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P58022 (LOXL2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 108. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Lysyl oxidase homolog 2

EC=1.4.3.13
Alternative name(s):
Lysyl oxidase-like protein 2
Gene names
Name:Loxl2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length776 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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 By similarity. Acts as a regulator of chondrocyte differentiation, probably by regulating expression of factors that control chondrocyte differentiation. Ref.4

Catalytic activity

Peptidyl-L-lysyl-peptide + O2 + H2O = peptidyl-allysyl-peptide + NH3 + H2O2.

Cofactor

Copper By similarity.

Contains 1 lysine tyrosylquinone By similarity.

Enzyme regulation

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

Subunit structure

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

Subcellular location

Secretedextracellular spaceextracellular matrixbasement membrane By similarity. Nucleus By similarity. Chromosome By similarity. Note: Associated with chromatin By similarity. 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

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). Ref.4

Induction

Strongly induced in hypoxia. 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 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.

Sequence similarities

Belongs to the lysyl oxidase family.

Contains 4 SRCR domains.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentBasement membrane
Chromosome
Extracellular matrix
Nucleus
Secreted
   Coding sequence diversityAlternative splicing
   DomainRepeat
Signal
   LigandCopper
Metal-binding
   Molecular functionChromatin regulator
Oxidoreductase
Repressor
   PTMDisulfide bond
Glycoprotein
LTQ
TPQ
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcollagen fibril organization

Inferred from sequence or structural similarity. Source: UniProtKB

endothelial cell migration

Inferred from sequence or structural similarity. Source: UniProtKB

endothelial cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

epithelial to mesenchymal transition

Inferred from sequence or structural similarity. Source: UniProtKB

histone modification

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of chondrocyte differentiation

Inferred from mutant phenotype Ref.4. Source: UniProtKB

protein deamination

Inferred from sequence or structural similarity. Source: UniProtKB

receptor-mediated endocytosis

Inferred from electronic annotation. Source: GOC

response to copper ion

Inferred from sequence or structural similarity. Source: UniProtKB

response to hypoxia

Inferred from direct assay Ref.3. Source: UniProtKB

sprouting angiogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentbasement membrane

Inferred from sequence or structural similarity. Source: UniProtKB

chromosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

extracellular space

Inferred from sequence or structural similarity. Source: UniProtKB

membrane

Inferred from electronic annotation. Source: InterPro

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionchromatin binding

Inferred from sequence or structural similarity. Source: UniProtKB

copper ion binding

Inferred from electronic annotation. Source: InterPro

methylated histone residue binding

Inferred from sequence or structural similarity. Source: UniProtKB

oligosaccharide binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein-lysine 6-oxidase activity

Inferred from sequence or structural similarity. Source: UniProtKB

scavenger receptor activity

Inferred from electronic annotation. Source: InterPro

transcription corepressor activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P58022-1)

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.
Isoform 2 (identifier: P58022-2)

The sequence of this isoform differs from the canonical sequence as follows:
     714-727: VVINPNYEVPESDF → PSNRVLVRAGQTPY
     728-776: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2525 Potential
Chain26 – 776751Lysyl oxidase homolog 2
PRO_0000042854

Regions

Domain61 – 162102SRCR 1
Domain191 – 305115SRCR 2
Domain329 – 428100SRCR 3
Domain438 – 546109SRCR 4
Region550 – 753204Lysyl-oxidase like By similarity

Sites

Metal binding6281Copper Potential
Metal binding6301Copper Potential
Metal binding6321Copper Potential

Amino acid modifications

Modified residue69112',4',5'-topaquinone By similarity
Glycosylation2671N-linked (GlcNAc...) Potential
Glycosylation2911N-linked (GlcNAc...) Potential
Glycosylation4581N-linked (GlcNAc...) Potential
Glycosylation6461N-linked (GlcNAc...) Potential
Disulfide bond87 ↔ 151 By similarity
Disulfide bond100 ↔ 161 By similarity
Disulfide bond131 ↔ 141 By similarity
Disulfide bond221 ↔ 294 By similarity
Disulfide bond234 ↔ 304 By similarity
Disulfide bond268 ↔ 278 By similarity
Disulfide bond354 ↔ 417 By similarity
Disulfide bond367 ↔ 427 By similarity
Disulfide bond398 ↔ 408 By similarity
Disulfide bond467 ↔ 532 By similarity
Disulfide bond480 ↔ 545 By similarity
Disulfide bond514 ↔ 524 By similarity
Disulfide bond575 ↔ 581 By similarity
Disulfide bond627 ↔ 675 By similarity
Disulfide bond659 ↔ 665 By similarity
Disulfide bond687 ↔ 697 By similarity
Disulfide bond734 ↔ 748 By similarity
Cross-link655 ↔ 691Lysine tyrosylquinone (Lys-Tyr) By similarity

Natural variations

Alternative sequence714 – 72714VVINP…PESDF → PSNRVLVRAGQTPY in isoform 2.
VSP_016231
Alternative sequence728 – 77649Missing in isoform 2.
VSP_016232

Experimental info

Sequence conflict3201K → E in BAC32186. Ref.1
Sequence conflict558 – 5603IVQ → HEE in AAF29046. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 22, 2005. Version 2.
Checksum: 9DE55C6F37DE5EEF

FASTA77687,003
        10         20         30         40         50         60 
MELHFGSCLS GCLALLVLLP SLSLAQYEGW PYQLQYPEYF QQPAPEHHQR QVPSDVVKIQ 

        70         80         90        100        110        120 
VRLAGQKRKH NEGRVEVYYE GQWGTVCDDD FSIHAAHVVC RQVGYVEAKS WAASSSYGPG 

