LOXL2_RAT
ID LOXL2_RAT Reviewed; 776 AA.
AC B5DF27; F1LPM2;
DT 13-JUN-2012, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2012, sequence version 2.
DT 03-AUG-2022, entry version 86.
DE RecName: Full=Lysyl oxidase homolog 2;
DE EC=1.4.3.13 {ECO:0000250|UniProtKB:Q9Y4K0};
DE AltName: Full=Lysyl oxidase-like protein 2;
DE Flags: Precursor;
GN Name=Loxl2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP SUBCELLULAR LOCATION.
RX PubMed=21835952; DOI=10.1182/blood-2010-10-313296;
RA Bignon M., Pichol-Thievend C., Hardouin J., Malbouyres M., Brechot N.,
RA Nasciutti L., Barret A., Teillon J., Guillon E., Etienne E., Caron M.,
RA Joubert-Caron R., Monnot C., Ruggiero F., Muller L., Germain S.;
RT "Lysyl oxidase-like protein-2 regulates sprouting angiogenesis and type IV
RT collagen assembly in the endothelial basement membrane.";
RL Blood 118:3979-3989(2011).
CC -!- FUNCTION: Mediates the post-translational oxidative deamination of
CC lysine residues on target proteins leading to the formation of
CC deaminated lysine (allysine). Acts as a transcription corepressor and
CC specifically mediates deamination of trimethylated 'Lys-4' of histone
CC H3 (H3K4me3), a specific tag for epigenetic transcriptional activation.
CC Shows no activity against histone H3 when it is trimethylated on 'Lys-
CC 9' (H3K9me3) or 'Lys-27' (H3K27me3) or when 'Lys-4' is monomethylated
CC (H3K4me1) or dimethylated (H3K4me2). Also mediates deamination of
CC methylated TAF10, a member of the transcription factor IID (TFIID)
CC complex, which induces release of TAF10 from promoters, leading to
CC inhibition of TFIID-dependent transcription. LOXL2-mediated deamination
CC of TAF10 results in transcriptional repression of genes required for
CC embryonic stem cell pluripotency including POU5F1/OCT4, NANOG, KLF4 and
CC SOX2. Involved in epithelial to mesenchymal transition (EMT) via
CC interaction with SNAI1 and participates in repression of E-cadherin
CC CDH1, probably by mediating deamination of histone H3. During EMT,
CC involved with SNAI1 in negatively regulating pericentromeric
CC heterochromatin transcription. SNAI1 recruits LOXL2 to pericentromeric
CC regions to oxidize histone H3 and repress transcription which leads to
CC release of heterochromatin component CBX5/HP1A, enabling chromatin
CC reorganization and acquisition of mesenchymal traits. Interacts with
CC the endoplasmic reticulum protein HSPA5 which activates the IRE1-XBP1
CC pathway of the unfolded protein response, leading to expression of
CC several transcription factors involved in EMT and subsequent EMT
CC induction. When secreted into the extracellular matrix, promotes cross-
CC linking of extracellular matrix proteins by mediating oxidative
CC deamination of peptidyl lysine residues in precursors to fibrous
CC collagen and elastin. Acts as a regulator of sprouting angiogenesis,
CC probably via collagen IV scaffolding. Acts as a regulator of
CC chondrocyte differentiation, probably by regulating expression of
CC factors that control chondrocyte differentiation.
CC {ECO:0000250|UniProtKB:P58022, ECO:0000250|UniProtKB:Q9Y4K0}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-lysyl-[protein] + O2 = (S)-2-amino-6-oxohexanoyl-
CC [protein] + H2O2 + NH4(+); Xref=Rhea:RHEA:24544, Rhea:RHEA-COMP:9752,
CC Rhea:RHEA-COMP:12448, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16240, ChEBI:CHEBI:28938, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:131803; EC=1.4.3.13;
CC Evidence={ECO:0000250|UniProtKB:Q9Y4K0};
CC -!- COFACTOR:
CC Name=Cu cation; Xref=ChEBI:CHEBI:23378;
CC Evidence={ECO:0000250|UniProtKB:Q9Y4K0};
CC -!- COFACTOR:
CC Name=lysine tyrosylquinone residue; Xref=ChEBI:CHEBI:20489;
CC Evidence={ECO:0000250|UniProtKB:Q9Y4K0};
CC Note=Contains 1 lysine tyrosylquinone. {ECO:0000250|UniProtKB:P33072,
CC ECO:0000250|UniProtKB:Q9Y4K0};
CC -!- ACTIVITY REGULATION: Specifically inhibited by a mouse monoclonal
CC antibody AB0023, inhibition occurs in a non-competitive manner.
