LOL2B_DANRE
ID LOL2B_DANRE Reviewed; 762 AA.
AC A1L1V4; A5WUR2; A6MH31; A9JRQ9;
DT 13-JUN-2012, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2007, sequence version 1.
DT 03-AUG-2022, entry version 112.
DE RecName: Full=Lysyl oxidase homolog 2B;
DE EC=1.4.3.13 {ECO:0000250|UniProtKB:Q9Y4K0};
DE AltName: Full=Lysyl oxidase-like protein 2B;
DE Flags: Precursor;
GN Name=loxl2b; ORFNames=si:dkeyp-32b1.1, zgc:158414;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RX PubMed=17543297; DOI=10.1016/j.ydbio.2007.04.029;
RA Gansner J.M., Mendelsohn B.A., Hultman K.A., Johnson S.L., Gitlin J.D.;
RT "Essential role of lysyl oxidases in notochord development.";
RL Dev. Biol. 307:202-213(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo, and Kidney;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP IDENTIFICATION.
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).
RN [5]
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=25959397; DOI=10.1016/j.molcel.2015.04.012;
RA Iturbide A., Pascual-Reguant L., Fargas L., Cebria J.P., Alsina B.,
RA Garcia de Herreros A., Peiro S.;
RT "LOXL2 oxidizes methylated TAF10 and controls TFIID-dependent genes during
RT neural progenitor differentiation.";
RL Mol. Cell 58:755-766(2015).
CC -!- FUNCTION: Mediates the post-translational oxidative deamination of
CC lysine residues on target proteins leading to the formation of
CC deaminated lysine (allysine) (By similarity). Acts as a transcription
CC corepressor and specifically mediates deamination of trimethylated
CC 'Lys-4' of histone H3 (H3K4me3), a specific tag for epigenetic
CC transcriptional activation (By similarity). Shows no activity against
CC histone H3 when it is trimethylated on 'Lys-9' (H3K9me3) or 'Lys-27'
CC (H3K27me3) or when 'Lys-4' is monomethylated (H3K4me1) or dimethylated
CC (H3K4me2) (By similarity). Also mediates deamination of methylated
CC TAF10, a member of the transcription factor IID (TFIID) complex, which
CC induces release of TAF10 from promoters, leading to inhibition of
CC TFIID-dependent transcription (By similarity). LOXL2-mediated
CC deamination of TAF10 results in transcriptional repression of genes
CC required for embryonic stem cell pluripotency (By similarity). Involved
CC in epithelial to mesenchymal transition (EMT) and participates in
CC repression of E-cadherin, probably by mediating deamination of histone
CC H3 (By similarity). When secreted into the extracellular matrix,
CC promotes cross-linking of extracellular matrix proteins by mediating
CC oxidative deamination of peptidyl lysine residues in precursors to
CC fibrous collagen and elastin (By similarity). Acts as a regulator of
CC sprouting angiogenesis, probably via collagen IV scaffolding
CC (PubMed:21835952). Acts as a regulator of chondrocyte differentiation,
CC probably by regulating expression of factors that control chondrocyte
CC differentiation (By similarity). Required with loxl2a for correct
CC expression of Sox2 and for neural differentiation (PubMed:25959397).
CC {ECO:0000250|UniProtKB:P58022, ECO:0000250|UniProtKB:Q9Y4K0,
CC ECO:0000269|PubMed:25959397}.
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 -!- DEVELOPMENTAL STAGE: Expression is initiated during early development
CC throughout the notochord and extinguished between 24 and 48 hours after
CC fertilization (PubMed:17543297). At 24 hours after fertilization,
CC expressed ubiquitously throughout the embryo (PubMed:25959397).
CC {ECO:0000269|PubMed:17543297, ECO:0000269|PubMed:25959397}.
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 -!- DISRUPTION PHENOTYPE: Morpholino knockdown of loxl2a and loxl2b in the
CC embryo results in increased expression of Sox2 in the central nervous
CC system, particularly in the eye, hindbrain and spinal cord. It also
CC leads to impaired neural differentiation with morphological defects in
CC the brain where the anterior brain is rounder than normal and the eyes
CC present a flatter curvature. Embryo development is also compromised.
CC {ECO:0000269|PubMed:25959397}.
CC -!- SIMILARITY: Belongs to the lysyl oxidase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAN88496.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; EF030482; ABM86968.1; -; mRNA.
DR EMBL; CT990639; CAQ13607.1; -; Genomic_DNA.
DR EMBL; CR545472; CAN88496.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BX323062; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC129226; AAI29227.1; -; mRNA.
DR EMBL; BC155756; AAI55757.1; -; mRNA.
DR RefSeq; NP_001074095.1; NM_001080626.1.
