NAAA_RABIT
ID NAAA_RABIT Reviewed; 358 AA.
AC G1T7U7;
DT 10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT 10-APR-2019, sequence version 2.
DT 03-AUG-2022, entry version 51.
DE RecName: Full=N-acylethanolamine-hydrolyzing acid amidase {ECO:0000250|UniProtKB:Q5KTC7};
DE EC=3.5.1.60 {ECO:0000250|UniProtKB:Q5KTC7};
DE AltName: Full=Acylsphingosine deacylase NAAA {ECO:0000250|UniProtKB:Q5KTC7};
DE EC=3.5.1.23 {ECO:0000250|UniProtKB:Q5KTC7};
DE Contains:
DE RecName: Full=N-acylethanolamine-hydrolyzing acid amidase subunit alpha;
DE Contains:
DE RecName: Full=N-acylethanolamine-hydrolyzing acid amidase subunit beta;
DE Flags: Precursor;
GN Name=NAAA {ECO:0000303|PubMed:30301806};
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986 {ECO:0000312|Proteomes:UP000001811};
RN [1] {ECO:0000312|Proteomes:UP000001811}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Thorbecke {ECO:0000312|Proteomes:UP000001811};
RX PubMed=21993624; DOI=10.1038/nature10530;
RA Lindblad-Toh K., Garber M., Zuk O., Lin M.F., Parker B.J., Washietl S.,
RA Kheradpour P., Ernst J., Jordan G., Mauceli E., Ward L.D., Lowe C.B.,
RA Holloway A.K., Clamp M., Gnerre S., Alfoldi J., Beal K., Chang J.,
RA Clawson H., Cuff J., Di Palma F., Fitzgerald S., Flicek P., Guttman M.,
RA Hubisz M.J., Jaffe D.B., Jungreis I., Kent W.J., Kostka D., Lara M.,
RA Martins A.L., Massingham T., Moltke I., Raney B.J., Rasmussen M.D.,
RA Robinson J., Stark A., Vilella A.J., Wen J., Xie X., Zody M.C., Baldwin J.,
RA Bloom T., Chin C.W., Heiman D., Nicol R., Nusbaum C., Young S.,
RA Wilkinson J., Worley K.C., Kovar C.L., Muzny D.M., Gibbs R.A., Cree A.,
RA Dihn H.H., Fowler G., Jhangiani S., Joshi V., Lee S., Lewis L.R.,
RA Nazareth L.V., Okwuonu G., Santibanez J., Warren W.C., Mardis E.R.,
RA Weinstock G.M., Wilson R.K., Delehaunty K., Dooling D., Fronik C.,
RA Fulton L., Fulton B., Graves T., Minx P., Sodergren E., Birney E.,
RA Margulies E.H., Herrero J., Green E.D., Haussler D., Siepel A., Goldman N.,
RA Pollard K.S., Pedersen J.S., Lander E.S., Kellis M.;
RT "A high-resolution map of human evolutionary constraint using 29 mammals.";
RL Nature 478:476-482(2011).
RN [2] {ECO:0007744|PDB:6DXZ, ECO:0007744|PDB:6DY0, ECO:0007744|PDB:6DY1}
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 31-126 AND 127-358 IN COMPLEXES
RP WITH SYNTHETIC INHIBITOR AND MYRISTATE, ACTIVE SITE, SUBUNIT, PROTEOLYTIC
RP CLEAVAGE, AND GLYCOSYLATION AT ASN-39; ASN-108 AND ASN-334.
RX PubMed=30301806; DOI=10.1073/pnas.1811759115;
RA Gorelik A., Gebai A., Illes K., Piomelli D., Nagar B.;
RT "Molecular mechanism of activation of the immunoregulatory amidase NAAA.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:E10032-E10040(2018).
CC -!- FUNCTION: Degrades bioactive fatty acid amides to their corresponding
CC acids, with the following preference: N-palmitoylethanolamine > N-
CC myristoylethanolamine > N-stearoylethanolamine > N-oleoylethanolamine >
CC N-linoleoylethanolamine > N-arachidonoylethanolamine.
