P18054 (LOX12_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Arachidonate 12-lipoxygenase, 12S-type
Short name=12S-LOX
Short name=12S-lipoxygenase
EC=1.13.11.31

Alternative name(s):
Platelet-type lipoxygenase 12

Gene names

Name:	ALOX12
Synonyms:	LOG12

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	663 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	Oxygenase and 14,15-leukotriene A4 synthase activity.
Catalytic activity	Arachidonate + O2 = (5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate.
Cofactor	Binds 1 iron ion per subunit.
Pathway	Lipid metabolism; leukotriene D4 biosynthesis.
Subcellular location	Cytoplasm.
Sequence similarities	Belongs to the lipoxygenase family. Contains 1 lipoxygenase domain. Contains 1 PLAT domain.

Ontologies

Keywords
Biological process	Leukotriene biosynthesis
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	Iron Metal-binding
Molecular function	Dioxygenase Oxidoreductase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	aging Inferred from electronic annotation. Source: Compara arachidonic acid metabolic process Traceable author statement. Source: Reactome cellular component movement Inferred from mutant phenotype PubMed 14669797. Source: UniProtKB cellular response to lipid Inferred from electronic annotation. Source: Compara fatty acid oxidation Inferred from mutant phenotype PubMed 15111312. Source: UniProtKB hepoxilin metabolic process Traceable author statement. Source: Reactome leukotriene biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW lipoxin metabolic process Traceable author statement. Source: Reactome lipoxygenase pathway Traceable author statement. Source: Reactome negative regulation of apoptotic process Inferred from mutant phenotype PubMed 15105833PubMed 15305153. Source: UniProtKB positive regulation of apoptotic process Inferred from electronic annotation. Source: Compara positive regulation of cell adhesion Inferred from mutant phenotype PubMed 14669797. Source: UniProtKB positive regulation of cell growth Inferred from mutant phenotype PubMed 14767568. Source: UniProtKB positive regulation of cell proliferation Inferred from mutant phenotype PubMed 15010818. Source: UniProtKB positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from electronic annotation. Source: Compara positive regulation of endothelial cell differentiation Inferred from electronic annotation. Source: Compara positive regulation of endothelial cell migration Inferred from electronic annotation. Source: Compara positive regulation of gene expression Inferred from electronic annotation. Source: Compara positive regulation of mitochondrial depolarization Inferred from electronic annotation. Source: Compara positive regulation of smooth muscle cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of vasodilation Inferred from electronic annotation. Source: Compara superoxide anion generation Non-traceable author statement PubMed 15107407. Source: UniProtKB
Cellular_component	cytosol Inferred from direct assay PubMed 15107407. Source: UniProtKB sarcolemma Inferred from direct assay PubMed 15107407. Source: UniProtKB
Molecular_function	arachidonate 12-lipoxygenase activity Inferred from direct assay Ref.2Ref.1. Source: UniProtKB hepoxilin A3 synthase activity Traceable author statement. Source: Reactome hepoxilin-epoxide hydrolase activity Inferred from sequence or structural similarity. Source: UniProtKB iron ion binding Inferred from electronic annotation. Source: InterPro lipoxygenase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
KRT5	P13647	7	EBI-1633210,EBI-702187
LMNA	P02545	4	EBI-1633210,EBI-351935

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 663

662

Arachidonate 12-lipoxygenase, 12S-type

PRO_0000220682

Regions

Domain

2 – 114

113

PLAT

Domain

115 – 663

549

Lipoxygenase

Sites

Metal binding

360

1

Iron; catalytic

Metal binding

365

1

Iron; catalytic

Metal binding

540

1

Iron; catalytic

Metal binding

544

1

Iron; catalytic By similarity

Metal binding

663

1

Iron; via carboxylate; catalytic By similarity

Natural variations

Natural variant

259

1

E → K.
Corresponds to variant rs4987104 [ dbSNP | Ensembl ].

VAR_030471

Natural variant

261

1

Q → R. Ref.2 Ref.4 Ref.5 Ref.11
Corresponds to variant rs1126667 [ dbSNP | Ensembl ].

VAR_018743

Natural variant

298

1

A → T.

VAR_004279

Natural variant

322

1

N → S. Ref.1 Ref.3 Ref.4
Corresponds to variant rs434473 [ dbSNP | Ensembl ].

VAR_018744

Natural variant

430

1

R → H. Ref.4
Corresponds to variant rs11571342 [ dbSNP | Ensembl ].

