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Protein

Lysyl oxidase homolog 2

Gene

Loxl2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

Functioni

Mediates the post-translational oxidative deamination of lysine residues on target proteins leading to the formation of deaminated lysine (allysine). Acts as a transcription corepressor and specifically mediates deamination of trimethylated 'Lys-4' of histone H3 (H3K4me3), a specific tag for epigenetic transcriptional activation. Shows no activity against histone H3 when it is trimethylated on 'Lys-9' (H3K9me3) or 'Lys-27' (H3K27me3) or when 'Lys-4' is monomethylated (H3K4me1) or dimethylated (H3K4me2). Also mediates deamination of methylated TAF10, a member of the transcription factor IID (TFIID) complex, which induces release of TAF10 from promoters, leading to inhibition of TFIID-dependent transcription. LOXL2-mediated deamination of TAF10 results in transcriptional repression of genes required for embryonic stem cell pluripotency including POU5F1/OCT4, NANOG, KLF4 and SOX2. Involved in epithelial to mesenchymal transition (EMT) via interaction with SNAI1 and participates in repression of E-cadherin CDH1, probably by mediating deamination of histone H3. During EMT, involved with SNAI1 in negatively regulating pericentromeric heterochromatin transcription. SNAI1 recruits LOXL2 to pericentromeric regions to oxidize histone H3 and repress transcription which leads to release of heterochromatin component CBX5/HP1A, enabling chromatin reorganization and acquisition of mesenchymal traits. Interacts with the endoplasmic reticulum protein HSPA5 which activates the IRE1-XBP1 pathway of the unfolded protein response, leading to expression of several transcription factors involved in EMT and subsequent EMT induction. When secreted into the 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. Acts as a regulator of chondrocyte differentiation, probably by regulating expression of factors that control chondrocyte differentiation.By similarity

Catalytic activityi

[Protein]-L-lysine + O2 + H2O = [protein]-(S)-2-amino-6-oxohexanoate + NH3 + H2O2.By similarity

Cofactori

Protein has several cofactor binding sites:
  • Cu cationBy similarity
  • lysine tyrosylquinone residueBy similarityNote: Contains 1 lysine tyrosylquinone.By similarity

Enzyme regulationi

Specifically inhibited by a mouse monoclonal antibody AB0023, inhibition occurs in a non-competitive manner.By similarity

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionChromatin regulator, Oxidoreductase, Repressor
Biological processTranscription, Transcription regulation
LigandCopper, Metal-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Lysyl oxidase homolog 2 (EC:1.4.3.13By similarity)
Alternative name(s):
Lysyl oxidase-like protein 2
Gene namesi
Name:Loxl2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi1308435 Loxl2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Basement membrane, Chromosome, Endoplasmic reticulum, Extracellular matrix, Nucleus, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 25Sequence analysisAdd BLAST25
ChainiPRO_000041800226 – 776Lysyl oxidase homolog 2Add BLAST751

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi87 ↔ 151PROSITE-ProRule annotation
Disulfide bondi100 ↔ 161PROSITE-ProRule annotation
Disulfide bondi131 ↔ 141PROSITE-ProRule annotation
Disulfide bondi221 ↔ 294PROSITE-ProRule annotation
Disulfide bondi234 ↔ 304PROSITE-ProRule annotation
Glycosylationi267N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi268 ↔ 278PROSITE-ProRule annotation
Glycosylationi291N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi354 ↔ 417PROSITE-ProRule annotation
Disulfide bondi367 ↔ 427PROSITE-ProRule annotation
Disulfide bondi398 ↔ 408PROSITE-ProRule annotation
Glycosylationi458N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi467 ↔ 532PROSITE-ProRule annotation
Disulfide bondi480 ↔ 545PROSITE-ProRule annotation
Disulfide bondi514 ↔ 524PROSITE-ProRule annotation
Disulfide bondi575 ↔ 581By similarity
Disulfide bondi627 ↔ 675By similarity
Glycosylationi646N-linked (GlcNAc...) asparagineSequence analysis1
Cross-linki655 ↔ 691Lysine tyrosylquinone (Lys-Tyr)By similarity
Disulfide bondi659 ↔ 665By similarity
Disulfide bondi687 ↔ 697By similarity
Modified residuei6912',4',5'-topaquinoneBy similarity1
Disulfide bondi734 ↔ 748By similarity

Post-translational modificationi

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.By similarity
N-glycosylated. N-glycosylation on Asn-458 and Asn-646 may be essential for proper folding and secretion; may be composed of a fucosylated carbohydrates attached to a trimannose N-linked glycan core.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, LTQ, TPQ

Proteomic databases

PaxDbiB5DF27
PeptideAtlasiB5DF27

Interactioni

Subunit structurei

Component of some chromatin repressor complex. Interacts with SNAI1. Interacts with TAF10. Interacts with HSPA5.By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000055457

Structurei

3D structure databases

SMRiB5DF27
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini61 – 162SRCR 1PROSITE-ProRule annotationAdd BLAST102
Domaini191 – 305SRCR 2PROSITE-ProRule annotationAdd BLAST115
Domaini329 – 428SRCR 3PROSITE-ProRule annotationAdd BLAST100
Domaini438 – 546SRCR 4PROSITE-ProRule annotationAdd BLAST109

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni550 – 753Lysyl-oxidase likeBy similarityAdd BLAST204

Domaini

The fourth SRCR domain plays a important role in optimizing the catalytic activity of the lysyl-oxidase like (LOX) catalytic domain.By similarity

Sequence similaritiesi

Belongs to the lysyl oxidase family.Curated

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

HOGENOMiHOG000220841
HOVERGENiHBG052336
InParanoidiB5DF27
KOiK00280

Family and domain databases

Gene3Di3.10.250.10, 4 hits
InterProiView protein in InterPro
IPR001695 Lysyl_oxidase
IPR019828 Lysyl_oxidase_CS
IPR001190 SRCR
IPR017448 SRCR-like_dom
IPR036772 SRCR-like_dom_sf
PfamiView protein in Pfam
PF01186 Lysyl_oxidase, 1 hit
PF00530 SRCR, 4 hits
PRINTSiPR00074 LYSYLOXIDASE
PR00258 SPERACTRCPTR
SMARTiView protein in SMART
SM00202 SR, 4 hits
SUPFAMiSSF56487 SSF56487, 4 hits
PROSITEiView protein in PROSITE
PS00926 LYSYL_OXIDASE, 1 hit
PS00420 SRCR_1, 2 hits
PS50287 SRCR_2, 4 hits

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

B5DF27-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEIPFGSCLY SCLALLVLLP SLSLAQYESW PYQLQYPEYF QQPPPEHHQH
60 70 80 90 100
QVPSDVVKIQ VRLAGQKRKH NEGRVEVYYE GQWGTVCDDD FSIHAAHVVC
110 120 130 140 150
REVGYVEAKS WTASSSYGPG EGPIWLDNIY CTGKESTLAA CSSNGWGVTD
160 170 180 190 200
CKHPEDVGVV CSEKRIPGFK FDNSLINQIE SLNIQVEDIR IRPILSAFRH
210 220 230 240 250
RKPVTEGYVE VKEGKAWKQI CDKHWTAKNS HVVCGMFGFP AEKTYNPKAY
260 270 280 290 300
KTFASRRKLR YWKFSMNCTG TEAHISSCKL GPPMFRDPVK NATCENGQPA
310 320 330 340 350
VVSCVPSQIF SPDGPSRFRK AYKPEQPLVR LRGGAQVGEG RVEVLKNGEW
360 370 380 390 400
GTVCDDKWDL VSASVVCREL GFGTAKEAVT GSRLGQGIGP IHLNEVQCTG
410 420 430 440 450
TEKSIIDCKL NTESQGCNHE EDAGVRCNIP IMGFQKKVRL NGGRNPYEGR
460 470 480 490 500
VEVLTERNGS LVWGNVCGQN WGIVEAMVVC RQLGLGFASN AFQETWYWHG
510 520 530 540 550
NIFANKVIMS GVKCSGTELS LAHCRHDEEV VCPEGGVQYG AGVACSETAP
560 570 580 590 600
DLVLNAEIVQ QTAYLEDRPM ALLQCAMEEN CLSASAVHTD PTRGHRRLLR
610 620 630 640 650
FSSQIHNNGQ SDFRPKNGRH AWIWHDCHRH YHSMEVFTYY DLLSLNGTKV
660 670 680 690 700
AEGHKASFCL EDTECEGDIQ KSYECANFGE QGITMGCWDM YRHDIDCQWI
710 720 730 740 750
DITDVPPGDY LFQVVINPNY EVPESDFSNN IMKCRSRYDG YRIWMYNCHV
760 770
GGAFSEETEQ KFEHFSGLLN NQLSVQ
Length:776
Mass (Da):87,185
Last modified:June 13, 2012 - v2
Checksum:i0ACE3544E7E8278A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti154P → T in AAI68900 (PubMed:15489334).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC168900 mRNA Translation: AAI68900.1
RefSeqiNP_001099517.2, NM_001106047.2
UniGeneiRn.219739

Genome annotation databases

GeneIDi290350
KEGGirno:290350
UCSCiRGD:1308435 rat

Similar proteinsi

Entry informationi

Entry nameiLOXL2_RAT
AccessioniPrimary (citable) accession number: B5DF27
Secondary accession number(s): F1LPM2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 13, 2012
Last sequence update: June 13, 2012
Last modified: April 25, 2018
This is version 68 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
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Main funding by: National Institutes of Health