AOAH_RABIT
ID AOAH_RABIT Reviewed; 575 AA.
AC O18823;
DT 13-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Acyloxyacyl hydrolase {ECO:0000250|UniProtKB:P28039};
DE EC=3.1.1.77 {ECO:0000250|UniProtKB:P28039};
DE Contains:
DE RecName: Full=Acyloxyacyl hydrolase small subunit {ECO:0000250|UniProtKB:P28039};
DE Contains:
DE RecName: Full=Acyloxyacyl hydrolase large subunit {ECO:0000250|UniProtKB:P28039};
DE Flags: Precursor;
GN Name=AOAH {ECO:0000250|UniProtKB:P28039};
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=New Zealand white;
RA Munford R.S., Fosmire S., Varley A.W., Staab J.F.;
RT "Human, murine, and lapine acyloxyacyl hydrolases share unique structural
RT features.";
RL Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0007744|PDB:5W7A, ECO:0007744|PDB:5W7B}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 23-153 AND 154-575 OF MUTANT
RP ALA-262 IN COMPLEX WITH CALCIUM AND BACTERIAL LIPOPOLYSACCHARIDE, COFACTOR,
RP SUBUNIT, GLYCOSYLATION AT ASN-58; ASN-206 AND ASN-466, DISULFIDE BONDS,
RP MUTAGENESIS OF SER-262, AND ACTIVE SITE.
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 (LPS). By
CC breaking down LPS, terminates the host response to bacterial infection
CC and prevents prolonged and damaging inflammatory responses. In
CC peritoneal macrophages, seems to be important for recovery from a state
CC of immune tolerance following infection by Gram-negative bacteria.
CC {ECO:0000250|UniProtKB:O35298}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 3-(acyloxy)acyl derivative of bacterial toxin + H2O = 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:0000250|UniProtKB:P28039};
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 -!- SUBUNIT: Heterodimer of the large and small subunits; disulfide-linked.
CC {ECO:0000269|PubMed:29343645}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P28039}.
CC Cytoplasmic vesicle {ECO:0000250|UniProtKB:P28039}. Note=Detected in
CC urine. {ECO:0000250|UniProtKB:O35298}.
CC -!- PTM: Cleaved into a large and a small subunit.
CC {ECO:0000250|UniProtKB:P28039}.
CC -!- PTM: The small subunit is N-glycosylated.
CC {ECO:0000250|UniProtKB:P28039}.
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DR EMBL; AF018173; AAB81183.1; -; mRNA.
DR RefSeq; NP_001075494.1; NM_001082025.1.
DR PDB; 5W7A; X-ray; 2.30 A; A=23-153, B=154-575.
DR PDB; 5W7B; X-ray; 1.90 A; A/B=23-153, C/D=154-575.
DR PDBsum; 5W7A; -.
DR PDBsum; 5W7B; -.
DR AlphaFoldDB; O18823; -.
DR SMR; O18823; -.
DR STRING; 9986.ENSOCUP00000012523; -.
DR iPTMnet; O18823; -.
DR PRIDE; O18823; -.
DR GeneID; 100008662; -.
DR KEGG; ocu:100008662; -.
DR CTD; 313; -.
DR eggNOG; ENOG502QVQW; Eukaryota.
DR HOGENOM; CLU_025769_0_0_1; -.
DR InParanoid; O18823; -.
DR OMA; AGQPFCH; -.
DR OrthoDB; 692811at2759; -.
DR TreeFam; TF329246; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0050528; F:acyloxyacyl hydrolase activity; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0006631; P:fatty acid metabolic process; ISS:UniProtKB.
DR GO; GO:0009104; P:lipopolysaccharide catabolic process; ISS:UniProtKB.
DR Gene3D; 3.40.50.1110; -; 1.
DR InterPro; IPR039676; AOAH.
DR InterPro; IPR001087; GDSL.
DR InterPro; IPR008138; SapB_2.
DR InterPro; IPR011001; Saposin-like.
