O75342 (LX12B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Arachidonate 12-lipoxygenase, 12R-type
Short name=12R-LOX
Short name=12R-lipoxygenase
EC=1.13.11.-

Alternative name(s):
Epidermis-type lipoxygenase 12

Gene names

Name:

ALOX12B

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	701 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Converts arachidonic acid to 12R-hydroperoxyeicosatetraenoic acid (12R-HPETE). Ref.1
Cofactor	Binds 1 iron ion per subunit By similarity.
Pathway	Lipid metabolism; leukotriene D4 biosynthesis.
Tissue specificity	Expressed in B-cells, hair follicles, foreskin keratinocytes and adult skin. Also expressed in psoriatic tissue. Ref.1
Involvement in disease	Defects in ALOX12B are a cause of non-bullous congenital ichthyosiform erythroderma (NCIE) [MIM:242100]. NCIE is a non-bullous ichthyosis, a skin disorder characterized by abnormal cornification of the epidermis. Most affected individuals are born with a tight, shiny, translucent covering called collodion membrane. The collodion membrane subsequently evolves into generalized scaling and intense redness of the skin. Clinical features are milder than in lamellar ichthyoses and demonstrate a greater variability in the intensity of erythema, size and type of scales. In contrast to lamellar ichthyoses, scales are usually white, fine and powdery, and palms and soles are severely affected. Patients suffer from palmoplantar keratoderma, often with painful fissures, digital contractures, and loss of pulp volume. Ref.5
Sequence similarities	Belongs to the lipoxygenase family. Contains 1 lipoxygenase domain. Contains 1 PLAT domain.

Ontologies

Keywords
Biological process	Leukotriene biosynthesis
Coding sequence diversity	Polymorphism
Disease	Disease mutation Ichthyosis
Ligand	Iron Metal-binding
Molecular function	Dioxygenase Oxidoreductase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	epidermis development Traceable author statement. Source: ProtInc leukotriene biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	arachidonate 12-lipoxygenase activity Traceable author statement. Source: ProtInc iron ion binding Inferred from electronic annotation. Source: InterPro lipoxygenase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 701	701	Arachidonate 12-lipoxygenase, 12R-type		PRO_0000220689
Regions
	Domain	2 – 119	118	PLAT
	Domain	120 – 701	582	Lipoxygenase
Sites
	Metal binding	398	1	Iron; catalytic By similarity
	Metal binding	403	1	Iron; catalytic By similarity
	Metal binding	578	1	Iron; catalytic By similarity
	Metal binding	582	1	Iron; catalytic By similarity
	Metal binding	701	1	Iron; via carboxylate; catalytic By similarity
Natural variations
	Natural variant	94	1	G → S. Corresponds to variant rs8077661 [ dbSNP | Ensembl ].		VAR_050000
	Natural variant	426	1	L → P in NCIE. Ref.5		VAR_015173
	Natural variant	578	1	H → Q in NCIE. Ref.5		VAR_015174

Sequences

	Sequence		Length	Mass (Da)
	O75342 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: C334075759F8B077	FASTA	701	80,356
	10 20 30 40 50 60 MATYKVRVAT GTDLLSGTRD SISLTIVGTQ GESHKQLLNH FGRDFATGAV GQYTVQCPQD 70 80 90 100 110 120 LGELIIIRLH KERYAFFPKD PWYCNYVQIC APNGRIYHFP AYQWMDGYET LALREATGKT 130 140 150 160 170 180 TADDSLPVLL EHRKEEIRAK QDFYHWRVFL PGLPSYVHIP SYRPPVRRHR NPNRPEWNGY 190 200 210 220 230 240 IPGFPILINF KATKFLNLNL RYSFLKTASF FVRLGPMALA FKVRGLLDCK HSWKRLKDIR 250 260 270 280 290 300 KIFPGKKSVV SEYVAEHWAE DTFFGYQYLN GVNPGLIRRC TRIPDKFPVT DDMVAPFLGE 310 320 330 340 350 360 GTCLQAELEK GNIYLADYRI MEGIPTVELS GRKQHHCAPL CLLHFGPEGK MMPIAIQLSQ 370 380 390 400 410 420 TPGPDCPIFL PSDSEWDWLL AKTWVRYAEF YSHEAIAHLL ETHLIAEAFC LALLRNLPMC 430 440 450 460 470 480 HPLYKLLIPH TRYTVQINSI GRAVLLNEGG LSAKGMSLGV EGFAGVMVRA LSELTYDSLY 490 500 510 520 530 540 LPNDFVERGV QDLPGYYYRD DSLAVWNALE KYVTEIITYY YPSDAAVEGD PELQSWVQEI 550 560 570 580 590 600 FKECLLGRES SGFPRCLRTV PELIRYVTIV IYTCSAKHAA VNTGQMEFTA WMPNFPASMR 610 620 630 640 650 660 NPPIQTKGLT TLETFMDTLP DVKTTCITLL VLWTLSREPD DRRPLGHFPD IHFVEEAPRR 670 680 690 700 SIEAFRQRLN QISHDIRQRN KCLPIPYYYL DPVLIENSIS I

