Arachidonate 5-lipoxygenase - Homo sapiens (Human)

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Reviewed, UniProtKB/Swiss-Prot P09917 (LOX5_HUMAN)

Last modified June 16, 2009. Version 109. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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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
Synonyms:	LOG5

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	674 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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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.
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-272. 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-272 prevents export from the nucleus.
Sequence similarities	Belongs to the lipoxygenase family. Contains 1 lipoxygenase domain. Contains 1 PLAT domain.

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Ontologies

Keywords
Biological process	Leukotriene biosynthesis
Cellular component	Cytoplasm Membrane Nucleus
Coding sequence diversity	Polymorphism
Ligand	Calcium Iron Metal-binding
Molecular function	Dioxygenase Oxidoreductase
PTM	Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	leukotriene biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nuclear envelope lumen Ref.12 Inferred from direct assay. Source: UniProtKB nuclear matrix Ref.16 Inferred from direct assay. Source: UniProtKB nuclear membrane Ref.12 Inferred from direct assay. Source: UniProtKB
Molecular function	arachidonate 5-lipoxygenase activity Ref.2 Traceable author statement. Source: ProtInc 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 Ref.16 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
COTL1	Q14019	3	EBI-79934,EBI-79926

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

Removed

Chain

2 – 674

673

Arachidonate 5-lipoxygenase

PRO_0000220693

Regions

Domain

2 – 118

117

PLAT

Domain

119 – 674

556

Lipoxygenase

Sites

Metal binding

Calcium 1; via carbonyl oxygen; structural By similarity

Metal binding

Calcium 2; via carbonyl oxygen; structural By similarity

Metal binding

Calcium 2; structural By similarity

Metal binding

Calcium 2; structural By similarity

Metal binding

Calcium 2; via carbonyl oxygen; structural By similarity

Metal binding

Calcium 2; structural By similarity

Metal binding

Calcium 1; via carbonyl oxygen; structural By similarity

Metal binding

Calcium 1; via carbonyl oxygen; structural By similarity

Metal binding

368

Iron; catalytic By similarity

Metal binding

373

Iron; catalytic By similarity

Metal binding

551

Iron; catalytic By similarity

Metal binding

555

Iron; catalytic By similarity

Metal binding

674

Iron; via carboxylate; catalytic By similarity

Amino acid modifications

Modified residue

272

Phosphoserine; by MAPKAPK2 Ref.13

Modified residue

524

Phosphoserine; by PKA Ref.14

Natural variations

Natural variant

254

E → K: dbSNP rs2228065. Ref.18

VAR_028018

Experimental info

Mutagenesis

272

S → A: Loss of phosphorylation site. Permits export from the nucleus.

Mutagenesis

359

D → N: No loss of activity. Ref.10 Ref.11

Mutagenesis

363

H → S or N: Still some substantial activity. Ref.10 Ref.11

Mutagenesis

368

H → S, N or A: No activity. Ref.10 Ref.11

Mutagenesis

373

H → S or N: No activity. Ref.10 Ref.11

Mutagenesis

377

E → Q: No activity. Ref.10 Ref.11

Mutagenesis

391

H → A: No activity. Ref.10 Ref.11

Mutagenesis

391

H → S or N: Still some substantial activity. Ref.10 Ref.11

Mutagenesis

400

H → A: No activity. Ref.10 Ref.11

Mutagenesis

400

H → S or N: Still some substantial activity. Ref.10 Ref.11

Mutagenesis

433

H → N or A: Almost no loss of activity. Ref.10 Ref.11

Mutagenesis

524

S → A: Prevents phosphorylation by PKA. Ref.14 Ref.10 Ref.11

Mutagenesis

551

H → N or A: No activity. Ref.10 Ref.11

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Sequences

Sequence

Length

Mass (Da)

Tools

P09917-1 [UniParc].

Last modified January 23, 2007. Version 2.
Checksum: 36F38C0A9E86BB21
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FASTA

674

77,983

        10         20         30         40         50         60 
MPSYTVTVAT GSQWFAGTDD YIYLSLVGSA GCSEKHLLDK PFYNDFERGA VDSYDVTVDE 

        70         80         90        100        110        120 
ELGEIQLVRI EKRKYWLNDD WYLKYITLKT PHGDYIEFPC YRWITGDVEV VLRDGRAKLA 

       130        140        150        160        170        180 
RDDQIHILKQ HRRKELETRQ KQYRWMEWNP GFPLSIDAKC HKDLPRDIQF DSEKGVDFVL 

       190        200        210        220        230        240 
NYSKAMENLF INRFMHMFQS SWNDFADFEK IFVKISNTIS ERVMNHWQED LMFGYQFLNG 