CC {ECO:0000250|UniProtKB:Q5KTC7}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-hexadecanoylethanolamine = ethanolamine +
CC hexadecanoate; Xref=Rhea:RHEA:45064, ChEBI:CHEBI:7896,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:57603, ChEBI:CHEBI:71464;
CC Evidence={ECO:0000250|UniProtKB:Q02083};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45065;
CC Evidence={ECO:0000250|UniProtKB:Q02083};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(long-chain fatty acyl)ethanolamine = a long-chain
CC fatty acid + ethanolamine; Xref=Rhea:RHEA:17505, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15897, ChEBI:CHEBI:57560, ChEBI:CHEBI:57603; EC=3.5.1.60;
CC Evidence={ECO:0000250|UniProtKB:Q02083};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17506;
CC Evidence={ECO:0000250|UniProtKB:Q02083};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-dodecanoylethanolamine = dodecanoate + ethanolamine;
CC Xref=Rhea:RHEA:45456, ChEBI:CHEBI:15377, ChEBI:CHEBI:18262,
CC ChEBI:CHEBI:57603, ChEBI:CHEBI:85263;
CC Evidence={ECO:0000250|UniProtKB:Q02083};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45457;
CC Evidence={ECO:0000250|UniProtKB:Q02083};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-tetradecanoylethanolamine = ethanolamine +
CC tetradecanoate; Xref=Rhea:RHEA:45452, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:30807, ChEBI:CHEBI:57603, ChEBI:CHEBI:85262;
CC Evidence={ECO:0000250|UniProtKB:Q02083};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45453;
CC Evidence={ECO:0000250|UniProtKB:Q02083};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an N-acylsphing-4-enine + H2O = a fatty acid + sphing-4-enine;
CC Xref=Rhea:RHEA:20856, ChEBI:CHEBI:15377, ChEBI:CHEBI:28868,
CC ChEBI:CHEBI:52639, ChEBI:CHEBI:57756; EC=3.5.1.23;
CC Evidence={ECO:0000250|UniProtKB:Q02083};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20857;
CC Evidence={ECO:0000250|UniProtKB:Q02083};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-hexadecanoylsphing-4-enine = hexadecanoate + sphing-4-
CC enine; Xref=Rhea:RHEA:38891, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:57756, ChEBI:CHEBI:72959;
CC Evidence={ECO:0000250|UniProtKB:Q02083};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38892;
CC Evidence={ECO:0000250|UniProtKB:Q02083};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-dodecanoylsphing-4-enine = dodecanoate + sphing-4-
CC enine; Xref=Rhea:RHEA:41291, ChEBI:CHEBI:15377, ChEBI:CHEBI:18262,
CC ChEBI:CHEBI:57756, ChEBI:CHEBI:72956;
CC Evidence={ECO:0000250|UniProtKB:Q02083};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41292;
CC Evidence={ECO:0000250|UniProtKB:Q02083};
CC -!- PATHWAY: Lipid metabolism; fatty acid metabolism.
CC {ECO:0000250|UniProtKB:Q02083}.
CC -!- SUBUNIT: Heterodimer of an alpha and a beta subunit, produced by
CC autocatalytic cleavage. {ECO:0000269|PubMed:30301806}.
CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000250|UniProtKB:Q02083}. Membrane
CC {ECO:0000250|UniProtKB:Q02083}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q02083}.
CC -!- PTM: N-glycosylated (PubMed:30301806). Tunicamycin treatment causes a
CC reduction in specific activity against N-palmitoylethanolamine (By
CC similarity). {ECO:0000250|UniProtKB:Q02083,
CC ECO:0000269|PubMed:30301806}.
CC -!- PTM: Autoproteolytic cleavage at pH 4.5 gives rise to the alpha and
CC beta subunit (PubMed:30301806). Cleavage gives rise to a conformation
CC change that activates the enzyme. The same catalytic Cys residue
CC mediates the autoproteolytic cleavage and subsequent hydrolysis of
CC lipid substrates (By similarity). {ECO:0000250|UniProtKB:Q02083,
CC ECO:0000269|PubMed:30301806}.
