P28300 (LYOX_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein-lysine 6-oxidase
EC=1.4.3.13

Alternative name(s):
Lysyl oxidase

Gene names

Name:

LOX

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	417 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	Responsible for the post-translational oxidative deamination of peptidyl lysine residues in precursors to fibrous collagen and elastin. In addition to cross-linking of extracellular matrix proteins, may have a direct role in tumor suppression.
Catalytic activity	Peptidyl-L-lysyl-peptide + O2 + H2O = peptidyl-allysyl-peptide + NH3 + H2O2.
Cofactor	Copper. Contains 1 lysine tyrosylquinone By similarity.
Subcellular location	Secreted › extracellular space.
Tissue specificity	Heart, placenta, skeletal muscle, kidney, lung and pancreas. Ref.3
Post-translational modification	The lysine tyrosylquinone cross-link (LTQ) is generated by condensation of the epsilon-amino group of a lysine with a topaquinone produced by oxidation of tyrosine. Proteolytically activated by BMP1 By similarity.
Miscellaneous	The propeptide plays a role in directing the deposition of this enzyme to elastic fibers, via interaction with tropoelastin By similarity.
Sequence similarities	Belongs to the lysyl oxidase family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Ligand	Copper Metal-binding
Molecular function	Oxidoreductase
PTM	Disulfide bond Glycoprotein LTQ TPQ
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	blood vessel development Inferred from electronic annotation. Source: Compara cellular protein modification process Traceable author statement Ref.1. Source: ProtInc collagen fibril organization Inferred from electronic annotation. Source: Compara elastic fiber assembly Inferred from electronic annotation. Source: Compara lung development Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to steroid hormone stimulus Inferred from electronic annotation. Source: Compara wound healing Inferred from electronic annotation. Source: Compara
Cellular_component	collagen Inferred from electronic annotation. Source: Compara extracellular space Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: Compara
Molecular_function	copper ion binding Traceable author statement Ref.2. Source: ProtInc protein-lysine 6-oxidase activity Traceable author statement Ref.8. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EFEMP2	O95967	4	EBI-3893481,EBI-743414
ELN	P15502	2	EBI-3893481,EBI-1222108
FBN1	P35555	2	EBI-3893481,EBI-2505934

