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Protein

Lysyl oxidase homolog 3

Gene

LOXL3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Both isoforms function as amine oxidases toward elastin and different types of collagens. Isoform 1 shows the highest activity toward collagen type VIII, while Isoform 2 presents the highest activity toward collagen type IV.1 Publication

Cofactori

Protein has several cofactor binding sites:

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi607 – 6071CopperSequence Analysis
Metal bindingi609 – 6091CopperSequence Analysis
Metal bindingi611 – 6111CopperSequence Analysis

GO - Molecular functioni

  1. copper ion binding Source: UniProtKB
  2. protein-lysine 6-oxidase activity Source: UniProtKB
  3. scavenger receptor activity Source: InterPro

GO - Biological processi

  1. epithelial to mesenchymal transition Source: UniProtKB
  2. negative regulation of transcription, DNA-templated Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Ligandi

Copper, Metal-binding

Enzyme and pathway databases

BRENDAi1.4.3.13. 2681.
ReactomeiREACT_150206. Crosslinking of collagen fibrils.
REACT_150366. Elastic fibre formation.

Names & Taxonomyi

Protein namesi
Recommended name:
Lysyl oxidase homolog 3 (EC:1.4.3.-)
Alternative name(s):
Lysyl oxidase-like protein 3
Gene namesi
Name:LOXL3
Synonyms:LOXL
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:13869. LOXL3.

Subcellular locationi

Isoform 2 :
  1. Cytoplasm 1 Publication
  2. Secretedextracellular space 1 Publication

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-SubCell
  2. extracellular region Source: UniProtKB
  3. extracellular space Source: UniProtKB-SubCell
  4. membrane Source: InterPro
  5. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA30430.

Polymorphism and mutation databases

BioMutaiLOXL3.
DMDMi14916616.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2525Sequence AnalysisAdd
BLAST
Chaini26 – 753728Lysyl oxidase homolog 3PRO_0000018533Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi70 ↔ 134PROSITE-ProRule annotation
Disulfide bondi83 ↔ 144PROSITE-ProRule annotation
Glycosylationi111 – 1111N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi114 ↔ 124PROSITE-ProRule annotation
Disulfide bondi201 ↔ 271PROSITE-ProRule annotation
Disulfide bondi214 ↔ 281PROSITE-ProRule annotation
Disulfide bondi248 ↔ 258PROSITE-ProRule annotation
Glycosylationi266 – 2661N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi332 ↔ 396PROSITE-ProRule annotation
Disulfide bondi345 ↔ 406PROSITE-ProRule annotation
Disulfide bondi376 ↔ 386PROSITE-ProRule annotation
Glycosylationi390 – 3901N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi446 ↔ 511PROSITE-ProRule annotation
Disulfide bondi459 ↔ 524PROSITE-ProRule annotation
Glycosylationi481 – 4811N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi492 ↔ 502PROSITE-ProRule annotation
Disulfide bondi554 ↔ 560PROSITE-ProRule annotation
Disulfide bondi606 ↔ 654PROSITE-ProRule annotation
Glycosylationi625 – 6251N-linked (GlcNAc...)Sequence Analysis
Cross-linki634 ↔ 670Lysine tyrosylquinone (Lys-Tyr)By similarity
Disulfide bondi638 ↔ 644PROSITE-ProRule annotation
Disulfide bondi666 ↔ 676PROSITE-ProRule annotation
Modified residuei670 – 67012',4',5'-topaquinoneBy similarity
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.

Keywords - PTMi

Disulfide bond, Glycoprotein, LTQ, TPQ

Proteomic databases

PaxDbiP58215.
PRIDEiP58215.

PTM databases

PhosphoSiteiP58215.

Expressioni

Tissue specificityi

Isoform 1 ia predominantly detected in the heart, placenta, lung, and small intestine, while isoform 2 is more highly detected in the kidney, pancreas, spleen, and thymus, and is absent in lung.1 Publication

Gene expression databases

BgeeiP58215.
CleanExiHS_LOXL3.
ExpressionAtlasiP58215. baseline and differential.
GenevestigatoriP58215.

Organism-specific databases

HPAiHPA035281.

Interactioni

Protein-protein interaction databases

BioGridi124210. 9 interactions.
IntActiP58215. 2 interactions.
MINTiMINT-1427254.
STRINGi9606.ENSP00000264094.

Structurei

3D structure databases

SMRiP58215. Positions 56-144, 304-406, 417-529.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini44 – 145102SRCR 1PROSITE-ProRule annotationAdd
BLAST
Domaini169 – 282114SRCR 2PROSITE-ProRule annotationAdd
BLAST
Domaini307 – 407101SRCR 3PROSITE-ProRule annotationAdd
BLAST
Domaini417 – 525109SRCR 4PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni529 – 732204Lysyl-oxidase likeAdd
BLAST

Sequence similaritiesi

Belongs to the lysyl oxidase family.Curated
Contains 4 SRCR domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiNOG40770.
GeneTreeiENSGT00760000119251.
HOGENOMiHOG000220841.
HOVERGENiHBG052336.
InParanoidiP58215.
KOiK00280.
OMAiTWYWDSG.
PhylomeDBiP58215.
TreeFamiTF326061.

