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 27-MAR-2024, entry version 204. 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; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC 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 of a RT 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 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 hydroxylase RT 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., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., 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., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA 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., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., 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., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA 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., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., 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 project: RT 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., Valtavaara M., RA 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 the RT collagen glucosyltransferase associated with the multifunctional lysyl RT 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 the RT human lysyl hydroxylase isoenzymes 1-3. The 30-kDa N-terminal fragment is RT 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; DOI=10.1016/s0945-053x(02)00071-9; RA Wang C., Luosujaervi H., Heikkinen J., Risteli M., Uitto L., 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., Myllylae R.; RT "The glycosyltransferase activities of lysyl hydroxylase 3 (LH3) in the RT 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 soluble RT 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., Buerckstuemmer T., RA 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., Wallis R., RA Myllylae R.; RT "Lysyl hydroxylase 3 modifies lysine residues to facilitate oligomerization RT 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., Ayoub D., RA 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] {ECO:0007744|PDB:6FXK, ECO:0007744|PDB:6FXM, ECO:0007744|PDB:6FXR, ECO:0007744|PDB:6FXT, ECO:0007744|PDB:6FXX, ECO:0007744|PDB:6FXY} RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 25-738 IN COMPLEXES WITH IRON; RP 2-OXOGLUTARATE; MANGANESE AND UDP, CATALYTIC ACTIVITY, FUNCTION, COFACTOR, RP SUBUNIT, DOMAIN, GLYCOSYLATION AT ASN-63 AND ASN-548, DISULFIDE BONDS, RP CHARACTERIZATION OF VARIANT BCARD SER-223, AND MUTAGENESIS OF TRP-75; RP TYR-114; THR-672; ARG-714 AND 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 hydroxylase RT and glycosyltransferase LH3."; RL Nat. Commun. 9:3163-3163(2018). RN [20] RP VARIANT BCARD SER-223, CHARACTERIZATION OF VARIANT BCARD SER-223, CATALYTIC RP 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 hydroxylase RT 3 gene."; RL Am. J. Hum. Genet. 