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UniProtKB - P58215 (LOXL3_HUMAN)

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Protein

Lysyl oxidase homolog 3

Gene

LOXL3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Protein-lysine 6-oxidase that mediates the oxidation of peptidyl lysine residues to allysine in target proteins (PubMed:17018530, PubMed:28065600). Catalyzes the post-translational oxidative deamination of peptidyl lysine residues in precursors of elastin and different types of collagens, a prerequisite in the formation of cross-links between collagens and elastin (PubMed:17018530). Required for somite boundary formation by catalyzing oxidation of fibronectin (FN1), enhancing integrin signaling in myofibers and their adhesion to the myotendinous junction (MTJ) (By similarity). Acts as a regulator of inflammatory response by inhibiting differentiation of naive CD4+ T-cells into T-helper Th17 or regulatory T-cells (Treg): acts by interacting with STAT3 in the nucleus and catalyzing both deacetylation and oxidation of lysine residues on STAT3, leading to disrupt STAT3 dimerization and inhibit STAT3 transcription activity (PubMed:28065600). Oxidation of lysine residues to allysine on STAT3 preferentially takes place on lysine residues that are acetylated (PubMed:28065600). Also able to catalyze deacetylation of lysine residues on STAT3 (PubMed:28065600).By similarity2 Publications
Isoform 1: Shows protein-lysine 6-oxidase activity toward elastin and different types of collagens, with the highest activity toward collagen type VIII (PubMed:17018530).1 Publication
Isoform 2: Shows protein-lysine 6-oxidase activity toward elastin and different types of collagens, with the highest activity toward collagen type IV (PubMed:17018530).1 Publication

Catalytic activityi

[Protein]-L-lysine + O2 + H2O = [protein]-(S)-2-amino-6-oxohexanoate + NH3 + H2O2.1 Publication
[protein]-N6-acetyl-L-lysine + O2 + H2O = [protein]-(S)-2-amino-6-oxohexanoate + acetamide + H2O2.1 Publication

Cofactori

Protein has several cofactor binding sites:
  • Cu cationBy similarity
  • lysine tyrosylquinone residueBy similarityNote: Contains 1 lysine tyrosylquinone.By similarity

Kineticsi

kcat is 0.058 sec(-1) with STAT3 acetylated at 'Lys-685' (for deacetylation activity). kcat is 0.022 sec(-1) with STAT3 acetylated at 'Lys-685' (for lysine 6-oxidase activity).1 Publication
  1. KM=6.72 µM for STAT3 acetylated at 'Lys-685' (for deacetylation activity)1 Publication
  2. KM=1.59 µM for STAT3 acetylated at 'Lys-685' (for lysine 6-oxidase activity)1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Metal bindingi607CopperSequence analysis1
    Metal bindingi609CopperSequence analysis1
    Metal bindingi611CopperSequence analysis1

    GO - Molecular functioni

    • copper ion binding Source: UniProtKB
    • fibronectin binding Source: UniProtKB
    • protein-lysine 6-oxidase activity Source: UniProtKB
    • scavenger receptor activity Source: InterPro
    View the complete GO annotation on QuickGO ...

    GO - Biological processi

    View the complete GO annotation on QuickGO ...

    Keywordsi

    Molecular functionOxidoreductase
    Biological processInflammatory response
    LigandCopper, Metal-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:ENSG00000115318-MONOMER
    BRENDAi1.4.3.13 2681
    ReactomeiR-HSA-1566948 Elastic fibre formation
    R-HSA-2243919 Crosslinking of collagen fibrils

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Lysyl oxidase homolog 3Curated (EC:1.4.3.-1 Publication, EC:1.4.3.131 Publication)
    Alternative name(s):
    Lysyl oxidase-like protein 31 Publication
    Gene namesi
    Name:LOXL31 PublicationImported
    Synonyms:LOXL1 Publication
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
    Proteomesi
    • UP000005640 Componenti: Chromosome 2

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000115318.11
    HGNCiHGNC:13869 LOXL3
    MIMi607163 gene
    neXtProtiNX_P58215

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Cytoplasm, Nucleus, Secreted

