Human Gene LOXL2 (ENST00000389131.8) from GENCODE V44
  Description: Homo sapiens lysyl oxidase like 2 (LOXL2), mRNA. (from RefSeq NM_002318)
RefSeq Summary (NM_002318): This gene encodes a member of the lysyl oxidase gene family. The prototypic member of the family is essential to the biogenesis of connective tissue, encoding an extracellular copper-dependent amine oxidase that catalyses the first step in the formation of crosslinks in collagens and elastin. A highly conserved amino acid sequence at the C-terminus end appears to be sufficient for amine oxidase activity, suggesting that each family member may retain this function. The N-terminus is poorly conserved and may impart additional roles in developmental regulation, senescence, tumor suppression, cell growth control, and chemotaxis to each member of the family. [provided by RefSeq, Jul 2008].
Gencode Transcript: ENST00000389131.8
Gencode Gene: ENSG00000134013.16
Transcript (Including UTRs)
   Position: hg38 chr8:23,296,897-23,404,120 Size: 107,224 Total Exon Count: 14 Strand: -
Coding Region
   Position: hg38 chr8:23,298,043-23,368,351 Size: 70,309 Coding Exon Count: 13 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr8:23,296,897-23,404,120)mRNA (may differ from genome)Protein (774 aa)
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HGNCHPRDLynxMalacardsMGIneXtProt
OMIMPubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: LOXL2_HUMAN
DESCRIPTION: RecName: Full=Lysyl oxidase homolog 2; EC=1.4.3.13; AltName: Full=Lysyl oxidase-like protein 2; AltName: Full=Lysyl oxidase-related protein 2; AltName: Full=Lysyl oxidase-related protein WS9-14; Flags: Precursor;
FUNCTION: Mediates the post-translational oxidative deamination of lysine residues on target proteins leading to the formation of deaminated lysine (allysine). When secreted in extracellular matrix, promotes cross-linking of extracellular matrix proteins by mediating oxidative deamination of peptidyl lysine residues in precursors to fibrous collagen and elastin. Acts as a regulator of sprouting angiogenesis, probably via collagen IV scaffolding. When nuclear, acts as a transcription corepressor and specifically mediates deamination of trimethylated 'Lys-4' of histone H3 (H3K4me3), a specific tag for epigenetic transcriptional activation. Involved in epithelial to mesenchymal transition (EMT) via interaction with SNAI1 and participates in repression of E- cadherin, probably by mediating deamination of histone H3. Also involved in E-cadherin repression following hypoxia, a hallmark of epithelial to mesenchymal transition believed to amplify tumor aggressiveness, suggesting that it may play a role in tumor progression. Acts as a regulator of chondrocyte differentiation, probably by regulating expression of factors that control chondrocyte differentiation.
CATALYTIC ACTIVITY: Peptidyl-L-lysyl-peptide + O(2) + H(2)O = peptidyl-allysyl-peptide + NH(3) + H(2)O(2).
COFACTOR: Copper (By similarity).
COFACTOR: Contains 1 lysine tyrosylquinone (By similarity).
ENZYME REGULATION: According to some reports, it is inhibited by beta-aminopropionitrile (BAPN) (PubMed:20439985). According to another report, it is not inhibited by beta-aminopropionitrile (BAPN) (PubMed:20306300). Specifically inhibited by a mouse monoclonal antibody AB0023, inhibition occurs in a non-competitive manner.
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=1.01 mM for 1,5-diaminopentane; KM=1.05 mM for spermine;
SUBUNIT: Component of some chromatin repressor complex. Interacts with SNAI1.
SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular matrix, basement membrane (By similarity). Nucleus. Chromosome. Note=Associated with chromatin. It is unclear how LOXL2 is nuclear: it contains a clear signal sequence and is predicted to localize in the extracellular medium. However, different reports confirmed the intracellular location and its key role in transcription regulation.
TISSUE SPECIFICITY: Expressed in many tissues. Highest expression in reproductive tissues, placenta, uterus and prostate. Up- regulated in a number of cancers cells and tissues.
INDUCTION: Strongly induced in hypoxia. Direct transcriptional target of HIF1A.
PTM: 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.
MISCELLANEOUS: Its overexpression in a number of cancer and its ability to promote epithelial to mesenchymal transition suggest that LOXL2 might play a role in tumor progression: expression is correlated with metastasis and decreased survival in patients with aggressive breast cancer (PubMed:21732535). Allosteric inhibition by AB0023 inhibits formation of the tumor microenvironment and reduces metastatic tumor burden in xenograft models (PubMed:20818376 and PubMed:21732535). However, inhibiting the enzyme activity of LOXL2 may not be sufficient, since mutants that lack enzyme activity or inhibition of the activity by AB0023 antibody does not prevent inhibition of the differentiation of keratinocytes, thereby promoting development of squamous cell carcinomas (PubMed:22157764).
SIMILARITY: Belongs to the lysyl oxidase family.
SIMILARITY: Contains 4 SRCR domains.
SEQUENCE CAUTION: Sequence=AAD34343.1; Type=Erroneous termination; Positions=775; Note=Translated as stop;

