAST
<p>Describes a propeptide, which is a part of a protein that is cleaved during maturation or activation. Once cleaved, a propeptide generally has no independent biological function.</p><p><a href='../manual/propep' target='_top'>More...</a></p>Propeptidei	32 – 133	102	1 Publication <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.6 "A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death." Suzuki Y., Imai Y., Nakayama H., Takahashi K., Takio K., Takahashi R. Mol. Cell 8:613-621(2001) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 134-458, INTERACTION WITH XIAP, MUTAGENESIS OF ALA-134.		PRO_0000026945	Add BLAST
<p>Describes the extent of a polypeptide chain in the mature protein following processing.</p><p><a href='../manual/chain' target='_top'>More...</a></p>Chaini	134 – 458	325	Serine protease HTRA2, mitochondrial		PRO_0000026946	Add BLAST

<p>Describes post-translational modifications (PTMs). This subsection complements the information provided at the sequence level or describes modifications for which position-specific data is not yet available.</p><p><a href='../manual/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationⁱ

<p>UniProtKB Keywords constitute a <a target="_top" href="/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='../help/keywords' target='_top'>More...</a></p>Keywords - PTMⁱ

Proteomic databases

2D gel databases

PTM databases

Miscellaneous databases

<p>Provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.</p><p><a href='../manual/expression_section' target='_top'>More...</a></p>Expressionⁱ

<p>Provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at the protein level’.</p><p><a href='../manual/tissue_specificity' target='_top'>More...</a></p>Tissue specificityⁱ

Gene expression databases

Organism-specific databases

<p>Provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.</p><p><a href='../manual/interaction_section' target='_top'>More...</a></p>Interactionⁱ

<p>Provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the ‘Function’ section).</p><p><a href='../manual/subunit_structure' target='_top'>More...</a></p>Subunit structureⁱ

<p>Provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.</p><p><a href='../manual/binary_interactions' target='_top'>More...</a></p>Binary interactionsⁱ

Protein-protein interaction databases

<p>Provides information on the tertiary structure of a protein.</p><p><a href='../manual/structure_section' target='_top'>More...</a></p>Structureⁱ