Family and domain databases

Gene3Di3.10.250.10. 4 hits.
InterProiIPR001695. Lysyl_oxidase.
IPR019828. Lysyl_oxidase_CS.
IPR001190. SRCR.
IPR017448. SRCR-like_dom.
[Graphical view]
PfamiPF01186. Lysyl_oxidase. 1 hit.
PF00530. SRCR. 4 hits.
[Graphical view]
PRINTSiPR00074. LYSYLOXIDASE.
PR00258. SPERACTRCPTR.
SMARTiSM00202. SR. 4 hits.
[Graphical view]
SUPFAMiSSF56487. SSF56487. 4 hits.
PROSITEiPS00926. LYSYL_OXIDASE. 1 hit.
PS00420. SRCR_1. 1 hit.
PS50287. SRCR_2. 4 hits.
[Graphical view]

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-sv1

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti159 – 1591E → K in AAK91134 (PubMed:11334717).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti615 – 6151I → F.
Corresponds to variant rs17010021 [ dbSNP | Ensembl ].
VAR_050011

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 361361Missing in isoform 2. 1 PublicationVSP_054417Add
BLAST
Alternative sequencei159 – 303145Missing in isoform 3. 1 PublicationVSP_054418Add
BLAST

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_001289164.1. [P58215-3]
NP_001276094.1. NM_001289165.1. [P58215-2]
NP_115992.1. NM_032603.3. [P58215-1]
UniGeneiHs.469045.

Genome annotation databases

EnsembliENST00000264094; ENSP00000264094; ENSG00000115318. [P58215-1]
ENST00000393937; ENSP00000377512; ENSG00000115318. [P58215-3]
GeneIDi84695.
KEGGihsa:84695.
UCSCiuc002smo.1. human. [P58215-1]
uc002smq.1. human.

Polymorphism and mutation databases

BioMutaiLOXL3.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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_001289164.1. [P58215-3]
NP_001276094.1. NM_001289165.1. [P58215-2]
NP_115992.1. NM_032603.3. [P58215-1]
UniGeneiHs.469045.

3D structure databases

SMRiP58215. Positions 56-144, 304-406, 417-529.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124210. 9 interactions.
IntActiP58215. 2 interactions.
MINTiMINT-1427254.
STRINGi9606.ENSP00000264094.

PTM databases

PhosphoSiteiP58215.

Polymorphism and mutation databases

BioMutaiLOXL3.
DMDMi14916616.

Proteomic databases

PaxDbiP58215.
PRIDEiP58215.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264094; ENSP00000264094; ENSG00000115318. [P58215-1]
ENST00000393937; ENSP00000377512; ENSG00000115318. [P58215-3]
GeneIDi84695.
KEGGihsa:84695.
UCSCiuc002smo.1. human. [P58215-1]
uc002smq.1. human.

Organism-specific databases

CTDi84695.
GeneCardsiGC02M074760.
HGNCiHGNC:13869. LOXL3.
HPAiHPA035281.
MIMi607163. gene.
neXtProtiNX_P58215.
PharmGKBiPA30430.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG40770.
GeneTreeiENSGT00760000119251.
HOGENOMiHOG000220841.
HOVERGENiHBG052336.
InParanoidiP58215.
KOiK00280.
OMAiTWYWDSG.
PhylomeDBiP58215.
TreeFamiTF326061.

Enzyme and pathway databases

BRENDAi1.4.3.13. 2681.
ReactomeiREACT_150206. Crosslinking of collagen fibrils.
REACT_150366. Elastic fibre formation.

Miscellaneous databases

ChiTaRSiLOXL3. human.
GeneWikiiLOXL3.
GenomeRNAii84695.
NextBioi74768.
PROiP58215.
SOURCEiSearch...

Gene expression databases

BgeeiP58215.
CleanExiHS_LOXL3.
ExpressionAtlasiP58215. baseline and differential.
GenevestigatoriP58215.

Family and domain databases

Gene3Di3.10.250.10. 4 hits.
InterProiIPR001695. Lysyl_oxidase.
IPR019828. Lysyl_oxidase_CS.
IPR001190. SRCR.
IPR017448. SRCR-like_dom.
[Graphical view]
PfamiPF01186. Lysyl_oxidase. 1 hit.
PF00530. SRCR. 4 hits.
[Graphical view]
PRINTSiPR00074. LYSYLOXIDASE.
PR00258. SPERACTRCPTR.
SMARTiSM00202. SR. 4 hits.
[Graphical view]
SUPFAMiSSF56487. SSF56487. 4 hits.
PROSITEiPS00926. LYSYL_OXIDASE. 1 hit.
PS00420. SRCR_1. 1 hit.
PS50287. SRCR_2. 4 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and characterization of a fourth human lysyl oxidase isoenzyme."
    Maki J.M., Kivirikko K.I.
    Biochem. J. 355:381-387(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  2. "Central nervous system, uterus, heart, and leukocyte expression of the LOXL3 gene, encoding a novel lysyl oxidase-like protein."
    Jourdan-Le Saux C., Tomshe A., Ujfalusi A., Jia L., Csiszar K.
    Genomics 74:211-218(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  3. "Cloning and characterization of a human lysyl oxidase-like 3 gene (hLOXL3)."
    Huang Y., Dai J., Tang R., Zhao W., Zhou Z., Wang W., Ying K., Xie Y., Mao Y.
    Matrix Biol. 20:153-157(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  4. "A tissue-specific variant of the human lysyl oxidase-like protein 3 (LOXL3) functions as an amine oxidase with substrate specificity."
    Lee J.-E., Kim Y.
    J. Biol. Chem. 281:37282-37290(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, SUBCELLULAR LOCATION (ISOFORM 2), TISSUE SPECIFICITY.
  5. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
    Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
    , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
    Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
    Tissue: Ovary.

Entry informationi

Entry nameiLOXL3_HUMAN
AccessioniPrimary (citable) accession number: P58215
Secondary accession number(s): D6W5J1
, Q2EHP2, Q6IPL7, Q96RS1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 11, 2001
Last sequence update: July 11, 2001
Last modified: April 29, 2015
This is version 126 of the entry and version 1 of the sequence. [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

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.