ID AOAH_HUMAN Reviewed; 575 AA. AC P28039; A4D1Y5; B7Z490; Q53F13; DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1992, sequence version 1. DT 02-SEP-2026, entry version 196. DE RecName: Full=Acyloxyacyl hydrolase {ECO:0000303|PubMed:1883828}; DE EC=3.1.1.77 {ECO:0000269|PubMed:1883828, ECO:0000269|PubMed:29343645, ECO:0000269|PubMed:8089145}; DE Contains: DE RecName: Full=Acyloxyacyl hydrolase small subunit {ECO:0000303|PubMed:1883828}; DE Contains: DE RecName: Full=Acyloxyacyl hydrolase large subunit {ECO:0000303|PubMed:1883828}; DE Flags: Precursor; GN Name=AOAH {ECO:0000303|PubMed:1883828}; 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] (ISOFORM 1), PROTEIN SEQUENCE OF 35-49 AND RP 157-185, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, PROTEOLYTIC CLEAVAGE, AND RP SUBCELLULAR LOCATION. RX PubMed=1883828; DOI=10.1021/bi00098a020; RA Hagen F.S., Grant F.J., Kuijper J.L., Slaughter C.A., Moomaw C.R., Orth K., RA O'Hara P.J., Munford R.S.; RT "Expression and characterization of recombinant human acyloxyacyl RT hydrolase, a leukocyte enzyme that deacylates bacterial RT lipopolysaccharides."; RL Biochemistry 30:8415-8423(1991). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Umbilical cord blood; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Synovial cell; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [4] 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ASN-28. RX PubMed=12690205; DOI=10.1126/science.1083423; RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D., RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., RA Adams M.D., Tsui L.-C.; RT "Human chromosome 7: DNA sequence and biology."; RL Science 300:767-772(2003). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ASN-28. 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 [8] RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, PROTEOLYTIC CLEAVAGE, SUBCELLULAR RP LOCATION, SIGNAL SEQUENCE CLEAVAGE SITE, GLYCOSYLATION AT ASN-59, AND RP MUTAGENESIS OF THR-61; SER-263; GLY-372 AND PRO-419. RX PubMed=8089145; DOI=10.1016/s0021-9258(17)31577-6; RA Staab J.F., Ginkel D.L., Rosenberg G.B., Munford R.S.; RT "A saposin-like domain influences the intracellular localization, RT stability, and catalytic activity of human acyloxyacyl hydrolase."; RL J. Biol. Chem. 269:23736-23742(1994). RN [9] {ECO:0007744|PDB:5W78, ECO:0007744|PDB:5W7C} RP X-RAY CRYSTALLOGRAPHY (2.23 ANGSTROMS) OF 24-152 AND 153-575 OF MUTANT RP ALA-263 IN COMPLEXES WITH CALCIUM; BACTERIAL LIPOPOLYSACCHARIDE CLEAVAGE RP PRODUCTS, FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, MUTAGENESIS OF RP LYS-173; SER-263; ARG-345 AND LYS-379, SUBUNIT, GLYCOSYLATION AT ASN-59; RP ASN-207; ASN-409 AND ASN-466, DISULFIDE BONDS, PROTEOLYTIC CLEAVAGE, AND RP ACTIVITY REGULATION. RX PubMed=29343645; DOI=10.1073/pnas.1719834115; RA Gorelik A., Illes K., Nagar B.; RT "Crystal structure of the mammalian lipopolysaccharide detoxifier."; RL Proc. Natl. Acad. Sci. U.S.A. 115:E896-E905(2018). CC -!