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Protein

Arachidonate 5-lipoxygenase

Gene

ALOX5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Catalyzes the first step in leukotriene biosynthesis, and thereby plays a role in inflammatory processes.1 Publication

Catalytic activityi

Arachidonate + O2 = leukotriene A4 + H2O.1 Publication

Cofactori

Protein has several cofactor binding sites:
  • Fe cationPROSITE-ProRule annotation1 PublicationNote: Binds 1 Fe cation per subunit.PROSITE-ProRule annotation1 Publication
  • Ca2+By similarityNote: Binds 2 calcium ions per subunit.By similarity

Pathwayi: leukotriene A4 biosynthesis

This protein is involved in the pathway leukotriene A4 biosynthesis, which is part of Lipid metabolism.
View all proteins of this organism that are known to be involved in the pathway leukotriene A4 biosynthesis and in Lipid metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi17Calcium 1; via carbonyl oxygen; structuralBy similarity1
Metal bindingi18Calcium 2; via carbonyl oxygen; structuralBy similarity1
Metal bindingi19Calcium 2; structuralBy similarity1
Metal bindingi44Calcium 2; structuralBy similarity1
Metal bindingi45Calcium 2; via carbonyl oxygen; structuralBy similarity1
Metal bindingi47Calcium 2; structuralBy similarity1
Metal bindingi79Calcium 1; via carbonyl oxygen; structuralBy similarity1
Metal bindingi80Calcium 1; via carbonyl oxygen; structuralBy similarity1
Sitei103Essential for stabilizing binding to COTL11
Metal bindingi368Iron; catalytic1
Metal bindingi373Iron; catalytic1
Metal bindingi551Iron; catalytic1
Metal bindingi555Iron; catalytic1
Metal bindingi674Iron; via carboxylate; catalytic1

GO - Molecular functioni

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

GO - Biological processi

Keywordsi

Molecular functionDioxygenase, Oxidoreductase
Biological processLeukotriene biosynthesis
LigandCalcium, Iron, Metal-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS00336-MONOMER
BRENDAi1.13.11.34 2681
ReactomeiR-HSA-2142688 Synthesis of 5-eicosatetraenoic acids
R-HSA-2142691 Synthesis of Leukotrienes (LT) and Eoxins (EX)
R-HSA-2142700 Synthesis of Lipoxins (LX)
R-HSA-6785807 Interleukin-4 and 13 signaling
R-HSA-6798695 Neutrophil degranulation
R-HSA-9012546 Interleukin-18 signaling
R-HSA-9018676 Biosynthesis of D-series resolvins
R-HSA-9018682 Biosynthesis of maresins
R-HSA-9018896 Biosynthesis of E-series 18(S)-resolvins
R-HSA-9020265 Biosynthesis of aspirin-triggered D-series resolvins
R-HSA-9023661 Biosynthesis of E-series 18(R)-resolvins
R-HSA-9026286 Biosynthesis of DPAn-3-derived protectins and resolvins
R-HSA-9026290 Biosynthesis of DPAn-3-derived maresins
R-HSA-9026403 Biosynthesis of DPAn-3-derived 13-series resolvins
R-HSA-9027604 Biosynthesis of electrophilic Omega-3 PUFA oxo-derivatives
SABIO-RKiP09917
SIGNORiP09917
UniPathwayiUPA00877

Chemistry databases

SwissLipidsiSLP:000000669

Names & Taxonomyi

Protein namesi
Recommended name:
Arachidonate 5-lipoxygenase (EC:1.13.11.34)
Short name:
5-LO
Short name:
5-lipoxygenase
Gene namesi
Name:ALOX5
Synonyms:LOG5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000012779.10
HGNCiHGNC:435 ALOX5
MIMi152390 gene
neXtProtiNX_P09917

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi103W → A: Abolishes binding to COTL1. 1 Publication1
Mutagenesisi272S → A: Loss of phosphorylation site. Permits export from the nucleus. 1 Publication1
Mutagenesisi359D → N: No loss of activity. 1
Mutagenesisi363H → S or N: Still some substantial activity. 1 Publication1
Mutagenesisi368H → S, N or A: No activity. 2 Publications1
Mutagenesisi373H → S or N: No activity. 2 Publications1
Mutagenesisi377E → Q: No activity. 1 Publication1
Mutagenesisi391H → A: No activity. 2 Publications1
Mutagenesisi391H → S or N: Still some substantial activity. 2 Publications1
Mutagenesisi400H → A: No activity. 2 Publications1
Mutagenesisi400H → S or N: Still some substantial activity. 2 Publications1
Mutagenesisi433H → N or A: Almost no loss of activity. 1
Mutagenesisi524S → A: Prevents phosphorylation by PKA. 1 Publication1
Mutagenesisi551H → N or A: No activity. 1 Publication1

