LYOX_BOVIN
ID LYOX_BOVIN Reviewed; 418 AA.
AC P33072; Q95L38;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 10-JAN-2006, sequence version 3.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=Protein-lysine 6-oxidase {ECO:0000250|UniProtKB:P28300};
DE EC=1.4.3.13 {ECO:0000250|UniProtKB:P28300};
DE AltName: Full=Lysyl oxidase;
DE Contains:
DE RecName: Full=Protein-lysine 6-oxidase, long form {ECO:0000250|UniProtKB:P28300};
DE Contains:
DE RecName: Full=Protein-lysine 6-oxidase, short form {ECO:0000250|UniProtKB:P28300};
DE Flags: Precursor;
GN Name=LOX {ECO:0000250|UniProtKB:P28300};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Skin;
RX PubMed=11684696; DOI=10.1074/jbc.m109499200;
RA Borel A., Eichenberger D., Farjanel J., Kessler E., Gleyzal C.,
RA Hulmes D.J.S., Sommer P., Font B.;
RT "Lysyl oxidase-like protein from bovine aorta. Isolation and maturation to
RT an active form by bone morphogenetic protein-1.";
RL J. Biol. Chem. 276:48944-48949(2001).
RN [2]
RP PROTEIN SEQUENCE OF 200-231; 266-284; 297-305; 316-323; 354-359; 379-398
RP AND 403-418.
RC TISSUE=Aorta;
RX PubMed=1973052; DOI=10.1021/bi00472a016;
RA Trackman P.C., Pratt A.M., Wolanski A., Tang S.-S., Offner G.D.,
RA Troxler R.F., Kagan H.M.;
RT "Cloning of rat aorta lysyl oxidase cDNA: complete codons and predicted
RT amino acid sequence.";
RL Biochemistry 29:4863-4870(1990).
RN [3]
RP COFACTOR, TOPAQUINONE AT TYR-356, AND CROSS-LINK 321-LYS-TYR-356.
RX PubMed=8688089; DOI=10.1126/science.273.5278.1078;
RA Wang S.X., Mure M., Medzihradszky K.F., Burlingame A.L., Brown D.E.,
RA Dooley D.M., Smith A.J., Kagan H.M., Klinman J.P.;
RT "A crosslinked cofactor in lysyl oxidase: redox function for amino acid
RT side chains.";
RL Science 273:1078-1084(1996).
RN [4]
RP DISULFIDE BONDS.
RX PubMed=21188434; DOI=10.1007/s00702-010-0560-y;
RA Chen X., Greenaway F.T.;
RT "Identification of the disulfide bonds of lysyl oxidase.";
RL J. Neural Transm. 118:1111-1114(2011).
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=31152061; DOI=10.1074/jbc.ra119.007806;
RA Rosell-Garcia T., Paradela A., Bravo G., Dupont L., Bekhouche M.,
RA Colige A., Rodriguez-Pascual F.;
RT "Differential cleavage of lysyl oxidase by the metalloproteinases BMP1 and
RT ADAMTS2/14 regulates collagen binding through a tyrosine sulfate domain.";
RL J. Biol. Chem. 294:11087-11100(2019).
CC -!- FUNCTION: Responsible for the post-translational oxidative deamination
CC of peptidyl lysine residues in precursors to fibrous collagen and
CC elastin. Regulator of Ras expression. May play a role in tumor
CC suppression. Plays a role in the aortic wall architecture (By
CC similarity). {ECO:0000250|UniProtKB:P28301}.
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:P28301};
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:0000269|PubMed:8688089};
CC Note=Contains 1 lysine tyrosylquinone. {ECO:0000269|PubMed:8688089};
CC -!- SUBUNIT: Interacts with MFAP4. Interacts (via propeptide) with EFEMP2;
CC this interaction is strong and facilitates formation of ternary
CC complexes with ELN during elastic fiber assembly; this interaction
CC limits interaction of EFEMP2 with FBLN5.
CC {ECO:0000250|UniProtKB:P28300}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:31152061}. Secreted,
CC extracellular space.
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:0000269|PubMed:8688089}.
CC -!- PTM: Proteolytically cleaved by BMP1 which removes the propeptide (By
CC similarity). Also proteolytically cleaved by ADAMTS2 and ADAMTS14, but
CC not by ADAMTS3, at an additional cleavage site downstream of the BMP1
CC cleavage site (By similarity). The propeptide plays a role in directing
CC the deposition of this enzyme to elastic fibers, via interaction with
CC tropoelastin (By similarity). Cleavage by BMP1 to remove the propeptide
CC does not increase enzymatic activity but increases binding to collagen
CC (By similarity). Cleavage by ADAMTS2 produces a form with reduced
CC collagen-binding activity (By similarity).