- FUNCTION: Removes the secondary (acyloxyacyl-linked) fatty acyl chains CC from the lipid A region of bacterial lipopolysaccharides CC (PubMed:1883828, PubMed:29343645, PubMed:8089145). By breaking down CC LPS, terminates the host response to bacterial infection and prevents CC prolonged and damaging inflammatory responses (By similarity). In CC peritoneal macrophages, seems to be important for recovery from a state CC of immune tolerance following infection by Gram-negative bacteria (By CC similarity). {ECO:0000250|UniProtKB:O35298, ECO:0000269|PubMed:1883828, CC ECO:0000269|PubMed:29343645, ECO:0000269|PubMed:8089145}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a 3-(acyloxy)acyl derivative of bacterial toxin + H2O = a 3- CC hydroxyacyl derivative of bacterial toxin + a fatty acid + H(+); CC Xref=Rhea:RHEA:12032, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:28868, ChEBI:CHEBI:136853, ChEBI:CHEBI:140675; CC EC=3.1.1.77; Evidence={ECO:0000269|PubMed:1883828, CC ECO:0000269|PubMed:29343645, ECO:0000269|PubMed:8089145}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Evidence={ECO:0000269|PubMed:29343645}; CC Note=Binds 3 Ca(2+) ions per subunit. The calcium ions probably have a CC structural role. {ECO:0000269|PubMed:29343645}; CC -!- ACTIVITY REGULATION: Inhibited by EDTA. {ECO:0000269|PubMed:29343645}. CC -!- SUBUNIT: Heterodimer of the large and small subunits; disulfide-linked. CC {ECO:0000269|PubMed:1883828, ECO:0000269|PubMed:29343645, CC ECO:0000269|PubMed:8089145}. CC -!- INTERACTION: CC P28039; Q15700: DLG2; NbExp=3; IntAct=EBI-1222067, EBI-80426; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:8089145, CC ECO:0000305|PubMed:1883828}. Cytoplasmic vesicle CC {ECO:0000269|PubMed:8089145}. Note=Detected in urine. CC {ECO:0000250|UniProtKB:O35298}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P28039-1; Sequence=Displayed; CC Name=2; CC IsoId=P28039-2; Sequence=VSP_042571; CC -!- PTM: Cleaved into a large and a small subunit. CC {ECO:0000269|PubMed:1883828, ECO:0000269|PubMed:29343645, CC ECO:0000269|PubMed:8089145}. CC -!- PTM: The small subunit is N-glycosylated. {ECO:0000269|PubMed:8089145}. 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; M62840; AAA35506.1; -; mRNA. DR EMBL; AK297016; BAH12476.1; -; mRNA. DR EMBL; AK223476; BAD97196.1; -; mRNA. DR EMBL; AC083876; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC087069; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH236951; EAL23977.1; -; Genomic_DNA. DR EMBL; CH471073; EAW94073.1; -; Genomic_DNA. DR EMBL; BC025698; AAH25698.1; -; mRNA. DR CCDS; CCDS5448.1; -. [P28039-1] DR CCDS; CCDS55102.1; -. [P28039-2] DR PIR; A40292; A40292. DR RefSeq; NP_001170977.1; NM_001177506.2. DR RefSeq; NP_001170978.1; NM_001177507.2. [P28039-2] DR RefSeq; NP_001628.1; NM_001637.4. [P28039-1] DR PDB; 5W78; X-ray; 2.27 A; A=24-152, B=153-575. DR PDB; 5W7C; X-ray; 2.23 A; A/B=24-152, C/D=153-575. DR AlphaFoldDB; P28039; -. DR SMR; P28039; -. DR BioGRID; 106810; 2. DR FunCoup; P28039; 65. DR IntAct; P28039; 2. DR STRING; 9606.ENSP00000479664; -. DR GuidetoPHARMACOLOGY; 2873; -. DR GlyCosmos; P28039; 4 sites, No reported glycans. DR GlyGen; P28039; 4 sites, 5 N-linked glycans (1 site). DR iPTMnet; P28039; -. DR PhosphoSitePlus; P28039; -. DR BioMuta; AOAH; -. DR DMDM; 113976; -. DR