ID PLOD3_HUMAN Reviewed; 738 AA. AC O60568; B2R6W6; Q540C3; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1998, sequence version 1. DT 13-FEB-2019, entry version 175. DE RecName: Full=Multifunctional procollagen lysine hydroxylase and glycosyltransferase LH3; DE Includes: DE RecName: Full=Procollagen-lysine,2-oxoglutarate 5-dioxygenase 3; DE EC=1.14.11.4 {ECO:0000269|PubMed:12475640, ECO:0000269|PubMed:18298658, ECO:0000269|PubMed:18834968, ECO:0000269|PubMed:30089812, ECO:0000269|PubMed:9582318, ECO:0000269|PubMed:9724729}; DE AltName: Full=Lysyl hydroxylase 3 {ECO:0000303|PubMed:9582318, ECO:0000303|PubMed:9724729}; DE Short=LH3 {ECO:0000303|PubMed:10686427}; DE Includes: DE RecName: Full=Procollagen glycosyltransferase; DE EC=2.4.1.50 {ECO:0000269|PubMed:12475640, ECO:0000269|PubMed:18298658, ECO:0000269|PubMed:18834968, ECO:0000269|PubMed:30089812}; DE EC=2.4.1.66 {ECO:0000269|PubMed:10934207, ECO:0000269|PubMed:11896059, ECO:0000269|PubMed:11956192, ECO:0000269|PubMed:12475640, ECO:0000269|PubMed:18298658, ECO:0000269|PubMed:18834968, ECO:0000269|PubMed:30089812}; DE AltName: Full=Galactosylhydroxylysine-glucosyltransferase; DE AltName: Full=Procollagen galactosyltransferase; DE AltName: Full=Procollagen glucosyltransferase; 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], FUNCTION, CATALYTIC ACTIVITY, AND TISSUE RP SPECIFICITY. RX 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], FUNCTION, CATALYTIC ACTIVITY, COFACTOR, RP BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY. RX 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 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 MRNA]. RC TISSUE=Small intestine; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [8] 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 [9] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP ASP-669. RX PubMed=10934207; DOI=10.1074/jbc.M006203200; RA Heikkinen J., Risteli M., Wang C., Latvala J., Rossi M., RA Valtavaara M., Myllylae R.; RT "Lysyl hydroxylase 3 is a multifunctional protein possessing collagen RT glucosyltransferase activity."; RL J. Biol. Chem. 275:36158-36163(2000). RN [10] RP CATALYTIC ACTIVITY, AND MUTAGENESIS OF CYS-144; 187-ASP--ASP-189; RP 187-ASP--ASP-191 AND LEU-208. RX PubMed=11896059; DOI=10.1074/jbc.M201389200; RA Wang C., Risteli M., Heikkinen J., Hussa A.K., Uitto L., Myllyla R.; RT "Identification of amino acids important for the catalytic activity of RT the collagen glucosyltransferase associated with the multifunctional RT lysyl hydroxylase 3 (LH3)."; RL J. Biol. Chem. 277:18568-18573(2002). RN [11] RP CATALYTIC ACTIVITY, FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=11956192; DOI=10.1074/jbc.M112077200; RA Rautavuoma K., Takaluoma K., Passoja K., Pirskanen A., Kvist A.P., RA Kivirikko K.I., Myllyharju J.; RT "Characterization of three fragments that constitute the monomers of RT the human lysyl hydroxylase isoenzymes 1-3. The 30-kDa N-terminal RT fragment is not required for lysyl hydroxylase activity."; RL J. Biol. Chem. 277:23084-23091(2002). RN [12] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND RP MUTAGENESIS OF CYS-144; 187-ASP--ASP-189 AND 187-ASP--ASP-191. RX PubMed=12475640; RA Wang C., Luosujaervi H., Heikkinen J., Risteli M., Uitto L., RA Myllylae R.; RT "The third activity for lysyl hydroxylase 3: galactosylation of RT hydroxylysyl residues in collagens in vitro."; RL Matrix Biol. 21:559-566(2002). RN [13] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF 187-ASP--ASP-191 AND RP ASP-669. RX PubMed=18298658; DOI=10.1111/j.1582-4934.2008.00286.x; RA Wang C., Kovanen V., Raudasoja P., Eskelinen S., Pospiech H., RA Myllylae R.; RT "The glycosyltransferase activities of lysyl hydroxylase 3 (LH3) in RT the extracellular space are important for cell growth and viability."; RL J. Cell. Mol. Med. 13:508-521(2009). RN [14] RP SUBCELLULAR LOCATION. RX PubMed=20470363; DOI=10.1186/1471-2121-11-33; RA Liefhebber J.M., Punt S., Spaan W.J., van Leeuwen H.C.; RT "The human collagen beta(1-O)galactosyltransferase, GLT25D1, is a RT soluble endoplasmic reticulum localized protein."; RL BMC Cell Biol. 11:33-33(2010). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [16] RP SUBCELLULAR LOCATION. RX PubMed=21465473; DOI=10.1002/jcp.22774; RA Wang C., Ristiluoma M.M., Salo A.M., Eskelinen S., Myllylae R.; RT "Lysyl hydroxylase 3 is secreted from cells by two pathways."; RL J. Cell. Physiol. 227:668-675(2012). RN [17] RP FUNCTION. RX PubMed=25419660; DOI=10.1371/journal.pone.0113498; RA Risteli M., Ruotsalainen H., Bergmann U., Venkatraman Girija U., RA Wallis R., Myllylae R.; RT "Lysyl hydroxylase 3 modifies lysine residues to facilitate RT oligomerization of mannan-binding lectin."; RL PLoS ONE 9:E113498-E113498(2014). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., RA Ayoub D., Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [19] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 25-738 IN COMPLEX WITH IRON; RP 2-OXOGLUTARATE; MANGANESE AND UDP-GLUCOSE, CATALYTIC ACTIVITY, RP FUNCTION, COFACTOR, SUBUNIT, DOMAIN, GLYCOSYLATION AT ASN-63 AND RP ASN-548, DISULFIDE BONDS, CHARACTERIZATION OF VARIANT LH3 DEFICIENCY RP SER-223, AND MUTAGENESIS OF TRP-75; TYR-114; THR-672; ARG-714 AND RP LEU-715. RX PubMed=30089812; DOI=10.1038/s41467-018-05631-5; RA Scietti L., Chiapparino A., De Giorgi F., Fumagalli M., Khoriauli L., RA Nergadze S., Basu S., Olieric V., Cucca L., Banushi B., Profumo A., RA Giulotto E., Gissen P., Forneris F.; RT "Molecular architecture of the multifunctional collagen lysyl RT hydroxylase and glycosyltransferase LH3."; RL Nat. Commun. 9:3163-3163(2018). RN [20] RP VARIANT LH3 DEFICIENCY SER-223, CHARACTERIZATION OF VARIANT LH3 RP DEFICIENCY SER-223, CATALYTIC ACTIVITY, AND FUNCTION. 