NucEnvDB

NucEnvDB

A database of Nuclear Envelope Proteins and their Interactions

Polyunsaturated fatty acid 5-lipoxygenase - Mus musculus - NucEnvDB

Polyunsaturated fatty acid 5-lipoxygenase (Mus musculus)

FASTA TEXT XML

Subcellular Location Biology & Function Cross-References

General Information

Protein Information
Protein Name	Polyunsaturated fatty acid 5-lipoxygenase
Accession Code	P48999
Gene	Alox5
Organism	Mus musculus \| House mouse (Taxonomy: 10090)
Part of Reference Proteome?	Yes
Sequence (Length: 674)
MPSYTVTVATGSQWFAGTDDYIYLSLIGSAGCSEKHLLDKAFYNDFERGAVDSYDVTVDEELGEIYLVKIEKRKYWLHDDWYLKYITLKTPHGDYIEFPCYRWITGEGEIVLRDGRAKLARDDQIHILKQ HRRKELEARQKQYRWMEWNPGFPLSIDAKCHKDLPRDIQFDSEKGVDFVLNYSKAMENLFINRFMHMFQSSWHDFADFEKIFVKISNTISERVKNHWQEDLMFGYQFLNGCNPVLIKRCTALPPKLPVTT EMVECSLERQLSLEQEVQEGNIFIVDYELLDGIDANKTDPCTHQFLAAPICLLYKNLANKIVPIAIQLNQTPGESNPIFLPTDSKYDWLLAKIWVRSSDFHVHQTITHLLRTHLVSEVFGIAMYRQLPAV HPLFKLLVAHVRFTIAINTKAREQLICEYGLFDKANATGGGGHVQMVQRAVQDLTYSSLCFPEAIKARGMDSTEDIPFYFYRDDGLLVWEAIQSFTMEVVSIYYENDQVVEEDQELQDFVKDVYVYGMRG KKASGFPKSIKSREKLSEYLTVVIFTASAQHAAVNFGQYDWCSWIPNAPPTMRAPPPTAKGVVTIEQIVDTLPDRGRSCWHLGAVWALSQFQENELFLGMYPEEHFIEKPVKEAMIRFRKNLEAIVSVIA ERNKNKKLPYYYLSPDRIPNSVAI

Subcellular Location

Description
Cytoplasm {By SimilarityUniProtKB:P09917, Sequence AnalysisPROSITE-ProRule:PRU00726, Experimental EvidencePubMed:7629107}. Nucleus matrix {Experimental EvidencePubMed:7629107}. Nucleus membrane {By SimilarityUniProtKB:P09917}; Peripheral membrane protein {By SimilarityUniProtKB:P09917}. Cytoplasm, perinuclear region {By SimilarityUniProtKB:P09917}. Cytoplasm, cytosol {By SimilarityUniProtKB:P09917}. Nucleus envelope {By SimilarityUniProtKB:P09917}. Nucleus intermembrane space {By SimilarityUniProtKB:P09917}. Note=Shuttles between cytoplasm and nucleus. Found exclusively in the nucleus, when phosphorylated on Ser- 272. Calcium binding promotes translocation from the cytosol and the nuclear matrix to the nuclear envelope and membrane association. {By SimilarityUniProtKB:P09917}.
Position in the Nuclear Envelope
Location	Location ID	Description
Nuclear Envelope	SL-0178	The nuclear envelope is a membrane system which surrounds the nucleoplasm of eukaryotic cells. It is composed of the nuclear lamina, nuclear pore complexes and two nuclear membranes. The space between the two membranes is called the nuclear intermembrane space.
Nuclear Membrane	SL-0182	The membrane surrounding the nucleus. This term is used when it is not known if the protein is found in or associated with the inner or outer nuclear membrane.
Nuclear Intermembrane Space	SL-0184	The nuclear intermembrane space is the space between the inner and outer nuclear membranes.
Perinuclear Region	SL-0198	The perinuclear region is the cytoplasmic region just around the nucleus.
Membrane Topology
Topology	Source	Annotation Type
Peripheral	UniProt	By Similarity {ECO:0000250\|UniProtKB:P09917}
Assigned Ontology terms

Cellular Component	Cytoplasm (GO:0005737) Cytosol (GO:0005829) Dendrite (GO:0030425) Nuclear Envelope (GO:0005635) Nuclear Envelope Lumen (GO:0005641) Nuclear Matrix (GO:0016363) Nuclear Membrane (GO:0031965) Nucleoplasm (GO:0005654) Nucleus (GO:0005634) Perinuclear Region Of Cytoplasm (GO:0048471) Sarcolemma (GO:0042383)

