LOXL3_HUMAN
ID LOXL3_HUMAN Reviewed; 753 AA.
AC P58215; D6W5J1; Q2EHP2; Q6IPL7; Q96RS1;
DT 11-JUL-2001, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2001, sequence version 1.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Lysyl oxidase homolog 3 {ECO:0000305};
DE EC=1.4.3.- {ECO:0000269|PubMed:28065600};
DE EC=1.4.3.13 {ECO:0000269|PubMed:28065600};
DE AltName: Full=Lysyl oxidase-like protein 3 {ECO:0000303|PubMed:11386757};
DE Flags: Precursor;
GN Name=LOXL3 {ECO:0000303|PubMed:11386757, ECO:0000312|HGNC:HGNC:13869};
GN Synonyms=LOXL {ECO:0000303|PubMed:11284725};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=11284725; DOI=10.1042/0264-6021:3550381;
RA Maki J.M., Kivirikko K.I.;
RT "Cloning and characterization of a fourth human lysyl oxidase isoenzyme.";
RL Biochem. J. 355:381-387(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=11386757; DOI=10.1006/geno.2001.6545;
RA Jourdan-Le Saux C., Tomshe A., Ujfalusi A., Jia L., Csiszar K.;
RT "Central nervous system, uterus, heart, and leukocyte expression of the
RT LOXL3 gene, encoding a novel lysyl oxidase-like protein.";
RL Genomics 74:211-218(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=11334717; DOI=10.1016/s0945-053x(01)00124-x;
RA Huang Y., Dai J., Tang R., Zhao W., Zhou Z., Wang W., Ying K., Xie Y.,
RA Mao Y.;
RT "Cloning and characterization of a human lysyl oxidase-like 3 gene
RT (hLOXL3).";
RL Matrix Biol. 20:153-157(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION (ISOFORMS 1 AND 2),
RP SUBCELLULAR LOCATION (ISOFORM 2), AND TISSUE SPECIFICITY.
RX PubMed=17018530; DOI=10.1074/jbc.m600977200;
RA Lee J.-E., Kim Y.;
RT "A tissue-specific variant of the human lysyl oxidase-like protein 3
RT (LOXL3) functions as an amine oxidase with substrate specificity.";
RL J. Biol. Chem. 281:37282-37290(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP INVOLVEMENT IN STICKLER SYNDROME, AND VARIANT TYR-676.
RX PubMed=25663169; DOI=10.1007/s00439-015-1531-z;
RA Alzahrani F., Al Hazzaa S.A., Tayeb H., Alkuraya F.S.;
RT "LOXL3, encoding lysyl oxidase-like 3, is mutated in a family with
RT autosomal recessive Stickler syndrome.";
RL Hum. Genet. 134:451-453(2015).
RN [9]
RP TISSUE SPECIFICITY.
RX PubMed=26218558; DOI=10.14670/hh-11-649;
RA Dudakova L., Sasaki T., Liskova P., Palos M., Jirsova K.;
RT "The presence of lysyl oxidase-like enzymes in human control and
RT keratoconic corneas.";
RL Histol. Histopathol. 31:63-71(2016).
RN [10]
RP INVOLVEMENT IN EARLY-ONSET HIGH MYOPIA.
RX PubMed=26957899;
RA Li J., Gao B., Xiao X., Li S., Jia X., Sun W., Guo X., Zhang Q.;
RT "Exome sequencing identified null mutations in LOXL3 associated with early-
RT onset high myopia.";
RL Mol. Vis. 22:161-167(2016).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR
RP LOCATION, INTERACTION WITH STAT3, AND MUTAGENESIS OF CYS-83; CYS-214;
RP CYS-345; CYS-376; CYS-446; CYS-459; CYS-492 AND 607-HIS--HIS-609.
RX PubMed=28065600; DOI=10.1016/j.molcel.2016.12.002;
RA Ma L., Huang C., Wang X.J., Xin D.E., Wang L.S., Zou Q.C., Zhang Y.S.,
RA Tan M.D., Wang Y.M., Zhao T.C., Chatterjee D., Altura R.A., Wang C.,
RA Xu Y.S., Yang J.H., Fan Y.S., Han B.H., Si J., Zhang X., Cheng J.,
RA Chang Z., Chin Y.E.;
RT "Lysyl oxidase 3 is a dual-specificity enzyme involved in STAT3
RT deacetylation and deacetylimination modulation.";
RL Mol. Cell 65:296-309(2017).