83:495-503(2008). RN [21] RP VARIANT BCARD 452-ARG--PRO-738 DEL. RX PubMed=30237576; DOI=10.1038/s41436-018-0138-x; RA Maddirevula S., Alzahrani F., Al-Owain M., Al Muhaizea M.A., Kayyali H.R., RA AlHashem A., Rahbeeni Z., Al-Otaibi M., Alzaidan H.I., Balobaid A., RA El Khashab H.Y., Bubshait D.K., Faden M., Yamani S.A., Dabbagh O., RA Al-Mureikhi M., Jasser A.A., Alsaif H.S., Alluhaydan I., Seidahmed M.Z., RA Alabbasi B.H., Almogarri I., Kurdi W., Akleh H., Qari A., Al Tala S.M., RA Alhomaidi S., Kentab A.Y., Salih M.A., Chedrawi A., Alameer S., Tabarki B., RA Shamseldin H.E., Patel N., Ibrahim N., Abdulwahab F., Samira M., Goljan E., RA Abouelhoda M., Meyer B.F., Hashem M., Shaheen R., AlShahwan S., RA Alfadhel M., Ben-Omran T., Al-Qattan M.M., Monies D., Alkuraya F.S.; RT "Autozygome and high throughput confirmation of disease genes candidacy."; RL Genet. Med. 21:736-742(2019). CC -!- FUNCTION: Multifunctional enzyme that catalyzes a series of essential CC post-translational modifications on Lys residues in procollagen CC (PubMed:11956192, PubMed:12475640, PubMed:18298658, PubMed:30089812, CC PubMed:18834968). Plays a redundant role in catalyzing the formation of CC hydroxylysine residues in -Xaa-Lys-Gly- sequences in collagens CC (PubMed:9582318, PubMed:9724729, PubMed:11956192, PubMed:12475640, CC PubMed:18298658, PubMed:30089812, PubMed:18834968). Plays a redundant CC role in 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 essential CC role by catalyzing the subsequent transfer of glucose moieties, giving CC rise to 1,2-glucosylgalactosyl-5-hydroxylysine residues CC (PubMed:10934207, PubMed:11896059, PubMed:11956192, PubMed:12475640, CC PubMed:18298658, PubMed:30089812, PubMed:18834968). Catalyzes CC hydroxylation and glycosylation of Lys residues in the MBL1 collagen- CC like domain, giving rise to hydroxylysine and 1,2-glucosylgalactosyl-5- CC hydroxylysine residues (PubMed:25419660). Essential for normal CC biosynthesis and secretion of type IV collagens (PubMed:18834968) CC (Probable). Essential for normal formation of basement membranes (By CC similarity). {ECO:0000250|UniProtKB:Q9R0E1, CC ECO:0000269|PubMed:10934207, ECO:0000269|PubMed:11896059, CC ECO:0000269|PubMed:11956192, ECO:0000269|PubMed:12475640, CC ECO:0000269|PubMed:18298658, ECO:0000269|PubMed:18834968, CC ECO:0000269|PubMed:25419660, ECO:0000269|PubMed:30089812, CC ECO:0000269|PubMed:9582318, ECO:0000269|PubMed:9724729, ECO:0000305}. CC -!- CATALYTIC ACTIVITY: CC Reaction=2-oxoglutarate + L-lysyl-[collagen] + O2 = (5R)-5-hydroxy-L- CC lysyl-[collagen] + CO2 + succinate; Xref=Rhea:RHEA:16569, Rhea:RHEA- CC COMP:12751, Rhea:RHEA-COMP:12752, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:29969, CC ChEBI:CHEBI:30031, ChEBI:CHEBI:133442; EC=1.14.11.4; CC Evidence={ECO:0000269|PubMed:10934207, ECO:0000269|PubMed:11956192, CC ECO:0000269|PubMed:12475640, ECO:0000269|PubMed:18298658, CC ECO:0000269|PubMed:18834968, ECO:0000269|PubMed:30089812, CC ECO:0000269|PubMed:9582318, ECO:0000269|PubMed:9724729}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5R)-5-hydroxy-L-lysyl-[collagen] + UDP-alpha-D-galactose = CC (5R)-5-O-(beta-D-galactosyl)-5-hydroxy-L-lysyl-[collagen] + H(+) + CC