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: Multifunctional enzyme that catalyzes a series of CC essential post-translational modifications on Lys residues in CC procollagen (PubMed:11956192, PubMed:12475640, PubMed:18298658, CC PubMed:30089812, PubMed:18834968). Plays a redundant role in CC catalyzing the formation of hydroxylysine residues in -Xaa-Lys- CC Gly- sequences in collagens (PubMed:9582318, PubMed:9724729, CC PubMed:11956192, PubMed:12475640, PubMed:18298658, CC PubMed:30089812, PubMed:18834968). Plays a redundant role in CC catalyzing the transfer of galactose onto hydroxylysine groups, CC giving rise to galactosyl 5-hydroxylysine (PubMed:12475640, CC PubMed:18298658, PubMed:30089812, PubMed:18834968). Has an CC essential role by catalyzing the subsequent transfer of glucose CC moieties, giving rise to 1,2-glucosylgalactosyl-5-hydroxylysine CC residues (PubMed:10934207, PubMed:11896059, PubMed:11956192, CC PubMed:12475640, PubMed:18298658, PubMed:30089812, CC PubMed:18834968). Catalyzes hydroxylation and glycosylation of Lys CC residues in the MBL1 collagen-like domain, giving rise to CC hydroxylysine and 1,2-glucosylgalactosyl-5-hydroxylysine residues CC (PubMed:25419660). Essential for normal biosynthesis and secretion CC of type IV collagens (PubMed:18834968) (Probable). Essential for CC normal formation of basement membranes (By similarity). CC {ECO:0000250|UniProtKB:Q9R0E1, ECO:0000269|PubMed:10934207, CC ECO:0000269|PubMed:11896059, ECO:0000269|PubMed:11956192, CC ECO:0000269|PubMed:12475640, ECO:0000269|PubMed:18298658, CC ECO:0000269|PubMed:18834968, ECO:0000269|PubMed:25419660, CC ECO:0000269|PubMed:30089812, ECO:0000269|PubMed:9582318, CC ECO:0000269|PubMed:9724729, ECO:0000305}. CC -!- CATALYTIC ACTIVITY: CC Reaction=2-oxoglutarate + L-lysyl-[procollagen] + O2 = (5R)-5- CC hydroxy-L-lysyl-[procollagen] + CO2 + succinate; CC Xref=Rhea:RHEA:16569, Rhea:RHEA-COMP:12751, Rhea:RHEA- CC COMP:12752, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, CC ChEBI:CHEBI:16810, ChEBI:CHEBI:29969, ChEBI:CHEBI:30031, CC ChEBI:CHEBI:133442; EC=1.14.11.4; CC Evidence={ECO:0000269|PubMed:10934207, CC ECO:0000269|PubMed:11956192, ECO:0000269|PubMed:12475640, CC ECO:0000269|PubMed:18298658, ECO:0000269|PubMed:18834968, CC ECO:0000269|PubMed:30089812, ECO:0000269|PubMed:9582318, CC ECO:0000269|PubMed:9724729}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5R)-5-hydroxy-L-lysyl-[procollagen] + UDP-alpha-D- CC galactose = (5R)-5-O-(beta-D-galactosyl)-5-hydroxy-L-lysyl- CC [procollagen] + H(+) + UDP; Xref=Rhea:RHEA:12637, Rhea:RHEA- CC COMP:12752, Rhea:RHEA-COMP:12753, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:58223, ChEBI:CHEBI:66914, ChEBI:CHEBI:133442, CC ChEBI:CHEBI:133443; EC=2.4.1.50; CC Evidence={ECO:0000269|PubMed:12475640, CC ECO:0000269|PubMed:18298658, ECO:0000269|PubMed:18834968, CC ECO:0000269|PubMed:30089812}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5R)-5-O-(beta-D-galactosyl)-5-hydroxy-L-lysyl- CC [procollagen] + UDP-alpha-D-glucose = (5R)-5-O-[alpha-D- CC glucosyl-(1->2)-beta-D-galactosyl]-5-hydroxy-L-lysyl- CC [procollagen] + H(+) + UDP; Xref=Rhea:RHEA:12576, Rhea:RHEA- CC COMP:12753, Rhea:RHEA-COMP:12754, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:58223, ChEBI:CHEBI:58885, ChEBI:CHEBI:133443, CC ChEBI:CHEBI:133452; EC=2.4.1.66; CC Evidence={ECO:0000269|PubMed:10934207, CC ECO:0000269|PubMed:11896059, ECO:0000269|PubMed:11956192, CC ECO:0000269|PubMed:12475640, ECO:0000269|PubMed:18298658, CC ECO:0000269|PubMed:18834968, ECO:0000269|PubMed:30089812}; CC -!