       130        140        150        160        170        180 
EGPIWLDNIY CTGKESTLAS CSSNGWGVTD CKHTEDVGVV CSEKRIPGFK FDNSLINQIE 

       190        200        210        220        230        240 
SLNIQVEDIR IRPILSAFRH RKPVTEGYVE VKEGKAWKQI CNKHWTAKNS HVVCGMFGFP 

       250        260        270        280        290        300 
AEKTYNPKAY KTFASRRKLR YWKFSMNCTG TEAHISSCKL GPSVTRDPVK NATCENGQPA 

       310        320        330        340        350        360 
VVSCVPSQIF SPDGPSRFRK AYKPEQPLVR LRGGAQVGEG RVEVLKNGEW GTICDDKWDL 

       370        380        390        400        410        420 
VSASVVCREL GFGTAKEAIT GSRLGQGIGP IHLNEVQCTG TEKSIIDCKF NTESQGCNHE 

       430        440        450        460        470        480 
EDAGVRCNIP IMGFQKKVRL NGGRNPYEGR VEVLTERNGS LVWGTVCGQN WGIVEAMVVC 

       490        500        510        520        530        540 
RQLGLGFASN AFQETWYWHG NIFANNVVMS GVKCSGTELS LAHCRHDEEV ACPEGGVRFG 

       550        560        570        580        590        600 
AGVACSETAP DLVLNAEIVQ QTAYLEDRPM SLLQCAMEEN CLSASAVHTD PTRGHRRLLR 

       610        620        630        640        650        660 
FSSQIHNNGQ SDFRPKNGRH AWIWHDCHRH YHSMEVFTYY DLLSLNGTKV AEGHKASFCL 

       670        680        690        700        710        720 
EDTECEGDIQ KSYECANFGE QGITMGCWDM YRHDIDCQWI DITDVPPGDY LFQVVINPNY 

       730        740        750        760        770 
EVPESDFSNN IMKCRSRYDG YRIWMYNCHV GGAFSEETEQ KFEHFSGLLN NQLSVQ 

« Hide

Isoform 2 [UniParc].

Checksum: 9A4A912D0BDA9FCC
Show »

FASTA72781,168

References

« Hide 'large scale' references
[1]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Strain: C57BL/6J.
Tissue: Embryo and Head.
[2]"The mouse lysyl oxidase-like 2 gene (mLOXL2) maps to chromosome 14 and is highly expressed in skin, lung and thymus."
Jourdan-Le Saux C., Le Saux O., Gleyzal C., Sommer P., Csiszar K.
Matrix Biol. 19:179-183(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 558-776 (ISOFORM 1).
[3]"Lysyl oxidase-like protein-2 regulates sprouting angiogenesis and type IV collagen assembly in the endothelial basement membrane."
Bignon M., Pichol-Thievend C., Hardouin J., Malbouyres M., Brechot N., Nasciutti L., Barret A., Teillon J., Guillon E., Etienne E., Caron M., Joubert-Caron R., Monnot C., Ruggiero F., Muller L., Germain S.
Blood 118:3979-3989(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[4]"Lysyl oxidase-like-2 (LOXL2) is a major isoform in chondrocytes and is critically required for differentiation."
Iftikhar M., Hurtado P., Bais M.V., Wigner N., Stephens D.N., Gerstenfeld L.C., Trackman P.C.
J. Biol. Chem. 286:909-918(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_201582.2. NM_033325.2.
XP_003688982.2. XM_003688934.3.
XP_006519810.1. XM_006519747.1.
UniGeneMm.116714.

3D structure databases

ProteinModelPortalP58022.
SMRP58022. Positions 71-162, 202-279, 325-429, 438-525.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP58022. 1 interaction.

PTM databases

PhosphoSiteP58022.

Proteomic databases

PRIDEP58022.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000022660; ENSMUSP00000022660; ENSMUSG00000034205. [P58022-1]
ENSMUST00000100420; ENSMUSP00000097987; ENSMUSG00000034205. [P58022-1]
GeneID100862072.
94352.
KEGGmmu:100862072.
mmu:94352.
UCSCuc007umn.3. mouse. [P58022-1]

Organism-specific databases

CTD4017.
MGIMGI:2137913. Loxl2.

Phylogenomic databases

eggNOGNOG40770.
GeneTreeENSGT00740000115380.
HOGENOMHOG000220841.
HOVERGENHBG052336.
InParanoidP58022.
KOK00280.
OMASSCANGM.
OrthoDBEOG7SN8C6.
TreeFamTF326061.

Gene expression databases

BgeeP58022.
CleanExMM_LOXL2.
GenevestigatorP58022.

Family and domain databases

InterProIPR001695. Lysyl_oxidase.
IPR019828. Lysyl_oxidase_CS.
IPR001190. SRCR.
IPR017448. Srcr_rcpt-rel.
[Graphical view]
PfamPF01186. Lysyl_oxidase. 1 hit.
PF00530. SRCR. 4 hits.
[Graphical view]
PRINTSPR00074. LYSYLOXIDASE.
PR00258. SPERACTRCPTR.
SMARTSM00202. SR. 4 hits.
[Graphical view]
SUPFAMSSF56487. SSF56487. 4 hits.
PROSITEPS00926. LYSYL_OXIDASE. 1 hit.
PS00420. SRCR_1. 2 hits.
PS50287. SRCR_2. 4 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSLOXL2. mouse.
NextBio352317.
PROP58022.
SOURCESearch...

Entry information

Entry nameLOXL2_MOUSE
AccessionPrimary (citable) accession number: P58022
Secondary accession number(s): Q8BRE6 expand/collapse secondary AC list , Q8BS86, Q8C4K0, Q9JJ39
Entry history
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: November 22, 2005
Last modified: March 19, 2014
This is version 108 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot