ABHD4_MOUSE
ID ABHD4_MOUSE Reviewed; 342 AA.
AC Q8VD66;
DT 27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=(Lyso)-N-acylphosphatidylethanolamine lipase {ECO:0000305};
DE EC=3.1.1.-;
DE AltName: Full=Alpha/beta hydrolase domain-containing protein 4 {ECO:0000305};
DE Short=Abhydrolase domain-containing protein 4 {ECO:0000312|MGI:MGI:1915938};
DE AltName: Full=Alpha/beta-hydrolase 4;
GN Name=Abhd4 {ECO:0000312|MGI:MGI:1915938};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
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 [3]
RP FUNCTION, TISSUE SPECIFICITY, AND CATALYTIC ACTIVITY.
RX PubMed=16818490; DOI=10.1074/jbc.m604660200;
RA Simon G.M., Cravatt B.F.;
RT "Endocannabinoid biosynthesis proceeding through glycerophospho-N-acyl
RT ethanolamine and a role for alpha/beta hydrolase 4 in this pathway.";
RL J. Biol. Chem. 281:26465-26472(2006).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Lung, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP DISRUPTION PHENOTYPE, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=25853435; DOI=10.1021/acs.biochem.5b00207;
RA Lee H.C., Simon G.M., Cravatt B.F.;
RT "ABHD4 regulates multiple classes of N-acyl phospholipids in the mammalian
RT central nervous system.";
RL Biochemistry 54:2539-2549(2015).
CC -!- FUNCTION: Lysophospholipase selective for N-acyl
CC phosphatidylethanolamine (NAPE). Contributes to the biosynthesis of N-
CC acyl ethanolamines, including the endocannabinoid anandamide by
CC hydrolyzing the sn-1 and sn-2 acyl chains from N-acyl
CC phosphatidylethanolamine (NAPE) generating glycerophospho-N-acyl
CC ethanolamine (GP-NAE), an intermediate for N-acyl ethanolamine
CC biosynthesis (PubMed:16818490, PubMed:25853435). Hydrolyzes substrates
CC bearing saturated, monounsaturated, polyunsaturated N-acyl chains
CC (PubMed:16818490, PubMed:25853435). Shows no significant activity
CC towards other lysophospholipids, including lysophosphatidylcholine,
CC lysophosphatidylethanolamine and lysophosphatidylserine
CC (PubMed:16818490). {ECO:0000269|PubMed:16818490,
CC ECO:0000269|PubMed:25853435}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-hexadecanoyl-1,2-di-(9Z-octadecenoyl)-sn-glycero-3-
CC phosphoethanolamine = (9Z)-octadecenoate + H(+) + N-hexadecanoyl-1-
CC (9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine;
CC Xref=Rhea:RHEA:45424, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:78097, ChEBI:CHEBI:85217;
CC Evidence={ECO:0000269|PubMed:16818490};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45425;
CC Evidence={ECO:0000305|PubMed:16818490};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-acyl-1,2-diacyl-sn-glycero-3-phosphoethanolamine = a
CC fatty acid + H(+) + N,1-diacyl-sn-glycero-3-phosphoethanolamine;
CC Xref=Rhea:RHEA:45460, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:28868, ChEBI:CHEBI:62537, ChEBI:CHEBI:85216;
CC Evidence={ECO:0000269|PubMed:16818490};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45461;
CC Evidence={ECO:0000305|PubMed:16818490};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-hexadecanoyl-1-(9Z-octadecenoyl)-sn-glycero-3-
CC phosphoethanolamine = (9Z)-octadecenoate + H(+) + N-hexadecanoyl-sn-
CC glycero-3-phosphoethanolamine; Xref=Rhea:RHEA:45384,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823,
CC ChEBI:CHEBI:85217, ChEBI:CHEBI:85226;
CC Evidence={ECO:0000269|PubMed:16818490, ECO:0000269|PubMed:25853435};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45385;
CC Evidence={ECO:0000269|PubMed:25853435};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-octadecanoyl-1-(9Z-octadecenoyl)-sn-glycero-3-
CC phosphoethanolamine = (9Z)-octadecenoate + H(+) + N-octadecanoyl-sn-
CC glycero-3-phospho-ethanolamine; Xref=Rhea:RHEA:45388,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823,
CC ChEBI:CHEBI:85219, ChEBI:CHEBI:85227;
CC Evidence={ECO:0000269|PubMed:16818490};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45389;
CC Evidence={ECO:0000305|PubMed:16818490};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-eicosanoyl-1-(9Z-octadecenoyl)-sn-glycero-3-
CC phosphoethanolamine = (9Z)-octadecenoate + H(+) + N-eicosanoyl-sn-
CC glycero-3-phosphoethanolamine; Xref=Rhea:RHEA:45392,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823,
CC ChEBI:CHEBI:85221, ChEBI:CHEBI:85228;
CC Evidence={ECO:0000269|PubMed:16818490};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45393;
CC Evidence={ECO:0000305|PubMed:16818490};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N,1-di-(9Z-octadecenoyl)-sn-glycero-3-
CC phosphoethanolamine = (9Z)-octadecenoate + H(+) + N-(9Z-
CC octadecenoyl)-sn-glycero-3-phosphoethanolamine; Xref=Rhea:RHEA:45396,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823,
CC ChEBI:CHEBI:85222, ChEBI:CHEBI:85229;
CC Evidence={ECO:0000269|PubMed:16818490};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45397;
CC Evidence={ECO:0000305|PubMed:16818490};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-1-(9Z-octadecenoyl)-
CC sn-glycero-3-phosphoethanolamine = (9Z)-octadecenoate + H(+) + N-
CC (5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphoethanolamine;
CC Xref=Rhea:RHEA:45400, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:85223, ChEBI:CHEBI:85230;
CC Evidence={ECO:0000269|PubMed:16818490};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45401;
CC Evidence={ECO:0000305|PubMed:16818490};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-octadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phospho-(N-
CC hexadecanoyl)-serine + H2O = (9Z)-octadecenoate + 1-octadecanoyl-2-
CC hydroxy-sn-glycero-3-phospho-(N-hexadecanoyl)-serine + H(+);
CC Xref=Rhea:RHEA:55236, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:138661, ChEBI:CHEBI:138662;
CC Evidence={ECO:0000269|PubMed:25853435};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55237;
CC Evidence={ECO:0000269|PubMed:25853435};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(1Z-octadecenoyl)-2-(9Z-octadecenoyl)-sn-glycero-3-phospho-
CC N-hexadecanoyl-ethanolamine + H2O = (9Z)-octadecenoate + 1-O-(1Z-
CC octadecenyl)-sn-glycero-3-phospho-N-hexadecanoyl-ethanolamine + H(+);
CC Xref=Rhea:RHEA:55240, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:137009, ChEBI:CHEBI:138663;
CC Evidence={ECO:0000269|PubMed:25853435};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55241;
CC Evidence={ECO:0000269|PubMed:25853435};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N,1-diacyl-sn-glycero-3-phosphoethanolamine = a fatty
CC acid + H(+) + N-acyl-sn-glycero-3-phosphoethanolamine;
CC Xref=Rhea:RHEA:45420, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:28868, ChEBI:CHEBI:85216, ChEBI:CHEBI:85225;
CC Evidence={ECO:0000269|PubMed:16818490};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45421;
CC Evidence={ECO:0000305|PubMed:16818490};
CC -!- TISSUE SPECIFICITY: Highest levels in the CNS and in testis,
CC intermediate levels in liver and kidney. Hardly detectable in heart.
CC {ECO:0000269|PubMed:16818490}.
CC -!- DISRUPTION PHENOTYPE: Homozygous knockout ABHD4 mice are born at the
CC expected Mendelian frequency, are viable and healthy, and show no overt
CC differences in their cage behavior compared to that of wild-type
CC littermates. {ECO:0000269|PubMed:25853435}.
CC -!- SIMILARITY: Belongs to the peptidase S33 family. ABHD4/ABHD5 subfamily.
CC {ECO:0000305}.
CC -!- CAUTION: Thr-291 is present instead of the conserved His which is
CC expected to be an active site residue. {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; AK049366; BAC33711.1; -; mRNA.
DR EMBL; BC017532; AAH17532.1; -; mRNA.
DR CCDS; CCDS56954.1; -.
DR RefSeq; NP_001192110.1; NM_001205181.1.
DR RefSeq; NP_598837.2; NM_134076.2.
