LOXL2_PONAB
ID LOXL2_PONAB Reviewed; 774 AA.
AC Q5RFQ6;
DT 10-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, 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 Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) 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 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: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 -!- 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-455 and Asn-644 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; CR857096; CAH89401.1; -; mRNA.
DR AlphaFoldDB; Q5RFQ6; -.
DR SMR; Q5RFQ6; -.
DR STRING; 9601.ENSPPYP00000023997; -.
DR PRIDE; Q5RFQ6; -.
DR eggNOG; ENOG502QSX8; Eukaryota.
DR InParanoid; Q5RFQ6; -.
DR Proteomes; UP000001595; Unplaced.
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; 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..774
FT /note="Lysyl oxidase homolog 2"
FT /id="PRO_0000045440"
FT DOMAIN 58..159
FT /note="SRCR 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DOMAIN 188..302
FT /note="SRCR 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DOMAIN 326..425
FT /note="SRCR 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DOMAIN 435..544
FT /note="SRCR 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT REGION 548..751
FT /note="Lysyl-oxidase like"
FT BINDING 549
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT BINDING 550
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT BINDING 626
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
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 722
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
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 727
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT BINDING 728
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT MOD_RES 689
FT /note="2',4',5'-topaquinone"
FT /evidence="ECO:0000250|UniProtKB:P33072"
FT CARBOHYD 288
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 455
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 644
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 84..148
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 97..158
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 128..138
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 218..291
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 231..301
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 265..275
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 351..414
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 364..424
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 395..405
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 464..530
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 477..543
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 511..521
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 573..625
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT DISULFID 579..695
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT DISULFID 657..673
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT DISULFID 663..685
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K0"
FT DISULFID 732..746
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT CROSSLNK 653..689
FT /note="Lysine tyrosylquinone (Lys-Tyr)"
FT /evidence="ECO:0000250|UniProtKB:P33072"
SQ SEQUENCE 774 AA; 86604 MW; FD8FABC858A83C41 CRC64;
MERPLCSHLC SCLAVLALLS PLSLAQYDSW PHYPEYFQQP APEYHQPQAP ANVAKIQLRL
AGQKRKHSEG RVEVYYDGQW GTVCDDDFSI HAAHVVCREL GYVEAKSWTA SSSYGKGEGP
IWLDNLHCTG NEATLAACTS NGWGVTDCKH TEDVGVVCSD KRIPGFKFDN SLINQIENLN
IQVEDIRIRA ILSTYRKRTP VTEGYVEVKE GKTWKQICDK HWTAKNSRVI CGMFGFPGER
TYNAKVYKMF ASRRKQRYWP FSMDCTGTEA HISSCKLGPQ VSLDPMKNVT CENGLPAVVS
CVPGQVFSPD GPSRFRKAYK PEQPLVRLRG GAYIGEGRVE VLKNGEWGTV CDDKWDLVSA
SVVCRELGFG SAKEAVTGSR LGQGIGPIHL NEIQCTGNEK SIIDCKFNTE SQGCNHEEDA
GVRCNTPAMG LQKKLRLNGG RNPYEGRVEV LVERNGSLVW GMVCGQNWGI VEAMVVCRQL
GLGFASNAFQ ETWYWHGDVN SNKVVMSGVK CSGTELSLAH CRHDGEDVAC PQGGVQYGAG
VACSETAPDL VLNAEMVQQT TYLEDRPMFM LQCAMEENCL SASAAQTNPT TGYRRLLRFS
SQIHNNGQSD FRPKNGRHAW IWHDCHRHYH SMEVFTHYDL LNLNGTKVAE GHKASFCLED
TECEGDIQKN YECANFGDQG ITMGCWDMYR HDIDCQWVDI TDVPPGDYLF QVVINPNFEV
AESDYSNNIM KCRSRYDGHR IWMYNCHIGG SFSEETEKKF GHFSGLLNNQ LSPQ
