LOXL2_CHICK
ID LOXL2_CHICK Reviewed; 774 AA.
AC E1C3U7;
DT 13-JUN-2012, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2010, sequence version 1.
DT 03-AUG-2022, entry version 65.
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 Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Red jungle fowl;
RX PubMed=15592404; DOI=10.1038/nature03154;
RA Hillier L.W., Miller W., Birney E., Warren W., Hardison R.C., Ponting C.P.,
RA Bork P., Burt D.W., Groenen M.A.M., Delany M.E., Dodgson J.B.,
RA Chinwalla A.T., Cliften P.F., Clifton S.W., Delehaunty K.D., Fronick C.,
RA Fulton R.S., Graves T.A., Kremitzki C., Layman D., Magrini V.,
RA McPherson J.D., Miner T.L., Minx P., Nash W.E., Nhan M.N., Nelson J.O.,
RA Oddy L.G., Pohl C.S., Randall-Maher J., Smith S.M., Wallis J.W.,
RA Yang S.-P., Romanov M.N., Rondelli C.M., Paton B., Smith J., Morrice D.,
RA Daniels L., Tempest H.G., Robertson L., Masabanda J.S., Griffin D.K.,
RA Vignal A., Fillon V., Jacobbson L., Kerje S., Andersson L.,
RA Crooijmans R.P., Aerts J., van der Poel J.J., Ellegren H., Caldwell R.B.,
RA Hubbard S.J., Grafham D.V., Kierzek A.M., McLaren S.R., Overton I.M.,
RA Arakawa H., Beattie K.J., Bezzubov Y., Boardman P.E., Bonfield J.K.,
RA Croning M.D.R., Davies R.M., Francis M.D., Humphray S.J., Scott C.E.,
RA Taylor R.G., Tickle C., Brown W.R.A., Rogers J., Buerstedde J.-M.,
RA Wilson S.A., Stubbs L., Ovcharenko I., Gordon L., Lucas S., Miller M.M.,
RA Inoko H., Shiina T., Kaufman J., Salomonsen J., Skjoedt K., Wong G.K.-S.,
RA Wang J., Liu B., Wang J., Yu J., Yang H., Nefedov M., Koriabine M.,
RA Dejong P.J., Goodstadt L., Webber C., Dickens N.J., Letunic I., Suyama M.,
RA Torrents D., von Mering C., Zdobnov E.M., Makova K., Nekrutenko A.,
RA Elnitski L., Eswara P., King D.C., Yang S.-P., Tyekucheva S.,
RA Radakrishnan A., Harris R.S., Chiaromonte F., Taylor J., He J.,
RA Rijnkels M., Griffiths-Jones S., Ureta-Vidal A., Hoffman M.M., Severin J.,
RA Searle S.M.J., Law A.S., Speed D., Waddington D., Cheng Z., Tuzun E.,
RA Eichler E., Bao Z., Flicek P., Shteynberg D.D., Brent M.R., Bye J.M.,
RA Huckle E.J., Chatterji S., Dewey C., Pachter L., Kouranov A.,
RA Mourelatos Z., Hatzigeorgiou A.G., Paterson A.H., Ivarie R., Brandstrom M.,
RA Axelsson E., Backstrom N., Berlin S., Webster M.T., Pourquie O.,
RA Reymond A., Ucla C., Antonarakis S.E., Long M., Emerson J.J., Betran E.,
RA Dupanloup I., Kaessmann H., Hinrichs A.S., Bejerano G., Furey T.S.,
RA Harte R.A., Raney B., Siepel A., Kent W.J., Haussler D., Eyras E.,
RA Castelo R., Abril J.F., Castellano S., Camara F., Parra G., Guigo R.,
RA Bourque G., Tesler G., Pevzner P.A., Smit A., Fulton L.A., Mardis E.R.,
RA Wilson R.K.;
RT "Sequence and comparative analysis of the chicken genome provide unique
RT perspectives on vertebrate evolution.";
RL Nature 432:695-716(2004).