CC -!- FUNCTION: Protein-lysine 6-oxidase that mediates the oxidation of
CC peptidyl lysine residues to allysine in target proteins
CC (PubMed:17018530, PubMed:28065600). Catalyzes the post-translational
CC oxidative deamination of peptidyl lysine residues in precursors of
CC elastin and different types of collagens, a prerequisite in the
CC formation of cross-links between collagens and elastin
CC (PubMed:17018530). Required for somite boundary formation by catalyzing
CC oxidation of fibronectin (FN1), enhancing integrin signaling in
CC myofibers and their adhesion to the myotendinous junction (MTJ) (By
CC similarity). Acts as a regulator of inflammatory response by inhibiting
CC differentiation of naive CD4(+) T-cells into T-helper Th17 or
CC regulatory T-cells (Treg): acts by interacting with STAT3 in the
CC nucleus and catalyzing both deacetylation and oxidation of lysine
CC residues on STAT3, leading to disrupt STAT3 dimerization and inhibit
CC STAT3 transcription activity (PubMed:28065600). Oxidation of lysine
CC residues to allysine on STAT3 preferentially takes place on lysine
CC residues that are acetylated (PubMed:28065600). Also able to catalyze
CC deacetylation of lysine residues on STAT3 (PubMed:28065600).
CC {ECO:0000250|UniProtKB:Q9Z175, ECO:0000269|PubMed:17018530,
CC ECO:0000269|PubMed:28065600}.
CC -!- FUNCTION: [Isoform 1]: Shows protein-lysine 6-oxidase activity toward
CC elastin and different types of collagens, with the highest activity
CC toward collagen type VIII (PubMed:17018530).
CC {ECO:0000269|PubMed:17018530}.
CC -!- FUNCTION: [Isoform 2]: Shows protein-lysine 6-oxidase activity toward
CC elastin and different types of collagens, with the highest activity
CC toward collagen type IV (PubMed:17018530).
CC {ECO:0000269|PubMed:17018530}.
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:0000269|PubMed:28065600};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(6)-acetyl-L-lysyl-[protein] + O2 = (S)-2-amino-6-
CC oxohexanoyl-[protein] + acetamide + H2O2; Xref=Rhea:RHEA:51648,
CC Rhea:RHEA-COMP:10731, Rhea:RHEA-COMP:12448, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:27856,
CC ChEBI:CHEBI:61930, ChEBI:CHEBI:131803;
CC Evidence={ECO:0000269|PubMed:28065600};
CC -!- COFACTOR:
CC Name=Cu cation; Xref=ChEBI:CHEBI:23378;
CC Evidence={ECO:0000250|UniProtKB:P16636};
CC -!- COFACTOR:
CC Name=lysine tyrosylquinone residue; Xref=ChEBI:CHEBI:20489;
CC Evidence={ECO:0000250|UniProtKB:P33072};
CC Note=Contains 1 lysine tyrosylquinone. {ECO:0000250|UniProtKB:P33072};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=6.72 uM for STAT3 acetylated at 'Lys-685' (for deacetylation
CC activity) {ECO:0000269|PubMed:28065600};
CC KM=1.59 uM for STAT3 acetylated at 'Lys-685' (for lysine 6-oxidase
CC activity) {ECO:0000269|PubMed:28065600};
CC Note=kcat is 0.058 sec(-1) with STAT3 acetylated at 'Lys-685' (for
CC deacetylation activity). kcat is 0.022 sec(-1) with STAT3 acetylated
CC at 'Lys-685' (for lysine 6-oxidase activity).
CC {ECO:0000269|PubMed:28065600};
CC -!- SUBUNIT: Interacts with STAT3 (PubMed:28065600).
CC {ECO:0000269|PubMed:28065600}.
CC -!- INTERACTION:
CC P58215; Q7TSK7: Adamtsl2; Xeno; NbExp=2; IntAct=EBI-723960, EBI-25406979;
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space
CC {ECO:0000250|UniProtKB:Q9Z175}. Cytoplasm
CC {ECO:0000269|PubMed:28065600}. Nucleus {ECO:0000269|PubMed:28065600}.