Organism-specific databases

DisGeNETi240
MalaCardsiALOX5
OpenTargetsiENSG00000012779
PharmGKBiPA46

Chemistry databases

ChEMBLiCHEMBL215
DrugBankiDB00233 Aminosalicylic Acid
DB01014 Balsalazide
DB00586 Diclofenac
DB00711 Diethylcarbamazine
DB01892 Hyperforin
DB04725 Licofelone
DB00179 Masoprocol
DB00939 Meclofenamic acid
DB00244 Mesalazine
DB01017 Minocycline
DB05431 MLN-977
DB00471 Montelukast
DB00795 Sulfasalazine
DB00163 Vitamin E
DB00744 Zileuton
GuidetoPHARMACOLOGYi1385

Polymorphism and mutation databases

BioMutaiALOX5
DMDMi126407

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002206931 – 674Arachidonate 5-lipoxygenaseAdd BLAST674

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei272Phosphoserine; by MAPKAPK22 Publications1
Modified residuei524Phosphoserine; by PKA1 Publication1

Post-translational modificationi

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.3 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP09917
PaxDbiP09917
PeptideAtlasiP09917
PRIDEiP09917
ProteomicsDBi52278

PTM databases

iPTMnetiP09917
PhosphoSitePlusiP09917

Miscellaneous databases

PMAP-CutDBiP09917

Expressioni

Gene expression databases

BgeeiENSG00000012779
CleanExiHS_ALOX5
ExpressionAtlasiP09917 baseline and differential
GenevisibleiP09917 HS

Organism-specific databases

HPAiHPA071285

Interactioni

Subunit structurei

Interacts with ALOX5AP and LTC4S. Interacts with COTL1, the interaction is required for stability and efficient catalytic activity.3 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi106741, 61 interactors
DIPiDIP-30950N
IntActiP09917, 27 interactors
MINTiP09917
STRINGi9606.ENSP00000363512

Chemistry databases

BindingDBiP09917

Structurei

Secondary structure

1674
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi4 – 10Combined sources7
Beta strandi20 – 30Combined sources11
Beta strandi36 – 38Combined sources3
Beta strandi51 – 56Combined sources6
Beta strandi64 – 73Combined sources10
Beta strandi75 – 77Combined sources3
Beta strandi81 – 89Combined sources9
Beta strandi95 – 104Combined sources10
Beta strandi106 – 108Combined sources3
Beta strandi110 – 113Combined sources4
Helixi120 – 122Combined sources3
Helixi126 – 142Combined sources17
Beta strandi155 – 157Combined sources3
Helixi161 – 163Combined sources3
Helixi166 – 168Combined sources3
Beta strandi171 – 176Combined sources6
Helixi178 – 188Combined sources11
Helixi192 – 194Combined sources3
Helixi205 – 212Combined sources8
Turni213 – 215Combined sources3
Helixi218 – 226Combined sources9
Helixi230 – 239Combined sources10
Helixi260 – 263Combined sources4
Turni264 – 266Combined sources3
Helixi273 – 278Combined sources6
Beta strandi282 – 286Combined sources5
Helixi288 – 290Combined sources3
Beta strandi297 – 300Combined sources4
Helixi303 – 306Combined sources4
Beta strandi310 – 315Combined sources6
Beta strandi321 – 331Combined sources11
Beta strandi333 – 336Combined sources4
Helixi345 – 365Combined sources21
Helixi366 – 372Combined sources7
Helixi373 – 386Combined sources14
Helixi392 – 397Combined sources6
Helixi398 – 400Combined sources3
Helixi404 – 414Combined sources11
Helixi421 – 423Combined sources3
Turni427 – 431Combined sources5
Helixi432 – 441Combined sources10
Helixi447 – 449Combined sources3
Helixi451 – 457Combined sources7
Turni463 – 465Combined sources3
Helixi470 – 493Combined sources24
Helixi497 – 501Combined sources5
Helixi504 – 515Combined sources12
Turni516 – 520Combined sources5
Helixi522 – 524Combined sources3
Helixi533 – 547Combined sources15
Helixi549 – 555Combined sources7
Helixi558 – 562Combined sources5
Helixi565 – 567Combined sources3
Beta strandi572 – 574Combined sources3
Beta strandi579 – 581Combined sources3
Helixi585 – 591Combined sources7
Helixi595 – 608Combined sources14
Helixi629 – 653Combined sources25
Helixi665 – 667Combined sources3
Beta strandi669 – 671Combined sources3

