P81383 (OXLA_OPHHA) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: L-amino-acid oxidase Short name=LAAO Short name=LAO Short name=Oh-LAAO EC=1.4.3.2
Organism	Ophiophagus hannah (King cobra) (Naja hannah)
Taxonomic identifier	8665 [NCBI]
Taxonomic lineage	Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Lepidosauria › Squamata › Scleroglossa › Serpentes › Colubroidea › Elapidae › Elapinae › Ophiophagus

Protein attributes

Sequence length	491 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	Catalyzes an oxidative deamination of predominantly hydrophobic and aromatic L-amino acids, thus producing hydrogen peroxide that may contribute to the diverse toxic effects of this enzyme. Unlike most snake L-amino-acid oxidases, this enzyme exhibits potent activity against L-Lys. Has also potent activity against L-Met, L-Leu, L-His, L-Lys and L-Ile. Its activity on platelet aggregation is controversial. It has potent inhibitory activity on platelet aggregation induced by ADP and the thromboxane analog U46619, but not by thrombin, mucetin, ristocetin and stejnulxin (Ref.1), but it has also been shown to induce platelet aggregation through the formation of hydrogen peroxide (Ref.7). It binds to bacteria and shows antibacterial activities by generating hydrogen peroxide. Binding and antibacterial activities are higher against Gram-positive than against Gram-negative bacteria. May also have an ability to induce hemorrhage, hemolysis, edema, apoptosis. Ref.3 Ref.4 Ref.5 Ref.7 Ref.8
Catalytic activity	An L-amino acid + H2O + O2 = a 2-oxo acid + NH3 + H2O2.
Cofactor	FAD. Ref.2 Ref.4
Subunit structure	Homodimer; non-covalently linked. Ref.2 Ref.3 Ref.4 Ref.5
Subcellular location	Secreted.
Tissue specificity	Expressed by the venom gland.
Post-translational modification	N-glycosylated Probable. Ref.1 Ref.2 Ref.3 Ref.4
Toxic dose	LD50 is 5 mg/kg by intravenous injection into mice.
Sequence similarities	Belongs to the flavin monoamine oxidase family. FIG1 subfamily.
Caution	The existence of two isoforms has been reported (Ref.6), and could explain the differences in sequence and kinetic parameters.
Biophysicochemical properties	Kinetic parameters: KM=2.3 mM for L-His (Ref.1) Ref.1 Ref.4 Ref.5 KM=2.9 mM for L-Ile (Ref.1) KM=2.2 mM for L-Leu (Ref.1) KM=2.6 mM for L-Lys (Ref.1) KM=0.7 mM for L-Met (Ref.1) KM=0.20 mM for L-Leu (Ref.5) KM=0.63 mM for L-Met (Ref.5) KM=0.10 mM for L-Phe (Ref.5) KM=0.10 mM for L-Trp (Ref.5) Temperature dependence: Exhibits unusual thermal stability. At pH 7.4, the enzyme retains full activity after incubation at 25 degrees Celsius for 30 days. Is stable at alkaline condition and is not inactivated by freezing.

Ontologies

Keywords
Biological process	Apoptosis Blood coagulation Cytolysis Hemolysis
Cellular component	Secreted
Domain	Signal
Ligand	FAD Flavoprotein
Molecular function	Antibiotic Antimicrobial Oxidoreductase Toxin
PTM	Disulfide bond Glycoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW blood coagulation Inferred from electronic annotation. Source: UniProtKB-KW cytolysis Inferred from electronic annotation. Source: UniProtKB-KW defense response to bacterium Inferred from electronic annotation. Source: UniProtKB-KW hemolysis in other organism Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	L-amino-acid oxidase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 20	20	Ref.1 Ref.2 Ref.3
	Chain	21 – 491	471	L-amino-acid oxidase		PRO_0000099871
Regions
	Nucleotide binding	61 – 62	2	FAD By similarity
	Nucleotide binding	81 – 82	2	FAD By similarity
	Nucleotide binding	103 – 106	4	FAD By similarity
	Nucleotide binding	472 – 477	6	FAD By similarity
	Nucleotide binding	472 – 473	2	Substrate By similarity
Sites
	Binding site	89	1	FAD By similarity
	Binding site	106	1	Substrate By similarity
	Binding site	269	1	FAD; via amide nitrogen and carbonyl oxygen By similarity
	Binding site	380	1	Substrate By similarity
	Binding site	465	1	FAD By similarity
Amino acid modifications
	Glycosylation	122	1	N-linked (GlcNAc...) Potential
	Glycosylation	238	1	N-linked (GlcNAc...) Potential
	Glycosylation	266	1	N-linked (GlcNAc...) Potential
	Glycosylation	410	1	N-linked (GlcNAc...) Potential
	Disulfide bond	28 ↔ 182		By similarity
	Disulfide bond	338 ↔ 420		By similarity
Experimental info
	Sequence conflict	21	1	H → S AA sequence Ref.3
	Sequence conflict	28	1	C → S AA sequence Ref.2
	Sequence conflict	28	1	C → S AA sequence Ref.3
	Sequence conflict	37	1	W → H AA sequence Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P81383 [UniParc]. Last modified September 21, 2011. Version 3. Checksum: 2FD1E740BD73313E	FASTA	491	55,977
	10 20 30 40 50 60 MNDFLLLLLV LFLGVPRSEN HVINLEECFQ EPEYENWLAT ASHGLTKTLN PKKIVIVGAG 70 80 90 100 110 120 ISGLTAAKLF REAGHEVVIL EASDRVGGRI KTHREDGWYV DVGPMRVPQT HRIVREYIKK 130 140 150 160 170 180 FNISLNPFRQ TDENAWYLIK HVRQKMSANN PENFGYQLNP NERGKSASQL FDETLDKVTD 190 200 210 220 230 240 DCTLQKEKYD SFSTKEYLIK EGKLSTGAVE MIGDFLNEEA GFHNSFLISV MDHFLFLNNS 250 260 270 280 290 300 FDEITGGFDQ LPERFFKDMD SIVHLNSTVE KIVHINNKVT VFYEGLSTNM RLVADYVLIT 310 320 330 340 350 360 ATARATRLIK FVPPLSIPKT RALRSLIYAS ATKIILVCTD KFWEKDGIHG GRSITDLPSR 370 380 390 400 410 420 VIYYPNHDFT NGIGVLLASY TWYSDSEFYT TLSDEKCVDV VMDDLVEIHN VSKDYLKSVC 430 440 450 460 470 480 GKHVVQKWAL DQYSMGAFST YTPYQITHYS QMLAQNEGRI YFAGEYTAHP HGWIETSMKS 490 AIREAINIHN A