Secondary structure

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
<p>Is used to indicate the positions of experimentally determined helical regions within the protein sequence.</p><p><a href='../manual/helix' target='_top'>More...</a></p>Helixi	143 – 146	4	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:1LCY
<p>Is used to indicate the positions of experimentally determined helical regions within the protein sequence.</p><p><a href='../manual/helix' target='_top'>More...</a></p>Helixi	149 – 157	9	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:1LCY
<p>Is used to indicate the positions of experimentally determined helical regions within the protein sequence.</p><p><a href='../manual/helix' target='_top'>More...</a></p>Helixi	158 – 160	3	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:1LCY
<p>Is used to indicate the positions of experimentally determined beta strands within the protein sequence.</p><p><a href='../manual/strand' target='_top'>More...</a></p>Beta strandi	161 – 170	10	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:1LCY
<p>Is used to indicate the positions of experimentally determined hydrogen-bonded turns within the protein sequence. These elements correspond to the <span class="caps">DSSP</span> secondary structure code ‘T’.</p><p><a href='../manual/turn' target='_top'>More...</a></p>Turni	171 – 174	4	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:1LCY
<p>Is used to indicate the positions of experimentally determined beta strands within the protein sequence.</p><p><a href='../manual/strand' target='_top'>More...</a></p>Beta strandi	175 – 188	14	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:1LCY
<p>Is used to indicate the positions of experimentally determined hydrogen-bonded turns within the protein sequence. These elements correspond to the <span class="caps">DSSP</span> secondary structure code ‘T’.</p><p><a href='../manual/turn' target='_top'>More...</a></p>Turni	189 – 191	3	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:1LCY
<p>Is used to indicate the positions of experimentally determined beta strands within the protein sequence.</p><p><a href='../manual/strand' target='_top'>More...</a></p>Beta strandi	192 – 195	4	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:1LCY
<p>Is used to indicate the positions of experimentally determined helical regions within the protein sequence.</p><p><a href='../manual/helix' target='_top'>More...</a></p>Helixi	197 – 200	4	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:1LCY
<p>Is used to indicate the positions of experimentally determined beta strands within the protein sequence.</p><p><a href='../manual/strand' target='_top'>More...</a></p>Beta strandi	204 – 209	6	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:1LCY
<p>Is used to indicate the positions of experimentally determined beta strands within the protein sequence.</p><p><a href='../manual/strand' target='_top'>More...</a></p>Beta strandi	215 – 224	10	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:1LCY
<p>Is used to indicate the positions of experimentally determined hydrogen-bonded turns within the protein sequence. These elements correspond to the <span class="caps">DSSP</span> secondary structure code ‘T’.</p><p><a href='../manual/turn' target='_top'>More...</a></p>Turni	225 – 228	4	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:1LCY
<p>Is used to indicate the positions of experimentally determined beta strands within the protein sequence.</p><p><a href='../manual/strand' target='_top'>More...</a></p>Beta strandi	229 – 233	5	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:1LCY
<p>Is used to indicate the positions of experimentally determined helical regions within the protein sequence.</p><p><a href='../manual/helix' target='_top'>More...</a></p>Helixi	248 – 250	3	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:1LCY
<p>Is used to indicate the positions of experimentally determined beta strands within the protein sequence.</p><p><a href='../manual/strand' target='_top'>More...</a></p>Beta strandi	256 – 259	4	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:1LCY
<p>Is used to indicate the positions of experimentally determined beta strands within the protein sequence.</p><p><a href='../manual/strand' target='_top'>More...</a></p>Beta strandi	265 – 268	4	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:1LCY
<p>Is used to indicate the positions of experimentally determined beta strands within the protein sequence.</p><p><a href='../manual/strand' target='_top'>More...</a></p>Beta strandi	271 – 275	5	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:1LCY
<p>Is used to indicate the positions of experimentally determined beta strands within the protein sequence.</p><p><a href='../manual/strand' target='_top'>More...</a></p>Beta strandi	295 – 299	5	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:1LCY
<p>Is used to indicate the positions of experimentally determined hydrogen-bonded turns within the protein sequence. These elements correspond to the <span class="caps">DSSP</span> secondary structure code ‘T’.</p><p><a href='../manual/turn' target='_top'>More...</a></p>Turni	303 – 307	5	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:1LCY
<p>Is used to indicate the positions of experimentally determined beta strands within the protein sequence.</p><p><a href='../manual/strand' target='_top'>More...</a></p>Beta strandi	308 – 312	5	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:1LCY
<p>Is used to indicate the positions of experimentally determined beta strands within the protein sequence.</p><p><a href='../manual/strand' target='_top'>More...</a></p>Beta strandi	317 – 326	10	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:1LCY
<p>Is used to indicate the positions of experimentally determined beta strands within the protein sequence.</p><p><a href='../manual/strand' target='_top'>More...</a></p>Beta strandi	329 – 334	6	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:1LCY
<p>Is used to indicate the positions of experimentally determined helical regions within the protein sequence.</p><p><a href='../manual/helix' target='_top'>More...</a></p>Helixi	335 – 341	7	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:1LCY
<p>Is used to indicate the positions of experimentally determined beta strands within the protein sequence.</p><p><a href='../manual/strand' target='_top'>More...</a></p>Beta strandi	364 – 368	5	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:1LCY
<p>Is used to indicate the positions of experimentally determined helical regions within the protein sequence.</p><p><a href='../manual/helix' target='_top'>More...</a></p>Helixi	371 – 377	7	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:1LCY
<p>Is used to indicate the positions of experimentally determined beta strands within the protein sequence.</p><p><a href='../manual/strand' target='_top'>More...</a></p>Beta strandi	391 – 396	6	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:1LCY
<p>Is used to indicate the positions of experimentally determined helical regions within the protein sequence.</p><p><a href='../manual/helix' target='_top'>More...</a></p>Helixi	401 – 405	5	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:1LCY
<p>Is used to indicate the positions of experimentally determined beta strands within the protein sequence.</p><p><a href='../manual/strand' target='_top'>More...</a></p>Beta strandi	412 – 416	5	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:1LCY
<p>Is used to indicate the positions of experimentally determined helical regions within the protein sequence.</p><p><a href='../manual/helix' target='_top'>More...</a></p>Helixi	424 – 431	8	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:1LCY
<p>Is used to indicate the positions of experimentally determined beta strands within the protein sequence.</p><p><a href='../manual/strand' target='_top'>More...</a></p>Beta strandi	435 – 443	9	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:1LCY
<p>Is used to indicate the positions of experimentally determined beta strands within the protein sequence.</p><p><a href='../manual/strand' target='_top'>More...</a></p>Beta strandi	446 – 452	7	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:1LCY