- COFACTOR: CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033; CC Evidence={ECO:0000269|PubMed:30089812, CC ECO:0000269|PubMed:9724729}; CC -!- COFACTOR: CC Name=L-ascorbate; Xref=ChEBI:CHEBI:38290; CC Evidence={ECO:0000269|PubMed:30089812, CC ECO:0000269|PubMed:9724729}; CC -!- COFACTOR: CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Evidence={ECO:0000269|PubMed:30089812}; CC -!- ACTIVITY REGULATION: Lysyl hydroxylase activity is strongly CC inhibited by imidazole. {ECO:0000269|PubMed:10934207}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=35 uM for UDP-galactose {ECO:0000269|PubMed:12475640}; CC KM=17 uM for UDP-glucose {ECO:0000269|PubMed:12475640}; CC KM=100 uM for 2-oxoglutarate {ECO:0000269|PubMed:11956192, CC ECO:0000269|PubMed:9724729}; CC KM=300 uM for ascorbate {ECO:0000269|PubMed:9724729}; CC KM=350 uM for ascorbate {ECO:0000269|PubMed:11956192}; CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:30089812}. CC -!- INTERACTION: CC Q5JST6:EFHC2; NbExp=8; IntAct=EBI-741582, EBI-2349927; CC A2ABF9:EHMT2; NbExp=3; IntAct=EBI-741582, EBI-10174566; CC Q96KQ7:EHMT2; NbExp=7; IntAct=EBI-741582, EBI-744366; CC Q96QF0:RAB3IP; NbExp=3; IntAct=EBI-741582, EBI-747844; CC Q96QF0-2:RAB3IP; NbExp=3; IntAct=EBI-741582, EBI-747865; CC Q9BQY4:RHOXF2; NbExp=2; IntAct=EBI-741582, EBI-372094; CC -!- SUBCELLULAR LOCATION: Rough endoplasmic reticulum CC {ECO:0000269|PubMed:10934207}. Endoplasmic reticulum lumen CC {ECO:0000269|PubMed:20470363}. Endoplasmic reticulum membrane CC {ECO:0000250|UniProtKB:Q9R0E1}; Peripheral membrane protein CC {ECO:0000250|UniProtKB:Q9R0E1}; Lumenal side CC {ECO:0000250|UniProtKB:Q9R0E1}. Secreted CC {ECO:0000269|PubMed:21465473}. Secreted, extracellular space CC {ECO:0000250|UniProtKB:Q9R0E1}. Note=The majority of the secreted CC protein is associated with the extracellular matrix. CC {ECO:0000250|UniProtKB:Q9R0E1}. CC -!- TISSUE SPECIFICITY: Ubiquitous (PubMed:9724729). Detected in CC heart, placenta and pancreas, and at lower levels in lung, liver CC and skeletal muscle (PubMed:9582318, PubMed:9724729). CC {ECO:0000269|PubMed:9582318, ECO:0000269|PubMed:9724729}. CC -!- DOMAIN: The N-terminal domain mediates glycosyltransferase CC activity. {ECO:0000269|PubMed:30089812}. CC -!- DOMAIN: The C-terminal domain that mediates lysyl hydroxylase CC activity is also important for homodimerization. CC {ECO:0000269|PubMed:30089812}. CC -!- DISEASE: Lysyl hydroxylase 3 deficiency (LH3 deficiency) CC [MIM:612394]: 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 {ECO:0000269|PubMed:18834968, ECO:0000269|PubMed:30089812}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. 