Arachidonate 5-lipoxygenase

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

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityⁱ

• (5Z,8Z,11Z,14Z)-eicosatetraenoate

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  • Search chemical reactions in Rhea for this molecule.
  • See the description of this molecule in ChEBI.

  + O₂

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  • See the description of this molecule in ChEBI.

  = H₂O

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  + leukotriene A₄

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  • See the description of this molecule in ChEBI.
  EC:1.13.11.34
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  • See the description of this EC number in ENZYME.
  Source: Rhea

  • Search for this reaction in UniProtKB.
  • See the description of this reaction in Rhea.

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  (5Z,8Z,11Z,14Z)-eicosatetraenoate

  • Search proteins in UniProtKB for this molecule.
  • Search chemical reactions in Rhea for this molecule.
  • See the description of this molecule in ChEBI.

  zoom

  +

  O₂

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  • See the description of this molecule in ChEBI.

  

  =

  H₂O

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  • See the description of this molecule in ChEBI.

  

  +

  leukotriene A₄

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  • See the description of this molecule in ChEBI.

  zoom

<p>This subsection of the 'Function' section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactorⁱ

• Fe cation
  • Search proteins in UniProtKB for this molecule.
  • Search chemical reactions in Rhea for this molecule.
  • See the description of this molecule in ChEBI.
  PROSITE-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:PRU00726
  Note: Binds 1 Fe cation per subunit.PROSITE-ProRule annotation

  Manual assertion according to rulesⁱ

  • PROSITE-ProRule:PRU00726
• Ca²⁺
  • Search proteins in UniProtKB for this molecule.
  • Search chemical reactions in Rhea for this molecule.
  • See the description of this molecule in ChEBI.
  By similarityNote: Binds 2 calcium ions per subunit.By similarity

Sites

<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><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functionⁱ

• arachidonate 5-lipoxygenase activity Source: UniProtKB
• iron ion binding Source: UniProtKB

GO - Biological processⁱ

• acute inflammatory response Source: RGD <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%2Dgo%2Devidence%2Dcodes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypeⁱ
  • "Zileuton reduces inflammatory reaction and brain damage following permanent cerebral ischemia in rats."
    Tu X.K., Yang W.Z., Wang C.H., Shi S.S., Zhang Y.L., Chen C.M., Yang Y.K., Jin C.D., Wen S.
    Inflammation 33:344-352(2010) [PubMed] [Europe PMC] [Abstract]
• dendritic cell migration Source: UniProtKB
• glucose homeostasis Source: UniProtKB
• humoral immune response Source: UniProtKB
• inflammatory response Source: RGDInferred from sequence orthologyⁱ
  • "Thioglycollate peritonitis in mice lacking C5, 5-lipoxygenase, or p47(phox): complement, leukotrienes, and reactive oxidants in acute inflammation."
    Segal B.H., Kuhns D.B., Ding L., Gallin J.I., Holland S.M.
    J. Leukoc. Biol. 71:410-416(2002) [PubMed] [Europe PMC] [Abstract]
• leukocyte chemotaxis involved in inflammatory response Source: UniProtKB
• leukocyte migration involved in inflammatory response Source: UniProtKB
• leukotriene A4 biosynthetic process Source: UniProtKB
• leukotriene biosynthetic process Source: UniProtKB
• leukotriene metabolic process Source: RGDInferred from sequence orthologyⁱ
  • "Thioglycollate peritonitis in mice lacking C5, 5-lipoxygenase, or p47(phox): complement, leukotrienes, and reactive oxidants in acute inflammation."
    Segal B.H., Kuhns D.B., Ding L., Gallin J.I., Holland S.M.
    J. Leukoc. Biol. 71:410-416(2002) [PubMed] [Europe PMC] [Abstract]
• leukotriene production involved in inflammatory response Source: RGDInferred from sequence orthologyⁱ
  • "Role of the 5-lipoxygenase-activating protein (FLAP) in murine acute inflammatory responses."
    Byrum R.S., Goulet J.L., Griffiths R.J., Koller B.H.
    J. Exp. Med. 185:1065-1075(1997) [PubMed] [Europe PMC] [Abstract]
• lipoxin biosynthetic process Source: UniProtKB
• negative regulation of angiogenesis Source: UniProtKB
• negative regulation of endothelial cell proliferation Source: UniProtKB
• negative regulation of inflammatory response Source: UniProtKB
• negative regulation of response to endoplasmic reticulum stress Source: UniProtKB
• negative regulation of sprouting angiogenesis Source: UniProtKB
• negative regulation of vascular wound healing Source: UniProtKB
• negative regulation of wound healing Source: UniProtKB
• positive regulation of bone mineralization Source: UniProtKB
• positive regulation of cytochrome-c oxidase activity Source: RGDInferred from mutant phenotypeⁱ
  • "Lipoxygenase-dependent superoxide release in skeletal muscle."
    Zuo L., Christofi F.L., Wright V.P., Bao S., Clanton T.L.
    J. Appl. Physiol. 97:661-668(2004) [PubMed] [Europe PMC] [Abstract]
• positive regulation of leukocyte adhesion to arterial endothelial cell Source: UniProtKB
• positive regulation of vasoconstriction Source: RGDInferred from mutant phenotypeⁱ
  • "Effect of 5-lipoxygenase blockade on blood pressure and acetylcholine-evoked endothelium-dependent contraction in aorta from spontaneously hypertensive rats."
    Lefebvre B., Caron F., Bessard G., Stanke-Labesque F.
    J. Hypertens. 24:85-93(2006) [PubMed] [Europe PMC] [Abstract]
• regulation of cellular response to oxidative stress Source: UniProtKB
• regulation of cytokine production involved in inflammatory response Source: UniProtKB
• regulation of fat cell differentiation Source: UniProtKB
• regulation of inflammatory response Source: UniProtKB
• regulation of inflammatory response to wounding Source: UniProtKB
• regulation of insulin secretion Source: UniProtKB
• regulation of reactive oxygen species biosynthetic process Source: UniProtKB
• response to hyperoxia Source: RGD <p>Inferred from Expression Pattern</p> <p>Covers cases where the annotation is inferred from the timing or location of expression of a gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#iep">GO evidence code guide</a></p> Inferred from expression patternⁱ
  • "Hyperoxia increases protein mass of 5-lipoxygenase and its activating protein, flap, and leukotriene B(4) output in newborn rat lungs."
    Hosford G.E., Koyanagi K.S., Leung W.I., Olson D.M.
    Exp. Lung Res. 28:671-684(2002) [PubMed] [Europe PMC] [Abstract]
• response to nutrient Source: RGDInferred from expression patternⁱ
  • "Protective effect of dietary curcumin and capsaicin on induced oxidation of low-density lipoprotein, iron-induced hepatotoxicity and carrageenan-induced inflammation in experimental rats."
    Manjunatha H., Srinivasan K.
    FEBS J. 273:4528-4537(2006) [PubMed] [Europe PMC] [Abstract]
• sensory perception of pain Source: RGDInferred from mutant phenotypeⁱ
  • "CJ-13610, an orally active inhibitor of 5-lipoxygenase is efficacious in preclinical models of pain."
    Cortes-Burgos L.A., Zweifel B.S., Settle S.L., Pufahl R.A., Anderson G.D., Hardy M.M., Weir D.E., Hu G., Happa F.A., Stewart Z., Muthian S., Graneto M.J., Masferrer J.L.
    Eur. J. Pharmacol. 617:59-67(2009) [PubMed] [Europe PMC] [Abstract]