CC {ECO:0000250|UniProtKB:P28300, ECO:0000250|UniProtKB:P28301}.
CC -!- PTM: Sulfated at Tyr-188 and also at either Tyr-184 or Tyr-185 which
CC enhances binding to collagen. {ECO:0000250|UniProtKB:P28300}.
CC -!- MISCELLANEOUS: The propeptide plays a role in directing the deposition
CC of this enzyme to elastic fibers, via interaction with tropoelastin.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the lysyl oxidase family. {ECO:0000305}.
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DR EMBL; AF421186; AAL13313.1; -; mRNA.
DR PIR; B30352; B30352.
DR STRING; 9913.ENSBTAP00000017275; -.
DR BindingDB; P33072; -.
DR ChEMBL; CHEMBL4523217; -.
DR PaxDb; P33072; -.
DR PRIDE; P33072; -.
DR eggNOG; ENOG502QWQR; Eukaryota.
DR InParanoid; P33072; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0005518; F:collagen binding; ISS:UniProtKB.
DR GO; GO:0005507; F:copper ion binding; IEA:InterPro.
DR GO; GO:0004720; F:protein-lysine 6-oxidase activity; ISS:UniProtKB.
DR GO; GO:0048514; P:blood vessel morphogenesis; ISS:UniProtKB.
DR GO; GO:0018057; P:peptidyl-lysine oxidation; ISS:UniProtKB.
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 Copper; Direct protein sequencing; Disulfide bond; Glycoprotein; LTQ;
KW Metal-binding; Oxidoreductase; Reference proteome; Secreted; Signal;
KW Sulfation; TPQ.
FT SIGNAL 1..20
FT /evidence="ECO:0000250|UniProtKB:P16636"
FT PROPEP 21..169
FT /note="Removed by BMP1"
FT /evidence="ECO:0000250|UniProtKB:P16636"
FT /id="PRO_0000045436"
FT CHAIN 170..418
FT /note="Protein-lysine 6-oxidase, long form"
FT /evidence="ECO:0000250|UniProtKB:P16636"
FT /id="PRO_0000045437"
FT CHAIN 220..418
FT /note="Protein-lysine 6-oxidase, short form"
FT /evidence="ECO:0000250|UniProtKB:P28300"
FT /id="PRO_0000447884"
FT REGION 58..84
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 129..175
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 214..418
FT /note="Lysyl-oxidase like"
FT COMPBIAS 131..151
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 293
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000255"
FT BINDING 295
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000255"
FT BINDING 297
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000255"
FT SITE 219..220
FT /note="Cleavage; by ADAMTS2 and ADAMTS14"
FT /evidence="ECO:0000250|UniProtKB:P28300"
FT MOD_RES 188
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P28300"
FT MOD_RES 356
FT /note="2',4',5'-topaquinone"
FT /evidence="ECO:0000269|PubMed:8688089"
FT CARBOHYD 80
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 96
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 143
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 239..245
FT /evidence="ECO:0000269|PubMed:21188434"
FT DISULFID 292..341
FT /evidence="ECO:0000269|PubMed:21188434"
FT DISULFID 325..331
FT /evidence="ECO:0000269|PubMed:21188434"
FT DISULFID 352..362
FT /evidence="ECO:0000269|PubMed:21188434"
FT DISULFID 399..413
FT /evidence="ECO:0000269|PubMed:21188434"
FT CROSSLNK 321..356
FT /note="Lysine tyrosylquinone (Lys-Tyr)"
FT /evidence="ECO:0000269|PubMed:8688089"
FT CONFLICT 413..414
FT /note="CT -> QS (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 418 AA; 47115 MW; EC4C0F36A29FD860 CRC64;
MRFAWTALLG SLQLCALVRC APPAASHRQP PREQAAAPGA WRQKIQWENN GQVFSLLSLG
SQYQPQRRRD PGATAPGAAN ATAPQMRTPI LLLRNNRTAA ARVRTAGPSA AAAGRPRPAA
RHWFQAGYST SGAHDAGTSR ADNQTAPGEV PTLSNLRPPN RVEVDGMVGD DPYNPYKYTD
DNPYYNYYDT YERPRPGSRY RPGYGTGYFQ YGLPDLVPDP YYIQASTYVQ KMAMYNLRCA
AEENCLASSA YRXDVRDYDH RVLLRFPQRV KNQGTSDFLP SRPRYSWEWH SCHQHYHSMD
EFSHYDLLDA STQRRVAEGH KASFCLEDTS CDYGYHRRFA CTAHTQGLSP GCYDTYNADI
DCQWIDITDV KPGNYILKVS VNPSYLVPES DYSNNVVRCE IRYTGHHAYA SGCTISPY
