LOXL1_HUMAN
ID LOXL1_HUMAN Reviewed; 574 AA.
AC Q08397; Q6NUL3; Q96BW7;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 2.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Lysyl oxidase homolog 1;
DE EC=1.4.3.-;
DE AltName: Full=Lysyl oxidase-like protein 1;
DE Short=LOL;
DE Flags: Precursor;
GN Name=LOXL1; Synonyms=LOXL;
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], AND VARIANT LEU-141.
RC TISSUE=Skin fibroblast;
RX PubMed=7689553; DOI=10.1016/s0021-9258(17)46643-9;
RA Kenyon K., Modi W.S., Contente S., Friedman R.M.;
RT "A novel human cDNA with a predicted protein similar to lysyl oxidase maps
RT to chromosome 15q24-q25.";
RL J. Biol. Chem. 268:18435-18437(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LEU-141.
RC TISSUE=Placenta;
RA Kenyon K., Sathya G., Contente S., Friedman R.M.;
RT "Structure of the human lysyl oxidase-like gene.";
RL Submitted (MAY-1995) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASP-153.
RC TISSUE=Amygdala;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASP-153.
RC TISSUE=Lung, and Placenta;
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 [6]
RP INTERACTION WITH EFEMP2.
RX PubMed=27339457; DOI=10.1016/j.matbio.2016.06.003;
RA Sasaki T., Hanisch F.G., Deutzmann R., Sakai L.Y., Sakuma T., Miyamoto T.,
RA Yamamoto T., Hannappel E., Chu M.L., Lanig H., von der Mark K.;
RT "Functional consequence of fibulin-4 missense mutations associated with
RT vascular and skeletal abnormalities and cutis laxa.";
RL Matrix Biol. 56:132-149(2016).
RN [7]
RP VARIANTS LEU-141 AND ASP-153, AND SUSCEPTIBILITY TO XFS.
RX PubMed=17690259; DOI=10.1126/science.1146554;
RA Thorleifsson G., Magnusson K.P., Sulem P., Walters G.B., Gudbjartsson D.F.,
RA Stefansson H., Jonsson T., Jonasdottir A., Jonasdottir A.,
RA Stefansdottir G., Masson G., Hardarson G.A., Petursson H., Arnarsson A.,
RA Motallebipour M., Wallerman O., Wadelius C., Gulcher J.R.,
RA Thorsteinsdottir U., Kong A., Jonasson F., Stefansson K.;
RT "Common sequence variants in the LOXL1 gene confer susceptibility to
RT exfoliation glaucoma.";
RL Science 317:1397-1400(2007).
RN [8]
RP ASSOCIATION OF VARIANTS LEU-141 AND ASP-153 WITH EXFOLIATION SYNDROME, AND
RP TISSUE SPECIFICITY.
RX PubMed=18037624; DOI=10.1093/hmg/ddm342;
RA Hewitt A.W., Sharma S., Burdon K.P., Wang J.J., Baird P.N., Dimasi D.P.,
RA Mackey D.A., Mitchell P., Craig J.E.;
RT "Ancestral LOXL1 variants are associated with pseudoexfoliation in
RT Caucasian Australians but with markedly lower penetrance than in Nordic
RT people.";
RL Hum. Mol. Genet. 17:710-716(2008).
RN [9]
RP VARIANT [LARGE SCALE ANALYSIS] LEU-141, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP ASSOCIATION OF VARIANTS LEU-141 AND ASP-153 WITH EXFOLIATION SYNDROME.
RX PubMed=19343041; DOI=10.1038/jhg.2009.28;
RA Lemmela S., Forsman E., Onkamo P., Nurmi H., Laivuori H., Kivela T.,
RA Puska P., Heger M., Eriksson A., Forsius H., Jarvela I.;
RT "Association of LOXL1 gene with Finnish exfoliation syndrome patients.";
RL J. Hum. Genet. 54:289-297(2009).
CC -!- FUNCTION: Active on elastin and collagen substrates. {ECO:0000250}.
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 -!- SUBUNIT: Interacts (via propeptide) with EFEMP2.
CC {ECO:0000269|PubMed:27339457}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in ocular tissues including the iris,
CC ciliary body, lens and optic nerve. Not detected in the retina.
CC {ECO:0000269|PubMed:18037624}.
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: Exfoliation syndrome (XFS) [MIM:177650]: A disorder
CC characterized by accumulation of abnormal fibrillar deposits in the
CC anterior segment of the eye. In addition to being a cause of glaucoma
CC and glaucomatous optic neuropathy, exfoliation syndrome has also been
CC associated with lens zonule weakness, cataract formation, and systemic
CC vascular complications due to deposition of exfoliation material in
CC extraocular tissues. {ECO:0000269|PubMed:18037624,
CC ECO:0000269|PubMed:19343041}. Note=Disease susceptibility is associated
CC with variants affecting the gene represented in this entry.