MassIVE; P28039; -. DR PaxDb; 9606-ENSP00000479664; -. DR PeptideAtlas; P28039; -. DR ProteomicsDB; 54435; -. [P28039-1] DR ProteomicsDB; 54436; -. [P28039-2] DR Antibodypedia; 26560; 148 antibodies from 25 providers. DR DNASU; 313; -. DR Ensembl; ENST00000612871.4; ENSP00000484305.1; ENSG00000136250.14. [P28039-2] DR Ensembl; ENST00000617537.5; ENSP00000483783.1; ENSG00000136250.14. [P28039-1] DR GeneID; 313; -. DR KEGG; hsa:313; -. DR MANE-Select; ENST00000617537.5; ENSP00000483783.1; NM_001637.4; NP_001628.1. DR UCSC; uc032zjw.2; human. [P28039-1] DR AGR; HGNC:548; -. DR ClinPGx; PA24838; -. DR CTD; 313; -. DR DisGeNET; 313; -. DR GeneCards; AOAH; -. DR HGNC; HGNC:548; AOAH. DR HPA; ENSG00000136250; Tissue enhanced (bone marrow, lymphoid tissue). DR MalaCards; AOAH; -. DR MIM; 102593; gene. DR OpenTargets; ENSG00000136250; -. DR VEuPathDB; HostDB:ENSG00000136250; -. DR eggNOG; ENOG502QVQW; Eukaryota. DR GeneTree; ENSGT00390000008427; -. DR HOGENOM; CLU_025769_0_0_1; -. DR InParanoid; P28039; -. DR OMA; PFCHLYP; -. DR OrthoDB; 14839at2759; -. DR PAN-GO; P28039; 4 GO annotations based on evolutionary models. DR PhylomeDB; P28039; -. DR BRENDA; 3.1.1.77; 2681. DR PathwayCommons; P28039; -. DR SignaLink; P28039; -. DR Agora; ENSG00000136250; -. DR BioGRID-ORCS; 313; 21 hits in 1155 CRISPR screens. DR ChiTaRS; AOAH; human. DR GeneWiki; AOAH; -. DR GenomeRNAi; 313; -. DR Pharos; P28039; Tchem. DR PRO; PR:P28039; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; P28039; protein. DR Bgee; ENSG00000136250; Expressed in granulocyte and 141 other cell types or tissues. DR ExpressionAtlas; P28039; baseline and differential. DR GO; GO:0031410; C:cytoplasmic vesicle; EXP:UniProtKB. DR GO; GO:0005576; C:extracellular region; EXP:UniProtKB. DR GO; GO:0050528; F:acyloxyacyl hydrolase activity; IDA:UniProtKB. DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB. DR GO; GO:0006631; P:fatty acid metabolic process; IDA:UniProtKB. DR GO; GO:0009104; P:lipopolysaccharide catabolic process; IDA:UniProtKB. DR GO; GO:0050728; P:negative regulation of inflammatory response; IBA:GO_Central. DR CDD; cd01826; acyloxyacyl_hydrolase_like; 1. DR FunFam; 1.10.225.10:FF:000009; Acyloxyacyl hydrolase; 1. DR Gene3D; 1.10.225.10; Saposin-like; 1. DR Gene3D; 3.40.50.1110; SGNH hydrolase; 1. DR InterPro; IPR039676; AOAH. DR InterPro; IPR048593; AOAH_Saposin_N. DR InterPro; IPR001087; GDSL. DR InterPro; IPR011001; Saposin-like. DR InterPro; IPR008139; SaposinB_dom. DR InterPro; IPR036514; SGNH_hydro_sf. DR PANTHER; PTHR15010; ACYLOXYACYL HYDROLASE; 1. DR PANTHER; PTHR15010:SF0; ACYLOXYACYL HYDROLASE; 1. DR Pfam; PF00657; Lipase_GDSL; 1. DR Pfam; PF20825; Saposin; 1. DR SMART; SM00741; SapB; 1. DR SUPFAM; SSF47862; Saposin; 1. DR SUPFAM; SSF52266; SGNH hydrolase; 1. DR PROSITE; PS50015; SAP_B; 1. DR PDBsum; 5W78; -. DR PDBsum; 5W7C; -. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Calcium; Cytoplasmic vesicle; KW Direct protein sequencing; Disulfide bond; Glycoprotein; Hydrolase; KW Lipid metabolism; Metal-binding; Proteomics identification; KW Reference proteome; Secreted; Signal; Zymogen. FT SIGNAL 1..23 FT /evidence="ECO:0000269|PubMed:8089145" FT PROPEP 24..34 FT /evidence="ECO:0000305|PubMed:1883828" FT /id="PRO_0000020739" FT CHAIN 35..156 FT /note="Acyloxyacyl hydrolase small subunit" FT /evidence="ECO:0000305|PubMed:1883828" FT /id="PRO_0000020740" FT CHAIN 157..575 FT /note="Acyloxyacyl hydrolase large subunit" FT /evidence="ECO:0000305|PubMed:1883828" FT /id="PRO_0000020741" FT DOMAIN 37..118 FT /note="Saposin B-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415" FT REGION 38..70 FT /note="Important for enzyme activity, localization to FT cytoplasmic vesicles, and protein stability" FT /evidence="ECO:0000269|PubMed:8089145" FT REGION 173..177 FT /note="Lipopolysaccharide binding" FT /evidence="ECO:0000250|UniProtKB:O18823" FT ACT_SITE 263 FT /evidence="ECO:0000305|PubMed:29343645, FT ECO:0000305|PubMed:8089145" FT BINDING 184 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:29343645" FT BINDING 186 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:29343645" FT BINDING 186 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:29343645" FT BINDING 188 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:29343645" FT BINDING 188 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:29343645" FT BINDING 190 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:29343645" FT BINDING 205 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:29343645" FT BINDING 205 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:29343645" FT BINDING 207 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:29343645" FT BINDING 208 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:29343645" FT BINDING 210 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:29343645" FT BINDING 213 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:29343645" FT BINDING 223 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:29343645" FT BINDING 227 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:29343645" FT BINDING 229 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:29343645" FT BINDING 231 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:29343645" FT BINDING 233 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:29343645" FT BINDING 245 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:29343645" FT SITE 345 FT /note="Interacts with lipopolysaccharide" FT /evidence="ECO:0000250|UniProtKB:O18823" FT CARBOHYD 59 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:29343645, FT ECO:0000305|PubMed:8089145, ECO:0007744|PDB:5W78" FT CARBOHYD 207 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:29343645, FT ECO:0007744|PDB:5W78" FT CARBOHYD 409 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:29343645, FT ECO:0007744|PDB:5W78" FT CARBOHYD 466 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:29343645, FT ECO:0007744|PDB:5W78" FT DISULFID 41..114 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415, FT ECO:0000269|PubMed:29343645, ECO:0007744|PDB:5W78, FT ECO:0007744|PDB:5W7C" FT DISULFID 44..108 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415, FT ECO:0000269|PubMed:29343645, ECO:0007744|PDB:5W78, FT ECO:0007744|PDB:5W7C" FT DISULFID 70..83 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415, FT