3D structure databases

Miscellaneous databases

<p>Provides information on sequence similarities with other proteins and the domain(s) present in a protein.</p><p><a href='../manual/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
<p>Describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.</p><p><a href='../manual/domain' target='_top'>More...</a></p>Domaini	364 – 445	82	PDZPROSITE-ProRule annotation <p>Manual validated information which has been generated by the UniProtKB automatic annotation system.</p> <p><a href="/manual/evidences#ECO:0000255">More…</a></p> Manual assertion according to rulesi PROSITE-ProRule:PRU00143			Add BLAST

Region

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
<p>Describes a region of interest that cannot be described in other subsections.</p><p><a href='../manual/region' target='_top'>More...</a></p>Regioni	166 – 342	177	Serine protease			Add BLAST

Motif

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
<p>Describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.</p><p><a href='../manual/motif' target='_top'>More...</a></p>Motifi	134 – 137	4	IAP-binding motif

<p>Provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.</p><p><a href='../manual/domain_cc' target='_top'>More...</a></p>Domainⁱ

<p>Provides information about the sequence similarity with other proteins.</p><p><a href='../manual/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesⁱ

<p>UniProtKB Keywords constitute a <a target="_top" href="/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='../help/keywords' target='_top'>More...</a></p>Keywords - Domainⁱ

Phylogenomic databases

Family and domain databases

<p>Displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including length and molecular weight.</p><p><a href='../manual/sequences_section' target='_top'>More...</a></p>Sequences (4)ⁱ

<p>Indicates if the canonical sequence displayed by default in the entry is complete or not.</p><p><a href='../manual/sequence_status' target='_top'>More...</a></p>Sequence statusⁱ: Complete.

<p>Indicates if the canonical sequence displayed by default in the entry is in its mature form or if it represents the precursor.</p><p><a href='../manual/sequence_processing' target='_top'>More...</a></p>Sequence processingⁱ: The displayed sequence is further processed into a mature form.

This entry describes 4<p>Lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.</p><p><a href='../manual/alternative_products' target='_top'>More...</a></p> isoformsⁱ produced by alternative splicing. Align

        10         20         30         40         50
MAAPRAGRGA GWSLRAWRAL GGIRWGRRPR LTPDLRALLT SGTSDPRARV 
        60         70         80         90        100
TYGTPSLWAR LSVGVTEPRA CLTSGTPGPR AQLTAVTPDT RTREASENSG 
       110        120        130        140        150
TRSRAWLAVA LGAGGAVLLL LWGGGRGPPA VLAAVPSPPP ASPRSQYNFI 
       160        170        180        190        200
ADVVEKTAPA VVYIEILDRH PFLGREVPIS NGSGFVVAAD GLIVTNAHVV 
       210        220        230        240        250
ADRRRVRVRL LSGDTYEAVV TAVDPVADIA TLRIQTKEPL PTLPLGRSAD 
       260        270        280        290        300
VRQGEFVVAM GSPFALQNTI TSGIVSSAQR PARDLGLPQT NVEYIQTDAA 
       310        320        330        340        350
IDFGNSGGPL VNLDGEVIGV NTMKVTAGIS FAIPSDRLRE FLHRGEKKNS 
       360        370        380        390        400
SSGISGSQRR YIGVMMLTLS PSILAELQLR EPSFPDVQHG VLIHKVILGS 
       410        420        430        440        450
PAHRAGLRPG DVILAIGEQM VQNAEDVYEA VRTQSQLAVQ IRRGRETLTL 