UDP; Xref=Rhea:RHEA:12637, Rhea:RHEA-COMP:12752, Rhea:RHEA- CC COMP:12753, ChEBI:CHEBI:15378, ChEBI:CHEBI:58223, ChEBI:CHEBI:66914, CC ChEBI:CHEBI:133442, ChEBI:CHEBI:133443; EC=2.4.1.50; CC Evidence={ECO:0000269|PubMed:12475640, ECO:0000269|PubMed:18298658, CC ECO:0000269|PubMed:18834968, ECO:0000269|PubMed:30089812}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5R)-5-O-(beta-D-galactosyl)-5-hydroxy-L-lysyl-[collagen] + CC UDP-alpha-D-glucose = (5R)-5-O-[alpha-D-glucosyl-(1->2)-beta-D- CC galactosyl]-5-hydroxy-L-lysyl-[collagen] + H(+) + UDP; CC Xref=Rhea:RHEA:12576, Rhea:RHEA-COMP:12753, Rhea:RHEA-COMP:12754, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:58223, ChEBI:CHEBI:58885, CC ChEBI:CHEBI:133443, ChEBI:CHEBI:133452; EC=2.4.1.66; CC Evidence={ECO:0000269|PubMed:10934207, ECO:0000269|PubMed:11896059, CC ECO:0000269|PubMed:11956192, ECO:0000269|PubMed:12475640, CC ECO:0000269|PubMed:18298658, ECO:0000269|PubMed:18834968, CC ECO:0000269|PubMed:30089812}; CC -!- COFACTOR: CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033; CC Evidence={ECO:0000269|PubMed:30089812, ECO:0000269|PubMed:9724729}; CC -!- COFACTOR: CC Name=L-ascorbate; Xref=ChEBI:CHEBI:38290; CC Evidence={ECO:0000269|PubMed:30089812, 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 inhibited CC 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 O60568; P38432: COIL; NbExp=3; IntAct=EBI-741582, EBI-945751; CC O60568; Q9UMD9: COL17A1; NbExp=3; IntAct=EBI-741582, EBI-2528742; CC O60568; Q6Q6R5-3: CRIP3; NbExp=3; IntAct=EBI-741582, EBI-12925520; CC O60568; Q5JST6: EFHC2; NbExp=12; IntAct=EBI-741582, EBI-2349927; CC O60568; A2ABF9: EHMT2; NbExp=3; IntAct=EBI-741582, EBI-10174566; CC O60568; Q96KQ7: EHMT2; NbExp=8; IntAct=EBI-741582, EBI-744366; CC O60568; Q9UHH9: IP6K2; NbExp=3; IntAct=EBI-741582, EBI-747509; CC O60568; Q7L273: KCTD9; NbExp=3; IntAct=EBI-741582, EBI-4397613; CC O60568; O15037: KHNYN; NbExp=3; IntAct=EBI-741582, EBI-6148525; CC O60568; Q96JM7-2: L3MBTL3; NbExp=3; IntAct=EBI-741582, EBI-11985629; CC O60568; Q15742: NAB2; NbExp=3; IntAct=EBI-741582, EBI-8641936; CC O60568; Q96QF0: RAB3IP; NbExp=4; IntAct=EBI-741582, EBI-747844; CC O60568; Q96QF0-2: RAB3IP; NbExp=3; IntAct=EBI-741582, EBI-747865; CC O60568; Q53GL6: RALY; NbExp=3; IntAct=EBI-741582, EBI-9512693; CC O60568; Q9BQY4: RHOXF2; NbExp=2; IntAct=EBI-741582, EBI-372094; CC O60568; O60504: SORBS3; NbExp=3; IntAct=EBI-741582, EBI-741237; CC O60568; Q6ZNG0: ZNF620; NbExp=3; IntAct=EBI-741582, EBI-4395669; 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 {ECO:0000269|PubMed:21465473}. CC Secreted, extracellular space {ECO:0000250|UniProtKB:Q9R0E1}. Note=The CC majority of the secreted protein is associated with the extracellular CC matrix. {ECO:0000250|UniProtKB:Q9R0E1}. CC -!- TISSUE SPECIFICITY: Ubiquitous (PubMed:9724729). Detected in heart, CC placenta and pancreas and at lower levels in lung, liver and skeletal CC muscle (PubMed:9582318, PubMed:9724729). {ECO:0000269|PubMed:9582318, CC ECO:0000269|PubMed:9724729}. CC -!