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; 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; AK312743; BAG35613.1; -; mRNA. DR EMBL; AC004876; AAD45831.1; -; Genomic_DNA. DR EMBL; CH471197; EAW50205.1; -; Genomic_DNA. DR EMBL; BC011674; AAH11674.1; -; mRNA. DR CCDS; CCDS5715.1; -. DR RefSeq; NP_001075.1; NM_001084.4. DR UniGene; Hs.153357; -. DR PDB; 6FXK; X-ray; 2.70 A; A=25-738. DR PDB; 6FXM; X-ray; 2.10 A; A=25-738. DR PDB; 6FXR; X-ray; 2.10 A; A=25-738. DR PDB; 6FXT; X-ray; 2.50 A; A=25-738. DR PDB; 6FXX; X-ray; 3.00 A; A=25-738. DR PDB; 6FXY; X-ray; 2.14 A; A=25-738. DR PDBsum; 6FXK; -. DR PDBsum; 6FXM; -. DR PDBsum; 6FXR; -. DR PDBsum; 6FXT; -. DR PDBsum; 6FXX; -. DR PDBsum; 6FXY; -. DR ProteinModelPortal; O60568; -. DR SMR; O60568; -. DR BioGrid; 114467; 63. DR CORUM; O60568; -. DR IntAct; O60568; 38. DR MINT; O60568; -. DR STRING; 9606.ENSP00000223127; -. DR DrugBank; DB00139; Succinic acid. DR DrugBank; DB00126; Vitamin C. DR MoonDB; O60568; Curated. DR MoonProt; O60568; -. DR GlyConnect; 1635; -. DR iPTMnet; O60568; -. DR PhosphoSitePlus; O60568; -. DR BioMuta; PLOD3; -. DR EPD; O60568; -. DR jPOST; O60568; -. DR MaxQB; O60568; -. DR PaxDb; O60568; -. DR PeptideAtlas; O60568; -. DR PRIDE; O60568; -. DR ProteomicsDB; 49474; -. DR Ensembl; ENST00000223127; ENSP00000223127; ENSG00000106397. DR GeneID; 8985; -. DR KEGG; hsa:8985; -. DR UCSC; uc003uyd.4; human. DR CTD; 8985; -. DR DisGeNET; 8985; -. DR EuPathDB; HostDB:ENSG00000106397.11; -. DR GeneCards; PLOD3; -. DR HGNC; HGNC:9083; PLOD3. DR HPA; HPA001236; -. DR MalaCards; PLOD3; -. DR MIM; 603066; gene. DR MIM; 612394; phenotype. DR neXtProt; NX_O60568; -. DR OpenTargets; ENSG00000106397; -. DR Orphanet; 300284; Connective tissue disorder due to lysyl hydroxylase-3 deficiency. DR PharmGKB; PA33413; -. DR eggNOG; KOG1971; Eukaryota. DR eggNOG; ENOG410Y4QU; LUCA. DR GeneTree; ENSGT00940000153705; -. DR HOGENOM; HOG000231099; -. DR HOVERGEN; HBG053618; -. DR InParanoid; O60568; -. DR KO; K13646; -. DR OMA; CIVSSPR; -. DR OrthoDB; 194164at2759; -. DR PhylomeDB; O60568; -. DR TreeFam; TF313826; -. DR BRENDA; 1.14.11.4; 2681. DR BRENDA; 2.4.1.50; 2681. DR BRENDA; 2.4.1.66; 2681. DR Reactome; R-HSA-1650814; Collagen biosynthesis and modifying enzymes. DR ChiTaRS; PLOD3; human. DR GeneWiki; PLOD3; -. DR GenomeRNAi; 8985; -. DR PRO; PR:O60568; -. DR Proteomes; UP000005640; Chromosome 7. DR Bgee; ENSG00000106397; Expressed in 220 organ(s), highest expression level in placenta. DR ExpressionAtlas; O60568; baseline and differential. DR Genevisible; O60568; HS. DR GO; GO:0062023; C:collagen-containing extracellular matrix; IEA:Ensembl. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:CAFA. DR GO; GO:0005788; C:endoplasmic reticulum lumen; IEA:UniProtKB-SubCell. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IDA:CAFA. DR GO; GO:0005791; C:rough endoplasmic reticulum; IEA:UniProtKB-SubCell. DR GO; GO:0005802; C:trans-Golgi network; IEA:Ensembl. DR GO; GO:0005506; F:iron ion binding; IEA:InterPro. DR GO; GO:0031418; F:L-ascorbic acid binding; IEA:UniProtKB-KW. DR GO; GO:0050211; F:procollagen galactosyltransferase activity; IMP:UniProtKB. DR GO; GO:0033823; F:procollagen glucosyltransferase activity; IMP:UniProtKB. DR GO; GO:0008475; F:procollagen-lysine 5-dioxygenase activity; IDA:CAFA. DR GO; GO:0070831; P:basement membrane assembly; IEA:Ensembl. DR GO; GO:0032870; P:cellular response to hormone stimulus; IEA:Ensembl. DR GO; GO:0030199; P:collagen