CC Note=It is unclear how LOXL3 is both intracellular (cytoplasmic and
CC nuclear) and extracellular: it contains a clear signal sequence and is
CC predicted to localize in the extracellular medium. However, the
CC intracellular location is clearly reported and at least another protein
CC of the family (LOXL2) also has intracellular and extracellular
CC localization despite the presence of a signal sequence
CC (PubMed:28065600). {ECO:0000269|PubMed:28065600}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Secreted, extracellular space
CC {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm
CC {ECO:0000269|PubMed:17018530}. Secreted, extracellular space
CC {ECO:0000269|PubMed:17018530}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P58215-1; Sequence=Displayed;
CC Name=2; Synonyms=LOXL3-sv1 {ECO:0000303|PubMed:17018530};
CC IsoId=P58215-2; Sequence=VSP_054417;
CC Name=3;
CC IsoId=P58215-3; Sequence=VSP_054418;
CC -!- TISSUE SPECIFICITY: Isoform 1: Predominantly detected in the heart,
CC placenta, lung, and small intestine (PubMed:17018530). Isoform 2:
CC Highly detected in the kidney, pancreas, spleen, and thymus, and is
CC absent in lung (PubMed:17018530). In eye, present in all layers of
CC corneas as well as in the limbus and conjunctiva (at protein level)
CC (PubMed:26218558). {ECO:0000269|PubMed:17018530,
CC ECO:0000269|PubMed:26218558}.
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:P33072}.
CC -!- DISEASE: Note=Defects in LOXL3 are found in a family with an autosomal
CC recessive form of Stickler syndrome, an inherited disorder that
CC associates ocular signs with more or less complete forms of Pierre
CC Robin sequence and sensorineural deafness (PubMed:25663169). Pierre
CC Robin sequence includes an opening in the roof of the mouth (a cleft
CC palate) (PubMed:25663169). The degree of hearing loss varies among
CC affected individuals and may become more severe over time
CC (PubMed:25663169). Syndrome expressivity is variable (PubMed:25663169).
CC Ocular disorders include non-progressive myopia with associated
CC chorioretinal degeneration (PubMed:25663169). Defects in LOXL3 are
CC found in another family with early-onset high myopia (PubMed:26957899).
CC The disease may be caused by variants affecting the gene represented in
CC this entry (PubMed:25663169, PubMed:26957899).
CC {ECO:0000269|PubMed:25663169, ECO:0000269|PubMed:26957899}.
CC -!- MISCELLANEOUS: [Isoform 2]: Misses three SRCR domains. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the lysyl oxidase family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/LOXL3ID44000ch2p13.html";
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; AF282619; AAK51671.1; -; mRNA.
DR EMBL; AF311313; AAK63205.1; -; mRNA.
DR EMBL; AF284815; AAK91134.1; -; mRNA.
DR EMBL; DQ378059; ABD23013.1; -; mRNA.
DR EMBL; AC005033; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC005041; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471053; EAW99615.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99616.1; -; Genomic_DNA.
DR EMBL; BC071865; AAH71865.1; -; mRNA.
DR CCDS; CCDS1953.1; -. [P58215-1]
DR CCDS; CCDS74527.1; -. [P58215-3]
DR RefSeq; NP_001276093.1; NM_001289164.2. [P58215-3]
DR RefSeq; NP_001276094.1; NM_001289165.1. [P58215-2]
DR RefSeq; NP_115992.1; NM_032603.4. [P58215-1]
DR RefSeq; XP_011531436.1; XM_011533134.2. [P58215-1]
DR RefSeq; XP_016860601.1; XM_017005112.1. [P58215-2]
DR AlphaFoldDB; P58215; -.
DR SMR; P58215; -.
DR BioGRID; 124210; 22.
DR IntAct; P58215; 5.
DR STRING; 9606.ENSP00000264094; -.
DR BindingDB; P58215; -.
DR ChEMBL; CHEMBL4105989; -.
DR GlyConnect; 1481; 3 N-Linked glycans (1 site).
DR GlyGen; P58215; 5 sites, 3 N-linked glycans (1 site).
DR iPTMnet; P58215; -.
DR PhosphoSitePlus; P58215; -.
DR BioMuta; LOXL3; -.
DR DMDM; 14916616; -.
DR EPD; P58215; -.
DR jPOST; P58215; -.
DR MassIVE; P58215; -.
DR PaxDb; P58215; -.
DR PeptideAtlas; P58215; -.
DR PRIDE; P58215; -.
DR ProteomicsDB; 57056; -. [P58215-1]
DR ProteomicsDB; 66450; -.
DR Antibodypedia; 31582; 184 antibodies from 21 providers.
DR DNASU; 84695; -.
DR Ensembl; ENST00000264094.8; ENSP00000264094.3; ENSG00000115318.12. [P58215-1]
DR Ensembl; ENST00000393937.6; ENSP00000377512.2; ENSG00000115318.12. [P58215-3]
DR GeneID; 84695; -.