- DOMAIN: The N-terminal domain mediates glycosyltransferase activity. CC {ECO:0000269|PubMed:30089812}. CC -!- DOMAIN: The C-terminal domain that mediates lysyl hydroxylase activity CC is also important for homodimerization. {ECO:0000269|PubMed:30089812}. CC -!- DISEASE: Bone fragility with contractures, arterial rupture, and CC deafness (BCARD) [MIM:612394]: An autosomal recessive connective tissue CC disorder, secondary to lysyl hydroxylase 3 deficiency. It is CC characterized by congenital malformations severely affecting multiple CC tissues and organs. Clinical features include growth retardation, CC craniofacial dysmorphism, popliteal and cerebral aneurysm, cerebral CC arterial hemorrhage, skin blistering and easy bruisability, and CC osteopenia. {ECO:0000269|PubMed:18834968, ECO:0000269|PubMed:30089812, CC ECO:0000269|PubMed:30237576}. Note=The disease is caused by variants CC affecting the gene 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 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 PDB; 6TE3; X-ray; 2.30 A; A=25-738. DR PDB; 6TEC; X-ray; 2.40 A; A=25-738. DR PDB; 6TES; X-ray; 2.20 A; A=25-738. DR PDB; 6TEU; X-ray; 3.00 A; A=25-738. DR PDB; 6TEX; X-ray; 2.30 A; A=25-738. DR PDB; 6TEZ; X-ray; 2.70 A; A=25-738. DR PDB; 6WFV; X-ray; 1.70 A; A=32-266. DR PDB; 8ONE; X-ray; 2.30 A; A=25-738. DR PDBsum; 6FXK; -. DR PDBsum; 6FXM; -. DR PDBsum; 6FXR; -. DR PDBsum; 6FXT; -. DR PDBsum; 6FXX; -. DR PDBsum; 6FXY; -. DR PDBsum; 6TE3; -. DR PDBsum; 6TEC; -. DR PDBsum; 6TES; -. DR PDBsum; 6TEU; -. DR PDBsum; 6TEX; -. DR PDBsum; 6TEZ; -. DR PDBsum; 6WFV; -. DR PDBsum; 8ONE; -. DR AlphaFoldDB; O60568; -. DR SASBDB; O60568; -. DR SMR; O60568; -. DR BioGRID; 114467; 163. DR CORUM; O60568; -. DR IntAct; O60568; 48. DR MINT; O60568; -. DR STRING; 9606.ENSP00000223127; -. DR DrugBank; DB00126; Ascorbic acid. DR DrugBank; DB00139; Succinic acid. DR MoonDB; O60568; Curated. DR MoonProt; O60568; -. DR GlyConnect; 1635; 9 N-Linked glycans (2 sites). DR GlyCosmos; O60568; 2 sites, 10 glycans. DR GlyGen; O60568; 6 sites, 12 N-linked glycans (2 sites), 2 O-linked glycans (3 sites). DR iPTMnet; O60568; -. DR PhosphoSitePlus; O60568; -. DR BioMuta; PLOD3; -. DR CPTAC; CPTAC-113; -. DR CPTAC; CPTAC-114; -. DR CPTAC; CPTAC-1501; -. DR EPD; O60568; -. DR jPOST; O60568; -. DR MassIVE; O60568; -. DR MaxQB; O60568; -. DR PaxDb; 9606-ENSP00000223127; -. DR PeptideAtlas; O60568; -. DR ProteomicsDB; 49474; -. DR Pumba; O60568; -. DR Antibodypedia; 16729; 209 antibodies from 26 providers. DR DNASU; 8985; -. DR Ensembl; ENST00000223127.8; ENSP00000223127.3; ENSG00000106397.12. DR GeneID; 8985; -. DR KEGG; hsa:8985; -. DR MANE-Select; ENST00000223127.8; ENSP00000223127.3; NM_001084.5; NP_001075.1. DR UCSC; uc003uyd.4; human. DR AGR; HGNC:9083; -. DR CTD; 8985; -. DR DisGeNET; 8985; -. DR GeneCards; PLOD3; -. DR HGNC; HGNC:9083; PLOD3. DR HPA; ENSG00000106397; Low tissue specificity. 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 VEuPathDB; HostDB:ENSG00000106397; -. DR eggNOG; KOG1971; Eukaryota. DR GeneTree; ENSGT01030000234558; -. DR HOGENOM; CLU_022320_1_0_1; -. DR InParanoid; O60568; -. DR OMA; ETMEDCG; -. DR OrthoDB; 5386101at2759; -. 