Reviewed, UniProtKB/Swiss-Prot P12527 (LOX5_RAT)

Names and origin

Protein names

Recommended name:
    Arachidonate 5-lipoxygenase
      Short name=5-lipoxygenase
      Short name=5-LO
    EC=1.13.11.34

Gene names

Name:

Alox5

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	673 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Catalyzes the first step in leukotriene biosynthesis, and thereby plays a role in inflammatory processes.
Catalytic activity	Arachidonate + O2 = leukotriene A4 + H2O.
Cofactor	Binds 1 iron ion per subunit By similarity. Binds 2 calcium ions per subunit By similarity.
Pathway	Lipid metabolism; leukotriene A4 biosynthesis.
Subunit structure	Interacts with ALOX5AP and LTC4S By similarity.
Subcellular location	Cytoplasm. Nucleus matrix. Nucleus membrane; Peripheral membrane protein. Note: Shuttles between cytoplasm and nucleus. Found exclusively in the nucleus, when phosphorylated on Ser-271. Calcium binding promotes translocation from the cytosol and the nuclear matrix to the nuclear envelope and membrane association.
Post-translational modification	Serine phosphorylation by MAPKAPK2 is stimulated by arachidonic acid. Phosphorylation on Ser-523 by PKA has an inhibitory effect. Phosphorylation on Ser-271 prevents export from the nucleus By similarity.
Sequence similarities	Belongs to the lipoxygenase family. Contains 1 lipoxygenase domain. Contains 1 PLAT domain.
Sequence caution	The sequence AAA41538.1 differs from that shown. Reason: Frameshift at position 667.

Ontologies

Keywords
Biological process	Leukotriene biosynthesis
Cellular component	Cytoplasm Membrane Nucleus
Ligand	Calcium Iron Metal-binding
Molecular function	Dioxygenase Oxidoreductase
PTM	Phosphoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	lipoxygenase pathway Inferred from mutant phenotype. Source: RGD oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of vasoconstriction Inferred from mutant phenotype. Source: RGD response to nutrient Inferred from expression pattern. Source: RGD
Cellular component	cytosol Inferred from sequence or structural similarity. Source: UniProtKB dendrite Inferred from direct assay. Source: RGD extrinsic to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell nuclear envelope lumen Inferred from sequence or structural similarity. Source: UniProtKB nuclear matrix Inferred from electronic annotation. Source: UniProtKB-SubCell nuclear membrane Inferred from sequence or structural similarity. Source: UniProtKB sarcolemma Inferred from direct assay. Source: RGD soluble fraction Inferred from direct assay. Source: RGD
Molecular function	arachidonate 5-lipoxygenase activity Inferred from mutant phenotype. Source: RGD calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW iron ion binding Inferred from electronic annotation. Source: UniProtKB-KW lipoxygenase activity Inferred from electronic annotation. Source: InterPro protein binding Traceable author statement. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed
	Chain	2 – 673	672	Arachidonate 5-lipoxygenase		PRO_0000220696
Regions
	Domain	2 – 117	116	PLAT
	Domain	118 – 673	556	Lipoxygenase
Sites
	Metal binding	17	1	Calcium 1; via carbonyl oxygen; structural By similarity
	Metal binding	18	1	Calcium 2; via carbonyl oxygen; structural By similarity
	Metal binding	19	1	Calcium 2; structural By similarity
	Metal binding	44	1	Calcium 2; structural By similarity
	Metal binding	45	1	Calcium 2; via carbonyl oxygen; structural By similarity
	Metal binding	47	1	Calcium 2; structural By similarity
	Metal binding	79	1	Calcium 1; via carbonyl oxygen; structural By similarity
	Metal binding	80	1	Calcium 1; via carbonyl oxygen; structural By similarity
	Metal binding	367	1	Iron; catalytic By similarity
	Metal binding	372	1	Iron; catalytic By similarity
	Metal binding	550	1	Iron; catalytic By similarity
	Metal binding	554	1	Iron; catalytic By similarity
	Metal binding	673	1	Iron; via carboxylate; catalytic By similarity
Amino acid modifications
	Modified residue	271	1	Phosphoserine By similarity
	Modified residue	523	1	Phosphoserine By similarity