CC -!- SIMILARITY: Belongs to the acid ceramidase family. {ECO:0000305}.
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; AAGW02022955; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PDB; 6DXZ; X-ray; 2.70 A; A=31-126, B=127-358.
DR PDB; 6DY0; X-ray; 3.01 A; A=31-126, B=127-358.
DR PDB; 6DY1; X-ray; 3.00 A; A=31-126, B=127-358.
DR PDBsum; 6DXZ; -.
DR PDBsum; 6DY0; -.
DR PDBsum; 6DY1; -.
DR AlphaFoldDB; G1T7U7; -.
DR SMR; G1T7U7; -.
DR STRING; 9986.ENSOCUP00000012603; -.
DR iPTMnet; G1T7U7; -.
DR eggNOG; ENOG502QT7H; Eukaryota.
DR HOGENOM; CLU_054401_0_0_1; -.
DR InParanoid; G1T7U7; -.
DR TreeFam; TF313219; -.
DR BRENDA; 3.5.1.60; 1749.
DR UniPathway; UPA00199; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0019898; C:extrinsic component of membrane; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0102121; F:ceramidase activity; IEA:UniProtKB-EC.
DR GO; GO:0017064; F:fatty acid amide hydrolase activity; ISS:UniProtKB.
DR GO; GO:0047412; F:N-(long-chain-acyl)ethanolamine deacylase activity; ISS:UniProtKB.
DR GO; GO:0017040; F:N-acylsphingosine amidohydrolase activity; ISS:UniProtKB.
DR GO; GO:0006631; P:fatty acid metabolic process; ISS:UniProtKB.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0070291; P:N-acylethanolamine metabolic process; ISS:UniProtKB.
DR GO; GO:0070292; P:N-acylphosphatidylethanolamine metabolic process; ISS:UniProtKB.
DR GO; GO:0006670; P:sphingosine metabolic process; ISS:UniProtKB.
DR InterPro; IPR016699; Acid_ceramidase-like.
DR InterPro; IPR029130; Acid_ceramidase_N.
DR InterPro; IPR029132; CBAH/NAAA_C.
DR Pfam; PF02275; CBAH; 1.
DR Pfam; PF15508; NAAA-beta; 1.
DR PIRSF; PIRSF017632; Acid_ceramidase-like; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Autocatalytic cleavage; Fatty acid metabolism; Glycoprotein;
KW Hydrolase; Lipid degradation; Lipid metabolism; Lysosome; Membrane;
KW Reference proteome; Signal; Zymogen.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..358
FT /note="N-acylethanolamine-hydrolyzing acid amidase"
FT /evidence="ECO:0000255"
FT /id="PRO_0000446527"
FT CHAIN 27..126
FT /note="N-acylethanolamine-hydrolyzing acid amidase subunit
FT alpha"
FT /evidence="ECO:0000305|PubMed:30301806"
FT /id="PRO_0000446528"
FT CHAIN 127..358
FT /note="N-acylethanolamine-hydrolyzing acid amidase subunit
FT beta"
FT /evidence="ECO:0000305|PubMed:30301806"
FT /id="PRO_0000446529"
FT ACT_SITE 127
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:30301806"
FT SITE 143
FT /note="Important for enzyme activity"
FT /evidence="ECO:0000250|UniProtKB:Q02083"
FT SITE 288
FT /note="Important for enzyme activity"
FT /evidence="ECO:0000250|UniProtKB:Q02083"