CC Susceptibility to exfoliation syndrome is conferred by a risk haplotype
CC that includes two LOXL1 coding non-synonymous SNPs (Arg141Leu and
CC Gly153Asp) and one intronic SNP. Arg141Leu and Gly153Asp are sufficient
CC to confer disease susceptibility in some populations.
CC -!- SIMILARITY: Belongs to the lysyl oxidase family. {ECO:0000305}.
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DR EMBL; L21186; AAA50162.1; -; mRNA.
DR EMBL; U24389; AAA68940.1; -; Genomic_DNA.
DR EMBL; U24395; AAA68940.1; JOINED; Genomic_DNA.
DR EMBL; U24394; AAA68940.1; JOINED; Genomic_DNA.
DR EMBL; U24393; AAA68940.1; JOINED; Genomic_DNA.
DR EMBL; U24391; AAA68940.1; JOINED; Genomic_DNA.
DR EMBL; U24390; AAA68940.1; JOINED; Genomic_DNA.
DR EMBL; AK314222; BAG36895.1; -; mRNA.
DR EMBL; AC108137; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC015090; AAH15090.1; -; mRNA.
DR EMBL; BC068542; AAH68542.1; -; mRNA.
DR CCDS; CCDS10253.1; -.
DR PIR; A48501; A48501.
DR RefSeq; NP_005567.2; NM_005576.3.
DR AlphaFoldDB; Q08397; -.
DR SMR; Q08397; -.
DR BioGRID; 110200; 13.
DR IntAct; Q08397; 9.
DR MINT; Q08397; -.
DR STRING; 9606.ENSP00000261921; -.
DR BindingDB; Q08397; -.
DR ChEMBL; CHEMBL4523279; -.
DR GlyGen; Q08397; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q08397; -.
DR PhosphoSitePlus; Q08397; -.
DR BioMuta; LOXL1; -.
DR DMDM; 189031484; -.
DR jPOST; Q08397; -.
DR MassIVE; Q08397; -.
DR PaxDb; Q08397; -.
DR PeptideAtlas; Q08397; -.
DR PRIDE; Q08397; -.
DR ProteomicsDB; 58607; -.
DR Antibodypedia; 26814; 277 antibodies from 28 providers.
DR DNASU; 4016; -.
DR Ensembl; ENST00000261921.8; ENSP00000261921.7; ENSG00000129038.16.
DR GeneID; 4016; -.
DR KEGG; hsa:4016; -.
DR MANE-Select; ENST00000261921.8; ENSP00000261921.7; NM_005576.4; NP_005567.2.
DR UCSC; uc002awc.2; human.
DR CTD; 4016; -.
DR DisGeNET; 4016; -.
DR GeneCards; LOXL1; -.
DR HGNC; HGNC:6665; LOXL1.
DR HPA; ENSG00000129038; Low tissue specificity.
DR MalaCards; LOXL1; -.
DR MIM; 153456; gene.
DR MIM; 177650; phenotype.
DR neXtProt; NX_Q08397; -.
DR OpenTargets; ENSG00000129038; -.
DR Orphanet; 529819; NON RARE IN EUROPE: Exfoliation syndrome.
DR PharmGKB; PA30428; -.
DR VEuPathDB; HostDB:ENSG00000129038; -.
DR eggNOG; ENOG502QWET; Eukaryota.
DR GeneTree; ENSGT00940000161080; -.
DR HOGENOM; CLU_002555_2_2_1; -.
DR InParanoid; Q08397; -.
DR OMA; YEPPFQP; -.
DR OrthoDB; 815466at2759; -.
DR PhylomeDB; Q08397; -.
DR TreeFam; TF326061; -.
DR PathwayCommons; Q08397; -.
DR Reactome; R-HSA-1566948; Elastic fibre formation.
DR Reactome; R-HSA-2243919; Crosslinking of collagen fibrils.
DR SignaLink; Q08397; -.
DR BioGRID-ORCS; 4016; 12 hits in 1060 CRISPR screens.
DR ChiTaRS; LOXL1; human.
DR GeneWiki; LOXL1; -.
DR GenomeRNAi; 4016; -.
DR Pharos; Q08397; Tbio.
DR PRO; PR:Q08397; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q08397; protein.
DR Bgee; ENSG00000129038; Expressed in thoracic aorta and 151 other tissues.
DR ExpressionAtlas; Q08397; baseline and differential.
DR Genevisible; Q08397; HS.
DR GO; GO:0001669; C:acrosomal vesicle; IEA:Ensembl.