Sequences

	Sequence		Length	Mass (Da)
	P12527-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 536B0BC27CB0A608	FASTA	673	78,087
	10 20 30 40 50 60 MPSYTVTVAT GSQWFAGTDD YIYLSLIGSA GCSEKHLLDK AFYNDFERGG RDSYDVTVDE 70 80 90 100 110 120 ELGEIYLVKI EKRKYRLHDD WYLKYITLKT PHDYIEFPCY RWITGEGEIV LRDGCAKLAR 130 140 150 160 170 180 DDQIHILKQH RRKELETRQK QYRWMEWNPG FPLSIDAKCH KDLPRDIQFD SEKGVDFVLN 190 200 210 220 230 240 YSKAMENLFI NRFMHMFQSS WHDFADFEKI FVKISNTISE RVKNHWQEDL MFGYQFLNGC 250 260 270 280 290 300 NPVLIKRCTE LPKKLPVTTE MVECSLERQL SLEQEVQEGN IFIVDYELLD GIDANKTDPC 310 320 330 340 350 360 THQFLAAPIC LLYKNLANKI VPIAIQLNQT PGEKNPIFLP TDSKYDWLLA KIWVRSSDFH 370 380 390 400 410 420 IHQTITHLLR THLVSEVFGI AMYRQLPAVH PLFKLLVAHV RFTIAINTKA REQLNCEYGL 430 440 450 460 470 480 FDKANATGGG GHVQMVQRAV QDLTYSSLCF PEAIKARGMD NTEDIPYYFY RDDGLLVWEA 490 500 510 520 530 540 IQSFTTEVVS IYYEDDQVVE EDQELQDFVK DVYVYGMRGR KASGFPKSIK SREKLSEYLT 550 560 570 580 590 600 VVIFTASAQH AAVNFGQYDW CSWIPNAPPT MRAPPPTAKG VVTIEQIVDT LPDRGRSCWH 610 620 630 640 650 660 LGAVWALSQF QENELFLGMY PEEHFIEKPV KEAMIRFRKN LEAIVSVIAE RNKNKKLPYY 670 YLSPDRIPNS VAI

References

[1]	"Isolation and characterization of a cDNA clone encoding rat 5-lipoxygenase." Balcarek J.M., Theisen T.W., Cook M.N., Varrichio A., Hwang S.-M., Strohsacker M.W., Crooke S.T. J. Biol. Chem. 263:13937-13941(1988) [PubMed: 3417684] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
[2]	"Crystallographic determination of the active site iron and its ligands in soybean lipoxygenase L-1." Minor W., Steczko J., Bolin J.T., Otwinowski Z., Axelrod B. Biochemistry 32:6320-6323(1993) [PubMed: 8518276] [Abstract] Cited for: SEQUENCE REVISION TO 667-670.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	J03960 mRNA. Translation: AAA41538.1. Frameshift.
IPI	IPI00194785.
PIR	A30882.
RefSeq	NP_036954.1.
UniGene	Rn.9662
3D structure databases
HSSP	HSSP built from PDB template 1LOX based on UniProtKB P12530.
ModBase	Search...
Protein-protein interaction databases
STRING	P12527.
PTM databases
PhosphoSite	P12527.
Genome annotation databases
Ensembl	ENSRNOT00000017633; ENSRNOP00000017633; ENSRNOG00000012972; Rattus norvegicus. [Genome view]
GeneID	25290.
KEGG	rno:25290.
Organism-specific databases
CTD	25290.
RGD	2096. Alox5.
Phylogenomic databases
HOVERGEN	P12527.
Enzyme and pathway databases
BRENDA	1.13.11.34. 248.
Gene expression databases
ArrayExpress	P12527.
Genevestigator	P12527.
GermOnline	ENSRNOG00000012972. Rattus norvegicus.
Family and domain databases
InterPro	IPR000907. LipOase. IPR013819. LipOase_C. IPR001024. LipOase_LH2. IPR001885. LipOase_mml. [Graphical view]
Gene3D	G3DSA:2.60.60.20. Lipase_LipOase. 1 hit.
PANTHER	PTHR11771. LipOase. 1 hit.
Pfam	PF00305. Lipoxygenase. 1 hit. PF01477. PLAT. 1 hit. [Graphical view]
PRINTS	PR00087. LIPOXYGENASE. PR00467. MAMLPOXGNASE.
SMART	SM00308. LH2. 1 hit. [Graphical view]
PROSITE	PS00711. LIPOXYGENASE_1. 1 hit. PS00081. LIPOXYGENASE_2. 1 hit. PS51393. LIPOXYGENASE_3. 1 hit. PS50095. PLAT. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	606033.

Entry information

Entry name

LOX5_RAT

Accession

Primary (citable) accession number: P12527

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	January 23, 2007
Last modified:	October 13, 2009
This is version 94 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)