ECO:0000269|PubMed:29343645, ECO:0007744|PDB:5W78, FT ECO:0007744|PDB:5W7C" FT DISULFID 123..453 FT /note="Interchain (between small and large subunit)" FT /evidence="ECO:0000269|PubMed:29343645, FT ECO:0007744|PDB:5W78, ECO:0007744|PDB:5W7C" FT DISULFID 160..169 FT /evidence="ECO:0000269|PubMed:29343645, FT ECO:0007744|PDB:5W78, ECO:0007744|PDB:5W7C" FT DISULFID 206..230 FT /evidence="ECO:0000269|PubMed:29343645, FT ECO:0007744|PDB:5W78, ECO:0007744|PDB:5W7C" FT DISULFID 249..329 FT /evidence="ECO:0000269|PubMed:29343645, FT ECO:0007744|PDB:5W78, ECO:0007744|PDB:5W7C" FT DISULFID 376..459 FT /evidence="ECO:0000269|PubMed:29343645, FT ECO:0007744|PDB:5W78, ECO:0007744|PDB:5W7C" FT VAR_SEQ 43..74 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_042571" FT VARIANT 28 FT /note="D -> N (in dbSNP:rs2228410)" FT /evidence="ECO:0000269|PubMed:12690205, ECO:0000269|Ref.6" FT /id="VAR_050663" FT VARIANT 166 FT /note="A -> T (in dbSNP:rs3735384)" FT /id="VAR_020133" FT VARIANT 266 FT /note="A -> G (in dbSNP:rs3735386)" FT /id="VAR_033513" FT MUTAGEN 61 FT /note="T->A: Loss of glycosylation. No effect on enzyme FT activity or localization to cytoplasmic vesicles." FT /evidence="ECO:0000269|PubMed:8089145" FT MUTAGEN 173 FT /note="K->E: No effect on enzyme activity." FT /evidence="ECO:0000269|PubMed:29343645" FT MUTAGEN 263 FT /note="S->A: Loss of enzyme activity." FT /evidence="ECO:0000269|PubMed:29343645" FT MUTAGEN 263 FT /note="S->L: Nearly abolishes catalytic activity." FT /evidence="ECO:0000269|PubMed:8089145" FT MUTAGEN 345 FT /note="R->E: No effect on enzyme activity; when associated FT with E-379." FT /evidence="ECO:0000269|PubMed:29343645" FT MUTAGEN 372 FT /note="G->M: Loss of enzyme activity with FT lipopolysaccharide, due to steric hindrance. No effect on FT activity with small, synthetic substrate." FT /evidence="ECO:0000269|PubMed:29343645" FT MUTAGEN 379 FT /note="K->E: No effect on enzyme activity; when associated FT with E-345." FT /evidence="ECO:0000269|PubMed:29343645" FT MUTAGEN 419 FT /note="P->M: Loss of enzyme activity with FT lipopolysaccharide, due to steric hindrance. No effect on FT activity with small, synthetic substrate." FT /evidence="ECO:0000269|PubMed:29343645" FT CONFLICT 222 FT /note="W -> C (in Ref. 6; BAD97196)" FT /evidence="ECO:0000305" FT HELIX 38..57 FT /evidence="ECO:0007829|PDB:5W7C" FT HELIX 62..72 FT /evidence="ECO:0007829|PDB:5W7C" FT HELIX 76..78 FT /evidence="ECO:0007829|PDB:5W7C" FT HELIX 79..86 FT /evidence="ECO:0007829|PDB:5W7C" FT HELIX 87..91 FT /evidence="ECO:0007829|PDB:5W7C" FT HELIX 92..99 FT /evidence="ECO:0007829|PDB:5W7C" FT HELIX 104..110 FT /evidence="ECO:0007829|PDB:5W7C" FT STRAND 118..120 FT /evidence="ECO:0007829|PDB:5W78" FT HELIX 121..123 FT /evidence="ECO:0007829|PDB:5W7C" FT HELIX 127..129 FT /evidence="ECO:0007829|PDB:5W78" FT HELIX 130..143 FT /evidence="ECO:0007829|PDB:5W7C" FT HELIX 159..161 FT /evidence="ECO:0007829|PDB:5W7C" FT HELIX 165..178 FT /evidence="ECO:0007829|PDB:5W7C" FT STRAND 192..198 FT /evidence="ECO:0007829|PDB:5W7C" FT TURN 199..201 FT /evidence="ECO:0007829|PDB:5W7C" FT HELIX 203..205 FT /evidence="ECO:0007829|PDB:5W7C" FT