YVTPEVTE                                             

        10         20         30         40         50
MAAPRAGRGA GWSLRAWRAL GGIRWGRRPR LTPDLRALLT SGTSDPRARV 
        60         70         80         90        100
TYGTPSLWAR LSVGVTEPRA CLTSGTPGPR AQLTAVTPDT RTREASENSG 
       110        120        130        140        150
TRSRAWLAVA LGAGGAVLLL LWGGGRGPPA VLAAVPSPPP ASPRSQYNFI 
       160        170        180        190        200
ADVVEKTAPA VVYIEILDRH PFLGREVPIS NGSGFVVAAD GLIVTNAHVV 
       210        220        230        240        250
ADRRRVRVRL LSGDTYEAVV TAVDPVADIA TLRIQTKFGN SGGPLVNLDG 
       260        270        280        290        300
EVIGVNTMKV TAGISFAIPS DRLREFLHRG EKKNSSSGIS GSQRRYIGVM 
       310        320        330        340        350
MLTLSPRAGL RPGDVILAIG EQMVQNAEDV YEAVRTQSQL AVQIRRGRET 
       360 
LTLYVTPEVT E                                  

        10         20         30         40         50
MAAPRAGRGA GWSLRAWRAL GGIRWGRRPR LTPDLRALLT SGTSDPRARV 
        60         70         80         90        100
TYGTPSLWAR LSVGVTEPRA CLTSGTPGPR AQLTAVTPDT RTREASENSG 
       110        120        130        140        150
TRSRAWLAVA LGAGGAVLLL LWGGGRGPPA VLAAVPSPPP ASPRSQYNFI 
       160        170        180        190        200
ADVVEKTAPA VVYIEILDRH PFLGREVPIS NGSGFVVAAD GLIVTNAHVV 
       210        220        230        240        250
ADRRRVRVRL LSGDTYEAVV TAVDPVADIA TLRIQTKEPL PTLPLGRSAD 
       260        270        280        290        300
VRQGEFVVAM GSPFALQNTI TSGIVSSAQR PARDLGLPQT NVEYIQTDAA 
       310        320        330        340        350
IDFGNSGGPL VNLARELGAV SLQDGEVIGV NTMKVTAGIS FAIPSDRLRE 
       360        370        380        390        400
FLHRGEKKNS SSGISGSQRR YIGVMMLTLS PRAGLRPGDV ILAIGEQMVQ 
       410        420        430 
NAEDVYEAVR TQSQLAVQIR RGRETLTLYV TPEVTE            

        10         20         30         40         50
MAAPRAGRGA GWSLRAWRAL GGIRWGRRPR LTPDLRALLT SGTSDPRARV 
        60         70         80         90        100
TYGTPSLWAR LSVGVTEPRA CLTSGTPGPR AQLTAVTPDT RTREASENSG 
       110        120        130        140        150
TRSRAWLAVA LGAGGAVLLL LWGGGRGPPA VLAAVPSPPP ASPRSQYNFI 
       160        170        180        190        200
ADVVEKTAPA VVYIEILDRH PFLGREVPIS NGSGFVVAAD GLIVTNAHVV 
       210        220        230        240        250
ADRRRVRVRL LSGDTYEAVV TAVDPVADIA TLRIQTKEPL PTLPLGRSAD 
       260        270        280        290        300
VRQGEFVVAM GSPFALQNTI TSGIVSSAQR PARDLGLPQT NVEYIQTDAA 
       310        320        330        340        350
IDFGNSGGPL VNLVSETSFL PRIPAPGQCG KGRFPLIQGC LVKFLSSSLL 
       360        370 
AISQYPTRSP QHLLVLLFGC PHPLLFV                       