DR KEGG; hsa:84695; -.
DR MANE-Select; ENST00000264094.8; ENSP00000264094.3; NM_032603.5; NP_115992.1.
DR UCSC; uc002smp.3; human. [P58215-1]
DR CTD; 84695; -.
DR DisGeNET; 84695; -.
DR GeneCards; LOXL3; -.
DR HGNC; HGNC:13869; LOXL3.
DR HPA; ENSG00000115318; Low tissue specificity.
DR MalaCards; LOXL3; -.
DR MIM; 607163; gene.
DR neXtProt; NX_P58215; -.
DR OpenTargets; ENSG00000115318; -.
DR Orphanet; 250984; Autosomal recessive Stickler syndrome.
DR PharmGKB; PA30430; -.
DR VEuPathDB; HostDB:ENSG00000115318; -.
DR eggNOG; ENOG502QSX8; Eukaryota.
DR GeneTree; ENSGT00940000158157; -.
DR InParanoid; P58215; -.
DR OMA; HLRWGLI; -.
DR OrthoDB; 815466at2759; -.
DR PhylomeDB; P58215; -.
DR TreeFam; TF326061; -.
DR BioCyc; MetaCyc:ENSG00000115318-MON; -.
DR BRENDA; 1.4.3.13; 2681.
DR PathwayCommons; P58215; -.
DR Reactome; R-HSA-1566948; Elastic fibre formation.
DR Reactome; R-HSA-2243919; Crosslinking of collagen fibrils.
DR SignaLink; P58215; -.
DR BioGRID-ORCS; 84695; 10 hits in 1073 CRISPR screens.
DR ChiTaRS; LOXL3; human.
DR GeneWiki; LOXL3; -.
DR GenomeRNAi; 84695; -.
DR Pharos; P58215; Tchem.
DR PRO; PR:P58215; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P58215; protein.
DR Bgee; ENSG00000115318; Expressed in tibia and 140 other tissues.
DR ExpressionAtlas; P58215; baseline and differential.
DR Genevisible; P58215; HS.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; IEA:InterPro.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005507; F:copper ion binding; NAS:UniProtKB.
DR GO; GO:0001968; F:fibronectin binding; ISS:UniProtKB.
DR GO; GO:0004720; F:protein-lysine 6-oxidase activity; IDA:UniProtKB.
DR GO; GO:0005044; F:scavenger receptor activity; IEA:InterPro.
DR GO; GO:0030199; P:collagen fibril organization; IBA:GO_Central.
DR GO; GO:0001837; P:epithelial to mesenchymal transition; IDA:UniProtKB.
DR GO; GO:1905590; P:fibronectin fibril organization; ISS:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; ISS:UniProtKB.
DR GO; GO:0030324; P:lung development; ISS:UniProtKB.
DR GO; GO:2000329; P:negative regulation of T-helper 17 cell lineage commitment; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0018057; P:peptidyl-lysine oxidation; IDA:UniProtKB.
DR GO; GO:2001046; P:positive regulation of integrin-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0060021; P:roof of mouth development; ISS:UniProtKB.
DR GO; GO:0061053; P:somite development; ISS:UniProtKB.
DR GO; GO:0021510; P:spinal cord development; 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 1: Evidence at protein level;
KW Alternative splicing; Copper; Cytoplasm; Deafness; Disulfide bond;
KW Glycoprotein; Inflammatory response; LTQ; Metal-binding; Nucleus;
KW Oxidoreductase; Reference proteome; Repeat; Secreted; Signal;
KW Stickler syndrome; TPQ.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..753
FT /note="Lysyl oxidase homolog 3"
FT /id="PRO_0000018533"
FT DOMAIN 44..145
FT /note="SRCR 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DOMAIN 169..282
FT /note="SRCR 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DOMAIN 307..407
FT /note="SRCR 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DOMAIN 417..525
FT /note="SRCR 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT REGION 290..315
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 529..732
FT /note="Lysyl-oxidase like"
FT BINDING 607
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000255"
FT BINDING 609
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000255"
FT BINDING 611
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000255"
FT MOD_RES 670
FT /note="2',4',5'-topaquinone"
FT /evidence="ECO:0000250|UniProtKB:P33072"
FT CARBOHYD 111
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 266
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 390
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 481
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 625
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 70..134
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 83..144
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 114..124
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 201..271
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 214..281
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 248..258
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 332..396
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 345..406
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 376..386
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 446..511
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 459..524
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 492..502
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 554..560
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 606..654
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 638..644
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 666..676
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 713..727
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT CROSSLNK 634..670
FT /note="Lysine tyrosylquinone (Lys-Tyr)"
FT /evidence="ECO:0000250|UniProtKB:P33072"
FT VAR_SEQ 1..361
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17018530"
FT /id="VSP_054417"
FT VAR_SEQ 159..303
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_054418"
FT VARIANT 615
FT /note="I -> F (in dbSNP:rs17010021)"
FT /id="VAR_050011"
FT VARIANT 676
FT /note="C -> Y (found in patients with Stickler syndrome;
FT sporadic case; unknown pathological significance;
FT dbSNP:rs786204838)"
FT /evidence="ECO:0000269|PubMed:25663169"
FT /id="VAR_077909"
FT MUTAGEN 83
FT /note="C->A: Impaired ability to mediate deacetylation of
FT STAT3; when associated with A-214; A-345 and A-459."
FT /evidence="ECO:0000269|PubMed:28065600"
FT MUTAGEN 214
FT /note="C->A: Impaired ability to mediate deacetylation of
FT STAT3; when associated with A-83; A-345 and A-459."
FT /evidence="ECO:0000269|PubMed:28065600"
FT MUTAGEN 345
FT /note="C->A: Impaired ability to mediate deacetylation of
FT STAT3; when associated with A-83; A-214 and A-459."
FT /evidence="ECO:0000269|PubMed:28065600"
FT MUTAGEN 376
FT /note="C->A: Impaired ability to mediate deacetylation of
FT STAT3; when associated with A-446 and A-492."
FT /evidence="ECO:0000269|PubMed:28065600"
FT MUTAGEN 446
FT /note="C->A: Impaired ability to mediate deacetylation of
FT STAT3; when associated with A-376 and A-492."
FT /evidence="ECO:0000269|PubMed:28065600"
FT MUTAGEN 459
FT /note="C->A: Impaired ability to mediate deacetylation of
FT STAT3; when associated with A-83; A-214 and A-345."
FT /evidence="ECO:0000269|PubMed:28065600"
FT MUTAGEN 492
FT /note="C->A: Impaired ability to mediate deacetylation of
FT STAT3; when associated with A-376 and A-446."
FT /evidence="ECO:0000269|PubMed:28065600"
FT MUTAGEN 607..609
FT /note="HGH->QGQ: Impaired ability to mediate deacetylation
FT of STAT3."
FT /evidence="ECO:0000269|PubMed:28065600"
FT CONFLICT 159
FT /note="E -> K (in Ref. 3; AAK91134)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 753 AA; 83166 MW; 582C46DA25E05A69 CRC64;
MRPVSVWQWS PWGLLLCLLC SSCLGSPSPS TGPEKKAGSQ GLRFRLAGFP RKPYEGRVEI
QRAGEWGTIC DDDFTLQAAH ILCRELGFTE ATGWTHSAKY GPGTGRIWLD NLSCSGTEQS
VTECASRGWG NSDCTHDEDA GVICKDQRLP GFSDSNVIEV EHHLQVEEVR IRPAVGWGRR
PLPVTEGLVE VRLPDGWSQV CDKGWSAHNS HVVCGMLGFP SEKRVNAAFY RLLAQRQQHS
FGLHGVACVG TEAHLSLCSL EFYRANDTAR CPGGGPAVVS CVPGPVYAAS SGQKKQQQSK
PQGEARVRLK GGAHPGEGRV EVLKASTWGT VCDRKWDLHA ASVVCRELGF GSAREALSGA
RMGQGMGAIH LSEVRCSGQE LSLWKCPHKN ITAEDCSHSQ DAGVRCNLPY TGAETRIRLS
GGRSQHEGRV EVQIGGPGPL RWGLICGDDW GTLEAMVACR QLGLGYANHG LQETWYWDSG
NITEVVMSGV RCTGTELSLD QCAHHGTHIT CKRTGTRFTA GVICSETASD LLLHSALVQE
TAYIEDRPLH MLYCAAEENC LASSARSANW PYGHRRLLRF SSQIHNLGRA DFRPKAGRHS
WVWHECHGHY HSMDIFTHYD ILTPNGTKVA EGHKASFCLE DTECQEDVSK RYECANFGEQ
GITVGCWDLY RHDIDCQWID ITDVKPGNYI LQVVINPNFE VAESDFTNNA MKCNCKYDGH
RIWVHNCHIG DAFSEEANRR FERYPGQTSN QII