Biology & Function

Description
Catalyzes the oxygenation of arachidonate to 5- hydroperoxyeicosatetraenoate (5-HPETE) followed by the dehydration to 5,6- epoxyeicosatetraenoate (Leukotriene A4/LTA4), the first two steps in the biosynthesis of leukotrienes, which are potent mediators of inflammation (PubMed:7629107, PubMed:7809134, PubMed:7969451, PubMed:23246375, PubMed:31642348). Also catalyzes the oxygenation of arachidonic acid into 8-hydroperoxyicosatetraenoic acid (8-HPETE) and 12-hydroperoxyicosatetraenoic acid (12-HPETE) (PubMed:23246375). Displays lipoxin synthase activity being able to convert (15S)-HETE into a conjugate tetraene (By similarity). Although arachidonate is the preferred substrate, this enzyme can also metabolize oxidized fatty acids derived from arachidonate such as (15S)-HETE, eicosapentaenoate (EPA) such as (18R)- and (18S)-HEPE or docosahexaenoate (DHA) which lead to the formation of specialized pro-resolving mediators (SPM) lipoxin and resolvins E and D respectively, therefore it participates in anti-inflammatory responses (PubMed:31642348). Oxidation of DHA directly inhibits endothelial cell proliferation and sprouting angiogenesis via peroxisome proliferator-activated receptor gamma (PPARgamma)(PubMed:21307302). It does not catalyze the oxygenation of linoleic acid and does not convert (5S)-HETE to lipoxin isomers (PubMed:31642348). In addition to inflammatory processes, participates in dendritic cell migration, wound healing through an antioxidant mechanism based on heme oxygenase-1 (HO-1) regulation expression, monocyte adhesion to the endothelium via ITGAM expression on monocytes (PubMed:24226420, PubMed:23720274, PubMed:17392829, PubMed:28965882). Moreover, it helps establish an adaptive humoral immunity by regulating primary resting B cells and follicular helper T cells and participates in the CD40-induced production of reactive oxygen species (ROS) after CD40 ligation in B cells through interaction with PIK3R1 that bridges ALOX5 with CD40 (PubMed:21224059). May also play a role in glucose homeostasis, regulation of insulin secretion and palmitic acid-induced insulin resistance via AMPK (PubMed:28694473, PubMed:18421434). Can regulate bone mineralization and fat cell differentiation increases in induced pluripotent stem cells (PubMed:24906289). {By SimilarityUniProtKB:P09917, Experimental EvidencePubMed:17392829, Experimental EvidencePubMed:18421434, Experimental EvidencePubMed:21224059, Experimental EvidencePubMed:21307302, Experimental EvidencePubMed:23246375, Experimental EvidencePubMed:23720274, Experimental EvidencePubMed:24226420, Experimental EvidencePubMed:24906289, Experimental EvidencePubMed:28694473, Experimental EvidencePubMed:28965882, Experimental EvidencePubMed:31642348, Experimental EvidencePubMed:7629107, Experimental EvidencePubMed:7809134, Experimental EvidencePubMed:7969451}.
Assigned Ontology terms

Biological Process	Acute Inflammatory Response (GO:0002526) Arachidonic Acid Metabolic Process (GO:0019369) Dendritic Cell Migration (GO:0036336) Glucose Homeostasis (GO:0042593) Hepoxilin Biosynthetic Process (GO:0051122) Humoral Immune Response (GO:0006959) Inflammatory Response (GO:0006954) Leukocyte Chemotaxis Involved In Inflammatory Response (GO:0002232) Leukocyte Migration Involved In Inflammatory Response (GO:0002523) Leukotriene A4 Biosynthetic Process (GO:1901753) Leukotriene Biosynthetic Process (GO:0019370) Leukotriene Metabolic Process (GO:0006691) Leukotriene Production Involved In Inflammatory Response (GO:0002540) Linoleic Acid Metabolic Process (GO:0043651) Lipid Oxidation (GO:0034440) Lipoxin Biosynthetic Process (GO:2001301) Lipoxygenase Pathway (GO:0019372) Negative Regulation Of Angiogenesis (GO:0016525) Negative Regulation Of Endothelial Cell Proliferation (GO:0001937) Negative Regulation Of Inflammatory Response (GO:0050728) Negative Regulation Of Response To Endoplasmic Reticulum Stress (GO:1903573) Negative Regulation Of Sprouting Angiogenesis (GO:1903671) Negative Regulation Of Vascular Wound Healing (GO:0061044) Negative Regulation Of Wound Healing (GO:0061045) Positive Regulation Of Bone Mineralization (GO:0030501) Positive Regulation Of Cytochrome-C Oxidase Activity (GO:1904960) Positive Regulation Of Leukocyte Adhesion To Arterial Endothelial Cell (GO:1904999) Positive Regulation Of Vasoconstriction (GO:0045907) Regulation Of Cellular Response To Oxidative Stress (GO:1900407) Regulation Of Cytokine Production Involved In Inflammatory Response (GO:1900015) Regulation Of Fat Cell Differentiation (GO:0045598) Regulation Of Inflammatory Response (GO:0050727) Regulation Of Inflammatory Response To Wounding (GO:0106014) Regulation Of Insulin Secretion (GO:0050796) Regulation Of Reactive Oxygen Species Biosynthetic Process (GO:1903426) Sensory Perception Of Pain (GO:0019233)
Molecular Function	Arachidonate 12(S)-Lipoxygenase Activity (GO:0004052) Arachidonate 5-Lipoxygenase Activity (GO:0004051) Arachidonate 8(S)-Lipoxygenase Activity (GO:0036403) Hydrolase Activity (GO:0016787) Iron Ion Binding (GO:0005506) Oxidoreductase Activity, Acting On Single Donors With Incorporation Of Molecular Oxygen, Incorporation Of Two Atoms Of Oxygen (GO:0016702)

Cross-References

Database	Links
UNIPROT	P48999 Q3TB75
Pfam	PF00305 PF01477
PROSITE	PS00711 PS00081 PS51393 PS50095

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