       250        260        270        280        290        300 
CNPVLIRRCT ELPEKLPVTT EMVECSLERQ LSLEQEVQQG NIFIVDFELL DGIDANKTDP 

       310        320        330        340        350        360 
CTLQFLAAPI CLLYKNLANK IVPIAIQLNQ IPGDENPIFL PSDAKYDWLL AKIWVRSSDF 

       370        380        390        400        410        420 
HVHQTITHLL RTHLVSEVFG IAMYRQLPAV HPIFKLLVAH VRFTIAINTK AREQLICECG 

       430        440        450        460        470        480 
LFDKANATGG GGHVQMVQRA MKDLTYASLC FPEAIKARGM ESKEDIPYYF YRDDGLLVWE 

       490        500        510        520        530        540 
AIRTFTAEVV DIYYEGDQVV EEDPELQDFV NDVYVYGMRG RKSSGFPKSV KSREQLSEYL 

       550        560        570        580        590        600 
TVVIFTASAQ HAAVNFGQYD WCSWIPNAPP TMRAPPPTAK GVVTIEQIVD TLPDRGRSCW 

       610        620        630        640        650        660 
HLGAVWALSQ FQENELFLGM YPEEHFIEKP VKEAMARFRK NLEAIVSVIA ERNKKKQLPY 

       670 
YYLSPDRIPN SVAI

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of the cDNA for human 5-lipoxygenase." Dixon R.A.F., Jones R.E., Diehl R.E., Bennett C.D., Kargman S., Rouzer C.A. Proc. Natl. Acad. Sci. U.S.A. 85:416-420(1988) [PubMed: 3422434] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
[2]	"Molecular cloning and amino acid sequence of human 5-lipoxygenase." Matsumoto T., Funk C.D., Raadmark O., Hoeoeg J.-O., Joernvall H., Samuelsson B. Proc. Natl. Acad. Sci. U.S.A. 85:26-30(1988) [PubMed: 2829172] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	Erratum Matsumoto T., Funk C.D., Raadmark O., Hoeoeg J.-O., Joernvall H., Samuelsson B. Proc. Natl. Acad. Sci. U.S.A. 85:3406-3406(1988)
[4]	"Molecular cloning and amino acid sequence of human 5-lipoxygenase." Matsumoto T., Funk C.D., Raadmark O., Hoeoeg J.-O., Joernvall H., Samuelsson B. Adv. Prostaglandin Thromboxane Leukotriene Res. 19:466-469(1989) [PubMed: 2526519] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
[5]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[7]	"Characterization of the human 5-lipoxygenase gene." Funk C.D., Hoshiko S., Matsumoto T., Raadmark O., Samuelsson B. Proc. Natl. Acad. Sci. U.S.A. 86:2587-2591(1989) [PubMed: 2565035] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-50.
[8]	"Characterization of the human 5-lipoxygenase gene promoter." Hoshiko S., Raadmark O., Samuelsson B. Proc. Natl. Acad. Sci. U.S.A. 87:9073-9077(1990) [PubMed: 2251250] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-11.
[9]	"Reversible, calcium-dependent membrane association of human leukocyte 5-lipoxygenase." Rouzer C.A., Samuelsson B. Proc. Natl. Acad. Sci. U.S.A. 84:7393-7397(1987) [PubMed: 3118366] [Abstract] Cited for: SUBCELLULAR LOCATION.
[10]	"Evaluation of the role of conserved His and Met residues among lipoxygenases by site-directed mutagenesis of recombinant human 5-lipoxygenase." Nguyen T., Falgueyret J.-P., Abramowitz M., Riendeau D. J. Biol. Chem. 266:22057-22062(1991) [PubMed: 1939225] [Abstract] Cited for: MUTAGENESIS OF SOME HISTIDINE RESIDUES.
[11]	"Mutagenesis studies on the amino acid residues involved in the iron-binding and the activity of human 5-lipoxygenase." Ishii S., Noguchi M., Miyano M., Matsumoto T., Noma M. Biochem. Biophys. Res. Commun. 182:1482-1490(1992) [PubMed: 1540191] [Abstract] Cited for: MUTAGENESIS OF SOME RESIDUES.
[12]	"5-lipoxygenase and 5-lipoxygenase-activating protein are localized in the nuclear envelope of activated human leukocytes." Woods J.W., Evans J.F., Ethier D., Scott S., Vickers P.J., Hearn L., Heibein J.A., Charleson S., Singer I.I. J. Exp. Med. 178:1935-1946(1993) [PubMed: 8245774] [Abstract] Cited for: SUBCELLULAR LOCATION.
[13]	"Arachidonic acid promotes phosphorylation of 5-lipoxygenase at Ser-271 by MAPK-activated protein kinase 2 (MK2)." Werz O., Szellas D., Steinhilber D., Radmark O. J. Biol. Chem. 277:14793-14800(2002) [PubMed: 11844797] [Abstract] Cited for: PHOSPHORYLATION AT SER-272.
[14]	"Protein kinase A inhibits leukotriene synthesis by phosphorylation of 5-lipoxygenase on serine 523." Luo M., Jones S.M., Phare S.M., Coffey M.J., Peters-Golden M., Brock T.G. J. Biol. Chem. 279:41512-41520(2004) [PubMed: 15280375] [Abstract] Cited for: PHOSPHORYLATION AT SER-524, MUTAGENESIS OF SER-524.
[15]	"Arachidonic acid regulates the translocation of 5-lipoxygenase to the nuclear membranes in human neutrophils." Flamand N., Lefebvre J., Surette M.E., Picard S., Borgeat P. J. Biol. Chem. 281:129-136(2006) [PubMed: 16275640] [Abstract] Cited for: SUBCELLULAR LOCATION.
[16]	"Distinct parts of leukotriene C(4) synthase interact with 5-lipoxygenase and 5-lipoxygenase activating protein." Strid T., Svartz J., Franck N., Hallin E., Ingelsson B., Soederstroem M., Hammarstroem S. Biochem. Biophys. Res. Commun. 381:518-522(2009) [PubMed: 19233132] [Abstract] Cited for: INTERACTION WITH ALOX5AP AND LTC4S, SUBCELLULAR LOCATION.
[17]	"Phosphorylation of serine 271 on 5-lipoxygenase and its role in nuclear export." Flamand N., Luo M., Peters-Golden M., Brock T.G. J. Biol. Chem. 284:306-313(2009) [PubMed: 18978352] [Abstract] Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-272, MUTAGENESIS OF SER-272.
[18]	"Arachidonate lipoxygenase (ALOX) and cyclooxygenase (COX) polymorphisms and colon cancer risk." Goodman J.E., Bowman E.D., Chanock S.J., Alberg A.J., Harris C.C. Carcinogenesis 25:2467-2472(2004) [PubMed: 15308583] [Abstract] Cited for: VARIANT LYS-254.
+	Additional computationally mapped references.