    Pathology & Biotechi

    Involvement in diseasei

    Defects in LOXL3 are found in a family with an autosomal recessive form of Stickler syndrome, an inherited disorder that associates ocular signs with more or less complete forms of Pierre Robin sequence and sensorineural deafness (PubMed:25663169). Pierre Robin sequence includes an opening in the roof of the mouth (a cleft palate) (PubMed:25663169). The degree of hearing loss varies among affected individuals and may become more severe over time (PubMed:25663169). Syndrome expressivity is variable (PubMed:25663169). Ocular disorders include non-progressive myopia with associated chorioretinal degeneration (PubMed:25663169). Defects in LOXL3 are found in another family with early-onset high myopia (PubMed:26957899). The disease may be caused by mutations affecting the gene represented in this entry (PubMed:25663169, PubMed:26957899).2 Publications

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi83C → A: Impaired ability to mediate deacetylation of STAT3; when associated with A-214; A-345 and A-459. 1 Publication1
    Mutagenesisi214C → A: Impaired ability to mediate deacetylation of STAT3; when associated with A-83; A-345 and A-459. 1 Publication1
    Mutagenesisi345C → A: Impaired ability to mediate deacetylation of STAT3; when associated with A-83; A-214 and A-459. 1 Publication1
    Mutagenesisi376C → A: Impaired ability to mediate deacetylation of STAT3; when associated with A-446 and A-492. 1 Publication1
    Mutagenesisi446C → A: Impaired ability to mediate deacetylation of STAT3; when associated with A-376 and A-492. 1 Publication1
    Mutagenesisi459C → A: Impaired ability to mediate deacetylation of STAT3; when associated with A-83; A-214 and A-345. 1 Publication1
    Mutagenesisi492C → A: Impaired ability to mediate deacetylation of STAT3; when associated with A-376 and A-446. 1 Publication1
    Mutagenesisi607 – 609HGH → QGQ: Impaired ability to mediate deacetylation of STAT3. 1 Publication3

    Keywords - Diseasei

    Deafness, Stickler syndrome

    Organism-specific databases

    DisGeNETi84695
    OpenTargetsiENSG00000115318
    PharmGKBiPA30430

    Polymorphism and mutation databases

    BioMutaiLOXL3
    DMDMi14916616

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Signal peptidei1 – 25Sequence analysisAdd BLAST25
    ChainiPRO_000001853326 – 753Lysyl oxidase homolog 3Add BLAST728

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Disulfide bondi70 ↔ 134PROSITE-ProRule annotation
    Disulfide bondi83 ↔ 144PROSITE-ProRule annotation
    Glycosylationi111N-linked (GlcNAc...) asparagineSequence analysis1
    Disulfide bondi114 ↔ 124PROSITE-ProRule annotation
    Disulfide bondi201 ↔ 271PROSITE-ProRule annotation
    Disulfide bondi214 ↔ 281PROSITE-ProRule annotation
    Disulfide bondi248 ↔ 258PROSITE-ProRule annotation
    Glycosylationi266N-linked (GlcNAc...) asparagineSequence analysis1
    Disulfide bondi332 ↔ 396PROSITE-ProRule annotation
    Disulfide bondi345 ↔ 406PROSITE-ProRule annotation
    Disulfide bondi376 ↔ 386PROSITE-ProRule annotation
    Glycosylationi390N-linked (GlcNAc...) asparagineSequence analysis1
    Disulfide bondi446 ↔ 511PROSITE-ProRule annotation
    Disulfide bondi459 ↔ 524PROSITE-ProRule annotation
    Glycosylationi481N-linked (GlcNAc...) asparagineSequence analysis1
    Disulfide bondi492 ↔ 502PROSITE-ProRule annotation
    Disulfide bondi554 ↔ 560PROSITE-ProRule annotation
    Disulfide bondi606 ↔ 654PROSITE-ProRule annotation
    Glycosylationi625N-linked (GlcNAc...) asparagineSequence analysis1
    Cross-linki634 ↔ 670Lysine tyrosylquinone (Lys-Tyr)By similarity
    Disulfide bondi638 ↔ 644PROSITE-ProRule annotation
    Disulfide bondi666 ↔ 676PROSITE-ProRule annotation
    Modified residuei6702',4',5'-topaquinoneBy similarity1
    Disulfide bondi713 ↔ 727PROSITE-ProRule annotation

    Post-translational modificationi

    The lysine tyrosylquinone cross-link (LTQ) is generated by condensation of the epsilon-amino group of a lysine with a topaquinone produced by oxidation of tyrosine.By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein, LTQ, TPQ

