ID   PLOD3_HUMAN             Reviewed;         738 AA.
AC   O60568; Q540C3;
DT   15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1998, sequence version 1.
DT   07-JUL-2009, entry version 82.
DE   RecName: Full=Procollagen-lysine,2-oxoglutarate 5-dioxygenase 3;
DE            EC=1.14.11.4;
DE   AltName: Full=Lysyl hydroxylase 3;
DE            Short=LH3;
DE   Flags: Precursor;
GN   Name=PLOD3;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   MEDLINE=98250732; PubMed=9582318; DOI=10.1074/jbc.273.21.12881;
RA   Valtavaara M., Szpirer C., Szpirer J., Myllylae R.;
RT   "Primary structure, tissue distribution, and chromosomal localization
RT   of a novel isoform of lysyl hydroxylase (lysyl hydroxylase 3).";
RL   J. Biol. Chem. 273:12881-12886(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   MEDLINE=98393670; PubMed=9724729; DOI=10.1073/pnas.95.18.10482;
RA   Passoja K., Rautavuoma K., Ala-Kokko L., Kosonen T., Kivirikko K.I.;
RT   "Cloning and characterization of a third human lysyl hydroxylase
RT   isoform.";
RL   Proc. Natl. Acad. Sci. U.S.A. 95:10482-10486(1998).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   MEDLINE=20153851; PubMed=10686427; DOI=10.1016/S0945-053X(99)00058-X;
RA   Rautavuoma K., Passoja K., Helaakoski T., Kivirikko K.I.;
RT   "Complete exon-intron organization of the gene for human lysyl
RT   hydroxylase 3 (LH3).";
RL   Matrix Biol. 19:73-79(2000).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Lian Z., Feitelson M.;
RT   "A gene upregulated by HBVX and is similar to LH3.";
RL   Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   MEDLINE=22737999; PubMed=12853948; DOI=10.1038/nature01782;
RA   Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA   Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R.,
RA   Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H.,
RA   Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A.,
RA   Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J.,
RA   Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A.,
RA   Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S.,
RA   Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M.,
RA   Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C.,
RA   Latreille P., Miller N., Johnson D., Murray J., Woessner J.P.,
RA   Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J.,
RA   Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L.,
RA   Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R.,
RA   Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA   Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K.,
RA   Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S.,
RA   Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M.,
RA   Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R.,
RA   Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D.,
RA   Waterston R.H., Wilson R.K.;
RT   "The DNA sequence of human chromosome 7.";
RL   Nature 424:157-164(2003).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Pancreas;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [7]
RP   IDENTIFICATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RA   Colinge J., Superti-Furga G., Bennett K.L.;
RL   Submitted (OCT-2008) to UniProtKB.
RN   [8]
RP   VARIANT LH3 DEFICIENCY SER-223.
RX   PubMed=18834968; DOI=10.1016/j.ajhg.2008.09.004;
RA   Salo A.M., Cox H., Farndon P., Moss C., Grindulis H., Risteli M.,
RA   Robins S.P., Myllylae R.;
RT   "A connective tissue disorder caused by mutations of the lysyl
RT   hydroxylase 3 gene.";
RL   Am. J. Hum. Genet. 83:495-503(2008).
CC   -!- FUNCTION: Forms hydroxylysine residues in -Xaa-Lys-Gly- sequences
CC       in collagens. These hydroxylysines serve as sites of attachment
CC       for carbohydrate units and are essential for the stability of the
CC       intermolecular collagen cross-links.
CC   -!- CATALYTIC ACTIVITY: Procollagen L-lysine + 2-oxoglutarate + O(2) =
CC       procollagen 5-hydroxy-L-lysine + succinate + CO(2).
CC   -!- COFACTOR: Iron.
CC   -!- COFACTOR: Ascorbate.
CC   -!- SUBUNIT: Homodimer.
CC   -!- INTERACTION:
CC       Q9BQY4:RHOXF2; NbExp=1; IntAct=EBI-741582, EBI-372094;
CC   -!- SUBCELLULAR LOCATION: Rough endoplasmic reticulum membrane;
CC       Peripheral membrane protein; Lumenal side.
CC   -!- DISEASE: Defects in PLOD3 are the cause of lysyl hydroxylase 3
CC       deficiency (LH3 deficiency) [MIM:612394]; also called bone
CC       fragility with contractures arterial rupture and deafness. LH3
CC       deficiency is a connective tissue disorder. The syndrome is
CC       characterized by congenital malformations severely affecting many
CC       tissues and organs and revealing features of several collagen
CC       disorders, most of them involving COL2A1 (type II collagen). The
CC       findings suggest that the failure of lysyl hydroxylation and
CC       hydroxylysyl carbohydrate addition, which affects many collagens,
CC       is the molecular basis of this syndrome.
CC   -!- SIMILARITY: Contains 1 PKHD (prolyl/lysyl hydroxylase) domain.
CC   -----------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution-NoDerivs License
CC   -----------------------------------------------------------------------
DR   EMBL; AF046889; AAC39753.1; -; mRNA.
DR   EMBL; AF068229; AAC34808.1; -; mRNA.
DR   EMBL; AF207069; AAF63701.1; -; Genomic_DNA.
DR   EMBL; AY220458; AAO61775.1; -; mRNA.
DR   EMBL; AC004876; AAD45831.1; -; Genomic_DNA.
DR   EMBL; BC011674; AAH11674.1; -; mRNA.
DR   IPI; IPI00030255; -.
DR   RefSeq; NP_001075.1; -.
DR   UniGene; Hs.153357; -.