FT CARBOHYD 39
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:30301806,
FT ECO:0007744|PDB:6DXZ"
FT CARBOHYD 108
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:30301806,
FT ECO:0007744|PDB:6DXZ"
FT CARBOHYD 310
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 334
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:30301806,
FT ECO:0007744|PDB:6DXZ"
FT CARBOHYD 356
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT STRAND 37..41
FT /evidence="ECO:0007829|PDB:6DXZ"
FT HELIX 50..53
FT /evidence="ECO:0007829|PDB:6DXZ"
FT HELIX 58..72
FT /evidence="ECO:0007829|PDB:6DXZ"
FT HELIX 75..83
FT /evidence="ECO:0007829|PDB:6DXZ"
FT HELIX 85..90
FT /evidence="ECO:0007829|PDB:6DXZ"
FT HELIX 94..107
FT /evidence="ECO:0007829|PDB:6DXZ"
FT HELIX 111..118
FT /evidence="ECO:0007829|PDB:6DXZ"
FT TURN 119..122
FT /evidence="ECO:0007829|PDB:6DXZ"
FT STRAND 128..133
FT /evidence="ECO:0007829|PDB:6DXZ"
FT STRAND 139..146
FT /evidence="ECO:0007829|PDB:6DXZ"
FT HELIX 150..156
FT /evidence="ECO:0007829|PDB:6DXZ"
FT STRAND 157..164
FT /evidence="ECO:0007829|PDB:6DXZ"
FT STRAND 167..175
FT /evidence="ECO:0007829|PDB:6DXZ"
FT STRAND 182..186
FT /evidence="ECO:0007829|PDB:6DXZ"
FT TURN 187..189
FT /evidence="ECO:0007829|PDB:6DXZ"
FT STRAND 190..196
FT /evidence="ECO:0007829|PDB:6DXZ"
FT HELIX 202..210
FT /evidence="ECO:0007829|PDB:6DXZ"
FT HELIX 217..227
FT /evidence="ECO:0007829|PDB:6DXZ"
FT HELIX 231..240
FT /evidence="ECO:0007829|PDB:6DXZ"
FT STRAND 243..245
FT /evidence="ECO:0007829|PDB:6DXZ"
FT STRAND 247..252
FT /evidence="ECO:0007829|PDB:6DXZ"
FT STRAND 259..264
FT /evidence="ECO:0007829|PDB:6DXZ"
FT STRAND 266..274
FT /evidence="ECO:0007829|PDB:6DXZ"
FT HELIX 277..279
FT /evidence="ECO:0007829|PDB:6DXZ"
FT STRAND 283..289
FT /evidence="ECO:0007829|PDB:6DXZ"
FT STRAND 297..299
FT /evidence="ECO:0007829|PDB:6DXZ"
FT HELIX 302..312
FT /evidence="ECO:0007829|PDB:6DXZ"
FT TURN 313..315
FT /evidence="ECO:0007829|PDB:6DY1"
FT HELIX 319..326
FT /evidence="ECO:0007829|PDB:6DXZ"
FT TURN 329..331
FT /evidence="ECO:0007829|PDB:6DXZ"
FT STRAND 336..342
FT /evidence="ECO:0007829|PDB:6DXZ"
FT HELIX 347..349
FT /evidence="ECO:0007829|PDB:6DXZ"
FT STRAND 351..354
FT /evidence="ECO:0007829|PDB:6DXZ"
SQ SEQUENCE 358 AA; 39877 MW; C561A4649BF9A533 CRC64;
MQGTGHPVRP VLELLLLLLL LAGVGGSTTA STPGPPLFNV SLDVAPERWL PVLRHYDVEL
VRAAVAQVIG DRVPKWVLAL IEKGALKLER LLPPPFTAEI RGMCDFLNLS LADGLLVNLA
YEYSAFCTSI VAQDSRGHVY HGRNLDYPYG SILRKLTVDV QFLKNGQIAF TGTTFIGYVG
LWTGQSPHKF TVSGDERDRG WWWENLVAAL FLRHSPISWL LRTTLSEAES FEAAVYRLAK
TPLIADVYYI VGGTNPREGV VITRNRDGPA DIWPLDPLKG VWFLVETNYD HWKPAPEEDD
RRTPAIKALN ATGQAKLSLE TLFQVLSVVP VYNNYTIYTT VMSAASPDKY MTRIRNPS
