LOXL2_XENLA
ID LOXL2_XENLA Reviewed; 765 AA.
AC Q08B63;
DT 13-JUN-2012, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2006, sequence version 1.
DT 03-AUG-2022, entry version 78.
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 laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Fat body;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (OCT-2006) 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; BC124862; AAI24863.1; -; mRNA.
DR RefSeq; NP_001121257.1; NM_001127785.1.
DR AlphaFoldDB; Q08B63; -.
DR SMR; Q08B63; -.
DR DNASU; 100158339; -.
DR GeneID; 100158339; -.
DR KEGG; xla:100158339; -.
DR CTD; 100158339; -.
DR Xenbase; XB-GENE-1010778; loxl2.L.
DR OrthoDB; 815466at2759; -.
DR Proteomes; UP000186698; Chromosome 3L.
DR Bgee; 100158339; Expressed in internal ear and 15 other tissues.
DR GO; GO:0005604; C:basement membrane; ISS:UniProtKB.
DR GO; GO:0000785; C:chromatin; ISS:UniProtKB.
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..765
FT /note="Lysyl oxidase homolog 2"
FT /id="PRO_0000418006"
FT DOMAIN 49..150
FT /note="SRCR 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DOMAIN 179..293
FT /note="SRCR 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DOMAIN 317..416
FT /note="SRCR 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DOMAIN 426..535
FT /note="SRCR 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT REGION 539..742
FT /note="Lysyl-oxidase like"
FT /evidence="ECO:0000250"
FT BINDING 540
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT BINDING 541
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT BINDING 617
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
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 713
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
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 718
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT BINDING 719
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT MOD_RES 680
FT /note="2',4',5'-topaquinone"
FT /evidence="ECO:0000250|UniProtKB:P33072"
FT CARBOHYD 279
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 446
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 635
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 75..139
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 88..149
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 119..129
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 209..282
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 222..292
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 256..266
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 342..405
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 355..415
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 386..396
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 455..521
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 468..534
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 502..512
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 564..616
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT DISULFID 570..686
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT DISULFID 648..664
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT DISULFID 654..676
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT DISULFID 723..737
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT CROSSLNK 644..680
FT /note="Lysine tyrosylquinone (Lys-Tyr)"
FT /evidence="ECO:0000250|UniProtKB:P33072"
SQ SEQUENCE 765 AA; 85656 MW; 978C9ACDFEDFDE51 CRC64;
MLVSHVFLLT LSLSVPSLGQ YEHWPYYPEY QGPPEPPPTQ PKIVPQIHVR LAGEKRKHNE
GRVEVYYEGE WGTVCDDDFS MYAAHIVCRE LGYQEAVSWS PSSKYGKGEG RIWLDNVNCN
GRERSIASCS SNGWGVTDCK HSEDVGVQCS DRRIPGFKVS NELPGHLEGL NIQVEDVRIR
PILSAYRKRV PVTEGFAEVK VQGSWRQVCN TQWSSKNSRV VCGMFGFPSE KKYNTKVYKM
FSSRRKHTYW QFSANCTGNE PHLSSCKVGG VLSPDPKTNQ TCSDGAPAVV SCTPGRAFAP
SPGTGFRKAF RQEQPLVRLR GGANVGEGRV EVLKNGEWGT VCDDKWNLVT ASVICRELGF
GSAKEALVGA QLGQGMGQIH MSEIQCNGFE KSLTDCKFNI HSQGCNHEED AAVRCNVPAM
GFENQVRLSG GRHPTEGRVE VLMERNGTLR WGTVCSETWG TMEAMIVCRQ LGLGFASHAF
QETWYWQGDI NADDVVMSGV KCSGTEMSLA HCRHDGANVN CPRGGGRFAA GVSCVETAPD
LVLNAALVEQ TTYLEDRPMF MLQCAHEEQC LASSADRTSP TTGYRRLLRF SSQIHNNGQA
DFRPKTGRHA WIWHDCHRHY HSMEVFTHYD LLTLNGTKVA EGHKASFCLE DSECEADIQK
QYVCANFGEQ GITVGCWDLY RHDIDCQWVD ITDVAPGDYF FQIIINPNQE VAESDYTNNI
MKCRCRYDGQ RIWMYNCHIG GSYSTETEEK FEHFSGLLNN QLSTR