fibril organization; IBA:GO_Central. DR GO; GO:0032963; P:collagen metabolic process; IBA:GO_Central. DR GO; GO:0001886; P:endothelial cell morphogenesis; IEA:Ensembl. DR GO; GO:0048730; P:epidermis morphogenesis; IEA:Ensembl. DR GO; GO:0046947; P:hydroxylysine biosynthetic process; IDA:CAFA. DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl. DR GO; GO:0060425; P:lung morphogenesis; IEA:Ensembl. DR GO; GO:0021915; P:neural tube development; IEA:Ensembl. DR GO; GO:0017185; P:peptidyl-lysine hydroxylation; IDA:CAFA. DR GO; GO:0008104; P:protein localization; IEA:Ensembl. DR GO; GO:0006493; P:protein O-linked glycosylation; IMP:CAFA. DR GO; GO:0042311; P:vasodilation; IEA:Ensembl. DR InterPro; IPR029044; Nucleotide-diphossugar_trans. DR InterPro; IPR005123; Oxoglu/Fe-dep_dioxygenase. DR InterPro; IPR006620; Pro_4_hyd_alph. DR InterPro; IPR001006; Procol_lys_dOase. DR Pfam; PF03171; 2OG-FeII_Oxy; 1. DR SMART; SM00702; P4Hc; 1. DR SUPFAM; SSF53448; SSF53448; 1. DR PROSITE; PS51471; FE2OG_OXY; 1. DR PROSITE; PS01325; LYS_HYDROXYLASE; 1. PE 1: Evidence at protein level; KW 3D-structure; Complete proteome; Dioxygenase; Disease mutation; KW Disulfide bond; Endoplasmic reticulum; Glycoprotein; KW Glycosyltransferase; Iron; Manganese; Membrane; Metal-binding; KW Multifunctional enzyme; Oxidoreductase; Polymorphism; KW Reference proteome; Secreted; Signal; Transferase; Vitamin C. FT SIGNAL 1 24 {ECO:0000255}. FT CHAIN 25 738 Multifunctional procollagen lysine FT hydroxylase and glycosyltransferase LH3. FT /FTId=PRO_0000024686. FT DOMAIN 647 738 Fe2OG dioxygenase. {ECO:0000255|PROSITE- FT ProRule:PRU00805}. FT REGION 25 290 Required for glycosyltransferase FT activity. {ECO:0000269|PubMed:18298658, FT ECO:0000269|PubMed:30089812}. FT REGION 44 46 UDP-sugar binding. {ECO:0000244|PDB:6FXY, FT ECO:0000269|PubMed:30089812}. FT REGION 112 114 UDP-sugar binding. {ECO:0000244|PDB:6FXY, FT ECO:0000269|PubMed:30089812}. FT REGION 256 259 UDP-sugar binding. {ECO:0000244|PDB:6FXY, FT ECO:0000269|PubMed:30089812}. FT REGION 295 520 Accessory region. FT {ECO:0000269|PubMed:30089812}. FT REGION 672 715 Important for dimerization. FT {ECO:0000269|PubMed:30089812}. FT METAL 112 112 Manganese. {ECO:0000244|PDB:6FXY, FT ECO:0000269|PubMed:30089812}. FT METAL 115 115 Manganese. {ECO:0000244|PDB:6FXY, FT ECO:0000269|PubMed:30089812}. FT METAL 253 253 Manganese. {ECO:0000244|PDB:6FXY, FT ECO:0000269|PubMed:30089812}. FT METAL 667 667 Iron. {ECO:0000244|PDB:6FXY, FT ECO:0000255|PROSITE-ProRule:PRU00805, FT ECO:0000269|PubMed:30089812}. FT METAL 669 669 Iron. {ECO:0000244|PDB:6FXY, FT ECO:0000255|PROSITE-ProRule:PRU00805, FT ECO:0000269|PubMed:30089812}. FT METAL 719 719 Iron. {ECO:0000244|PDB:6FXY, FT ECO:0000255|PROSITE-ProRule:PRU00805, FT ECO:0000269|PubMed:30089812}. FT BINDING 599 599 2-oxoglutarate. {ECO:0000244|PDB:6FXY, FT ECO:0000269|PubMed:30089812}. FT BINDING 656 656 2-oxoglutarate. {ECO:0000244|PDB:6FXY, FT ECO:0000269|PubMed:30089812}. FT BINDING 676 676 2-oxoglutarate. {ECO:0000244|PDB:6FXY, FT ECO:0000269|PubMed:30089812}. FT BINDING 729 729 