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 PathwayCommons; O60568; -. DR Reactome; R-HSA-1650814; Collagen biosynthesis and modifying enzymes. DR SignaLink; O60568; -. DR BioGRID-ORCS; 8985; 15 hits in 1163 CRISPR screens. DR ChiTaRS; PLOD3; human. DR GeneWiki; PLOD3; -. DR GenomeRNAi; 8985; -. DR Pharos; O60568; Tbio. DR PRO; PR:O60568; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; O60568; Protein. DR Bgee; ENSG00000106397; Expressed in stromal cell of endometrium and 191 other cell types or tissues. DR ExpressionAtlas; O60568; baseline and differential. 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; EXP:DisProt. DR GO; GO:0031418; F:L-ascorbic acid binding; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; EXP:DisProt. 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:0036094; F:small molecule binding; EXP:DisProt. DR GO; GO:0070831; P:basement membrane assembly; IEA:Ensembl. DR GO; GO:0030199; P:collagen fibril organization; TAS:Reactome. DR GO; GO:0032963; P:collagen metabolic process; IEA:Ensembl. 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; IEA:Ensembl. 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 CDD; cd23002; GT_LH3; 1. DR Gene3D; 2.60.120.620; q2cbj1_9rhob like domain; 1. DR InterPro; IPR044861; IPNS-like_FE2OG_OXY. 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 PANTHER; PTHR10730:SF7; MULTIFUNCTIONAL PROCOLLAGEN LYSINE HYDROXYLASE AND GLYCOSYLTRANSFERASE LH3; 1. DR PANTHER; PTHR10730; PROCOLLAGEN-LYSINE,2-OXOGLUTARATE 5-DIOXYGENASE/GLYCOSYLTRANSFERASE 25 FAMILY MEMBER; 1. DR Pfam; PF03171; 2OG-FeII_Oxy; 1. DR SMART; SM00702; P4Hc; 1. DR SUPFAM; SSF53448; Nucleotide-diphospho-sugar transferases; 1. DR PROSITE; PS51471; FE2OG_OXY; 1. DR PROSITE; PS01325; LYS_HYDROXYLASE; 1. DR Genevisible; O60568; HS. PE 1: Evidence at protein level; KW 3D-structure; Dioxygenase; Disease variant; Disulfide bond; KW Endoplasmic reticulum; Glycoprotein; Glycosyltransferase; Iron; Manganese; KW Membrane; Metal-binding; Multifunctional enzyme; Oxidoreductase; KW Reference proteome; Secreted; Signal; Transferase; Vitamin C. FT SIGNAL 1..24 FT /evidence="ECO:0000255" FT CHAIN 25..738 FT /note="Multifunctional procollagen lysine hydroxylase and FT glycosyltransferase LH3" FT /id="PRO_0000024686" FT DOMAIN 647..738 FT /note="Fe2OG dioxygenase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805" FT REGION 25..290 FT /note="Required for glycosyltransferase activity" FT /evidence="ECO:0000269|PubMed:18298658, FT ECO:0000269|PubMed:30089812" FT REGION 295..520 FT /note="Accessory region" FT /evidence="ECO:0000269|PubMed:30089812" FT REGION 672..715 FT /note="Important for dimerization" FT /evidence="ECO:0000269|PubMed:30089812" FT BINDING 44..46 FT /ligand="UDP" FT /ligand_id="ChEBI:CHEBI:58223" FT /evidence="ECO:0000269|PubMed:30089812, FT ECO:0007744|PDB:6FXY" FT BINDING 112..114 FT /ligand="UDP" FT /ligand_id="ChEBI:CHEBI:58223" FT /evidence="ECO:0000269|PubMed:30089812, FT ECO:0007744|PDB:6FXY" FT BINDING 112 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /evidence="ECO:0000269|PubMed:30089812, FT ECO:0007744|PDB:6FXY" FT BINDING 115 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /evidence="ECO:0000269|PubMed:30089812, FT ECO:0007744|PDB:6FXY" FT BINDING 253 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /evidence="ECO:0000269|PubMed:30089812, FT ECO:0007744|PDB:6FXY" FT BINDING 256..259 FT /ligand="UDP" FT /ligand_id="ChEBI:CHEBI:58223" FT /evidence="ECO:0000269|PubMed:30089812, FT ECO:0007744|PDB:6FXY" FT BINDING 599 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000269|PubMed:30089812, FT ECO:0007744|PDB:6FXY" FT BINDING 656 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000269|PubMed:30089812, FT ECO:0007744|PDB:6FXY" FT BINDING 667 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805, FT ECO:0000269|PubMed:30089812, ECO:0007744|PDB:6FXY" FT BINDING 669 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805, FT ECO:0000269|PubMed:30089812, ECO:0007744|PDB:6FXY" FT BINDING 676 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000269|PubMed:30089812, FT ECO:0007744|PDB:6FXY" FT BINDING 719 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805, FT ECO:0000269|PubMed:30089812, ECO:0007744|PDB:6FXY" FT BINDING 729 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000269|PubMed:30089812, FT ECO:0007744|PDB:6FXY" FT CARBOHYD 63 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:30089812, FT ECO:0007744|PDB:6FXY" FT CARBOHYD 548 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:30089812, FT ECO:0007744|PDB:6FXY" FT DISULFID 279..282 FT /evidence="ECO:0000269|PubMed:30089812, FT ECO:0007744|PDB:6FXY" FT DISULFID 379..385 FT /evidence="ECO:0000269|PubMed:30089812, FT ECO:0007744|PDB:6FXY" FT DISULFID 563..698 FT /evidence="ECO:0000269|PubMed:30089812, FT ECO:0007744|PDB:6FXY" FT VARIANT 151 FT /note="A -> V (in dbSNP:rs35627324)" FT /id="VAR_051708" FT VARIANT 223 FT /note="N -> S (in BCARD; generates a new glycosylation FT site; decreases protein stability; strongly decreases lysyl FT hydroxylase activity and nearly abolishes FT glycosyltransferase activity; dbSNP:rs121434414)" FT /evidence="ECO:0000269|PubMed:18834968, FT ECO:0000269|PubMed:30089812" FT /id="VAR_054913" FT VARIANT 286 FT /note="R -> W (in dbSNP:rs1134907)" FT /id="VAR_012075" FT VARIANT 452..738 FT /note="Missing (in BCARD; uncertain significance)" FT /evidence="ECO:0000269|PubMed:30237576" FT /id="VAR_082150" FT MUTAGEN 75 FT /note="W->A: Decreased lysyl hydroxylase activity and loss FT of glycosyltransferase activity." FT /evidence="ECO:0000269|PubMed:30089812" FT MUTAGEN 114 FT /note="Y->A: Decreased lysyl hydroxylase and FT glycosyltransferase activity." FT /evidence="ECO:0000269|PubMed:30089812" FT MUTAGEN 144 FT /note="C->I: Strongly reduced glucosyltransferase activity. FT Strongly reduced galactosyltransferase activity." FT /evidence="ECO:0000269|PubMed:11896059, FT ECO:0000269|PubMed:12475640" FT