HELIX 221..223 FT /evidence="ECO:0007829|PDB:5W7C" FT STRAND 224..226 FT /evidence="ECO:0007829|PDB:5W7C" FT STRAND 230..232 FT /evidence="ECO:0007829|PDB:5W7C" FT TURN 238..240 FT /evidence="ECO:0007829|PDB:5W7C" FT HELIX 244..249 FT /evidence="ECO:0007829|PDB:5W7C" FT STRAND 256..261 FT /evidence="ECO:0007829|PDB:5W7C" FT TURN 263..267 FT /evidence="ECO:0007829|PDB:5W7C" FT HELIX 272..274 FT /evidence="ECO:0007829|PDB:5W7C" FT HELIX 277..279 FT /evidence="ECO:0007829|PDB:5W7C" FT HELIX 282..285 FT /evidence="ECO:0007829|PDB:5W7C" FT HELIX 288..293 FT /evidence="ECO:0007829|PDB:5W7C" FT TURN 294..296 FT /evidence="ECO:0007829|PDB:5W7C" FT HELIX 299..301 FT /evidence="ECO:0007829|PDB:5W7C" FT TURN 303..305 FT /evidence="ECO:0007829|PDB:5W7C" FT STRAND 311..313 FT /evidence="ECO:0007829|PDB:5W7C" FT HELIX 319..326 FT /evidence="ECO:0007829|PDB:5W7C" FT HELIX 328..330 FT /evidence="ECO:0007829|PDB:5W7C" FT STRAND 334..338 FT /evidence="ECO:0007829|PDB:5W7C" FT TURN 344..346 FT /evidence="ECO:0007829|PDB:5W7C" FT HELIX 347..349 FT /evidence="ECO:0007829|PDB:5W7C" FT HELIX 351..353 FT /evidence="ECO:0007829|PDB:5W7C" FT TURN 358..360 FT /evidence="ECO:0007829|PDB:5W7C" FT STRAND 364..369 FT /evidence="ECO:0007829|PDB:5W7C" FT TURN 373..375 FT /evidence="ECO:0007829|PDB:5W7C" FT STRAND 379..381 FT /evidence="ECO:0007829|PDB:5W7C" FT TURN 383..385 FT /evidence="ECO:0007829|PDB:5W7C" FT HELIX 389..404 FT /evidence="ECO:0007829|PDB:5W7C" FT STRAND 411..416 FT /evidence="ECO:0007829|PDB:5W7C" FT HELIX 417..419 FT /evidence="ECO:0007829|PDB:5W7C" FT HELIX 422..428 FT /evidence="ECO:0007829|PDB:5W7C" FT HELIX 434..436 FT /evidence="ECO:0007829|PDB:5W7C" FT TURN 437..440 FT /evidence="ECO:0007829|PDB:5W7C" FT HELIX 444..454 FT /evidence="ECO:0007829|PDB:5W7C" FT TURN 460..462 FT /evidence="ECO:0007829|PDB:5W7C" FT STRAND 463..465 FT /evidence="ECO:0007829|PDB:5W7C" FT HELIX 467..490 FT /evidence="ECO:0007829|PDB:5W7C" FT STRAND 496..501 FT /evidence="ECO:0007829|PDB:5W7C" FT HELIX 505..514 FT /evidence="ECO:0007829|PDB:5W7C" FT HELIX 519..522 FT /evidence="ECO:0007829|PDB:5W7C" FT TURN 525..527 FT /evidence="ECO:0007829|PDB:5W7C" FT STRAND 528..531 FT /evidence="ECO:0007829|PDB:5W7C" FT HELIX 533..550 FT /evidence="ECO:0007829|PDB:5W7C" FT HELIX 552..555 FT /evidence="ECO:0007829|PDB:5W7C" FT HELIX 557..559 FT /evidence="ECO:0007829|PDB:5W7C" FT HELIX 562..569 FT /evidence="ECO:0007829|PDB:5W7C" FT TURN 570..573 FT /evidence="ECO:0007829|PDB:5W7C" SQ SEQUENCE 575 AA; 65105 MW; E3B3853DBD308AF7 CRC64; MQSPWKILTV APLFLLLSLQ SSASPANDDQ SRPSLSNGHT CVGCVLVVSV IEQLAQVHNS TVQASMERLC SYLPEKLFLK TTCYLVIDKF GSDIIKLLSA DMNADVVCHT LEFCKQNTGQ PLCHLYPLPK ETWKFTLQKA RQIVKKSPIL KYSRSGSDIC SLPVLAKICQ KIKLAMEQSV PFKDVDSDKY SVFPTLRGYH WRGRDCNDSD ESVYPGRRPN NWDVHQDSNC NGIWGVDPKD GVPYEKKFCE GSQPRGIILL GDSAGAHFHI SPEWITASQM SLNSFINLPT ALTNELDWPQ LSGATGFLDS TVGIKEKSIY LRLWKRNHCN HRDYQNISRN GASSRNLKKF IESLSRNKVL DYPAIVIYAM IGNDVCSGKS DPVPAMTTPE KLYSNVMQTL KHLNSHLPNG SHVILYGLPD GTFLWDNLHN RYHPLGQLNK DMTYAQLYSF LNCLQVSPCH GWMSSNKTLR TLTSERAEQL SNTLKKIAAS EKFTNFNLFY MDFAFHEIIQ EWQKRGGQPW QLIEPVDGFH PNEVALLLLA DHFWKKVQLQ WPQILGKENP FNPQIKQVFG DQGGH //