DR GO; GO:0005604; C:basement membrane; IEA:Ensembl.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0005576; C:extracellular region; TAS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005507; F:copper ion binding; IEA:InterPro.
DR GO; GO:0004720; F:protein-lysine 6-oxidase activity; IBA:GO_Central.
DR GO; GO:0035904; P:aorta development; IEA:Ensembl.
DR GO; GO:0030199; P:collagen fibril organization; IBA:GO_Central.
DR GO; GO:0018057; P:peptidyl-lysine oxidation; IBA:GO_Central.
DR GO; GO:0018277; P:protein deamination; TAS:UniProtKB.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR InterPro; IPR001695; Lysyl_oxidase.
DR InterPro; IPR019828; Lysyl_oxidase_CS.
DR Pfam; PF01186; Lysyl_oxidase; 1.
DR PRINTS; PR00074; LYSYLOXIDASE.
DR PROSITE; PS00926; LYSYL_OXIDASE; 1.
PE 1: Evidence at protein level;
KW Cleavage on pair of basic residues; Copper; Disulfide bond; Glaucoma; LTQ;
KW Metal-binding; Oxidoreductase; Reference proteome; Secreted; Signal; TPQ.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT PROPEP 26..94
FT /evidence="ECO:0000250"
FT /id="PRO_0000018528"
FT CHAIN 95..574
FT /note="Lysyl oxidase homolog 1"
FT /id="PRO_0000018529"
FT REGION 62..123
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 239..374
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 370..574
FT /note="Lysyl-oxidase like"
FT COMPBIAS 62..87
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 248..270
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 310..337
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 449
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000255"
FT BINDING 451
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000255"
FT BINDING 453
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000255"
FT MOD_RES 512
FT /note="2',4',5'-topaquinone; alternate"
FT /evidence="ECO:0000250|UniProtKB:P33072"
FT DISULFID 395..401
FT /evidence="ECO:0000250|UniProtKB:P33072"
FT DISULFID 448..497
FT /evidence="ECO:0000250|UniProtKB:P33072"
FT DISULFID 481..487
FT /evidence="ECO:0000250|UniProtKB:P33072"
FT DISULFID 508..518
FT /evidence="ECO:0000250|UniProtKB:P33072"
FT DISULFID 555..569
FT /evidence="ECO:0000250|UniProtKB:P33072"
FT CROSSLNK 477..512
FT /note="Lysine tyrosylquinone (Lys-Tyr); alternate"
FT /evidence="ECO:0000250|UniProtKB:P33072"
FT VARIANT 141
FT /note="R -> L (associated with exfoliation syndrome in the
FT presence of D-153; dbSNP:rs1048661)"
FT /evidence="ECO:0000269|PubMed:17690259,
FT ECO:0000269|PubMed:18037624, ECO:0000269|PubMed:19343041,
FT ECO:0000269|PubMed:7689553, ECO:0000269|Ref.2,
FT ECO:0007744|PubMed:18669648"
FT /id="VAR_028436"
FT VARIANT 153
FT /note="G -> D (associated with exfoliation syndrome in the
FT presence of L-141; dbSNP:rs3825942)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17690259"
FT /id="VAR_022135"
SQ SEQUENCE 574 AA; 63110 MW; 7570FEFB3E09066D CRC64;
MALARGSRQL GALVWGACLC VLVHGQQAQP GQGSDPARWR QLIQWENNGQ VYSLLNSGSE
YVPAGPQRSE SSSRVLLAGA PQAQQRRSHG SPRRRQAPSL PLPGRVGSDT VRGQARHPFG
FGQVPDNWRE VAVGDSTGMA RARTSVSQQR HGGSASSVSA SAFASTYRQQ PSYPQQFPYP
QAPFVSQYEN YDPASRTYDQ GFVYYRPAGG GVGAGAAAVA SAGVIYPYQP RARYEEYGGG
EELPEYPPQG FYPAPERPYV PPPPPPPDGL DRRYSHSLYS EGTPGFEQAY PDPGPEAAQA
HGGDPRLGWY PPYANPPPEA YGPPRALEPP YLPVRSSDTP PPGGERNGAQ QGRLSVGSVY
RPNQNGRGLP DLVPDPNYVQ ASTYVQRAHL YSLRCAAEEK CLASTAYAPE ATDYDVRVLL
RFPQRVKNQG TADFLPNRPR HTWEWHSCHQ HYHSMDEFSH YDLLDAATGK KVAEGHKASF
CLEDSTCDFG NLKRYACTSH TQGLSPGCYD TYNADIDCQW IDITDVQPGN YILKVHVNPK
YIVLESDFTN NVVRCNIHYT GRYVSATNCK IVQS