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 -!- 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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AADN02055455; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AADN02055456; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AADN02055457; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; E1C3U7; -.
DR SMR; E1C3U7; -.
DR STRING; 9031.ENSGALP00000000547; -.
DR PaxDb; E1C3U7; -.
DR VEuPathDB; HostDB:geneid_419533; -.
DR eggNOG; ENOG502QSX8; Eukaryota.
DR InParanoid; E1C3U7; -.
DR PhylomeDB; E1C3U7; -.
DR TreeFam; TF326061; -.
DR Proteomes; UP000000539; 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; 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 3: Inferred from homology;
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..24
FT /evidence="ECO:0000255"
FT CHAIN 25..774
FT /note="Lysyl oxidase homolog 2"
FT /id="PRO_0000418003"
FT DOMAIN 57..158
FT /note="SRCR 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DOMAIN 187..301
FT /note="SRCR 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DOMAIN 325..424
FT /note="SRCR 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DOMAIN 434..543
FT /note="SRCR 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT REGION 547..751
FT /note="Lysyl-oxidase like"
FT /evidence="ECO:0000250"
FT BINDING 548
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT BINDING 549
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT BINDING 625
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT BINDING 627
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT BINDING 629
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
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 BINDING 723
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 727
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT MOD_RES 688
FT /note="2',4',5'-topaquinone"
FT /evidence="ECO:0000250|UniProtKB:P33072"
FT CARBOHYD 287
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 454
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 643
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 83..147
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 96..157
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 127..137
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 217..290
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 230..300
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 264..274
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 350..413
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 363..423
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 394..404
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 463..529
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 476..542
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 510..520
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 572..624
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT DISULFID 578..694
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT DISULFID 656..672
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT DISULFID 662..684
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT CROSSLNK 652..688
FT /note="Lysine tyrosylquinone (Lys-Tyr)"
FT /evidence="ECO:0000250|UniProtKB:P33072"
SQ SEQUENCE 774 AA; 86965 MW; 6556E6278361BBC8 CRC64;
MEGFLGFNHN HCFIVLFFVS LSLAQYEHWP YLPGYPEPPP QVYQPPRRPA DVPKIQLRLA
GQKRKHNEGR VEVFYNGEWG TVCDDDFSIH AAHVICRELG YVEAVSWLPS SKYGKGEGKI
WMDNVHCNGK EATLAACTSN GWGVTDCKHT EDVGVVCSEK RIPGFKFDNS LLNQIENMNI
QVEDIRIRPI LATYRKRVPV TEGYVEVKDE GTWKQICDKH WTMKNSRVVC GMFGFPSERK
YNTKVYKMFA SRRKQHYWAY SMDCTGNEAH ISSCKLGNHL NVDTEKNATC DNGMPAVASC
VPGRAFAPSS HSGFRKAFRQ EQPLVRLKGG ANTGEGRVEV LKNGEWGTVC DDNWNLVSAS
VVCRELGFGS AKEAITGARL GQGMGPIHLN EIDCTGFEKS LTDCKFNMES QGCNHEEDAA
VRCNVPAMGF QNQLRLVGGR NPYEGRVEVL AERNGTLRWG TVCSQGWSTV EAMVVCRQLG
LGFASHAFQE TWYWHGDVSA DSVVMSGVKC SGTEMSLAHC RHDGADVSCP RGGGRFGAGV
SCSETAPDLV LNAELVEQTA YLEDRPMFML QCAQEENCLA SSAVNTSVTS GYRRLLRFSS
QIHNNGQSDF RPKNGRHAWV WHDCHRHYHS MEVFTHYDLL NLNGTKVAEG HKASFCLEDT
ECEADVQKQY ECANFGEQGI TVGCWDVYRH DIDCQWIDIT DVPPGDYLFQ VVINPNYEVA
ESDYSNNVMK CRSRYDGQRI WMYNSVHNGA NQDGDTEERF SAYWKLGNSI LFSR