VAR_018745

Experimental info

Sequence conflict

189 – 192

4

RVYT → PCLH in AAA51533. Ref.3

Sequence conflict

345

1

S → C in AAA51533. Ref.3

Sequence conflict

389

1

L → P in AAA60056. Ref.1

Secondary structure

1

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663

Helix Strand Turn

Details...

Helix

182 – 195

14

Beta strand

198 – 200

3

Helix

203 – 207

5

Helix

213 – 221

9

Helix

225 – 234

10

Helix

258 – 269

12

Beta strand

273 – 277

5

Helix

279 – 281

3

Beta strand

300 – 305

6

Beta strand

311 – 319

9

Beta strand

325 – 327

3

Helix

337 – 357

21

Helix

358 – 364

7

Helix

365 – 378

14

Helix

384 – 389

6

Helix

390 – 392

3

Helix

426 – 434

9

Turn

438 – 441

4

Helix

443 – 449

7

Helix

459 – 482

24

Helix

486 – 491

6

Helix

493 – 503

11

Turn

504 – 508

5

Helix

510 – 512

3

Helix

522 – 536

15

Helix

538 – 544

7

Helix

547 – 551

5

Helix

554 – 556

3

Beta strand

567 – 571

5

Helix

574 – 580

7

Helix

584 – 597

14

Helix

618 – 643

26

Helix

654 – 656

3

Beta strand

657 – 660

4

Sequences

	Sequence		Length	Mass (Da)
	P18054 [UniParc]. Last modified February 6, 2007. Version 4. Checksum: C4D6D5B320666A77	FASTA	663	75,694
	10 20 30 40 50 60 MGRYRIRVAT GAWLFSGSYN RVQLWLVGTR GEAELELQLR PARGEEEEFD HDVAEDLGLL 70 80 90 100 110 120 QFVRLRKHHW LVDDAWFCDR ITVQGPGACA EVAFPCYRWV QGEDILSLPE GTARLPGDNA 130 140 150 160 170 180 LDMFQKHREK ELKDRQQIYC WATWKEGLPL TIAADRKDDL PPNMRFHEEK RLDFEWTLKA 190 200 210 220 230 240 GALEMALKRV YTLLSSWNCL EDFDQIFWGQ KSALAEKVRQ CWQDDELFSY QFLNGANPML 250 260 270 280 290 300 LRRSTSLPSR LVLPSGMEEL QAQLEKELQN GSLFEADFIL LDGIPANVIR GEKQYLAAPL 310 320 330 340 350 360 VMLKMEPNGK LQPMVIQIQP PNPSSPTPTL FLPSDPPLAW LLAKSWVRNS DFQLHEIQYH 370 380 390 400 410 420 LLNTHLVAEV IAVATMRCLP GLHPIFKFLI PHIRYTMEIN TRARTQLISD GGIFDKAVST 430 440 450 460 470 480 GGGGHVQLLR RAAAQLTYCS LCPPDDLADR GLLGLPGALY AHDALRLWEI IARYVEGIVH 490 500 510 520 530 540 LFYQRDDIVK GDPELQAWCR EITEVGLCQA QDRGFPVSFQ SQSQLCHFLT MCVFTCTAQH 550 560 570 580 590 600 AAINQGQLDW YAWVPNAPCT MRMPPPTTKE DVTMATVMGS LPDVRQACLQ MAISWHLSRR 610 620 630 640 650 660 QPDMVPLGHH KEKYFSGPKP KAVLNQFRTD LEKLEKEITA RNEQLDWPYE YLKPSCIENS VTI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning, primary structure, and expression of the human platelet/erythroleukemia cell 12-lipoxygenase." Funk C.D., Furci L., Fitzgerald G.A. Proc. Natl. Acad. Sci. U.S.A. 87:5638-5642(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT SER-322.
[2]	"Cloning of the cDNA for human 12-lipoxygenase." Izumi T., Hoshiko S., Raadmark O., Samuelsson B. Proc. Natl. Acad. Sci. U.S.A. 87:7477-7481(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ARG-261.
[3]	"Molecular cloning and expression of human arachidonate 12-lipoxygenase." Yoshimoto T., Yamamoto Y., Arakawa T., Suzuki H., Yamamoto S., Yokoyama C., Tanabe T., Toh H. Biochem. Biophys. Res. Commun. 172:1230-1235(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT SER-322.
[4]	SeattleSNPs variation discovery resource Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-261; SER-322 AND HIS-430.
[5]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ARG-261.
[6]	"Structure and chromosomal localization of human arachidonate 12-lipoxygenase gene." Yoshimoto T., Arakawa T., Hada T., Yamamoto S., Takahashi E. J. Biol. Chem. 267:24805-24809(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-112.
[7]	"Characterization of human 12-lipoxygenase genes." Funk C.D., Funk L.B., Fitzgerald G.A., Samuelsson B. Proc. Natl. Acad. Sci. U.S.A. 89:3962-3966(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-45.
[8]	"Epidermis contains platelet-type 12-lipoxygenase that is overexpressed in germinal layer keratinocytes in psoriasis." Hussain H., Shornick L.P., Shannon V.R., Wilson J.D., Funk C.D., Pentland A.P., Holtzman M.J. Am. J. Physiol. 266:C243-C253(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 340-427. Tissue: Skin.
[9]	"EU-IMAGE: full-insert length sequencing of human cDNA clones." Persson A.E., Lundeberg J., Uhlen M. Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 531-663.
[10]	"Crystal structure of the lipoxygenase domain of human arachidonate 12-lipoxygenase, 12s-type." Structural genomics consortium (SGC) Submitted (FEB-2009) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 172-662 IN COMPLEX WITH IRON IONS.
[11]	"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] [Europe PMC] [Abstract] Cited for: VARIANT ARG-261.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M35418 mRNA. Translation: AAA60056.1.
M58704 mRNA. Translation: AAA59523.1.
M62982 mRNA. Translation: AAA51533.1.
AY527817 Genomic DNA. Translation: AAS00094.1.
BC069557 mRNA. Translation: AAH69557.1.
D12638 Genomic DNA. Translation: BAA02162.1.
M87004 Genomic DNA. Translation: AAA51587.1.
S68587 mRNA. Translation: AAD14020.1.
AF143883 mRNA. Translation: AAD32700.1.