    Proteomic databases

    EPDiP58215
    PaxDbiP58215
    PeptideAtlasiP58215
    PRIDEiP58215
    ProteomicsDBi57056

    PTM databases

    iPTMnetiP58215
    PhosphoSitePlusiP58215

    Expressioni

    Tissue specificityi

    Isoform 1: Predominantly detected in the heart, placenta, lung, and small intestine (PubMed:17018530). Isoform 2: Highly detected in the kidney, pancreas, spleen, and thymus, and is absent in lung (PubMed:17018530). In eye, present in all layers of corneas as well as in the limbus and conjunctiva (at protein level) (PubMed:26218558).2 Publications

    Gene expression databases

    BgeeiENSG00000115318
    CleanExiHS_LOXL3
    ExpressionAtlasiP58215 baseline and differential
    GenevisibleiP58215 HS

    Organism-specific databases

    HPAiHPA035281

    Interactioni

    Subunit structurei

    Interacts with STAT3 (PubMed:28065600).1 Publication

    GO - Molecular functioni

    View the complete GO annotation on QuickGO ...

    Protein-protein interaction databases

    BioGridi124210, 12 interactors
    IntActiP58215, 4 interactors
    STRINGi9606.ENSP00000264094

    Structurei

    3D structure databases

    ProteinModelPortaliP58215
    SMRiP58215
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini44 – 145SRCR 1PROSITE-ProRule annotationAdd BLAST102
    Domaini169 – 282SRCR 2PROSITE-ProRule annotationAdd BLAST114
    Domaini307 – 407SRCR 3PROSITE-ProRule annotationAdd BLAST101
    Domaini417 – 525SRCR 4PROSITE-ProRule annotationAdd BLAST109

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni529 – 732Lysyl-oxidase likeAdd BLAST204

    Sequence similaritiesi

    Belongs to the lysyl oxidase family.Curated

    Keywords - Domaini

    Repeat, Signal

    Phylogenomic databases

    eggNOGiENOG410IE2X Eukaryota
    ENOG410XSN1 LUCA
    GeneTreeiENSGT00900000140830
    HOGENOMiHOG000220841
    HOVERGENiHBG052336
    InParanoidiP58215
    KOiK00280
    OMAiTWYWDSG
    OrthoDBiEOG091G02XD
    PhylomeDBiP58215
    TreeFamiTF326061

    Family and domain databases

    Gene3Di3.10.250.10, 4 hits
    InterProiView protein in InterPro
    IPR001695 Lysyl_oxidase
    IPR019828 Lysyl_oxidase_CS
    IPR001190 SRCR
    IPR017448 SRCR-like_dom
    IPR036772 SRCR-like_dom_sf
    PfamiView protein in Pfam
    PF01186 Lysyl_oxidase, 1 hit
    PF00530 SRCR, 4 hits
    PRINTSiPR00074 LYSYLOXIDASE
    PR00258 SPERACTRCPTR
    SMARTiView protein in SMART
    SM00202 SR, 4 hits
    SUPFAMiSSF56487 SSF56487, 4 hits
    PROSITEiView protein in PROSITE
    PS00926 LYSYL_OXIDASE, 1 hit
    PS00420 SRCR_1, 1 hit
    PS50287 SRCR_2, 4 hits