MUTAGEN 187..191 FT /note="DDDDD->ADAAA: Loss of glucosyltransferase activity. FT Loss of galactosyltransferase activity." FT /evidence="ECO:0000269|PubMed:11896059, FT ECO:0000269|PubMed:12475640, ECO:0000269|PubMed:18298658" FT MUTAGEN 187..189 FT /note="DDD->ADA: Nearly abolishes glucosyltransferase FT activity. Nearly abolishes galactosyltransferase activity." FT /evidence="ECO:0000269|PubMed:11896059, FT ECO:0000269|PubMed:12475640" FT MUTAGEN 208 FT /note="L->I: Reduced glucosyltransferase activity." FT /evidence="ECO:0000269|PubMed:11896059" FT MUTAGEN 669 FT /note="D->A: Strongly decreased lysyl hydroxylase activity. FT No effect on glycosyltransferase activity." FT /evidence="ECO:0000269|PubMed:10934207, FT ECO:0000269|PubMed:18298658" FT MUTAGEN 672 FT /note="T->N: Loss of dimerization. Loss of lysyl FT hydroxylase activity and decreased glycosyltransferase FT activity." FT /evidence="ECO:0000269|PubMed:30089812" FT MUTAGEN 714 FT /note="R->N: Loss of dimerization. Loss of lysyl FT hydroxylase activity and no effect on glycosyltransferase FT activity." FT /evidence="ECO:0000269|PubMed:30089812" FT MUTAGEN 715 FT /note="L->D: No effect on dimerization, lysyl hydroxylase FT and glycosyltransferase activity." FT /evidence="ECO:0000269|PubMed:30089812" FT MUTAGEN 715 FT /note="L->R: Loss of lysyl hydroxylase activity and FT decreased glycosyltransferase activity." FT /evidence="ECO:0000269|PubMed:30089812" FT HELIX 36..38 FT /evidence="ECO:0007829|PDB:6WFV" FT STRAND 39..44 FT /evidence="ECO:0007829|PDB:6WFV" FT HELIX 50..61 FT /evidence="ECO:0007829|PDB:6WFV" FT STRAND 66..69 FT /evidence="ECO:0007829|PDB:6WFV" FT STRAND 71..73 FT /evidence="ECO:0007829|PDB:8ONE" FT TURN 80..82 FT /evidence="ECO:0007829|PDB:6FXR" FT HELIX 87..97 FT /evidence="ECO:0007829|PDB:6WFV" FT HELIX 98..100 FT /evidence="ECO:0007829|PDB:6WFV" FT STRAND 107..113 FT /evidence="ECO:0007829|PDB:6WFV" FT STRAND 116..118 FT /evidence="ECO:0007829|PDB:6WFV" FT HELIX 122..132 FT /evidence="ECO:0007829|PDB:6WFV" FT STRAND 135..143 FT /evidence="ECO:0007829|PDB:6WFV" FT HELIX 148..153 FT /evidence="ECO:0007829|PDB:6WFV" FT STRAND 158..160 FT /evidence="ECO:0007829|PDB:6FXM" FT STRAND 163..172 FT /evidence="ECO:0007829|PDB:6WFV" FT HELIX 173..180 FT /evidence="ECO:0007829|PDB:6WFV" FT STRAND 187..189 FT /evidence="ECO:0007829|PDB:6FXK" FT HELIX 191..199 FT /evidence="ECO:0007829|PDB:6WFV" FT HELIX 202..208 FT /evidence="ECO:0007829|PDB:6WFV" FT STRAND 210..212 FT /evidence="ECO:0007829|PDB:6WFV" FT STRAND 217..221 FT /evidence="ECO:0007829|PDB:6WFV" FT TURN 223..225 FT /evidence="ECO:0007829|PDB:6WFV" FT HELIX 226..228 FT /evidence="ECO:0007829|PDB:6WFV" FT STRAND 229..234 FT /evidence="ECO:0007829|PDB:6WFV" FT STRAND 237..242 FT /evidence="ECO:0007829|PDB:6WFV" FT TURN 243..246 FT /evidence="ECO:0007829|PDB:6WFV" FT STRAND 250..253 FT /evidence="ECO:0007829|PDB:6WFV" FT HELIX 256..264 FT /evidence="ECO:0007829|PDB:6WFV" FT TURN 267..272 FT /evidence="ECO:0007829|PDB:6FXM" FT TURN 275..277 FT /evidence="ECO:0007829|PDB:6FXM" FT