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Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Cross-references

Sequence databases

J03600 mRNA. Translation: AAA36183.1.
J03571 mRNA. Translation: AAA65450.1.
J04520 Genomic DNA. Translation: AAA59522.1.
AL731567 Genomic DNA. Translation: CAI41243.1.
BC130332 mRNA. Translation: AAI30333.1.
BC132677 mRNA. Translation: AAI32678.1.
M38191 Genomic DNA. Translation: AAA63212.1.

IPI

IPI00218916.

PIR

DAHUAL. A28117.

RefSeq

NP_000689.1.

UniGene

Hs.89499

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2ABV	model	-	A	2-674	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P09917. 1 interaction.

PTM databases

PhosphoSite

P09917.

Proteomic databases

PRIDE

P09917.

Genome annotation databases

Ensembl

ENSG00000012779. Homo sapiens. [Contig view]

GeneID

240.

KEGG

hsa:240.

NMPDR

fig|9606.3.peg.3842.

Organism-specific databases

GeneCards

GC10P045189.

H-InvDB

HIX0035390.

HGNC

HGNC:435. ALOX5.

HPA

CAB005066.

MIM

152390. gene.

PharmGKB

PA46.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P09917.

HOVERGEN

P09917.

OMA

P09917. GVVTIEQ.

Enzyme and pathway databases

BRENDA

1.13.11.34. 247.

Gene expression databases

Bgee

P09917.

CleanEx

HS_ALOX5.

GermOnline

ENSG00000012779. Homo sapiens.

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

DrugBank

DB00711. Diethylcarbamazine.
DB00741. Hydrocortisone.
DB01097. Leflunomide.
DB00179. Masoprocol.
DB00939. Meclofenamic acid.
DB01017. Minocycline.
DB00471. Montelukast.
DB01103. Quinacrine.
DB00163. Vitamin E.
DB00744. Zileuton.

NextBio

956.

PMAP-CutDB

P09917.

SOURCE

Search...

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Entry information

Entry name

LOX5_HUMAN

Accession

Primary (citable) accession number: P09917
Secondary accession number(s): Q5JQ14

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 109 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PATHWAY comments

Index of metabolic and biosynthesis pathways

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Sequences

References

Web resources

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents