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 10-JUN-2026, entry version 195. 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 MYP28. 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). RN [12] RP INVOLVEMENT IN MYP28. RX PubMed=33456446; DOI=10.3389/fgene.2020.580484; RA Maddirevula S., Shamseldin H.E., Sirr A., Alabdi L., Lo R.S., Ewida N., RA Al-Qahtani M., Hashem M., Abdulwahab F., Aboyousef O., Kaya N., Monies D., RA Salem M.H., Al Harbi N., Aldhalaan H.M., Alzaidan H., Almanea H.M., RA Alsalamah A.K., Al Mutairi F., Ismail S., Abdel-Salam G.M.H., Alhashem A., RA Asery A., Faqeih E., Al-Qassmi A., Al-Hamoudi W., Algoufi T., Shagrani M., RA Dudley A.M., Alkuraya F.S.; RT "Exploiting the Autozygome to Support Previously Published Mendelian Gene- RT Disease Associations: An Update."; RL Front. Genet. 11:580484-580484(2020). 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=L-lysyl-[protein] + O2 + H2O = (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=N(6)-acetyl-L-lysyl-[protein] + O2 + H2O = acetamide + (S)-2- CC amino-6-oxohexanoyl-[protein] + 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). CC {ECO:0000269|PubMed:25663169}. CC -!- DISEASE: Myopia 28, autosomal recessive (MYP28) [MIM:619781]: A form of CC myopia, a refractive error of the eye, in which parallel rays from a CC distant object come to focus in front of the retina, vision being CC better for near objects than for far. MYP28 patients are affected by CC early-onset high myopia in the first decade of life. Retinal detachment CC may occur, and early-onset cataract has been reported. CC {ECO:0000269|PubMed:26957899, ECO:0000269|PubMed:33456446}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. 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="https://atlasgeneticsoncology.org/gene/44000/LOXL3"; 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_001289164.3. [P58215-3] DR RefSeq; NP_001276094.1; NM_001289165.2. [P58215-2] DR RefSeq; NP_115992.1; NM_032603.5. [P58215-1] DR RefSeq; XP_011531436.1; XM_011533134.3. [P58215-1] DR RefSeq; XP_024308944.1; XM_024453176.2. [P58215-1] DR RefSeq; XP_024308945.1; XM_024453177.2. [P58215-1] DR RefSeq; XP_024308946.1; XM_024453178.2. [P58215-1] DR RefSeq; XP_054200194.1; XM_054344219.1. [P58215-1] DR RefSeq; XP_054200195.1; XM_054344220.1. [P58215-1] DR RefSeq; XP_054200196.1; XM_054344221.1. [P58215-1] DR RefSeq; XP_054200197.1; XM_054344222.1. [P58215-1] DR AlphaFoldDB; P58215; -. DR SMR; P58215; -. DR BioGRID; 124210; 26. DR FunCoup; P58215; 235. DR IntAct; P58215; 29. DR NDEx; IQUERY-CP-LOXL3; 2 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000264094; -. DR BindingDB; P58215; -. DR ChEMBL; CHEMBL4105989; -. DR DrugCentral; P58215; -. DR GlyConnect; P58215; 3 N-Linked glycans (1 site). DR GlyCosmos; P58215; 5 sites, 3 glycans. DR GlyGen; P58215; 5 sites, 8 N-linked glycans (1 site). DR iPTMnet; P58215; -. DR PhosphoSitePlus; P58215; -. DR BioMuta; LOXL3; -. DR DMDM; 14916616; -. DR jPOST; P58215; -. DR MassIVE; P58215; -. DR PaxDb; 9606-ENSP00000264094; -. DR PeptideAtlas; P58215; -. DR ProteomicsDB; 57056; -. [P58215-1] DR ProteomicsDB; 66450; -. DR Antibodypedia; 31582; 177 antibodies from 21 providers. DR DNASU; 84695; -. DR Ensembl; ENST00000264094.8; ENSP00000264094.3; ENSG00000115318.13. [P58215-1] DR Ensembl; ENST00000393937.6; ENSP00000377512.2; ENSG00000115318.13. [P58215-3] DR Ensembl; ENST00000853956.1; ENSP00000524015.1; ENSG00000115318.13. [P58215-1] DR Ensembl; ENST00000853957.1; ENSP00000524016.1; ENSG00000115318.13. [P58215-1] DR Ensembl; ENST00000853958.1; ENSP00000524017.1; ENSG00000115318.13. [P58215-1] DR Ensembl; ENST00000853959.1; ENSP00000524018.1; ENSG00000115318.13. [P58215-1] DR Ensembl; ENST00000934363.1; ENSP00000604422.1; ENSG00000115318.13. [P58215-3] DR Ensembl; ENST00000946465.1; ENSP00000616524.1; ENSG00000115318.13. [P58215-1] DR Ensembl; ENST00000946466.1; ENSP00000616525.1; ENSG00000115318.13. [P58215-1] DR Ensembl; ENST00000946467.1; ENSP00000616526.1; ENSG00000115318.13. [P58215-1] 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 AGR; HGNC:13869; -. DR ClinPGx; PA30430; -. 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 MIM; 619781; phenotype. DR OpenTargets; ENSG00000115318; -. DR Orphanet; 250984; Autosomal recessive Stickler syndrome. DR VEuPathDB; HostDB:ENSG00000115318; -. DR eggNOG; ENOG502QSX8; Eukaryota. DR GeneTree; ENSGT00940000158157; -. DR InParanoid; P58215; -. DR OMA; HWGLICG; -. DR OrthoDB; 547291at2759; -. DR PAN-GO; P58215; 4 GO annotations based on evolutionary models. DR PhylomeDB; P58215; -. DR BioCyc; MetaCyc:ENSG00000115318-MONOMER; -. 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 Agora; ENSG00000115318; -. DR BioGRID-ORCS; 84695; 10 hits in 1151 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 141 other cell types or tissues. DR ExpressionAtlas; P58215; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0071953; C:elastic fiber; TAS:GO_Central. DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central. 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:0001527; C:microfibril; TAS:GO_Central. 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: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:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:2000329; P:negative regulation of T-helper 17 cell lineage commitment; IDA:UniProt. 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 FunFam; 3.10.250.10:FF:000001; Lysyl oxidase 4 isoform X1; 2. DR FunFam; 3.10.250.10:FF:000008; Lysyl oxidase homolog 2; 1. DR FunFam; 3.10.250.10:FF:000022; lysyl oxidase homolog 3 isoform X2; 1. DR Gene3D; 3.10.250.10; SRCR-like domain; 4. DR InterPro; IPR050912; LOX-like_protein. DR InterPro; IPR001695; Lysyl_oxidase. DR InterPro; IPR019828; Lysyl_oxidase_CS. DR InterPro; IPR001190; SRCR. DR InterPro; IPR036772; SRCR-like_dom_sf. DR PANTHER; PTHR45817:SF2; LYSYL OXIDASE HOMOLOG 3; 1. DR PANTHER; PTHR45817; LYSYL OXIDASE-LIKE-RELATED; 1. 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; SRCR-like; 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; Proteomics identification; Reference proteome; Repeat; KW Secreted; Signal; 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 COMPBIAS 290..302 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" 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 uncertain significance; 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 //