STRAND 278..280 FT /evidence="ECO:0007829|PDB:6FXM" FT HELIX 281..284 FT /evidence="ECO:0007829|PDB:6FXM" FT STRAND 291..293 FT /evidence="ECO:0007829|PDB:6TEU" FT STRAND 298..304 FT /evidence="ECO:0007829|PDB:6FXM" FT HELIX 311..318 FT /evidence="ECO:0007829|PDB:6FXM" FT STRAND 321..323 FT /evidence="ECO:0007829|PDB:8ONE" FT HELIX 325..327 FT /evidence="ECO:0007829|PDB:6FXM" FT STRAND 328..334 FT /evidence="ECO:0007829|PDB:6FXM" FT HELIX 337..339 FT /evidence="ECO:0007829|PDB:6FXM" FT HELIX 340..353 FT /evidence="ECO:0007829|PDB:6FXM" FT STRAND 354..360 FT /evidence="ECO:0007829|PDB:6FXM" FT HELIX 362..364 FT /evidence="ECO:0007829|PDB:6FXM" FT HELIX 368..380 FT /evidence="ECO:0007829|PDB:6FXM" FT STRAND 387..392 FT /evidence="ECO:0007829|PDB:6FXM" FT STRAND 395..397 FT /evidence="ECO:0007829|PDB:6FXM" FT HELIX 402..408 FT /evidence="ECO:0007829|PDB:6FXM" FT STRAND 412..416 FT /evidence="ECO:0007829|PDB:6FXM" FT STRAND 418..420 FT /evidence="ECO:0007829|PDB:6FXM" FT STRAND 426..432 FT /evidence="ECO:0007829|PDB:6FXM" FT STRAND 436..439 FT /evidence="ECO:0007829|PDB:6FXR" FT HELIX 444..448 FT /evidence="ECO:0007829|PDB:6FXM" FT STRAND 454..461 FT /evidence="ECO:0007829|PDB:6FXM" FT STRAND 463..468 FT /evidence="ECO:0007829|PDB:6FXM" FT HELIX 469..474 FT /evidence="ECO:0007829|PDB:6FXM" FT STRAND 484..487 FT /evidence="ECO:0007829|PDB:6FXM" FT HELIX 489..499 FT /evidence="ECO:0007829|PDB:6FXM" FT STRAND 504..507 FT /evidence="ECO:0007829|PDB:6FXM" FT STRAND 513..515 FT /evidence="ECO:0007829|PDB:6FXM" FT STRAND 525..527 FT /evidence="ECO:0007829|PDB:6FXM" FT HELIX 528..531 FT /evidence="ECO:0007829|PDB:6FXM" FT TURN 533..535 FT /evidence="ECO:0007829|PDB:6FXM" FT HELIX 537..544 FT /evidence="ECO:0007829|PDB:6FXM" FT HELIX 549..554 FT /evidence="ECO:0007829|PDB:6FXM" FT STRAND 560..563 FT /evidence="ECO:0007829|PDB:6FXM" FT STRAND 566..570 FT /evidence="ECO:0007829|PDB:6FXM" FT HELIX 574..587 FT /evidence="ECO:0007829|PDB:6FXM" FT STRAND 599..601 FT /evidence="ECO:0007829|PDB:6FXR" FT STRAND 602..604 FT /evidence="ECO:0007829|PDB:6TES" FT STRAND 610..613 FT /evidence="ECO:0007829|PDB:6FXM" FT HELIX 614..617 FT /evidence="ECO:0007829|PDB:6FXM" FT HELIX 620..629 FT /evidence="ECO:0007829|PDB:6FXM" FT HELIX 631..638 FT /evidence="ECO:0007829|PDB:6FXM" FT STRAND 648..656 FT /evidence="ECO:0007829|PDB:6FXM" FT STRAND 658..660 FT /evidence="ECO:0007829|PDB:6FXM" FT STRAND 664..678 FT /evidence="ECO:0007829|PDB:6FXM" FT TURN 683..685 FT /evidence="ECO:0007829|PDB:6FXM" FT STRAND 686..688 FT /evidence="ECO:0007829|PDB:6FXM" FT STRAND 691..693 FT /evidence="ECO:0007829|PDB:6FXM" FT HELIX 694..696 FT /evidence="ECO:0007829|PDB:6FXM" FT STRAND 698..700 FT /evidence="ECO:0007829|PDB:6FXM" FT STRAND 707..712 FT /evidence="ECO:0007829|PDB:6FXM" FT STRAND 714..716 FT /evidence="ECO:0007829|PDB:6FXM" FT STRAND 719..721 FT /evidence="ECO:0007829|PDB:6FXM" FT STRAND 724..727 FT /evidence="ECO:0007829|PDB:6FXM" FT STRAND 729..736 FT /evidence="ECO:0007829|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 //