DR InterPro; IPR008139; SaposinB_dom.
DR InterPro; IPR036514; SGNH_hydro_sf.
DR PANTHER; PTHR15010; PTHR15010; 1.
DR Pfam; PF00657; Lipase_GDSL; 1.
DR Pfam; PF03489; SapB_2; 1.
DR SMART; SM00741; SapB; 1.
DR SUPFAM; SSF47862; SSF47862; 1.
DR PROSITE; PS50015; SAP_B; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Cytoplasmic vesicle; Disulfide bond; Glycoprotein;
KW Hydrolase; Lipid metabolism; Metal-binding; Reference proteome; Secreted;
KW Signal; Zymogen.
FT SIGNAL 1..25
FT /evidence="ECO:0000250|UniProtKB:P28039"
FT PROPEP 26..34
FT /evidence="ECO:0000250|UniProtKB:P28039"
FT /id="PRO_0000041815"
FT CHAIN 35..156
FT /note="Acyloxyacyl hydrolase small subunit"
FT /evidence="ECO:0000250|UniProtKB:P28039"
FT /id="PRO_0000041816"
FT CHAIN 157..575
FT /note="Acyloxyacyl hydrolase large subunit"
FT /evidence="ECO:0000250|UniProtKB:P28039"
FT /id="PRO_0000041817"
FT DOMAIN 36..117
FT /note="Saposin B-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT REGION 37..69
FT /note="Important for enzyme activity, localization to
FT cytoplasmic vesicles, and protein stability"
FT /evidence="ECO:0000250|UniProtKB:P28039"
FT REGION 172..176
FT /note="Lipopolysaccharide binding"
FT /evidence="ECO:0000305|PubMed:29343645"
FT ACT_SITE 262
FT /evidence="ECO:0000305|PubMed:29343645"
FT BINDING 183
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:29343645,
FT ECO:0007744|PDB:5W7A, ECO:0007744|PDB:5W7B"
FT BINDING 185
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:29343645,
FT ECO:0007744|PDB:5W7A, ECO:0007744|PDB:5W7B"
FT BINDING 185
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:29343645,
FT ECO:0007744|PDB:5W7A"
FT BINDING 187
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:29343645,
FT ECO:0007744|PDB:5W7A, ECO:0007744|PDB:5W7B"
FT BINDING 187
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:29343645,
FT ECO:0007744|PDB:5W7A"
FT BINDING 189
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:29343645,
FT ECO:0007744|PDB:5W7A, ECO:0007744|PDB:5W7B"
FT BINDING 204
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:29343645,
FT ECO:0007744|PDB:5W7B"
FT BINDING 204
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:29343645,
FT ECO:0007744|PDB:5W7A"
FT BINDING 206
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:29343645,
FT ECO:0007744|PDB:5W7A"
FT BINDING 207
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:29343645,
FT ECO:0007744|PDB:5W7A, ECO:0007744|PDB:5W7B"
FT BINDING 209
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:29343645,
FT ECO:0007744|PDB:5W7A"
FT BINDING 212
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:29343645,
FT ECO:0007744|PDB:5W7A"
FT BINDING 222
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:29343645,
FT ECO:0007744|PDB:5W7A"
FT BINDING 226