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A 12R-lipoxygenase in human skin: mechanistic evidence, molecular cloning, and expression." Boeglin W.E., Kim R.B., Brash A.R. Proc. Natl. Acad. Sci. U.S.A. 95:6744-6749(1998) [PubMed: 9618483] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY. Tissue: Hair follicle.
[2]	"Human 12(R)-lipoxygenase and the mouse ortholog. Molecular cloning, expression, and gene chromosomal assignment." Sun D., McDonnell M., Chen X.-S., Lakkis M.M., Li H., Isaacs S.N., Elsea S.H., Patel P.I., Funk C.D. J. Biol. Chem. 273:33540-33547(1998) [PubMed: 9837935] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION. Tissue: B-cell.
[3]	"A gene cluster encoding human epidermis-type lipoxygenases at chromosome 17p13.1: cloning, physical mapping, and expression." Krieg P., Marks F., Fuerstenberger G. Genomics 73:323-330(2001) [PubMed: 11350124] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"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.
[5]	"Lipoxygenase-3 (ALOXE3) and 12(R)-lipoxygenase (ALOX12B) are mutated in non-bullous congenital ichthyosiform erythroderma (NCIE) linked to chromosome 17p13.1." Jobard F., Lefevre C., Karaduman A., Blanchet-Bardon C., Emre S., Weissenbach J., Ozguc M., Lathrop M., Prud'homme J.-F., Fischer J. Hum. Mol. Genet. 11:107-113(2002) [PubMed: 11773004] [Abstract] Cited for: VARIANTS NCIE PRO-426 AND GLN-578.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF038461 mRNA. Translation: AAC39770.1. AF059250 mRNA. Translation: AAC79680.1. AJ305026, AJ305027 Genomic DNA. Translation: CAC34520.1. BC041058 mRNA. Translation: AAH41058.1.
IPI	IPI00025278.
RefSeq	NP_001130.1. NM_001139.2.
UniGene	Hs.136574.
3D structure databases
ProteinModelPortal	O75342.
SMR	O75342. Positions 2-701.
ModBase	Search...
Protein-protein interaction databases
STRING	O75342.
PTM databases
PhosphoSite	O75342.
Proteomic databases
PRIDE	O75342.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000319144; ENSP00000315167; ENSG00000179477.
GeneID	242.
KEGG	hsa:242.
UCSC	uc002gjy.1. human.
Organism-specific databases
CTD	242.
GeneCards	GC17M007975.
H-InvDB	HIX0027119.
HGNC	HGNC:430. ALOX12B.
HPA	HPA024002.
MIM	242100. phenotype. 603741. gene.
neXtProt	NX_O75342.
Orphanet	79394. Congenital nonbullous ichthyosiform erythroderma.
PharmGKB	PA24722.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG06594.
GeneTree	ENSGT00550000074415.
HOGENOM	HBG443995.
HOVERGEN	HBG005150.
InParanoid	O75342.
OMA	YVHIPSY.
OrthoDB	EOG48SGSH.
PhylomeDB	O75342.
Enzyme and pathway databases
Pathway_Interaction_DB	il23pathway. IL23-mediated signaling events.
Gene expression databases
ArrayExpress	O75342.
Bgee	O75342.
CleanEx	HS_ALOX12B.
Genevestigator	O75342.
GermOnline	ENSG00000179477. Homo sapiens.
Family and domain databases
InterPro	IPR008976. Lipase_LipOase. IPR000907. LipOase. IPR013819. LipOase_C. IPR020834. LipOase_CS. IPR020833. LipOase_Fe_BS. IPR001024. LipOase_LH2. IPR001885. LipOase_mml. [Graphical view]
Gene3D	G3DSA:2.60.60.20. Lipase_LipOase. 1 hit.
KO	K08021.
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]
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
NextBio	966.
SOURCE	Search...

Entry information

Entry name

LX12B_HUMAN

Accession

Primary (citable) accession number: O75342

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 11, 2001
Last sequence update:	November 1, 1998
Last modified:	January 25, 2012
This is version 106 of the entry and version 1 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.