LOX3A_DANRE
ID LOX3A_DANRE Reviewed; 739 AA.
AC F1RD85; A6MH32; X1WBP7;
DT 15-MAR-2017, integrated into UniProtKB/Swiss-Prot.
DT 03-MAY-2011, sequence version 1.
DT 03-AUG-2022, entry version 67.
DE RecName: Full=Lysyl oxidase homolog 3A {ECO:0000305};
DE EC=1.4.3.- {ECO:0000250|UniProtKB:P58215};
DE EC=1.4.3.13 {ECO:0000250|UniProtKB:P58215};
DE AltName: Full=Lysyl oxidase-like protein 3A {ECO:0000305};
DE Flags: Precursor;
GN Name=loxl3a {ECO:0000303|PubMed:21244857,
GN ECO:0000312|ZFIN:ZDB-GENE-070818-2};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 472-739.
RX PubMed=17543297; DOI=10.1016/j.ydbio.2007.04.029;
RA Gansner J.M., Mendelsohn B.A., Hultman K.A., Johnson S.L., Gitlin J.D.;
RT "Essential role of lysyl oxidases in notochord development.";
RL Dev. Biol. 307:202-213(2007).
RN [3]
RP DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX PubMed=21244857; DOI=10.1016/j.matbio.2010.12.002;
RA van Boxtel A.L., Gansner J.M., Hakvoort H.W., Snell H., Legler J.,
RA Gitlin J.D.;
RT "Lysyl oxidase-like 3b is critical for cartilage maturation during
RT zebrafish craniofacial development.";
RL Matrix Biol. 30:178-187(2011).
CC -!- FUNCTION: Protein-lysine 6-oxidase that mediates the oxidation of
CC peptidyl lysine residues to allysine in target proteins. Catalyzes the
CC post-translational oxidative deamination of peptidyl lysine residues in
CC precursors of elastin and different types of collagens, a prerequisite
CC in the formation of cross-links between collagens and elastin. Can
CC mediate oxidation of lysine residues that are acetylated. Also able to
CC catalyze deacetylation of lysine residues (By similarity).
CC {ECO:0000250|UniProtKB:P58215, ECO:0000250|UniProtKB:Q9Z175}.
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:P58215};
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:0000250|UniProtKB:P58215};
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 -!- SUBCELLULAR LOCATION: Secreted, extracellular space
CC {ECO:0000250|UniProtKB:Q9Z175}. Cytoplasm
CC {ECO:0000250|UniProtKB:P58215}. Nucleus {ECO:0000250|UniProtKB:P58215}.
CC Note=It is unclear how loxl3a 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 {ECO:0000250|UniProtKB:P58215}.
CC -!- DEVELOPMENTAL STAGE: Weakly expressed at 30 hours post fertilization
CC (hpf) in the ventral head mesenchyme, but not spatially restricted
CC after this time-point. {ECO:0000269|PubMed:21244857}.
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 -!- DISRUPTION PHENOTYPE: No visible phenotype.
CC {ECO:0000269|PubMed:21244857}.
CC -!- SIMILARITY: Belongs to the lysyl oxidase family. {ECO:0000305}.
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; FP085411; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; FP085432; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; EF030483; ABM86969.1; -; mRNA.
DR RefSeq; XP_005173146.1; XM_005173089.3.
DR AlphaFoldDB; F1RD85; -.
DR SMR; F1RD85; -.
DR STRING; 7955.ENSDARP00000127639; -.
DR PaxDb; F1RD85; -.
DR Ensembl; ENSDART00000054866; ENSDARP00000054865; ENSDARG00000076306.
DR Ensembl; ENSDART00000181151; ENSDARP00000157309; ENSDARG00000076306.
DR GeneID; 568839; -.
DR CTD; 568839; -.
DR ZFIN; ZDB-GENE-070818-2; loxl3a.
DR eggNOG; ENOG502QSX8; Eukaryota.