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:29343645,
FT ECO:0007744|PDB:5W7A"
FT BINDING 228
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:29343645,
FT ECO:0007744|PDB:5W7A"
FT BINDING 230
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:29343645,
FT ECO:0007744|PDB:5W7A"
FT BINDING 232
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:29343645,
FT ECO:0007744|PDB:5W7A"
FT BINDING 244
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:29343645,
FT ECO:0007744|PDB:5W7A"
FT SITE 344
FT /note="Interacts with lipopolysaccharide"
FT /evidence="ECO:0000305|PubMed:29343645"
FT SITE 378
FT /note="Interacts with lipopolysaccharide"
FT /evidence="ECO:0000305|PubMed:29343645"
FT CARBOHYD 58
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:29343645,
FT ECO:0007744|PDB:5W7B"
FT CARBOHYD 206
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:29343645,
FT ECO:0007744|PDB:5W7B"
FT CARBOHYD 466
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:29343645,
FT ECO:0007744|PDB:5W7B"
FT DISULFID 40..113
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT ECO:0000269|PubMed:29343645, ECO:0007744|PDB:5W7A,
FT ECO:0007744|PDB:5W7B"
FT DISULFID 43..107
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT ECO:0000269|PubMed:29343645, ECO:0007744|PDB:5W7A,
FT ECO:0007744|PDB:5W7B"
FT DISULFID 69..82
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT ECO:0000269|PubMed:29343645, ECO:0007744|PDB:5W7A,
FT ECO:0007744|PDB:5W7B"
FT DISULFID 122..453
FT /note="Interchain (between small and large subunit)"
FT /evidence="ECO:0000269|PubMed:29343645,
FT ECO:0007744|PDB:5W7A, ECO:0007744|PDB:5W7B"
FT DISULFID 159..168
FT /evidence="ECO:0000269|PubMed:29343645,
FT ECO:0007744|PDB:5W7B"
FT DISULFID 205..229
FT /evidence="ECO:0000269|PubMed:29343645,
FT ECO:0007744|PDB:5W7A, ECO:0007744|PDB:5W7B"
FT DISULFID 248..328
FT /evidence="ECO:0000269|PubMed:29343645,
FT ECO:0007744|PDB:5W7A, ECO:0007744|PDB:5W7B"
FT DISULFID 375..459
FT /evidence="ECO:0000269|PubMed:29343645,
FT ECO:0007744|PDB:5W7A, ECO:0007744|PDB:5W7B"
FT MUTAGEN 262
FT /note="S->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:29343645"
FT HELIX 37..56
FT /evidence="ECO:0007829|PDB:5W7B"
FT HELIX 61..71
FT /evidence="ECO:0007829|PDB:5W7B"
FT HELIX 75..77
FT /evidence="ECO:0007829|PDB:5W7B"
FT HELIX 78..94
FT /evidence="ECO:0007829|PDB:5W7B"
FT HELIX 95..97
FT /evidence="ECO:0007829|PDB:5W7A"
FT HELIX 103..109
FT /evidence="ECO:0007829|PDB:5W7B"
FT HELIX 162..177
FT /evidence="ECO:0007829|PDB:5W7B"
FT STRAND 191..194
FT /evidence="ECO:0007829|PDB:5W7B"
FT TURN 198..200
FT /evidence="ECO:0007829|PDB:5W7B"
FT HELIX 219..222
FT /evidence="ECO:0007829|PDB:5W7B"
FT STRAND 223..225
FT /evidence="ECO:0007829|PDB:5W7B"
FT STRAND 229..231