Natural variant

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	72 – 72	1	L → P.1 Publication <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.13 "Genetic variability in the mitochondrial serine protease HTRA2 contributes to risk for Parkinson disease." Bogaerts V., Nuytemans K., Reumers J., Pals P., Engelborghs S., Pickut B., Corsmit E., Peeters K., Schymkowitz J., De Deyn P.P., Cras P., Rousseau F., Theuns J., Van Broeckhoven C. Hum. Mutat. 29:832-840(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PRO-72; SER-141 AND TRP-404, ASSOCIATION WITH INCREASED RISK OF PARKINSON DISEASE. Corresponds to variant rs150047108 [ dbSNP | Ensembl ].		VAR_046134
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	141 – 141	1	A → S Polymorphism; associated with a 2.15-fold increased risk of PD; reduced protease activity. 2 Publications <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.12 "Loss of function mutations in the gene encoding Omi/HtrA2 in Parkinson's disease." Strauss K.M., Martins L.M., Plun-Favreau H., Marx F.P., Kautzmann S., Berg D., Gasser T., Wszolek Z., Mueller T., Bornemann A., Wolburg H., Downward J., Riess O., Schulz J.B., Krueger R. Hum. Mol. Genet. 14:2099-2111(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PARK13 SER-399, VARIANT SER-141, CHARACTERIZATION OF VARIANTS SER-141 AND SER-399. Ref.13 "Genetic variability in the mitochondrial serine protease HTRA2 contributes to risk for Parkinson disease." Bogaerts V., Nuytemans K., Reumers J., Pals P., Engelborghs S., Pickut B., Corsmit E., Peeters K., Schymkowitz J., De Deyn P.P., Cras P., Rousseau F., Theuns J., Van Broeckhoven C. Hum. Mutat. 29:832-840(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PRO-72; SER-141 AND TRP-404, ASSOCIATION WITH INCREASED RISK OF PARKINSON DISEASE. Corresponds to variant rs72470544 [ dbSNP | Ensembl ].		VAR_027349
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	399 – 399	1	G → S in PARK13; reduced protease activity. 1 Publication <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.12 "Loss of function mutations in the gene encoding Omi/HtrA2 in Parkinson's disease." Strauss K.M., Martins L.M., Plun-Favreau H., Marx F.P., Kautzmann S., Berg D., Gasser T., Wszolek Z., Mueller T., Bornemann A., Wolburg H., Downward J., Riess O., Schulz J.B., Krueger R. Hum. Mol. Genet. 14:2099-2111(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PARK13 SER-399, VARIANT SER-141, CHARACTERIZATION OF VARIANTS SER-141 AND SER-399. Corresponds to variant rs72470545 [ dbSNP | Ensembl ].		VAR_027350
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	404 – 404	1	R → W Could be associated with an increased risk of developing PD. 1 Publication <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.13 "Genetic variability in the mitochondrial serine protease HTRA2 contributes to risk for Parkinson disease." Bogaerts V., Nuytemans K., Reumers J., Pals P., Engelborghs S., Pickut B., Corsmit E., Peeters K., Schymkowitz J., De Deyn P.P., Cras P., Rousseau F., Theuns J., Van Broeckhoven C. Hum. Mutat. 29:832-840(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PRO-72; SER-141 AND TRP-404, ASSOCIATION WITH INCREASED RISK OF PARKINSON DISEASE.		VAR_046135