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Potential
	Propeptide	22 – 168	147	By similarity		PRO_0000018520
	Chain	169 – 417	249	Protein-lysine 6-oxidase		PRO_0000018521
Regions
	Region	213 – 417	205	Lysyl-oxidase like
Sites
	Metal binding	292	1	Copper Potential
	Metal binding	294	1	Copper Potential
	Metal binding	296	1	Copper Potential
Amino acid modifications
	Modified residue	355	1	2',4',5'-topaquinone By similarity
	Glycosylation	81	1	N-linked (GlcNAc...) Potential
	Glycosylation	97	1	N-linked (GlcNAc...) Potential
	Glycosylation	144	1	N-linked (GlcNAc...) Potential
	Disulfide bond	238 ↔ 244		By similarity
	Disulfide bond	291 ↔ 340		By similarity
	Disulfide bond	324 ↔ 330		By similarity
	Disulfide bond	351 ↔ 361		By similarity
	Disulfide bond	398 ↔ 412		By similarity
	Cross-link	320 ↔ 355		Lysine tyrosylquinone (Lys-Tyr) By similarity
Natural variations
	Natural variant	158	1	R → Q. Ref.5 Ref.9 Corresponds to variant rs1800449 [ dbSNP | Ensembl ].		VAR_004282
Experimental info
	Sequence conflict	30	1	Q → H Ref.3
	Sequence conflict	31	1	P → A Ref.3
	Sequence conflict	95	1	R → A Ref.3
	Sequence conflict	102	1	A → G in AAB21243. Ref.1
	Sequence conflict	137	1	A → R in AAA59525. Ref.2
	Sequence conflict	137	1	A → R in AAB23549. Ref.2
	Sequence conflict	139	1	A → P in AAB21243. Ref.1
	Sequence conflict	304 – 305	2	YD → LY in AAB21243. Ref.1
	Sequence conflict	315	1	V → W in AAB21243. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P28300 [UniParc]. Last modified October 1, 1993. Version 2. Checksum: 6412A78443E03F04	FASTA	417	46,944
	10 20 30 40 50 60 MRFAWTVLLL GPLQLCALVH CAPPAAGQQQ PPREPPAAPG AWRQQIQWEN NGQVFSLLSL 70 80 90 100 110 120 GSQYQPQRRR DPGAAVPGAA NASAQQPRTP ILLIRDNRTA AARTRTAGSS GVTAGRPRPT 130 140 150 160 170 180 ARHWFQAGYS TSRAREAGAS RAENQTAPGE VPALSNLRPP SRVDGMVGDD PYNPYKYSDD 190 200 210 220 230 240 NPYYNYYDTY ERPRPGGRYR PGYGTGYFQY GLPDLVADPY YIQASTYVQK MSMYNLRCAA 250 260 270 280 290 300 EENCLASTAY RADVRDYDHR VLLRFPQRVK NQGTSDFLPS RPRYSWEWHS CHQHYHSMDE 310 320 330 340 350 360 FSHYDLLDAN TQRRVAEGHK ASFCLEDTSC DYGYHRRFAC TAHTQGLSPG CYDTYGADID 370 380 390 400 410 CQWIDITDVK PGNYILKVSV NPSYLVPESD YTNNVVRCDI RYTGHHAYAS GCTISPY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of human lysyl oxidase and assignment of the gene to chromosome 5q23.3-31.2." Haemaelaeinen E.-R., Jones T.A., Sheer D., Taskinen K., Pihlajaniemi T., Kivirikko K.I. Genomics 11:508-516(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The complete derived amino acid sequence of human lysyl oxidase and assignment of the gene to chromosome 5 (extensive sequence homology with the murine ras recision gene)." Mariani T.J., Trackman P.C., Kagan H.M., Eddy R.L., Shows T.B., Boyd C.D., Deak S.B. Matrix 12:242-248(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Skin.
[3]	"A new gene with sequence and structural similarity to the gene encoding human lysyl oxidase." Kim Y., Boyd C.D., Csiszar K. J. Biol. Chem. 270:7176-7182(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[4]	"Epigenetic inhibition of lysyl oxidase transcription after transformation by ras oncogene." Contente S., Kenyon K., Sriraman P., Subramanyan S., Friedman R.M. Mol. Cell. Biochem. 194:79-91(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLN-158.
[6]	"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]. Tissue: Lung.
[7]	"Structure of the human lysyl oxidase gene." Haemaelaeinen E.-R., Kemppainen R., Pihlajaniemi T., Kivirikko K.I. Genomics 17:544-548(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-213.
[8]	"Characterization of the human lysyl oxidase gene locus." Svinarich D.M., Twomey T.A., Macauley S.P., Krebs C.J., Yang T.P., Krawetz S.A. J. Biol. Chem. 267:14382-14387(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 55-216. Tissue: Blood.
[9]	"A restriction fragment length polymorphism results in a nonconservative amino acid substitution encoded within the first exon of the human lysyl oxidase gene." Csiszar K., Mariani T.J., Gosin J.S., Deak S.B., Boyd C.D. Genomics 16:401-406(1993) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GLN-158.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	S78694 mRNA. Translation: AAB21243.1. M94054 mRNA. Translation: AAA59525.1. S45875 mRNA. Translation: AAB23549.1. AF039291 mRNA. Translation: AAD02130.1. AK312269 mRNA. Translation: BAG35200.1. BC074820 mRNA. Translation: AAH74820.1. BC074872 mRNA. Translation: AAH74872.1. BC089436 mRNA. Translation: AAH89436.1. L16895 Genomic DNA. Translation: AAA16870.1. M84150 Genomic DNA. Translation: AAA59541.1.
IPI	IPI00002802.
PIR	OXHUL. A47529.
RefSeq	NP_002308.2. NM_002317.5.
UniGene	Hs.102267.
3D structure databases
ProteinModelPortal	P28300.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-49007N.
IntAct	P28300. 6 interactions.
STRING	9606.ENSP00000231004.
PTM databases
PhosphoSite	P28300.
Polymorphism databases
DMDM	417269.
Proteomic databases
PaxDb	P28300.
PeptideAtlas	P28300.
PRIDE	P28300.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000231004; ENSP00000231004; ENSG00000113083.
GeneID	4015.
KEGG	hsa:4015.
UCSC	uc003ksu.3. human.
Organism-specific databases
CTD	4015.
GeneCards	GC05M121429.
HGNC	HGNC:6664. LOX.
MIM	153455. gene.
neXtProt	NX_P28300.
PharmGKB	PA30427.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG69196.
HOGENOM	HOG000234262.
HOVERGEN	HBG000226.
InParanoid	P28300.
KO	K00277.
OMA	YSDDNPY.
OrthoDB	EOG402WSF.
PhylomeDB	P28300.
Enzyme and pathway databases
Reactome	REACT_118779. Extracellular matrix organization.
Gene expression databases
ArrayExpress	P28300.
Bgee	P28300.
CleanEx	HS_LOX.
Genevestigator	P28300.
GermOnline	ENSG00000113083. Homo sapiens.
Family and domain databases
InterPro	IPR001695. Lysyl_oxidase. IPR019828. Lysyl_oxidase_CS. [Graphical view]
Pfam	PF01186. Lysyl_oxidase. 1 hit. [Graphical view]
PRINTS	PR00074. LYSYLOXIDASE.
PROSITE	PS00926. LYSYL_OXIDASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P28300.
ChEMBL	CHEMBL2249.
ChiTaRS	LOX. human.
GenomeRNAi	4015.
NextBio	15752.
PMAP-CutDB	P28300.
SOURCE	Search...

Entry information

Entry name

LYOX_HUMAN

Accession

Primary (citable) accession number: P28300
Secondary accession number(s): B2R5Q3, Q5FWF0

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	October 1, 1993
Last modified:	April 3, 2013
This is version 133 of the entry and version 2 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.