3D structure databases

ProteinModelPortaliP09917
SMRiP09917
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP09917

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini2 – 118PLATPROSITE-ProRule annotationAdd BLAST117
Domaini119 – 674LipoxygenasePROSITE-ProRule annotationAdd BLAST556

Sequence similaritiesi

Belongs to the lipoxygenase family.Curated

Phylogenomic databases

eggNOGiENOG410IF0U Eukaryota
ENOG410YN4N LUCA
GeneTreeiENSGT00550000074415
HOGENOMiHOG000234358
HOVERGENiHBG005150
InParanoidiP09917
KOiK00461
OMAiCYRWITG
OrthoDBiEOG091G04A4
PhylomeDBiP09917
TreeFamiTF105320

Family and domain databases

InterProiView protein in InterPro
IPR000907 LipOase
IPR013819 LipOase_C
IPR036226 LipOase_C_sf
IPR020834 LipOase_CS
IPR020833 LipOase_Fe_BS
IPR001885 LipOase_mml
IPR001024 PLAT/LH2_dom
IPR036392 PLAT/LH2_dom_sf
PANTHERiPTHR11771 PTHR11771, 1 hit
PfamiView protein in Pfam
PF00305 Lipoxygenase, 1 hit
PF01477 PLAT, 1 hit
PRINTSiPR00087 LIPOXYGENASE
PR00467 MAMLPOXGNASE
SMARTiView protein in SMART
SM00308 LH2, 1 hit
SUPFAMiSSF48484 SSF48484, 1 hit
SSF49723 SSF49723, 1 hit
PROSITEiView protein in PROSITE
PS00711 LIPOXYGENASE_1, 1 hit
PS00081 LIPOXYGENASE_2, 1 hit
PS51393 LIPOXYGENASE_3, 1 hit
PS50095 PLAT, 1 hit

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: P09917-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MPSYTVTVAT GSQWFAGTDD YIYLSLVGSA GCSEKHLLDK PFYNDFERGA
60 70 80 90 100
VDSYDVTVDE ELGEIQLVRI EKRKYWLNDD WYLKYITLKT PHGDYIEFPC
110 120 130 140 150
YRWITGDVEV VLRDGRAKLA RDDQIHILKQ HRRKELETRQ KQYRWMEWNP
160 170 180 190 200
GFPLSIDAKC HKDLPRDIQF DSEKGVDFVL NYSKAMENLF INRFMHMFQS
210 220 230 240 250
SWNDFADFEK IFVKISNTIS ERVMNHWQED LMFGYQFLNG CNPVLIRRCT
260 270 280 290 300
ELPEKLPVTT EMVECSLERQ LSLEQEVQQG NIFIVDFELL DGIDANKTDP
310 320 330 340 350
CTLQFLAAPI CLLYKNLANK IVPIAIQLNQ IPGDENPIFL PSDAKYDWLL
360 370 380 390 400
AKIWVRSSDF HVHQTITHLL RTHLVSEVFG IAMYRQLPAV HPIFKLLVAH
410 420 430 440 450
VRFTIAINTK AREQLICECG LFDKANATGG GGHVQMVQRA MKDLTYASLC
460 470 480 490 500
FPEAIKARGM ESKEDIPYYF YRDDGLLVWE AIRTFTAEVV DIYYEGDQVV
510 520 530 540 550
EEDPELQDFV NDVYVYGMRG RKSSGFPKSV KSREQLSEYL TVVIFTASAQ
560 570 580 590 600
HAAVNFGQYD WCSWIPNAPP TMRAPPPTAK GVVTIEQIVD TLPDRGRSCW
610 620 630 640 650
HLGAVWALSQ FQENELFLGM YPEEHFIEKP VKEAMARFRK NLEAIVSVIA
660 670
ERNKKKQLPY YYLSPDRIPN SVAI
Length:674
Mass (Da):77,983
Last modified:January 23, 2007 - v2
Checksum:i36F38C0A9E86BB21
GO
Isoform 2 (identifier: P09917-2) [UniParc]FASTAAdd to basket
Also known as: Delta-13

The sequence of this isoform differs from the canonical sequence as follows:
     559-615: Missing.