-  Primer design for this transcript
 

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-  MalaCards Disease Associations
  MalaCards Gene Search: LOXL2
Diseases sorted by gene-association score: hyperostosis cranialis interna (19), craniometaphyseal dysplasia (5)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 53.24 RPKM in Cells - Cultured fibroblasts
Total median expression: 242.84 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -94.20250-0.377 Picture PostScript Text
3' UTR -376.701146-0.329 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001695 - Lysyl_oxidase
IPR019828 - Lysyl_oxidase_CS
IPR001190 - Srcr_rcpt
IPR017448 - Srcr_rcpt-rel

Pfam Domains:
PF01186 - Lysyl oxidase
PF00530 - Scavenger receptor cysteine-rich domain

ModBase Predicted Comparative 3D Structure on Q9Y4K0
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserGenome BrowserGenome BrowserNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsemblEnsembl  
Protein SequenceProtein SequenceProtein SequenceProtein Sequence  
AlignmentAlignmentAlignmentAlignment  

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004720 protein-lysine 6-oxidase activity
GO:0005044 scavenger receptor activity
GO:0005507 copper ion binding
GO:0005515 protein binding
GO:0009055 electron carrier activity
GO:0016491 oxidoreductase activity
GO:0016641 oxidoreductase activity, acting on the CH-NH2 group of donors, oxygen as acceptor
GO:0046872 metal ion binding
GO:0070492 oligosaccharide binding

Biological Process:
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0001666 response to hypoxia
GO:0001837 epithelial to mesenchymal transition
GO:0001935 endothelial cell proliferation
GO:0002040 sprouting angiogenesis
GO:0006325 chromatin organization
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006464 cellular protein modification process
GO:0006898 receptor-mediated endocytosis
GO:0007155 cell adhesion
GO:0007568 aging
GO:0010718 positive regulation of epithelial to mesenchymal transition
GO:0018057 peptidyl-lysine oxidation
GO:0022900 electron transport chain
GO:0030199 collagen fibril organization
GO:0032332 positive regulation of chondrocyte differentiation
GO:0043542 endothelial cell migration
GO:0045892 negative regulation of transcription, DNA-templated
GO:0046688 response to copper ion
GO:0055114 oxidation-reduction process
GO:0070828 heterochromatin organization
GO:1902455 negative regulation of stem cell population maintenance

Cellular Component:
GO:0000785 chromatin
GO:0005576 extracellular region
GO:0005604 basement membrane
GO:0005615 extracellular space
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005694 chromosome
GO:0005783 endoplasmic reticulum
GO:0016020 membrane
GO:0031012 extracellular matrix