Alternative sequence

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
<p>Describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting. The information stored in this subsection is used to automatically construct alternative protein sequence(s) for display.</p><p><a href='../manual/var_seq' target='_top'>More...</a></p>Alternative sequencei	238 – 302	65	Missing in isoform 2. 1 Publication <p>Manually curated information that is based on statements in scientific articles for which there is no experimental support.</p> <p><a href="/manual/evidences#ECO:0000303">More…</a></p> Manual assertion based on opinion ini Ref.3 "Tissue-specific splicing of Omi stress-regulated endoprotease leads to an inactive protease with a modified PDZ motif." Faccio L., Fusco C., Viel A., Zervos A.S. Genomics 68:343-347(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).		VSP_005359	Add BLAST
<p>Describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting. The information stored in this subsection is used to automatically construct alternative protein sequence(s) for display.</p><p><a href='../manual/var_seq' target='_top'>More...</a></p>Alternative sequencei	313 – 313	1	L → LARELGAVSLQ in isoform 3. 1 Publication <p>Manually curated information that is based on statements in scientific articles for which there is no experimental support.</p> <p><a href="/manual/evidences#ECO:0000303">More…</a></p> Manual assertion based on opinion ini Ref.2 "Characterization of human HtrA2, a novel serine protease involved in the mammalian cellular stress response." Gray C.W., Ward R.V., Karran E.H., Turconi S., Rowles A., Viglienghi D., Southan C., Barton A., Fantom K.G., West A., Savopoulos J.W., Hassan N.J., Clinkenbeard H., Hanning C., Amegadzie B., Davis J.B., Dingwall C., Livi G.P., Creasy C.L. Eur. J. Biochem. 267:5699-5710(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3 AND 4), CHARACTERIZATION.		VSP_005360
<p>Describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting. The information stored in this subsection is used to automatically construct alternative protein sequence(s) for display.</p><p><a href='../manual/var_seq' target='_top'>More...</a></p>Alternative sequencei	314 – 458	145	DGEVI…PEVTE → VSETSFLPRIPAPGQCGKGR FPLIQGCLVKFLSSSLLAIS QYPTRSPQHLLVLLFGCPHP LLFV in isoform 4. 1 Publication <p>Manually curated information that is based on statements in scientific articles for which there is no experimental support.</p> <p><a href="/manual/evidences#ECO:0000303">More…</a></p> Manual assertion based on opinion ini Ref.2 "Characterization of human HtrA2, a novel serine protease involved in the mammalian cellular stress response." Gray C.W., Ward R.V., Karran E.H., Turconi S., Rowles A., Viglienghi D., Southan C., Barton A., Fantom K.G., West A., Savopoulos J.W., Hassan N.J., Clinkenbeard H., Hanning C., Amegadzie B., Davis J.B., Dingwall C., Livi G.P., Creasy C.L. Eur. J. Biochem. 267:5699-5710(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3 AND 4), CHARACTERIZATION.		VSP_005362	Add BLAST
<p>Describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting. The information stored in this subsection is used to automatically construct alternative protein sequence(s) for display.</p><p><a href='../manual/var_seq' target='_top'>More...</a></p>Alternative sequencei	372 – 403	32	Missing in isoform 2 and isoform 3. 2 Publications <p>Manually curated information that is based on statements in scientific articles for which there is no experimental support.</p> <p><a href="/manual/evidences#ECO:0000303">More…</a></p> Manual assertion based on opinion ini Ref.2 "Characterization of human HtrA2, a novel serine protease involved in the mammalian cellular stress response." Gray C.W., Ward R.V., Karran E.H., Turconi S., Rowles A., Viglienghi D., Southan C., Barton A., Fantom K.G., West A., Savopoulos J.W., Hassan N.J., Clinkenbeard H., Hanning C., Amegadzie B., Davis J.B., Dingwall C., Livi G.P., Creasy C.L. Eur. J. Biochem. 267:5699-5710(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3 AND 4), CHARACTERIZATION. Ref.3 "Tissue-specific splicing of Omi stress-regulated endoprotease leads to an inactive protease with a modified PDZ motif." Faccio L., Fusco C., Viel A., Zervos A.S. Genomics 68:343-347(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).		VSP_005361	Add BLAST

Sequence databases

Genome annotation databases

<p>UniProtKB Keywords constitute a <a target="_top" href="/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='../help/keywords' target='_top'>More...</a></p>Keywords - Coding sequence diversityⁱ

<p>Is used to point to information related to entries and found in data collections other than UniProtKB.</p><p><a href='../manual/cross_references_section' target='_top'>More...</a></p> Cross-referencesⁱ

<p>Provides links to various web resources that are relevant for a specific protein.</p><p><a href='../manual/web_resource' target='_top'>More...</a></p> Web resourcesⁱ

Sequence databases

3D structure databases

Protein-protein interaction databases

Protein family/group databases

PTM databases

2D gel databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>Contains the literature citations that are the sources of data used to annotate the entry. Each reference is numbered and contains several subsections allowing a precise description of a given citation.</p><p><a href='../manual/publications_section' target='_top'>More...</a></p>Publicationsⁱ

1. "Characterization of a novel human serine protease that has extensive homology to bacterial heat shock endoprotease HtrA and is regulated by kidney ischemia."
   Faccio L., Fusco C., Chen A., Martinotti S., Bonventre J.V., Zervos A.S.
   J. Biol. Chem. 275:2581-2588(2000) [PubMed] [Europe PMC] [Abstract]
   Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), MUTAGENESIS OF SER-306.
2. "Characterization of human HtrA2, a novel serine protease involved in the mammalian cellular stress response."
   Gray C.W., Ward R.V., Karran E.H., Turconi S., Rowles A., Viglienghi D., Southan C., Barton A., Fantom K.G., West A., Savopoulos J.W., Hassan N.J., Clinkenbeard H., Hanning C., Amegadzie B., Davis J.B., Dingwall C., Livi G.P., Creasy C.L.
   Eur. J. Biochem. 267:5699-5710(2000) [PubMed] [Europe PMC] [Abstract]
   Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3 AND 4), CHARACTERIZATION.
   Tissue: Brain.
   