Show »
Length:617
Mass (Da):71,564
Checksum:i3DE1D2FE62471315
GO
Isoform 3 (identifier: P09917-3) [UniParc]FASTAAdd to basket
Also known as: delta-p10

The sequence of this isoform differs from the canonical sequence as follows:
     424-455: Missing.

Show »
Length:642
Mass (Da):74,635
Checksum:iE9A8CCA67CF74DB6
GO
Isoform 4 (identifier: P09917-4) [UniParc]FASTAAdd to basket
Also known as: delta-10-13

The sequence of this isoform differs from the canonical sequence as follows:
     425-533: ANATGGGGHV...SGFPKSVKSR → VHGRGGRHLL...EPRGHCQRDC
     534-674: Missing.

Show »
Length:533
Mass (Da):61,244
Checksum:i6C57FD0816BD2D9E
GO
Isoform 5 (identifier: P09917-5) [UniParc]FASTAAdd to basket
Also known as: alpha-10

The sequence of this isoform differs from the canonical sequence as follows:
     485-674: Missing.

Show »
Length:484
Mass (Da):56,291
Checksum:i4A500F8D7404EC9D
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_028018254E → K1 PublicationCorresponds to variant dbSNP:rs2228065Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_053534424 – 455Missing in isoform 3. 1 PublicationAdd BLAST32
Alternative sequenceiVSP_053535425 – 533ANATG…SVKSR → VHGRGGRHLLRGRPGGGGGP GAAGLRERCLRVRHAGPQVL RLPQVGQEPGAAVGVPDRGD LHRLRPARRGQLRPAVPGHV PRRAFYREACEGSHGPIPQE PRGHCQRDC in isoform 4. 1 PublicationAdd BLAST109
Alternative sequenceiVSP_053536485 – 674Missing in isoform 5. 1 PublicationAdd BLAST190
Alternative sequenceiVSP_053537534 – 674Missing in isoform 4. 1 PublicationAdd BLAST141
Alternative sequenceiVSP_046998559 – 615Missing in isoform 2. 2 PublicationsAdd BLAST57

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J03600 mRNA Translation: AAA36183.1
J03571 mRNA Translation: AAA65450.1
HM592258 mRNA Translation: ADR30798.1
HM592259 mRNA Translation: ADR30799.1
HM592260 mRNA Translation: ADR30800.1
HM592261 mRNA Translation: ADR30801.1
J04520 Genomic DNA Translation: AAA59522.1
AL731567 Genomic DNA No translation available.
BC130332 mRNA Translation: AAI30333.1
BC132677 mRNA Translation: AAI32678.1
BC143985 mRNA Translation: AAI43986.1
M38191 Genomic DNA Translation: AAA63212.1
CCDSiCCDS58078.1 [P09917-2]
CCDS7212.1 [P09917-1]
PIRiA28117 DAHUAL
RefSeqiNP_000689.1, NM_000698.4 [P09917-1]
NP_001243082.1, NM_001256153.2 [P09917-3]
NP_001243083.1, NM_001256154.2 [P09917-2]
NP_001307790.1, NM_001320861.1
UniGeneiHs.89499

Genome annotation databases

EnsembliENST00000374391; ENSP00000363512; ENSG00000012779 [P09917-1]
ENST00000542434; ENSP00000437634; ENSG00000012779 [P09917-2]
ENST00000610656; ENSP00000484468; ENSG00000275565 [P09917-1]
ENST00000622021; ENSP00000479958; ENSG00000275565 [P09917-2]
GeneIDi240
KEGGihsa:240
UCSCiuc001jce.5 human [P09917-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiLOX5_HUMAN
AccessioniPrimary (citable) accession number: P09917
Secondary accession number(s): B7ZLS0
, E5FPY5, E5FPY7, E5FPY8, Q5JQ14
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: January 23, 2007
Last modified: July 18, 2018
This is version 197 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: 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. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

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