-  Descriptions from all associated GenBank mRNAs
  AF117949 - Homo sapiens lysyl oxidase-like protein 2 (LOXL2) mRNA, complete cds.
BC000594 - Homo sapiens lysyl oxidase-like 2, mRNA (cDNA clone MGC:1709 IMAGE:3347512), complete cds.
U89942 - Human lysyl oxidase-related protein (WS9-14) mRNA, complete cds.
AK222477 - Homo sapiens mRNA for lysyl oxidase-like 2 variant, clone: adKA02811.
AK312266 - Homo sapiens cDNA, FLJ92562, highly similar to Homo sapiens lysyl oxidase-like 2 (LOXL2), mRNA.
DQ892685 - Synthetic construct clone IMAGE:100005315; FLH188866.01X; RZPDo839G1173D lysyl oxidase-like 2 (LOXL2) gene, encodes complete protein.
DQ895929 - Synthetic construct Homo sapiens clone IMAGE:100010389; FLH188862.01L; RZPDo839G1163D lysyl oxidase-like 2 (LOXL2) gene, encodes complete protein.
KF975332 - Homo sapiens lysyl oxidase-like 2 protein isoform b (LOXL2) mRNA, partial cds, alternatively spliced.
KF928961 - Homo sapiens lysyl oxidase-like 2 delta e13 (LOXL2) mRNA, complete cds, alternatively spliced.
AK293292 - Homo sapiens cDNA FLJ53707 complete cds, highly similar to Lysyl oxidase homolog 2 precursor (EC 1.4.3.-).
BC020481 - Homo sapiens lysyl oxidase-like 2, mRNA (cDNA clone IMAGE:3873591).
AK124508 - Homo sapiens cDNA FLJ42517 fis, clone BRACE2047835, highly similar to Human lysyl oxidase-related protein (WS9-14) mRNA.
AK098436 - Homo sapiens cDNA FLJ25570 fis, clone JTH04865, highly similar to Human lysyl oxidase-related protein (WS9-14) mRNA.
JD316369 - Sequence 297393 from Patent EP1572962.
JD217547 - Sequence 198571 from Patent EP1572962.
JD231001 - Sequence 212025 from Patent EP1572962.
JD491110 - Sequence 472134 from Patent EP1572962.
JD094523 - Sequence 75547 from Patent EP1572962.
JD244945 - Sequence 225969 from Patent EP1572962.
JD049239 - Sequence 30263 from Patent EP1572962.
JD327844 - Sequence 308868 from Patent EP1572962.
JD330467 - Sequence 311491 from Patent EP1572962.
JD244502 - Sequence 225526 from Patent EP1572962.
JD148819 - Sequence 129843 from Patent EP1572962.
JD552772 - Sequence 533796 from Patent EP1572962.
JD149735 - Sequence 130759 from Patent EP1572962.
JD169487 - Sequence 150511 from Patent EP1572962.
JD295917 - Sequence 276941 from Patent EP1572962.
JD493744 - Sequence 474768 from Patent EP1572962.
JD430753 - Sequence 411777 from Patent EP1572962.
JD339990 - Sequence 321014 from Patent EP1572962.
JD547816 - Sequence 528840 from Patent EP1572962.
JD125313 - Sequence 106337 from Patent EP1572962.
JD435111 - Sequence 416135 from Patent EP1572962.
JD194014 - Sequence 175038 from Patent EP1572962.
JD502320 - Sequence 483344 from Patent EP1572962.
LF210140 - JP 2014500723-A/17643: Polycomb-Associated Non-Coding RNAs.
MA445717 - JP 2018138019-A/17643: Polycomb-Associated Non-Coding RNAs.
LF335079 - JP 2014500723-A/142582: Polycomb-Associated Non-Coding RNAs.
MA570656 - JP 2018138019-A/142582: Polycomb-Associated Non-Coding RNAs.
JD527429 - Sequence 508453 from Patent EP1572962.
JD065177 - Sequence 46201 from Patent EP1572962.
JD202138 - Sequence 183162 from Patent EP1572962.
JD222450 - Sequence 203474 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q9Y4K0 (Reactome details) participates in the following event(s):

R-HSA-2022141 Prolysyl oxidase activation
R-HSA-2002466 Formation of allysine by LOX
R-HSA-2395340 Formation of hydroxyallysine by LOX
R-HSA-2243919 Crosslinking of collagen fibrils
R-HSA-2022090 Assembly of collagen fibrils and other multimeric structures
R-HSA-1474290 Collagen formation
R-HSA-1566948 Elastic fibre formation
R-HSA-1474244 Extracellular matrix organization

-  Other Names for This Gene
  Alternate Gene Symbols: B2R5Q0, ENST00000389131.1, ENST00000389131.2, ENST00000389131.3, ENST00000389131.4, ENST00000389131.5, ENST00000389131.6, ENST00000389131.7, LOXL2_HUMAN, NM_002318, Q53HV3, Q9BW70, Q9Y4K0, Q9Y5Y8, uc003xdh.1, uc003xdh.2, uc003xdh.3
UCSC ID: ENST00000389131.8
RefSeq Accession: NM_002318
Protein: Q9Y4K0 (aka LOXL2_HUMAN or LOL2_HUMAN)
CCDS: CCDS34864.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.