DR AlphaFoldDB; Q8VD66; -.
DR SMR; Q8VD66; -.
DR BioGRID; 222867; 3.
DR STRING; 10090.ENSMUSP00000044134; -.
DR SwissLipids; SLP:000001119; -.
DR ESTHER; mouse-abhd4; CGI-58_ABHD5_ABHD4.
DR MEROPS; S33.013; -.
DR iPTMnet; Q8VD66; -.
DR PhosphoSitePlus; Q8VD66; -.
DR EPD; Q8VD66; -.
DR MaxQB; Q8VD66; -.
DR PaxDb; Q8VD66; -.
DR PRIDE; Q8VD66; -.
DR ProteomicsDB; 285906; -.
DR Antibodypedia; 4; 231 antibodies from 31 providers.
DR DNASU; 105501; -.
DR Ensembl; ENSMUST00000041197; ENSMUSP00000044134; ENSMUSG00000040997.
DR GeneID; 105501; -.
DR KEGG; mmu:105501; -.
DR UCSC; uc007tvo.2; mouse.
DR CTD; 63874; -.
DR MGI; MGI:1915938; Abhd4.
DR VEuPathDB; HostDB:ENSMUSG00000040997; -.
DR eggNOG; KOG4409; Eukaryota.
DR GeneTree; ENSGT00390000016277; -.
DR InParanoid; Q8VD66; -.
DR OMA; DWMDPEG; -.
DR OrthoDB; 1555935at2759; -.
DR PhylomeDB; Q8VD66; -.
DR Reactome; R-MMU-1482839; Acyl chain remodelling of PE.
DR BioGRID-ORCS; 105501; 1 hit in 76 CRISPR screens.
DR ChiTaRS; Abhd4; mouse.
DR PRO; PR:Q8VD66; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q8VD66; protein.
DR Bgee; ENSMUSG00000040997; Expressed in adrenal gland and 257 other tissues.
DR ExpressionAtlas; Q8VD66; baseline and differential.
DR GO; GO:0005811; C:lipid droplet; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0052689; F:carboxylic ester hydrolase activity; IBA:GO_Central.
DR GO; GO:0042171; F:lysophosphatidic acid acyltransferase activity; IBA:GO_Central.
DR GO; GO:0004622; F:lysophospholipase activity; IDA:MGI.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0055088; P:lipid homeostasis; IBA:GO_Central.
DR GO; GO:0070291; P:N-acylethanolamine metabolic process; IDA:MGI.
DR GO; GO:0070292; P:N-acylphosphatidylethanolamine metabolic process; IMP:UniProtKB.
DR GO; GO:0006654; P:phosphatidic acid biosynthetic process; IBA:GO_Central.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR000073; AB_hydrolase_1.
DR Pfam; PF00561; Abhydrolase_1; 1.
DR PRINTS; PR00111; ABHYDROLASE.
DR SUPFAM; SSF53474; SSF53474; 1.
PE 1: Evidence at protein level;
KW Hydrolase; Lipid degradation; Lipid metabolism; Reference proteome.
FT CHAIN 1..342
FT /note="(Lyso)-N-acylphosphatidylethanolamine lipase"
FT /id="PRO_0000080865"
FT DOMAIN 70..323
FT /note="AB hydrolase-1"
FT /evidence="ECO:0000255"
SQ SEQUENCE 342 AA; 38861 MW; 902E8AA7133FFF99 CRC64;
MADDLEQQPQ GWLSSWLPTW RPTSMSQLKN VEARILQCLQ NKFLARYVSL PNQNKIWTVT
VSPEQKDRTP LVMVHGFGGG VGLWILNMDS LSARRTLHTF DLLGFGRSSR PTFPRDPEGA
EDEFVASIET WRETMGIPTM ILLGHSLGGF LATSYSIKYP ERVKHLILVD PWGFPLRPTD
PSEIRAPPTW VKAVASVLGR SNPLAVLRVA GPWGPGLVQR FRPDFKRKFA DFFEDDTISE
YIYHCNAQNP SGETAFKAMM ESFGWARRPM LERIHLIRKD VPITMIYGAN TWIDTSTGKK
VKMQRPDSYV RDMEIEGASH HVYADQPHIF NAVVEEICNS VD