IPI

IPI00218915.

PIR

A38283.

RefSeq

NP_000688.2. NM_000697.2.

UniGene

Hs.654431.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2ABU	model	-	A	2-663	[»]
3D3L	X-ray	2.60	A/B	172-662	[»]

ProteinModelPortal

P18054.

ModBase

Search...

Protein-protein interaction databases

IntAct

P18054. 4 interactions.

MINT

MINT-1206406.

STRING

9606.ENSP00000251535.

PTM databases

PhosphoSite

P18054.

Polymorphism databases

DMDM

125987838.

Proteomic databases

PaxDb

P18054.

PRIDE

P18054.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000251535; ENSP00000251535; ENSG00000108839.

GeneID

239.

KEGG

hsa:239.

UCSC

uc002gdx.4. human.

Organism-specific databases

CTD

239.

GeneCards

GC17P006899.

H-InvDB

HIX0039067.

HGNC

HGNC:429. ALOX12.

HPA

CAB019287.
HPA010691.

MIM

152391. gene.

neXtProt

NX_P18054.

PharmGKB

PA45.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG69653.

HOGENOM

HOG000234358.

HOVERGEN

HBG005150.

InParanoid

P18054.

KO

K00458.

OMA

HHKEKYF.

OrthoDB

EOG4W0XCM.

PhylomeDB

P18054.

Enzyme and pathway databases

BioCyc

MetaCyc:HS03167-MONOMER.

Reactome

REACT_111217. Metabolism.

UniPathway

UPA00880.

Gene expression databases

Bgee

P18054.

CleanEx

HS_ALOX12.

Genevestigator

P18054.

GermOnline

ENSG00000108839. Homo sapiens.

Family and domain databases

Gene3D

2.60.60.20. 1 hit.

InterPro

IPR008976. Lipase_LipOase.
IPR000907. LipOase.
IPR013819. LipOase_C.
IPR020834. LipOase_CS.
IPR020833. LipOase_Fe_BS.
IPR001024. LipOase_LH2.
IPR001885. LipOase_mml.
[Graphical view]

PANTHER

PTHR11771. PTHR11771. 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]

SUPFAM

SSF49723. Lipase_LipOase. 1 hit.
SSF48484. Lipoxygenase. 1 hit.

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

BindingDB

P18054.

ChEMBL

CHEMBL3687.

EvolutionaryTrace

P18054.

GenomeRNAi

239.

NextBio

952.

SOURCE

Search...

Entry information

Entry name

LOX12_HUMAN

Accession

Primary (citable) accession number: P18054
Secondary accession number(s): O95569, Q6ISF8, Q9UQM4

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	February 6, 2007
Last modified:	May 29, 2013
This is version 147 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.