PLOD3_HUMAN
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 03-AUG-2022, entry version 195.
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 LH3 DEFICIENCY SER-223, AND MUTAGENESIS OF
RP TRP-75; 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 LH3 DEFICIENCY SER-223, CHARACTERIZATION OF VARIANT LH3 DEFICIENCY
RP 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 hydroxylase
RT 3 gene.";
RL Am. J. Hum. Genet. 83:495-503(2008).
RN [21]
RP VARIANT LH3 DEFICIENCY 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: Lysyl hydroxylase 3 deficiency (LH3 deficiency) [MIM:612394]:
CC Connective tissue disorder. The syndrome is characterized by congenital
CC malformations severely affecting many tissues and organs and revealing
CC features of several collagen disorders, most of them involving COL2A1
CC (type II collagen). The findings suggest that the failure of lysyl
CC hydroxylation and hydroxylysyl carbohydrate addition, which affects
CC many collagens, is the molecular basis of this syndrome.
CC {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.
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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 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 AlphaFoldDB; O60568; -.
DR SASBDB; O60568; -.
DR SMR; O60568; -.
DR BioGRID; 114467; 150.
DR CORUM; O60568; -.
DR IntAct; O60568; 47.
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 GlyGen; O60568; 3 sites, 10 N-linked glycans (2 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; O60568; -.
DR PeptideAtlas; O60568; -.
DR PRIDE; O60568; -.
DR ProteomicsDB; 49474; -.
DR Antibodypedia; 16729; 190 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 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; NLFPGYH; -.
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 PathwayCommons; O60568; -.
DR Reactome; R-HSA-1650814; Collagen biosynthesis and modifying enzymes.
DR SignaLink; O60568; -.
DR BioGRID-ORCS; 8985; 15 hits in 1083 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 189 other tissues.
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: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 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 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; 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 LH3 deficiency; generates a new
FT glycosylation site; decreases protein stability; strongly
FT decreases lysyl 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 LH3 deficiency; unknown pathological
FT 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:6FXT"
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:6FXT"
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