DR   IntAct; O60568; 6.
DR   PhosphoSite; O60568; -.
DR   PeptideAtlas; O60568; -.
DR   PRIDE; O60568; -.
DR   Ensembl; ENSG00000106397; Homo sapiens.
DR   GeneID; 8985; -.
DR   KEGG; hsa:8985; -.
DR   UCSC; uc003uyd.1; human.
DR   GeneCards; GC07M100635; -.
DR   H-InvDB; HIX0006947; -.
DR   HGNC; HGNC:9083; PLOD3.
DR   MIM; 603066; gene.
DR   MIM; 612394; phenotype.
DR   PharmGKB; PA33413; -.
DR   HOGENOM; O60568; -.
DR   HOVERGEN; O60568; -.
DR   OMA; O60568; SAEFFNY.
DR   BRENDA; 1.14.11.4; 247.
DR   DrugBank; DB00139; Succinic acid.
DR   DrugBank; DB00126; Vitamin C.
DR   NextBio; 33693; -.
DR   ArrayExpress; O60568; -.
DR   Bgee; O60568; -.
DR   CleanEx; HS_PLOD3; -.
DR   GermOnline; ENSG00000106397; Homo sapiens.
DR   GO; GO:0030867; C:rough endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005506; F:iron ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0031418; F:L-ascorbic acid binding; IEA:UniProtKB-KW.
DR   GO; GO:0016702; F:oxidoreductase activity, acting on single d...; IEA:UniProtKB-KW.
DR   GO; GO:0008475; F:procollagen-lysine 5-dioxygenase activity; TAS:ProtInc.
DR   GO; GO:0005515; F:protein binding; IPI:IntAct.
DR   GO; GO:0055114; P:oxidation reduction; IEA:UniProtKB-KW.
DR   GO; GO:0006464; P:protein modification process; TAS:ProtInc.
DR   InterPro; IPR005123; Oxoglutarate/Fe-dep_Oase.
DR   InterPro; IPR006620; Pro_4_hyd_alph.
DR   InterPro; IPR001006; Procol_lys_dOase.
DR   Pfam; PF03171; 2OG-FeII_Oxy; 1.
DR   ProDom; PD011578; ProcolLys_dioxy; 1.
DR   SMART; SM00702; P4Hc; 1.
DR   PROSITE; PS01325; LYS_HYDROXYLASE; 1.
PE   1: Evidence at protein level;
KW   Complete proteome; Dioxygenase; Disease mutation;
KW   Endoplasmic reticulum; Glycoprotein; Iron; Membrane; Metal-binding;
KW   Oxidoreductase; Polymorphism; Signal; Vitamin C.
FT   SIGNAL        1     24       Potential.
FT   CHAIN        25    738       Procollagen-lysine,2-oxoglutarate 5-
FT                                dioxygenase 3.
FT                                /FTId=PRO_0000024686.
FT   DOMAIN      565    738       PKHD.
FT   ACT_SITE    729    729       Potential.
FT   METAL       667    667       Iron (By similarity).
FT   METAL       669    669       Iron (By similarity).
FT   METAL       719    719       Iron (By similarity).
FT   CARBOHYD     63     63       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    548    548       N-linked (GlcNAc...) (Potential).
FT   VARIANT     151    151       A -> V (in dbSNP:rs35627324).
FT                                /FTId=VAR_051708.
FT   VARIANT     223    223       N -> S (in LH3 deficiency).
FT                                /FTId=VAR_054913.
FT   VARIANT     286    286       R -> W (in dbSNP:rs1134907).
FT                                /FTId=VAR_012075.
SQ   SEQUENCE   738 AA;  84785 MW;  08424B46985941F9 CRC64;
     MTSSGPGPRF LLLLPLLLPP AASASDRPRG RDPVNPEKLL VITVATAETE GYLRFLRSAE
     FFNYTVRTLG LGEEWRGGDV ARTVGGGQKV RWLKKEMEKY ADREDMIIMF VDSYDVILAG
     SPTELLKKFV QSGSRLLFSA ESFCWPEWGL AEQYPEVGTG KRFLNSGGFI GFATTIHQIV
     RQWKYKDDDD DQLFYTRLYL DPGLREKLSL NLDHKSRIFQ NLNGALDEVV LKFDRNRVRI
     RNVAYDTLPI VVHGNGPTKL QLNYLGNYVP NGWTPEGGCG FCNQDRRTLP GGQPPPRVFL
     AVFVEQPTPF LPRFLQRLLL LDYPPDRVTL FLHNNEVFHE PHIADSWPQL QDHFSAVKLV
     GPEEALSPGE ARDMAMDLCR QDPECEFYFS LDADAVLTNL QTLRILIEEN RKVIAPMLSR
     HGKLWSNFWG ALSPDEYYAR SEDYVELVQR KRVGVWNVPY ISQAYVIRGD TLRMELPQRD
     VFSGSDTDPD MAFCKSFRDK GIFLHLSNQH EFGRLLATSR YDTEHLHPDL WQIFDNPVDW
     KEQYIHENYS RALEGEGIVE QPCPDVYWFP LLSEQMCDEL VAEMEHYGQW SGGRHEDSRL
     AGGYENVPTV DIHMKQVGYE DQWLQLLRTY VGPMTESLFP GYHTKARAVM NFVVRYRPDE
     QPSLRPHHDS STFTLNVALN HKGLDYEGGG CRFLRYDCVI SSPRKGWALL HPGRLTHYHE
     GLPTTWGTRY IMVSFVDP
//