    Sequences (3)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: P58215-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MRPVSVWQWS PWGLLLCLLC SSCLGSPSPS TGPEKKAGSQ GLRFRLAGFP 
            60         70         80         90        100
    RKPYEGRVEI QRAGEWGTIC DDDFTLQAAH ILCRELGFTE ATGWTHSAKY 
           110        120        130        140        150
    GPGTGRIWLD NLSCSGTEQS VTECASRGWG NSDCTHDEDA GVICKDQRLP 
           160        170        180        190        200
    GFSDSNVIEV EHHLQVEEVR IRPAVGWGRR PLPVTEGLVE VRLPDGWSQV 
           210        220        230        240        250
    CDKGWSAHNS HVVCGMLGFP SEKRVNAAFY RLLAQRQQHS FGLHGVACVG 
           260        270        280        290        300
    TEAHLSLCSL EFYRANDTAR CPGGGPAVVS CVPGPVYAAS SGQKKQQQSK 
           310        320        330        340        350
    PQGEARVRLK GGAHPGEGRV EVLKASTWGT VCDRKWDLHA ASVVCRELGF 
           360        370        380        390        400
    GSAREALSGA RMGQGMGAIH LSEVRCSGQE LSLWKCPHKN ITAEDCSHSQ 
           410        420        430        440        450
    DAGVRCNLPY TGAETRIRLS GGRSQHEGRV EVQIGGPGPL RWGLICGDDW 
           460        470        480        490        500
    GTLEAMVACR QLGLGYANHG LQETWYWDSG NITEVVMSGV RCTGTELSLD 
           510        520        530        540        550
    QCAHHGTHIT CKRTGTRFTA GVICSETASD LLLHSALVQE TAYIEDRPLH 
           560        570        580        590        600
    MLYCAAEENC LASSARSANW PYGHRRLLRF SSQIHNLGRA DFRPKAGRHS 
           610        620        630        640        650
    WVWHECHGHY HSMDIFTHYD ILTPNGTKVA EGHKASFCLE DTECQEDVSK 
           660        670        680        690        700
    RYECANFGEQ GITVGCWDLY RHDIDCQWID ITDVKPGNYI LQVVINPNFE 
           710        720        730        740        750
    VAESDFTNNA MKCNCKYDGH RIWVHNCHIG DAFSEEANRR FERYPGQTSN 

    QII
    Length:753
    Mass (Da):83,166
    Last modified:July 11, 2001 - v1
    Checksum:i582C46DA25E05A69
    GO
    Isoform 2 (identifier: P58215-2) [UniParc]FASTAAdd to basket
    Also known as: LOXL3-sv11 Publication

    The sequence of this isoform differs from the canonical sequence as follows:
         1-361: Missing.

    Note: Misses three SRCR domains.
    Show »
    Length:392
    Mass (Da):44,049
    Checksum:iEF83ED2AB3CE9EC0
    GO
    Isoform 3 (identifier: P58215-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         159-303: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:608
    Mass (Da):67,445
    Checksum:iB33B22A417B184DD
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti159E → K in AAK91134 (PubMed:11334717).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_050011615I → F. Corresponds to variant dbSNP:rs17010021EnsemblClinVar.1
    Natural variantiVAR_077909676C → Y Found in patients with Stickler syndrome; sporadic case; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs786204838EnsemblClinVar.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0544171 – 361Missing in isoform 2. 1 PublicationAdd BLAST361
    Alternative sequenceiVSP_054418159 – 303Missing in isoform 3. 1 PublicationAdd BLAST145

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    		AF282619 mRNA Translation: AAK51671.1
    AF311313 mRNA Translation: AAK63205.1
    AF284815 mRNA Translation: AAK91134.1
    DQ378059 mRNA Translation: ABD23013.1
    AC005033 Genomic DNA No translation available.
    AC005041 Genomic DNA No translation available.
    CH471053 Genomic DNA Translation: EAW99615.1
    CH471053 Genomic DNA Translation: EAW99616.1
    BC071865 mRNA Translation: AAH71865.1
    CCDSiCCDS1953.1 [P58215-1]
    CCDS74527.1 [P58215-3]
    RefSeqiNP_001276093.1, NM_001289164.2 [P58215-3]
    NP_001276094.1, NM_001289165.1 [P58215-2]
    NP_115992.1, NM_032603.4 [P58215-1]
    XP_011531436.1, XM_011533134.2 [P58215-1]
    XP_016860601.1, XM_017005112.1 [P58215-2]
    UniGeneiHs.469045

    Genome annotation databases

    EnsembliENST00000264094; ENSP00000264094; ENSG00000115318 [P58215-1]
    ENST00000393937; ENSP00000377512; ENSG00000115318 [P58215-3]
    GeneIDi84695
    KEGGihsa:84695
    UCSCiuc002smp.3 human [P58215-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Similar proteinsi

    Entry informationi

    Entry nameiLOXL3_HUMAN
    AccessioniPrimary (citable) accession number: P58215
    Secondary accession number(s): D6W5J1
    , Q2EHP2, Q6IPL7, Q96RS1
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 11, 2001
    Last sequence update: July 11, 2001
    Last modified: June 20, 2018
    This is version 152 of the entry and version 1 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 2
      Human chromosome 2: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

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