Reviewed, UniProtKB/Swiss-Prot P18054 (LOX12_HUMAN)

Names and origin

Protein names

Recommended name:
    Arachidonate 12-lipoxygenase, 12S-type
      Short name=12-LOX
    EC=1.13.11.31
Alternative name(s):
    Platelet-type lipoxygenase 12

Gene names

Name:	ALOX12
Synonyms:	LOG12

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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
Gene Ontology (GO)
Biological process	anti-apoptosis Inferred from mutant phenotype. Source: UniProtKB cell motion Inferred from mutant phenotype. Source: UniProtKB fatty acid oxidation Inferred from mutant phenotype. Source: UniProtKB leukotriene biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of cell adhesion Inferred from mutant phenotype. Source: UniProtKB positive regulation of cell growth Inferred from mutant phenotype. Source: UniProtKB positive regulation of cell proliferation Inferred from mutant phenotype. Source: UniProtKB superoxide anion generation Non-traceable author statement. Source: UniProtKB
Cellular component	cytosol Inferred from direct assay. Source: UniProtKB sarcolemma Inferred from direct assay. Source: UniProtKB
Molecular function	arachidonate 12-lipoxygenase activity Ref.1 Ref.2 Inferred from direct assay. Source: UniProtKB hepoxilin-epoxide hydrolase activity Inferred from sequence or structural similarity. Source: UniProtKB iron ion binding Inferred from electronic annotation. Source: UniProtKB-KW lipoxygenase activity Inferred from electronic annotation. Source: InterPro protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ITGB4	P16144	2	EBI-1633210,EBI-948678
KRT5	P13647	3	EBI-1633210,EBI-702187
LMNA	P02545	3	EBI-1633210,EBI-351935
TRIB1	Q96RU8	2	EBI-1633210,EBI-492555

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: dbSNP rs4987104.

VAR_030471

Natural variant

261

1

Q → R: dbSNP rs1126667. Ref.2 Ref.4 Ref.5 Ref.11

VAR_018743

Natural variant

298

1

A → T

VAR_004279

Natural variant

322

1

N → S: dbSNP rs434473. Ref.4 Ref.1 Ref.3

VAR_018744

Natural variant

430

1

R → H: dbSNP rs11571342. Ref.4

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

183 – 195

13

Beta strand

198 – 200

3

Helix

203 – 207

5

Helix

213 – 221

9

Helix

225 – 230

6

Turn

231 – 233

3

Helix

258 – 269

12

Beta strand

273 – 277

5

Helix

279 – 281

3

Beta strand

300 – 306

7

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 – 475

17

Helix

479 – 482

4

Helix

486 – 489

4

Helix

493 – 503

11

Helix

510 – 512

3

Helix

522 – 536

15

Helix

538 – 544

7

Helix

548 – 551

4

Helix

554 – 556

3

Beta strand

567 – 571

5

Helix

574 – 577

4

Helix

584 – 597

14

Helix

619 – 643

25

Helix

654 – 656

3

Beta strand

657 – 660

4

Sequences

	Sequence		Length	Mass (Da)
	P18054-1 [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: 2377602] [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: 2217179] [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: 2244907] [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: 15489334] [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: 1447217] [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: 1570320] [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: 8304420] [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: 15308583] [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

EMBLGenBankDDBJ

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.

UniGene

Hs.654431

3D structure databases

PDBPDBe

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

ModBase

Search...

Protein-protein interaction databases

IntAct

P18054. 4 interactions.

STRING

P18054.

Proteomic databases

PRIDE

P18054.

Genome annotation databases

Ensembl

ENST00000251535; ENSP00000251535; ENSG00000108839; Homo sapiens. [Genome view]
ENST00000406228; ENSP00000384466; ENSG00000108839; Homo sapiens. [Genome view]

GeneID

239.

KEGG

hsa:239.

NMPDR

fig|9606.3.peg.12986.

UCSC

uc002gdx.2. human.

Organism-specific databases

CTD

239.

GeneCards

GC17P006840.

H-InvDB

HIX0039067.

HGNC

HGNC:429. ALOX12.

HPA

CAB019287.
HPA010691.

MIM

152391. gene.

PharmGKB

PA45.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P18054.

HOVERGEN

P18054.

OMA

ACLQMAI.

Enzyme and pathway databases

BRENDA

1.13.11.31. 247.

Gene expression databases

ArrayExpress

P18054.

Bgee

P18054.

CleanEx

HS_ALOX12.

Genevestigator

P18054.

GermOnline

ENSG00000108839. 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

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:	November 3, 2009
This is version 114 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.