3. "Tissue-specific splicing of Omi stress-regulated endoprotease leads to an inactive protease with a modified PDZ motif."
   Faccio L., Fusco C., Viel A., Zervos A.S.
   Genomics 68:343-347(2000) [PubMed] [Europe PMC] [Abstract]
   Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
   Tissue: Kidney.
   
4. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.

   , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
   Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
   Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
5. "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: Brain.
   
6. "A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death."
   Suzuki Y., Imai Y., Nakayama H., Takahashi K., Takio K., Takahashi R.
   Mol. Cell 8:613-621(2001) [PubMed] [Europe PMC] [Abstract]
   Cited for: PROTEIN SEQUENCE OF 134-458, INTERACTION WITH XIAP, MUTAGENESIS OF ALA-134.
7. "Expression, purification, and functional analysis of the human serine protease HtrA2."
   Savopoulos J.W., Carter P.S., Turconi S., Pettman G.R., Karran E.H., Gray C.W., Ward R.V., Jenkins O., Creasy C.L.
   Protein Expr. Purif. 19:227-234(2000) [PubMed] [Europe PMC] [Abstract]
   Cited for: CHARACTERIZATION.
8. "Dual role of BRUCE as an antiapoptotic IAP and a chimeric E2/E3 ubiquitin ligase."
   Bartke T., Pohl C., Pyrowolakis G., Jentsch S.
   Mol. Cell 14:801-811(2004) [PubMed] [Europe PMC] [Abstract]
   Cited for: FUNCTION, INTERACTION WITH BIRC6/BRUCE.
9. "THAP5 is a human cardiac-specific inhibitor of cell cycle that is cleaved by the proapoptotic Omi/HtrA2 protease during cell death."
   Balakrishnan M.P., Cilenti L., Mashak Z., Popat P., Alnemri E.S., Zervos A.S.
   Am. J. Physiol. 297:H643-H653(2009) [PubMed] [Europe PMC] [Abstract]
   Cited for: FUNCTION, INTERACTION WITH THAP5.
10. "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].
11. "Structural insights into the pro-apoptotic function of mitochondrial serine protease HtrA2/Omi."
    Li W., Srinivasula S.M., Chai J., Li P., Wu J.W., Zhang Z., Alnemri E.S., Shi Y.
    Nat. Struct. Biol. 9:436-441(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 134-458, SUBUNIT.
12. "Loss of function mutations in the gene encoding Omi/HtrA2 in Parkinson's disease."
    Strauss K.M., Martins L.M., Plun-Favreau H., Marx F.P., Kautzmann S., Berg D., Gasser T., Wszolek Z., Mueller T., Bornemann A., Wolburg H., Downward J., Riess O., Schulz J.B., Krueger R.
    Hum. Mol. Genet. 14:2099-2111(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT PARK13 SER-399, VARIANT SER-141, CHARACTERIZATION OF VARIANTS SER-141 AND SER-399.
13. "Genetic variability in the mitochondrial serine protease HTRA2 contributes to risk for Parkinson disease."
    Bogaerts V., Nuytemans K., Reumers J., Pals P., Engelborghs S., Pickut B., Corsmit E., Peeters K., Schymkowitz J., De Deyn P.P., Cras P., Rousseau F., Theuns J., Van Broeckhoven C.
    Hum. Mutat. 29:832-840(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS PRO-72; SER-141 AND TRP-404, ASSOCIATION WITH INCREASED RISK OF PARKINSON DISEASE.

<p>Provides general information on the entry.</p><p><a href='../manual/entry_information_section' target='_top'>More...</a></p>Entry informationⁱ

<p>Contains any relevant information that doesn’t fit in any other defined sections</p><p><a href='../manual/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousⁱ

<p>UniProtKB Keywords constitute a <a target="_top" href="/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='../help/keywords' target='_top'>More...</a></p>Keywords - Technical termⁱ

Documents

1. Human chromosome 2
   Human chromosome 2: 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

External Data

<p>Provides links to the UniProt Reference Clusters (<a href="/help/uniref">UniRef</a>). UniRef consists of clusters for UniProtKB sequences (including isoforms) and selected UniParc sequences, in order to obtain complete coverage of the sequence space at resolutions of 100%, 90% and 50% identity.</p><p><a href='../manual/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsⁱ