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Protein

Lysyl oxidase homolog 2

Gene

Loxl2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Mediates the post-translational oxidative deamination of lysine residues on target proteins leading to the formation of deaminated lysine (allysine) (By similarity). Acts as a transcription corepressor and specifically mediates deamination of trimethylated 'Lys-4' of histone H3 (H3K4me3), a specific tag for epigenetic transcriptional activation (By similarity). 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) (By similarity). 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 (By similarity). LOXL2-mediated deamination of TAF10 results in transcriptional repression of genes required for embryonic stem cell pluripotency including POU5F1/OCT4, NANOG, KLF4 and SOX2 (PubMed:25959397). 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 (By similarity). During EMT, involved with SNAI1 in negatively regulating pericentromeric heterochromatin transcription (By similarity). 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 (By similarity). 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 (By similarity). 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 (By similarity). Acts as a regulator of sprouting angiogenesis, probably via collagen IV scaffolding (By similarity). Acts as a regulator of chondrocyte differentiation, probably by regulating expression of factors that control chondrocyte differentiation (PubMed:21071451).By similarity2 Publications

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi628CopperSequence analysis1
Metal bindingi630CopperSequence analysis1
Metal bindingi632CopperSequence analysis1

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-MMU-1566948 Elastic fibre formation
R-MMU-2243919 Crosslinking of collagen fibrils

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 14

Organism-specific databases

MGIiMGI:2137913 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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi547 – 667Missing : Abolishes oxidase activity and secretion but does not affect binding to the CDH1 promoter, repression of CDH1 transcription, interaction with SNAI1, binding to the CDH1 promoter, repression of CDH1 transcription or ability to induce EMT. 1 PublicationAdd BLAST121

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 25Sequence analysisAdd BLAST25
ChainiPRO_000004285426 – 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 ↔ 581PROSITE-ProRule annotation
Disulfide bondi627 ↔ 675PROSITE-ProRule annotation
Glycosylationi646N-linked (GlcNAc...) asparagineSequence analysis1
Cross-linki655 ↔ 691Lysine tyrosylquinone (Lys-Tyr)By similarity
Disulfide bondi659 ↔ 665PROSITE-ProRule annotation
Disulfide bondi687 ↔ 697PROSITE-ProRule annotation
Modified residuei6912',4',5'-topaquinoneBy similarity1
Disulfide bondi734 ↔ 748PROSITE-ProRule annotation

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

MaxQBiP58022
PaxDbiP58022
PeptideAtlasiP58022
PRIDEiP58022

PTM databases

PhosphoSitePlusiP58022

Expressioni

Tissue specificityi

Ubiquitous. Highest expression in skin, lung and thymus. Present in chondrocytes: mainly expressed by chondrocytes in healing fractures and in epiphyseal growth plates (at protein level).1 Publication

Inductioni

Strongly induced in hypoxia.1 Publication

Gene expression databases

BgeeiENSMUSG00000034205
CleanExiMM_LOXL2
GenevisibleiP58022 MM

Interactioni

Subunit structurei

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

Protein-protein interaction databases

IntActiP58022, 1 interactor
STRINGi10090.ENSMUSP00000022660

Structurei

3D structure databases

ProteinModelPortaliP58022
SMRiP58022
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

Sequence similaritiesi

Belongs to the lysyl oxidase family.Curated

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiENOG410IE2X Eukaryota
ENOG410XSN1 LUCA
GeneTreeiENSGT00900000140830
HOGENOMiHOG000220841
HOVERGENiHBG052336
InParanoidiP58022
KOiK00280
OMAiFSMDCTG
OrthoDBiEOG091G02XD
PhylomeDBiP58022
TreeFamiTF326061

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

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P58022-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MELHFGSCLS GCLALLVLLP SLSLAQYEGW PYQLQYPEYF QQPAPEHHQR
60 70 80 90 100
QVPSDVVKIQ VRLAGQKRKH NEGRVEVYYE GQWGTVCDDD FSIHAAHVVC
110 120 130 140 150
RQVGYVEAKS WAASSSYGPG EGPIWLDNIY CTGKESTLAS CSSNGWGVTD
160 170 180 190 200
CKHTEDVGVV CSEKRIPGFK FDNSLINQIE SLNIQVEDIR IRPILSAFRH
210 220 230 240 250
RKPVTEGYVE VKEGKAWKQI CNKHWTAKNS HVVCGMFGFP AEKTYNPKAY
260 270 280 290 300
KTFASRRKLR YWKFSMNCTG TEAHISSCKL GPSVTRDPVK NATCENGQPA
310 320 330 340 350
VVSCVPSQIF SPDGPSRFRK AYKPEQPLVR LRGGAQVGEG RVEVLKNGEW
360 370 380 390 400
GTICDDKWDL VSASVVCREL GFGTAKEAIT GSRLGQGIGP IHLNEVQCTG
410 420 430 440 450
TEKSIIDCKF NTESQGCNHE EDAGVRCNIP IMGFQKKVRL NGGRNPYEGR
460 470 480 490 500
VEVLTERNGS LVWGTVCGQN WGIVEAMVVC RQLGLGFASN AFQETWYWHG
510 520 530 540 550
NIFANNVVMS GVKCSGTELS LAHCRHDEEV ACPEGGVRFG AGVACSETAP
560 570 580 590 600
DLVLNAEIVQ QTAYLEDRPM SLLQCAMEEN 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):87,003
Last modified:November 22, 2005 - v2
Checksum:i9DE55C6F37DE5EEF
GO
Isoform 2 (identifier: P58022-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     714-727: VVINPNYEVPESDF → PSNRVLVRAGQTPY
     728-776: Missing.

Note: No experimental confirmation available.
Show »
Length:727
Mass (Da):81,168
Checksum:i9A4A912D0BDA9FCC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti320K → E in BAC32186 (PubMed:16141072).Curated1
Sequence conflicti558 – 560IVQ → HEE in AAF29046 (PubMed:10842102).Curated3

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_016231714 – 727VVINP…PESDF → PSNRVLVRAGQTPY in isoform 2. 1 PublicationAdd BLAST14
Alternative sequenceiVSP_016232728 – 776Missing in isoform 2. 1 PublicationAdd BLAST49

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK034957 mRNA Translation: BAC28894.1
AK045019 mRNA Translation: BAC32186.1
AK081898 mRNA Translation: BAC38364.1
AK145323 mRNA Translation: BAE26367.1
AK159386 mRNA Translation: BAE35041.1
AF117951 mRNA Translation: AAF29046.1
CCDSiCCDS27241.1 [P58022-1]
RefSeqiNP_201582.2, NM_033325.2 [P58022-1]
XP_006519810.1, XM_006519747.2 [P58022-1]
UniGeneiMm.116714

Genome annotation databases

EnsembliENSMUST00000022660; ENSMUSP00000022660; ENSMUSG00000034205 [P58022-1]
ENSMUST00000100420; ENSMUSP00000097987; ENSMUSG00000034205 [P58022-1]
GeneIDi94352
KEGGimmu:94352
UCSCiuc007umn.3 mouse [P58022-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiLOXL2_MOUSE
AccessioniPrimary (citable) accession number: P58022
Secondary accession number(s): Q8BRE6
, Q8BS86, Q8C4K0, Q9JJ39
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: November 22, 2005
Last modified: April 25, 2018
This is version 140 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