CC {ECO:0000250|UniProtKB:Q9Y4K0}.
CC -!- SUBUNIT: Component of some chromatin repressor complex. Interacts with
CC SNAI1. Interacts with TAF10. Interacts with HSPA5. Interacts with
CC EFEMP2 (By similarity). {ECO:0000250|UniProtKB:Q9Y4K0}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix, basement membrane {ECO:0000269|PubMed:21835952}. Nucleus
CC {ECO:0000250|UniProtKB:Q9Y4K0}. Chromosome
CC {ECO:0000250|UniProtKB:Q9Y4K0}. Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:Q9Y4K0}. Note=Associated with chromatin. It is
CC unclear how LOXL2 is nuclear as it contains a signal sequence and has
CC been shown to be secreted. However, a number of reports confirm its
CC intracellular location and its key role in transcription regulation.
CC {ECO:0000250|UniProtKB:Q9Y4K0}.
CC -!- DOMAIN: The fourth SRCR domain plays an important role in optimizing
CC the catalytic activity of the lysyl-oxidase like (LOX) catalytic
CC domain. {ECO:0000250}.
CC -!- PTM: The lysine tyrosylquinone cross-link (LTQ) is generated by
CC condensation of the epsilon-amino group of a lysine with a topaquinone
CC produced by oxidation of tyrosine. {ECO:0000250|UniProtKB:Q9Y4K0}.
CC -!- PTM: N-glycosylated. N-glycosylation on Asn-458 and Asn-646 may be
CC essential for proper folding and secretion; may be composed of a
CC fucosylated carbohydrates attached to a trimannose N-linked glycan
CC core. {ECO:0000250|UniProtKB:Q9Y4K0}.
CC -!- SIMILARITY: Belongs to the lysyl oxidase family. {ECO:0000305}.
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DR EMBL; BC168900; AAI68900.1; -; mRNA.
DR RefSeq; NP_001099517.2; NM_001106047.2.
DR AlphaFoldDB; B5DF27; -.
DR SMR; B5DF27; -.
DR STRING; 10116.ENSRNOP00000055457; -.
DR BindingDB; B5DF27; -.
DR ChEMBL; CHEMBL4105908; -.
DR GlyGen; B5DF27; 4 sites.
DR jPOST; B5DF27; -.
DR PaxDb; B5DF27; -.
DR PeptideAtlas; B5DF27; -.
DR PRIDE; B5DF27; -.
DR GeneID; 290350; -.
DR KEGG; rno:290350; -.
DR UCSC; RGD:1308435; rat.
DR CTD; 4017; -.
DR RGD; 1308435; Loxl2.
DR eggNOG; ENOG502QSX8; Eukaryota.
DR InParanoid; B5DF27; -.
DR OrthoDB; 815466at2759; -.
DR Reactome; R-RNO-1566948; Elastic fibre formation.
DR Reactome; R-RNO-2243919; Crosslinking of collagen fibrils.
DR PRO; PR:B5DF27; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005604; C:basement membrane; IDA:UniProtKB.
DR GO; GO:0000785; C:chromatin; ISS:UniProtKB.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; IEA:InterPro.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0005507; F:copper ion binding; ISS:UniProtKB.
DR GO; GO:0070492; F:oligosaccharide binding; ISS:UniProtKB.
DR GO; GO:0004720; F:protein-lysine 6-oxidase activity; ISS:UniProtKB.
DR GO; GO:0005044; F:scavenger receptor activity; IEA:InterPro.
DR GO; GO:0030199; P:collagen fibril organization; ISS:UniProtKB.
DR GO; GO:0043542; P:endothelial cell migration; ISS:UniProtKB.
DR GO; GO:0001935; P:endothelial cell proliferation; ISS:UniProtKB.
DR GO; GO:0001837; P:epithelial to mesenchymal transition; ISS:UniProtKB.
DR GO; GO:0070828; P:heterochromatin organization; ISS:UniProtKB.
DR GO; GO:1902455; P:negative regulation of stem cell population maintenance; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0018057; P:peptidyl-lysine oxidation; ISS:UniProtKB.
DR GO; GO:0032332; P:positive regulation of chondrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; ISS:UniProtKB.
DR GO; GO:0036211; P:protein modification process; ISS:UniProtKB.
DR GO; GO:0046688; P:response to copper ion; ISS:UniProtKB.
DR GO; GO:0001666; P:response to hypoxia; ISS:UniProtKB.
DR GO; GO:0002040; P:sprouting angiogenesis; ISS:UniProtKB.
DR Gene3D; 3.10.250.10; -; 4.
DR InterPro; IPR001695; Lysyl_oxidase.