2-oxoglutarate. {ECO:0000244|PDB:6FXY, FT ECO:0000269|PubMed:30089812}. FT CARBOHYD 63 63 N-linked (GlcNAc...) asparagine. FT {ECO:0000244|PDB:6FXY, FT ECO:0000269|PubMed:30089812}. FT CARBOHYD 548 548 N-linked (GlcNAc...) asparagine. FT {ECO:0000244|PDB:6FXY, FT ECO:0000269|PubMed:30089812}. FT DISULFID 279 282 {ECO:0000244|PDB:6FXY, FT ECO:0000269|PubMed:30089812}. FT DISULFID 379 385 {ECO:0000244|PDB:6FXY, FT ECO:0000269|PubMed:30089812}. FT DISULFID 563 698 {ECO:0000244|PDB:6FXY, FT ECO:0000269|PubMed:30089812}. FT VARIANT 151 151 A -> V (in dbSNP:rs35627324). FT /FTId=VAR_051708. FT VARIANT 223 223 N -> S (in LH3 deficiency; generates a FT new glycosylation site; decreases protein FT stability; strongly decreases lysyl FT hydroxylase activity and nearly abolishes FT glycosyltransferase activity; FT dbSNP:rs121434414). FT {ECO:0000269|PubMed:18834968, FT ECO:0000269|PubMed:30089812}. FT /FTId=VAR_054913. FT VARIANT 286 286 R -> W (in dbSNP:rs1134907). FT /FTId=VAR_012075. FT MUTAGEN 75 75 W->A: Decreased lysyl hydroxylase FT activity and loss of glycosyltransferase FT activity. {ECO:0000269|PubMed:30089812}. FT MUTAGEN 114 114 Y->A: Decreased lysyl hydroxylase and FT glycosyltransferase activity. FT {ECO:0000269|PubMed:30089812}. FT MUTAGEN 144 144 C->I: Strongly reduced FT glucosyltransferase activity. Strongly FT reduced galactosyltransferase activity. FT {ECO:0000269|PubMed:11896059, FT ECO:0000269|PubMed:12475640}. FT MUTAGEN 187 191 DDDDD->ADAAA: Loss of glucosyltransferase FT activity. Loss of galactosyltransferase FT activity. {ECO:0000269|PubMed:11896059, FT ECO:0000269|PubMed:12475640, FT ECO:0000269|PubMed:18298658}. FT MUTAGEN 187 189 DDD->ADA: Nearly abolishes FT glucosyltransferase activity. Nearly FT abolishes galactosyltransferase activity. FT {ECO:0000269|PubMed:11896059, FT ECO:0000269|PubMed:12475640}. FT MUTAGEN 208 208 L->I: Reduced glucosyltransferase FT activity. {ECO:0000269|PubMed:11896059}. FT MUTAGEN 669 669 D->A: Strongly decreased lysyl FT hydroxylase activity. No effect on FT glycosyltransferase activity. FT {ECO:0000269|PubMed:10934207, FT ECO:0000269|PubMed:18298658}. FT MUTAGEN 672 672 T->N: Loss of dimerization. Loss of lysyl FT hydroxylase activity and decreased FT glycosyltransferase activity. FT {ECO:0000269|PubMed:30089812}. FT MUTAGEN 714 714 R->N: Loss of dimerization. Loss of lysyl FT hydroxylase activity and no effect on FT glycosyltransferase activity. FT {ECO:0000269|PubMed:30089812}. FT MUTAGEN 715 715 L->D: No effect on dimerization, lysyl FT hydroxylase and glycosyltransferase FT activity. {ECO:0000269|PubMed:30089812}. FT MUTAGEN 715 715 L->R: Loss of lysyl hydroxylase activity FT and decreased glycosyltransferase FT activity. {ECO:0000269|PubMed:30089812}. FT HELIX 36 38 {ECO:0000244|PDB:6FXM}. FT STRAND 39 44 {ECO:0000244|PDB:6FXM}. FT HELIX 50 61 {ECO:0000244|PDB:6FXM}. FT STRAND 66 69 {ECO:0000244|PDB:6FXM}. FT STRAND 71 73 {ECO:0000244|PDB:6FXT}. FT TURN 80 82 {ECO:0000244|PDB:6FXR}. FT HELIX 87 97 {ECO:0000244|PDB:6FXM}. FT HELIX 98 100 {ECO:0000244|PDB:6FXM}. FT STRAND 107 111 {ECO:0000244|PDB:6FXM}. FT STRAND 116 118 {ECO:0000244|PDB:6FXM}. FT HELIX 122 132 {ECO:0000244|PDB:6FXM}. FT STRAND 135 142 {ECO:0000244|PDB:6FXM}. FT HELIX 149 152 {ECO:0000244|PDB:6FXM}. FT STRAND 158 160 {ECO:0000244|PDB:6FXM}. FT STRAND 163 172 {ECO:0000244|PDB:6FXM}. FT HELIX 173 180 {ECO:0000244|PDB:6FXM}. FT STRAND 187 189 {ECO:0000244|PDB:6FXK}. FT HELIX 191 199 {ECO:0000244|PDB:6FXM}. FT HELIX 202 207 {ECO:0000244|PDB:6FXM}. FT STRAND 210 213 {ECO:0000244|PDB:6FXM}. FT STRAND 217 221 {ECO:0000244|PDB:6FXM}. FT HELIX 226 228 {ECO:0000244|PDB:6FXM}. FT STRAND 229 233 {ECO:0000244|PDB:6FXM}. FT STRAND 238 242 {ECO:0000244|PDB:6FXM}. FT TURN 243 246 {ECO:0000244|PDB:6FXM}. FT STRAND 250 253 {ECO:0000244|PDB:6FXM}. FT HELIX 259 266 {ECO:0000244|PDB:6FXM}. FT TURN 267 272 {ECO:0000244|PDB:6FXM}. FT TURN 275 277 {ECO:0000244|PDB:6FXM}. FT STRAND 278 280 {ECO:0000244|PDB:6FXM}. FT HELIX 281 284 {ECO:0000244|PDB:6FXM}. FT STRAND 298 304 {ECO:0000244|PDB:6FXM}. FT HELIX 311 318 {ECO:0000244|PDB:6FXM}. FT STRAND 321 323 {ECO:0000244|PDB:6FXT}. FT HELIX 325 327 {ECO:0000244|PDB:6FXM}. FT STRAND 328 334 {ECO:0000244|PDB:6FXM}. FT HELIX 337 339 {ECO:0000244|PDB:6FXM}. FT HELIX 340 353 {ECO:0000244|PDB:6FXM}. FT STRAND 354 360 {ECO:0000244|PDB:6FXM}. FT HELIX 362 364 {ECO:0000244|PDB:6FXM}. FT HELIX 368 380 {ECO:0000244|PDB:6FXM}. FT STRAND 387 392 {ECO:0000244|PDB:6FXM}. FT STRAND 395 397 {ECO:0000244|PDB:6FXM}. FT HELIX 402 408 {ECO:0000244|PDB:6FXM}. FT STRAND 412 416 {ECO:0000244|PDB:6FXM}. FT STRAND 418 420 {ECO:0000244|PDB:6FXM}. FT STRAND 426 432 {ECO:0000244|PDB:6FXM}. FT STRAND 436 439 {ECO:0000244|PDB:6FXR}. FT HELIX 444 448 {ECO:0000244|PDB:6FXM}. FT STRAND 454 461 {ECO:0000244|PDB:6FXM}. FT STRAND 463 468 {ECO:0000244|PDB:6FXM}. FT HELIX 469 474 {ECO:0000244|PDB:6FXM}. FT STRAND 484 487 {ECO:0000244|PDB:6FXM}. FT HELIX 489 499 {ECO:0000244|PDB:6FXM}. FT STRAND 504 507 {ECO:0000244|PDB:6FXM}. FT STRAND 513 515 {ECO:0000244|PDB:6FXM}. FT STRAND 525 527 {ECO:0000244|PDB:6FXM}. FT HELIX 528 531 {ECO:0000244|PDB:6FXM}. FT TURN 533 535 {ECO:0000244|PDB:6FXM}. FT HELIX 537 544 {ECO:0000244|PDB:6FXM}. FT HELIX 549 554 {ECO:0000244|PDB:6FXM}. FT STRAND 560 563 {ECO:0000244|PDB:6FXM}. FT STRAND 566 570 {ECO:0000244|PDB:6FXM}. FT HELIX 574 587 {ECO:0000244|PDB:6FXM}. FT STRAND 599 601 {ECO:0000244|PDB:6FXR}. FT STRAND 610 613 {ECO:0000244|PDB:6FXM}. FT HELIX 614 617 {ECO:0000244|PDB:6FXM}. FT HELIX 620 629 {ECO:0000244|PDB:6FXM}. FT HELIX 631 638 {ECO:0000244|PDB:6FXM}. FT STRAND 648 656 {ECO:0000244|PDB:6FXM}. FT STRAND 658 660 {ECO:0000244|PDB:6FXM}. FT STRAND 664 678 {ECO:0000244|PDB:6FXM}. FT TURN 683 685 {ECO:0000244|PDB:6FXM}. FT STRAND 686 688 {ECO:0000244|PDB:6FXM}. FT STRAND 691 693 {ECO:0000244|PDB:6FXM}. FT HELIX 694 696 {ECO:0000244|PDB:6FXM}. FT STRAND 698 700 {ECO:0000244|PDB:6FXM}. FT STRAND 707 712 {ECO:0000244|PDB:6FXM}. FT STRAND 714 716 {ECO:0000244|PDB:6FXM}. FT STRAND 719 721 {ECO:0000244|PDB:6FXM}. FT STRAND 724 727 {ECO:0000244|PDB:6FXM}. FT STRAND 729 736 {ECO:0000244|PDB:6FXM}. 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 //