DR GeneTree; ENSGT00940000158157; -.
DR HOGENOM; CLU_002555_3_0_1; -.
DR InParanoid; F1RD85; -.
DR OrthoDB; 815466at2759; -.
DR PhylomeDB; F1RD85; -.
DR TreeFam; TF326061; -.
DR BRENDA; 1.4.3.13; 928.
DR PRO; PR:F1RD85; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 14.
DR Bgee; ENSDARG00000076306; Expressed in zone of skin and 13 other tissues.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; 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:0005507; F:copper ion binding; IEA:InterPro.
DR GO; GO:0001968; F:fibronectin 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; IBA:GO_Central.
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:0018057; P:peptidyl-lysine oxidation; ISS: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; 2.
DR PROSITE; PS50287; SRCR_2; 4.
PE 2: Evidence at transcript level;
KW Copper; Cytoplasm; Disulfide bond; Glycoprotein; LTQ; Metal-binding;
KW Nucleus; Oxidoreductase; Reference proteome; Repeat; Secreted; Signal; TPQ.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..739
FT /note="Lysyl oxidase homolog 3A"
FT /evidence="ECO:0000255"
FT /id="PRO_5003269238"
FT DOMAIN 38..139
FT /note="SRCR 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DOMAIN 166..272
FT /note="SRCR 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DOMAIN 293..393
FT /note="SRCR 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DOMAIN 403..511
FT /note="SRCR 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT MOD_RES 656
FT /note="2',4',5'-topaquinone"
FT /evidence="ECO:0000250|UniProtKB:P33072"
FT CARBOHYD 256
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 468
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 611
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 64..128
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 77..138
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 108..118
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 196..261
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 209..271
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 238..248
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 318..382
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 331..392
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 362..372
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 433..497
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 446..510
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 479..489
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT CROSSLNK 620..656
FT /note="Lysine tyrosylquinone (Lys-Tyr)"
FT /evidence="ECO:0000250|UniProtKB:P33072"
SQ SEQUENCE 739 AA; 82133 MW; 4EC48A1F52FF06D7 CRC64;
MLRSELRDMV VAMVLWGILL PFCLSQTTSP SQDGKIKFRL AGYPRKHNEG RIEVFYNREW
GTICDDDFTL ANAHVLCRQL GFVEALSWSH SAKYGPGSGK IWLDNVICGG SENSIEKCVS
RGWGNSDCTH QEDAGVICKD ERLPGFAESN IIEMQVDEKR MEKIRLRPLK GAHAGRLPVT
EGVVEVKFKE GWGHICNTGW TIKNSRVVCG MMGFPSQRSV GKKPNSLKSA YRIHSVTCSG
NEAHLSACTM EFSRANSSAP CPGGGAAVVS CVPGLQFTQG RVRKAKLNPV PQMRLKGGAR
AGEGRVEVLK GSEWGTVCDD HWNLQSASVV CRELGFGTAK EALTGARMGQ GMGPIYMNEV
QCGGDEKSLW DCPHQSITAE DCKHTEDASV ICNIPYMGFE KLMRLTGGRT RLEGRVELLL
PAGGGVRDWG LICGDGWTSR EAMVVCRQLG LGHASSGLRE TWYWDSSNVT EMVMSGVKCK
GDEMTLTDCQ HHSVVSCKRA GAQFSAGVIC SDMASDLVLN APLVEQTVYI EDRPLHLLYC
AAEENCLAKS AAQASWPYGH RRLLRFSSEI HNIGKADFRP RLGRHSWVWH ECHRHYHSMD
IFTYYDLLSL NGTKVADGHK ASFCLEDTEC HEGVSKRYEC ANFGEQGITV GCWDLYRHDI
DCQWIDITDV SPGNYILQVI INPNFEVAES DFTNNAMRCN CKYDGHRVWL HKCHLGDSFS
EEAEKEFEHY PGQLNNKIS