DR RefSeq; XP_009299828.1; XM_009301553.2.
DR AlphaFoldDB; A1L1V4; -.
DR SMR; A1L1V4; -.
DR STRING; 7955.ENSDARP00000118755; -.
DR PaxDb; A1L1V4; -.
DR Ensembl; ENSDART00000064701; ENSDARP00000064700; ENSDARG00000044074.
DR Ensembl; ENSDART00000144013; ENSDARP00000118755; ENSDARG00000044074.
DR Ensembl; ENSDART00000184129; ENSDARP00000146651; ENSDARG00000044074.
DR Ensembl; ENSDART00000185815; ENSDARP00000157626; ENSDARG00000044074.
DR GeneID; 791144; -.
DR KEGG; dre:791144; -.
DR CTD; 791144; -.
DR ZFIN; ZDB-GENE-050208-29; loxl2b.
DR eggNOG; ENOG502QSX8; Eukaryota.
DR GeneTree; ENSGT00940000155874; -.
DR HOGENOM; CLU_002555_3_0_1; -.
DR InParanoid; A1L1V4; -.
DR OMA; YCTGKEA; -.
DR OrthoDB; 815466at2759; -.
DR PhylomeDB; A1L1V4; -.
DR TreeFam; TF326061; -.
DR BRENDA; 1.4.3.13; 928.
DR Reactome; R-DRE-1566948; Elastic fibre formation.
DR Reactome; R-DRE-2243919; Crosslinking of collagen fibrils.
DR PRO; PR:A1L1V4; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 5.
DR Bgee; ENSDARG00000044074; Expressed in head mesenchyme and 23 other tissues.
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; IBA:GO_Central.
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: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: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..20
FT /evidence="ECO:0000255"
FT CHAIN 21..762
FT /note="Lysyl oxidase homolog 2B"
FT /id="PRO_0000418005"
FT DOMAIN 53..154
FT /note="SRCR 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DOMAIN 183..292
FT /note="SRCR 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DOMAIN 316..417
FT /note="SRCR 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DOMAIN 427..536
FT /note="SRCR 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT REGION 540..742
FT /note="Lysyl-oxidase like"
FT /evidence="ECO:0000250"
FT BINDING 541
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT BINDING 542
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 278
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 447
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 79..143
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 92..153
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 123..133
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 213..281
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 226..291
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 260..270
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 341..406
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 354..416
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 385..395
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 456..522
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 469..535
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 503..513
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 565..616
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT DISULFID 571..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"
FT CONFLICT 128
FT /note="K -> E (in Ref. 3; AAI55757)"
FT /evidence="ECO:0000305"
FT CONFLICT 230
FT /note="G -> S (in Ref. 1; ABM86968)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 762 AA; 85503 MW; 9FBAF7387A40DF45 CRC64;
MLALWSISFV LLCSWRLSYA QYEHLGFAIA YQEPEQDLYT PPELPADTPR IQLRLAGEKR
KHNEGRVEVF YEGEWGTVCD DDFTIHAAQV ICRELGYFEA ISWSPSSKYG KGEGRIWFDN
VHCKGKEKSL AQCESNGIGV SDCKHSEDVG VVCSDKRIPG FKFVNTLTNN INSLNIQVED
VRIRPILASY RKRIPVTEGY VEVKDGGKWK QICDDEWTQM NSRVICGMFG FPGQKRYNTR
VYKMFARRRK PSYWDYTINC TGKEAHLSSC TLGHTLSNST CEEGTPVVVS CIPGRAFAPT
PMTGYKKAFR QEQPLVRLRG GAVVGEGRVE VLKNGEWGTI CDDNWNLLAA TVVCRELGFG
SAKEALSGGQ LGQGMGPVHM NEVQCSGFEK SVTECSFNME KDSEGCSHEE DAGVKCNVPA
MGFQQRLRLS GGRNPFEGRV EVLVERNGSL VWGTVCGEGW TTMEAMVVCR QLGLGFASNA
FQETWYWPGA VNADAVVMSG VRCAGTEMSL SHCLHHGEYL SCPKGGGRFA AGVSCSETAP
DLVLNPQVVE QTTYLEDRPM FMLQCAYEEN CLASTSSATP ANSPRRLLRF SSQIHNNGQS
DFRPKISREN WVWHDCHRHY HSMEVFTHYD LLSTNGTKVA EGHKASFCLE DSECDEGIEK
RYECANFGEQ GITVGCWDTY RHDIDCQWVD ITDVKPGDYI FQIVINPNYE VAESDYTNNI
VKCRCRYDGH RIWMYNCHIG GSFSAETEDT FPGLINNQVT HR
