LOXL2_XENTR
ID LOXL2_XENTR Reviewed; 767 AA.
AC B4F6N6; F7END9;
DT 13-JUN-2012, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2012, sequence version 2.
DT 03-AUG-2022, entry version 72.
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 Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Silurana.
OX NCBI_TaxID=8364;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=20431018; DOI=10.1126/science.1183670;
RA Hellsten U., Harland R.M., Gilchrist M.J., Hendrix D., Jurka J.,
RA Kapitonov V., Ovcharenko I., Putnam N.H., Shu S., Taher L., Blitz I.L.,
RA Blumberg B., Dichmann D.S., Dubchak I., Amaya E., Detter J.C., Fletcher R.,
RA Gerhard D.S., Goodstein D., Graves T., Grigoriev I.V., Grimwood J.,
RA Kawashima T., Lindquist E., Lucas S.M., Mead P.E., Mitros T., Ogino H.,
RA Ohta Y., Poliakov A.V., Pollet N., Robert J., Salamov A., Sater A.K.,
RA Schmutz J., Terry A., Vize P.D., Warren W.C., Wells D., Wills A.,
RA Wilson R.K., Zimmerman L.B., Zorn A.M., Grainger R., Grammer T.,
RA Khokha M.K., Richardson P.M., Rokhsar D.S.;
RT "The genome of the Western clawed frog Xenopus tropicalis.";
RL Science 328:633-636(2010).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=N6; TISSUE=Fat body;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (JUL-2008) to the EMBL/GenBank/DDBJ databases.
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. Involved in epithelial to mesenchymal
CC transition (EMT) and participates in repression of E-cadherin, probably
CC by mediating deamination of histone H3. When secreted into the
CC extracellular matrix, promotes cross-linking of extracellular matrix
CC proteins by mediating oxidative deamination of peptidyl lysine residues
CC in precursors to fibrous collagen and elastin. Acts as a regulator of
CC sprouting angiogenesis, probably via collagen IV scaffolding. Acts as a
CC regulator of chondrocyte differentiation, probably by regulating
CC expression of 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 -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix, basement membrane {ECO:0000250|UniProtKB:Q9Y4K0}. 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 -!- 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 -!- SIMILARITY: Belongs to the lysyl oxidase family. {ECO:0000305}.
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DR EMBL; AAMC01014210; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01014211; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01014212; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01014213; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01014214; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01014215; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01014216; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01014217; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01014218; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01014219; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01014220; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01014221; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01014222; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01014223; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01014224; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01014225; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01014226; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC167947; AAI67947.1; -; mRNA.
DR RefSeq; NP_001135520.1; NM_001142048.1.
DR AlphaFoldDB; B4F6N6; -.
DR SMR; B4F6N6; -.
DR STRING; 8364.ENSXETP00000016976; -.
DR GeneID; 100216062; -.
DR KEGG; xtr:100216062; -.
DR CTD; 4017; -.
DR Xenbase; XB-GENE-1010775; loxl2.
DR eggNOG; ENOG502QSX8; Eukaryota.
DR InParanoid; B4F6N6; -.
DR OrthoDB; 815466at2759; -.
DR Reactome; R-XTR-2243919; Crosslinking of collagen fibrils.
DR Proteomes; UP000008143; Chromosome 3.
DR Proteomes; UP000790000; Unplaced.
DR GO; GO:0005604; C:basement membrane; ISS: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; 1.
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..19
FT /evidence="ECO:0000255"
FT CHAIN 20..767
FT /note="Lysyl oxidase homolog 2"
FT /id="PRO_0000418007"
FT DOMAIN 51..152
FT /note="SRCR 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DOMAIN 181..295
FT /note="SRCR 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DOMAIN 319..418
FT /note="SRCR 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DOMAIN 428..537
FT /note="SRCR 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT REGION 541..744
FT /note="Lysyl-oxidase like"
FT /evidence="ECO:0000250"
FT BINDING 542
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT BINDING 543
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT BINDING 619
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT BINDING 621
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT BINDING 623
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT BINDING 715
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT BINDING 717
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT BINDING 720
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT BINDING 721
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT MOD_RES 682
FT /note="2',4',5'-topaquinone"
FT /evidence="ECO:0000250|UniProtKB:P33072"
FT CARBOHYD 281
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 448
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 637
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 77..141
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 90..151
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 121..131
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 211..284
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 224..294
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 258..268
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 344..407
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 357..417
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 388..398
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 457..523
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 470..536
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 504..514
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 566..618
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT DISULFID 572..688
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT DISULFID 650..666
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT DISULFID 656..678
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT DISULFID 725..739
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT CROSSLNK 646..682
FT /note="Lysine tyrosylquinone (Lys-Tyr)"
FT /evidence="ECO:0000250|UniProtKB:P33072"
FT CONFLICT 309
FT /note="G -> R (in Ref. 2; AAI67947)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 767 AA; 85683 MW; BB7B467174A98552 CRC64;
MLVTHIFLLT LSLSVPTLGQ YEHWLYYPEY QASQAPEPLP TPARNVPQIH VRLAGEKRKH
NEGRVEVYYE GEWGTVCDDD FSMYAAHIVC RELGYQDAVS WSPSSKYGKG EGRIWLDNVN
CNGREKSIAS CGSNGWGVTD CKHSEDVGVQ CSDRRIPGFK VSNELPGQLE GLNIQVEEVR
IRAILSAYRK RVPVTEGFVE VKVQGSWRQV CNAEWSSKNS RVVCGMFGFP AEKKFNNKVY
KLFSSRRKHT YWQFSANCTG NEAHLSSCKV GGVLTPDPKT NQTCSDGSPA VVSCTPGRAF
APSPGTGFGK AFRQEQPLVR LRGGANTGEG RVEVLKNGEW GTICDDKWNL VTASVVCREL
GFGSAKEALA GAQMGQGMGH IHMSEIQCNG FEKSLIDCKF NVHSQGCNHE EDAAVRCNVP
AMGFENQVRL SGGRHPTEGR VEVLMERNGT LRWGTVCSDT WGTMEAMIVC RQLGLGFASH
AFQETWYWQG DINADDVVMS GVKCSGTEMS LAHCRHDGAN INCPRGGGRF AAGVSCVETA
PDLVLNAALV EQTTYLEDRP MFMLQCAHEE QCLSSSADRT SPTTGYRRLL RFSSQIHNNG
QADFRPKTGR HSWIWHDCHR HYHSMEVFTH YDLLSLNGTK VAEGHKASFC LEDSECETDV
QKQYACANFG EQGITVGCWD VYRHDIDCQW VDITDVAPGD YFFQVIINPN QEVAESDYTN
NIMKCRCRYD GHRIWMYNCH IGGSYSTETE EKFEHFSGLM NNQLSTR