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/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>Keywordsⁱ

Enzyme and pathway databases

<p>This section 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><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyⁱ

Organism-specific databases

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

Keywords - Cellular componentⁱ

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechⁱ

Chemistry databases

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

Molecule processing

Amino acid modifications

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationⁱ

Keywords - PTMⁱ

Proteomic databases

PTM databases

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

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section 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 <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structureⁱ

Protein-protein interaction databases

Chemistry databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structureⁱ

3D structure databases

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

Domains and Repeats

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesⁱ

Phylogenomic databases

Family and domain databases

<p>This section 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 <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequence (1+)ⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusⁱ: Complete.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

        10         20         30         40         50
MPSYTVTVAT GSQWFAGTDD YIYLSLIGSA GCSEKHLLDK AFYNDFERGG 
        60         70         80         90        100
RDSYDVTVDE ELGEIYLVKI EKRKYRLHDD WYLKYITLKT PHDYIEFPCY 
       110        120        130        140        150
RWITGEGEIV LRDGCAKLAR DDQIHILKQH RRKELETRQK QYRWMEWNPG 
       160        170        180        190        200
FPLSIDAKCH KDLPRDIQFD SEKGVDFVLN YSKAMENLFI NRFMHMFQSS 
       210        220        230        240        250
WHDFADFEKI FVKISNTISE RVKNHWQEDL MFGYQFLNGC NPVLIKRCTE 
       260        270        280        290        300
LPKKLPVTTE MVECSLERQL SLEQEVQEGN IFIVDYELLD GIDANKTDPC 
       310        320        330        340        350
THQFLAAPIC LLYKNLANKI VPIAIQLNQT PGEKNPIFLP TDSKYDWLLA 
       360        370        380        390        400
KIWVRSSDFH IHQTITHLLR THLVSEVFGI AMYRQLPAVH PLFKLLVAHV 
       410        420        430        440        450
RFTIAINTKA REQLNCEYGL FDKANATGGG GHVQMVQRAV QDLTYSSLCF 
       460        470        480        490        500
PEAIKARGMD NTEDIPYYFY RDDGLLVWEA IQSFTTEVVS IYYEDDQVVE 
       510        520        530        540        550
EDQELQDFVK DVYVYGMRGR KASGFPKSIK SREKLSEYLT VVIFTASAQH 
       560        570        580        590        600
AAVNFGQYDW CSWIPNAPPT MRAPPPTAKG VVTIEQIVDT LPDRGRSCWH 
       610        620        630        640        650
LGAVWALSQF QENELFLGMY PEEHFIEKPV KEAMIRFRKN LEAIVSVIAE 
       660        670 
RNKNKKLPYY YLSPDRIPNS VAI                              

<p>This subsection of the 'Sequence' section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautionⁱ

Sequence databases

Genome annotation databases

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsⁱ

• 90% Identity
• 50% Identity

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

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationⁱ

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousⁱ

Keywords - Technical termⁱ

Documents

1. SIMILARITY comments
   Index of protein domains and families
2. PATHWAY comments
   Index of metabolic and biosynthesis pathways