References

[1]	"Molecular characterization of L-amino acid oxidase from king cobra venom." Jin Y., Lee W.-H., Zeng L., Zhang Y. Toxicon 50:479-489(2007) [PubMed: 17543361] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 21-45; 121-129; 189-195; 272-278 AND 428-439, IDENTIFICATION BY MASS SPECTROMETRY, GLYCOSYLATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE SPECIFICITY. Tissue: Venom and Venom gland.
[2]	"Purification and properties of the L-amino acid oxidase from Malayan pit viper (Calloselasma rhodostoma) venom." Ponnudurai G., Chung M.C.M., Tan N.-H. Arch. Biochem. Biophys. 313:373-378(1994) [PubMed: 8080286] [Abstract] Cited for: PROTEIN SEQUENCE OF 21-39, SUBUNIT, GLYCOSYLATION, COFACTOR. Tissue: Venom.
[3]	"Characterization and cytotoxicity of L-amino acid oxidase from the venom of king cobra (Ophiophagus hannah)." Ahn M.Y., Lee B.M., Kim Y.S. Int. J. Biochem. Cell Biol. 29:911-919(1997) [PubMed: 9304806] [Abstract] Cited for: PROTEIN SEQUENCE OF 21-35, FUNCTION, SUBUNIT, GLYCOSYLATION. Tissue: Venom.
[4]	"Isolation and characterization of an unusual form of L-amino acid oxidase from King cobra (Ophiophagus hannah) venom." Tan N.H., Saifuddin M.N. Biochem. Int. 19:937-944(1989) [PubMed: 2619759] [Abstract] Cited for: FUNCTION, COFACTOR, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES, GLYCOSYLATION, TOXIC DOSE.
[5]	"Substrate specificity of king cobra (Ophiophagus hannah) venom L-amino acid oxidase." Tan N.H., Saifuddin M.N. Int. J. Biochem. 23:323-327(1991) [PubMed: 2044840] [Abstract] Cited for: FUNCTION, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE SPECIFICITY. Tissue: Venom.
[6]	"The edema inducing activity of Ophiophagus hannah (king cobra) venom L-amino acid oxidase." Tan N.-H., Choy S.-K. Toxicon 32:539-539(1994) Cited for: ISOFORM.
[7]	"Purification and characterization of L-amino acid oxidase from king cobra (Ophiophagus hannah) venom and its effects on human platelet aggregation." Li Z.Y., Yu T.F., Lian E.C. Toxicon 32:1349-1358(1994) [PubMed: 7886693] [Abstract] Cited for: FUNCTION. Tissue: Venom.
[8]	"Antibacterial action of a heat-stable form of L-amino acid oxidase isolated from king cobra (Ophiophagus hannah) venom." Lee M.L., Tan N.H., Fung S.Y., Sekaran S.D. Comp. Biochem. Physiol. 153:237-242(2011) [PubMed: 21059402] [Abstract] Cited for: FUNCTION, ANTIBACTERIAL ACTIVITY. Tissue: Venom.

Cross-references

Sequence databases
EMBL GenBank DDBJ	EF080831 mRNA. Translation: ABN72538.1.
3D structure databases
ProteinModelPortal	P81383.
SMR	P81383. Positions 25-491.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Family and domain databases
InterPro	IPR002937. Amino_oxidase. IPR001613. Flavin_amine_oxidase. [Graphical view]
Pfam	PF01593. Amino_oxidase. 1 hit. [Graphical view]
PRINTS	PR00757. AMINEOXDASEF.
ProtoNet	Search...

Entry information

Entry name

OXLA_OPHHA

Accession

Primary (citable) accession number: P81383
Secondary accession number(s): A8QL50

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	September 21, 2011
Last modified:	January 25, 2012
This is version 44 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Animal Toxin Annotation Program

Annotation program

Chordata Protein Annotation Program