DR InterPro; IPR019828; Lysyl_oxidase_CS.
DR InterPro; IPR001190; SRCR.
DR InterPro; IPR017448; SRCR-like_dom.
DR InterPro; IPR036772; SRCR-like_dom_sf.
DR Pfam; PF01186; Lysyl_oxidase; 1.
DR Pfam; PF00530; SRCR; 4.
DR PRINTS; PR00074; LYSYLOXIDASE.
DR PRINTS; PR00258; SPERACTRCPTR.
DR SMART; SM00202; SR; 4.
DR SUPFAM; SSF56487; SSF56487; 4.
DR PROSITE; PS00926; LYSYL_OXIDASE; 1.
DR PROSITE; PS00420; SRCR_1; 2.
DR PROSITE; PS50287; SRCR_2; 4.
PE 2: Evidence at transcript level;
KW Basement membrane; Calcium; Chromatin regulator; Chromosome; Copper;
KW Disulfide bond; Endoplasmic reticulum; Extracellular matrix; Glycoprotein;
KW LTQ; Metal-binding; Nucleus; Oxidoreductase; Reference proteome; Repeat;
KW Repressor; Secreted; Signal; TPQ; Transcription; Transcription regulation.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..776
FT /note="Lysyl oxidase homolog 2"
FT /id="PRO_0000418002"
FT DOMAIN 61..162
FT /note="SRCR 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DOMAIN 191..305
FT /note="SRCR 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DOMAIN 329..428
FT /note="SRCR 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DOMAIN 438..546
FT /note="SRCR 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT REGION 550..753
FT /note="Lysyl-oxidase like"
FT /evidence="ECO:0000250"
FT BINDING 551
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT BINDING 552
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT BINDING 628
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT BINDING 630
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT BINDING 632
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT BINDING 724
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT BINDING 726
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT BINDING 729
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT BINDING 730
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT MOD_RES 691
FT /note="2',4',5'-topaquinone"
FT /evidence="ECO:0000250|UniProtKB:P33072"
FT CARBOHYD 267
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 291
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 458
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 646
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 87..151
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 100..161
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 131..141
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 221..294
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 234..304
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 268..278
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 354..417
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 367..427
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 398..408
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 467..532
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 480..545
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 514..524
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 575..627
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT DISULFID 581..697
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT DISULFID 659..675
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT DISULFID 665..687
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT DISULFID 734..748
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT CROSSLNK 655..691
FT /note="Lysine tyrosylquinone (Lys-Tyr)"
FT /evidence="ECO:0000250|UniProtKB:P33072"
FT CONFLICT 154
FT /note="P -> T (in Ref. 2; AAI68900)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 776 AA; 87185 MW; 0ACE3544E7E8278A CRC64;
MEIPFGSCLY SCLALLVLLP SLSLAQYESW PYQLQYPEYF QQPPPEHHQH QVPSDVVKIQ
VRLAGQKRKH NEGRVEVYYE GQWGTVCDDD FSIHAAHVVC REVGYVEAKS WTASSSYGPG
EGPIWLDNIY CTGKESTLAA CSSNGWGVTD CKHPEDVGVV CSEKRIPGFK FDNSLINQIE
SLNIQVEDIR IRPILSAFRH RKPVTEGYVE VKEGKAWKQI CDKHWTAKNS HVVCGMFGFP
AEKTYNPKAY KTFASRRKLR YWKFSMNCTG TEAHISSCKL GPPMFRDPVK NATCENGQPA
VVSCVPSQIF SPDGPSRFRK AYKPEQPLVR LRGGAQVGEG RVEVLKNGEW GTVCDDKWDL
VSASVVCREL GFGTAKEAVT GSRLGQGIGP IHLNEVQCTG TEKSIIDCKL NTESQGCNHE
EDAGVRCNIP IMGFQKKVRL NGGRNPYEGR VEVLTERNGS LVWGNVCGQN WGIVEAMVVC
RQLGLGFASN AFQETWYWHG NIFANKVIMS GVKCSGTELS LAHCRHDEEV VCPEGGVQYG
AGVACSETAP DLVLNAEIVQ QTAYLEDRPM ALLQCAMEEN CLSASAVHTD PTRGHRRLLR
FSSQIHNNGQ SDFRPKNGRH AWIWHDCHRH YHSMEVFTYY DLLSLNGTKV AEGHKASFCL
EDTECEGDIQ KSYECANFGE QGITMGCWDM YRHDIDCQWI DITDVPPGDY LFQVVINPNY
EVPESDFSNN IMKCRSRYDG YRIWMYNCHV GGAFSEETEQ KFEHFSGLLN NQLSVQ