FT /evidence="ECO:0007829|PDB:5W7B"
FT TURN 237..239
FT /evidence="ECO:0007829|PDB:5W7B"
FT HELIX 243..248
FT /evidence="ECO:0007829|PDB:5W7B"
FT STRAND 249..251
FT /evidence="ECO:0007829|PDB:5W7A"
FT STRAND 255..260
FT /evidence="ECO:0007829|PDB:5W7B"
FT HELIX 262..265
FT /evidence="ECO:0007829|PDB:5W7B"
FT HELIX 271..273
FT /evidence="ECO:0007829|PDB:5W7B"
FT HELIX 276..278
FT /evidence="ECO:0007829|PDB:5W7B"
FT TURN 281..286
FT /evidence="ECO:0007829|PDB:5W7B"
FT HELIX 287..292
FT /evidence="ECO:0007829|PDB:5W7B"
FT TURN 293..295
FT /evidence="ECO:0007829|PDB:5W7B"
FT HELIX 298..300
FT /evidence="ECO:0007829|PDB:5W7B"
FT TURN 302..304
FT /evidence="ECO:0007829|PDB:5W7B"
FT HELIX 318..325
FT /evidence="ECO:0007829|PDB:5W7B"
FT HELIX 327..329
FT /evidence="ECO:0007829|PDB:5W7B"
FT STRAND 333..335
FT /evidence="ECO:0007829|PDB:5W7B"
FT TURN 343..345
FT /evidence="ECO:0007829|PDB:5W7B"
FT HELIX 346..352
FT /evidence="ECO:0007829|PDB:5W7B"
FT TURN 357..359
FT /evidence="ECO:0007829|PDB:5W7B"
FT STRAND 363..368
FT /evidence="ECO:0007829|PDB:5W7B"
FT TURN 372..374
FT /evidence="ECO:0007829|PDB:5W7B"
FT HELIX 382..385
FT /evidence="ECO:0007829|PDB:5W7B"
FT HELIX 389..404
FT /evidence="ECO:0007829|PDB:5W7B"
FT STRAND 411..416
FT /evidence="ECO:0007829|PDB:5W7B"
FT HELIX 423..428
FT /evidence="ECO:0007829|PDB:5W7B"
FT HELIX 434..436
FT /evidence="ECO:0007829|PDB:5W7B"
FT TURN 437..440
FT /evidence="ECO:0007829|PDB:5W7B"
FT HELIX 444..453
FT /evidence="ECO:0007829|PDB:5W7B"
FT TURN 460..462
FT /evidence="ECO:0007829|PDB:5W7B"
FT HELIX 467..490
FT /evidence="ECO:0007829|PDB:5W7B"
FT STRAND 496..501
FT /evidence="ECO:0007829|PDB:5W7B"
FT HELIX 505..514
FT /evidence="ECO:0007829|PDB:5W7B"
FT HELIX 519..522
FT /evidence="ECO:0007829|PDB:5W7B"
FT TURN 525..527
FT /evidence="ECO:0007829|PDB:5W7B"
FT STRAND 528..531
FT /evidence="ECO:0007829|PDB:5W7B"
FT HELIX 533..550
FT /evidence="ECO:0007829|PDB:5W7B"
FT HELIX 552..555
FT /evidence="ECO:0007829|PDB:5W7B"
FT HELIX 562..569
FT /evidence="ECO:0007829|PDB:5W7B"
FT TURN 570..573
FT /evidence="ECO:0007829|PDB:5W7B"
SQ SEQUENCE 575 AA; 65053 MW; 5AB2CDADE568492B CRC64;
MKSPWRILVV SPLLLLPLHS STSRAHDNQP GTIRSDHYTC VGCVLVVSVI EQLAQVHNST
VQASMERLCS YLPEEWVLKT ACYMMVHVFG ADIIKLFDKD VNADVVCHTL EFCKQEPGQP
LCHLYPLPKE SWKFTLEKAR HIVKQSPIMK YTRSGAGICS LPFLAKICQK IKLAIKNSVP
IKDVDSDKYS IFPTLRGYHW RGRDCNDSDK TVYPGRRPDN WDAHRDSNCN GIWGVDPKDG
IPYEKKFCEG SQPRGIILLG DSAGAHFHIP PEWLTVSQMS VNSFLNLPTA VTNELDWPQL
SGTTGFLDSA SKIKENSIYL RLRKRNRCNH RDYQNISKNG ASSRNVKSLI ESLSRNQLLD
HPAIVIYAMI GNDVCNGRKT DPVSAMTTPE QLYANVLKML EALNSHLPTG SHVILYGLAH
GAFLWDTLHS RYHPLGQLNK DVTYTQLYSF LGCLQVSPCP GWMSANETLR ALTSERAQQL
SETLRKIAAS KKFTNFNLFY LDFAFQEVVE EWQKMGGQPW ELIEAVDGFH PNEVALLLFA
DQLWEKVQRQ WPDVLGKENP FNPQIEEVFG DQGGH
