ID   ABHD5_HUMAN             Reviewed;         349 AA.
AC   Q8WTS1; B2R9K0; Q9Y369;
DT   30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2002, sequence version 1.
DT   03-NOV-2009, entry version 74.
DE   RecName: Full=1-acylglycerol-3-phosphate O-acyltransferase ABHD5;
DE            EC=2.3.1.51;
DE   AltName: Full=Abhydrolase domain-containing protein 5;
DE   AltName: Full=Lipid droplet-binding protein CGI-58;
GN   Name=ABHD5; Synonyms=NCIE2; ORFNames=CGI-58;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY, AND VARIANTS
RP   CDS LYS-7; PRO-130 AND LYS-260.
RX   PubMed=11590543; DOI=10.1086/324121;
RA   Lefevre C., Jobard F., Caux F., Bouadjar B., Karaduman A., Heilig R.,
RA   Lakhdar H., Wollenberg A., Verret J.-L., Weissenbach J., Oezguec M.,
RA   Lathrop M., Prud'homme J.-F., Fischer J.;
RT   "Mutations in CGI-58, the gene encoding a new protein of the
RT   esterase/lipase/thioesterase subfamily, in Chanarin-Dorfman
RT   syndrome.";
RL   Am. J. Hum. Genet. 69:1002-1012(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   MEDLINE=20272150; PubMed=10810093; DOI=10.1101/gr.10.5.703;
RA   Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.;
RT   "Identification of novel human genes evolutionarily conserved in
RT   Caenorhabditis elegans by comparative proteomics.";
RL   Genome Res. 10:703-713(2000).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Substantia nigra;
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.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   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.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., 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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16641997; DOI=10.1038/nature04728;
RA   Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA   Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA   Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA   Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA   Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA   Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA   Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA   Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA   Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA   Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA   Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA   Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA   Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA   Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA   Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA   Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA   Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA   Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA   Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA   Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA   Gibbs R.A.;
RT   "The DNA sequence, annotation and analysis of human chromosome 3.";
RL   Nature 440:1194-1198(2006).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Skin;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [7]
RP   FUNCTION, AND CHARACTERIZATION OF VARIANTS CDS PRO-130 AND LYS-260.
RX   PubMed=16679289; DOI=10.1016/j.cmet.2006.03.005;
RA   Lass A., Zimmermann R., Haemmerle G., Riederer M., Schoiswohl G.,
RA   Schweiger M., Kienesberger P., Strauss J.G., Gorkiewicz G.,
RA   Zechner R.;
RT   "Adipose triglyceride lipase-mediated lipolysis of cellular fat stores
RT   is activated by CGI-58 and defective in Chanarin-Dorfman Syndrome.";
RL   Cell Metab. 3:309-319(2006).
RN   [8]
RP   FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL
RP   STAGE, AND INDUCTION.
RX   PubMed=18832586; DOI=10.2353/ajpath.2008.080005;
RA   Akiyama M., Sakai K., Takayama C., Yanagi T., Yamanaka Y.,
RA   McMillan J.R., Shimizu H.;
RT   "CGI-58 is an alpha/beta-hydrolase within lipid transporting lamellar
RT   granules of differentiated keratinocytes.";
RL   Am. J. Pathol. 173:1349-1360(2008).
RN   [9]
RP   FUNCTION, CATALYTIC ACTIVITY, AND CHARACTERIZATION OF VARIANTS CDS
RP   PRO-130 AND LYS-260.
RX   PubMed=18606822; DOI=10.1074/jbc.M801783200;
RA   Ghosh A.K., Ramakrishnan G., Chandramohan C., Rajasekharan R.;
RT   "CGI-58, the causative gene for Chanarin-Dorfman syndrome, mediates
RT   acylation of lysophosphatidic acid.";
RL   J. Biol. Chem. 283:24525-24533(2008).
RN   [10]
RP   VARIANT ARG-82.
RX   PubMed=15967942; DOI=10.1001/archderm.141.6.798;
RA   Schleinitz N., Fischer J., Sanchez A., Veit V., Harle J.-R.,
RA   Pelissier J.-F.;
RT   "Two new mutations of the ABHD5 gene in a new adult case of Chanarin
RT   Dorfman syndrome: an uncommon lipid storage disease.";
RL   Arch. Dermatol. 141:798-800(2005).
RN   [11]
RP   VARIANT CDS GLY-115.
RX   PubMed=17495960; DOI=10.1038/sj.jid.5700860;
RA   Ben Selma Z., Yilmaz S., Schischmanoff P.O., Blom A., Ozogul C.,
RA   Laroche L., Caux F.;
RT   "A novel S115G mutation of CGI-58 in a Turkish patient with Dorfman-
RT   Chanarin syndrome.";
RL   J. Invest. Dermatol. 127:2273-2276(2007).
CC   -!- FUNCTION: Lysophosphatidic acid acyltransferase which functions in
CC       phosphatidic acid biosynthesis. May regulate the cellular storage
CC       of triacylglycerol through activation of the phospholipase PNPLA2.
CC       Involved in keratinocyte differentiation.
CC   -!- CATALYTIC ACTIVITY: Acyl-CoA + 1-acyl-sn-glycerol 3-phosphate =
CC       CoA + 1,2-diacyl-sn-glycerol 3-phosphate.
CC   -!- SUBUNIT: Interacts with ADRP, PLIN and PNPLA2 (By similarity).
CC   -!- SUBCELLULAR LOCATION: Cytoplasm. Lipid droplet (By similarity).
CC       Note=Colocalized with PLIN and ADRP on the surface of lipid
CC       droplets. The localization is dependent upon the metabolic status
CC       of the adipocytes and the activity of PKA (By similarity).
CC   -!- TISSUE SPECIFICITY: Widely expressed in various tissues, including
CC       lymphocytes, liver, skeletal muscle and brain. Expressed by upper
CC       epidermal layers and dermal fibroblasts in skin, hepatocytes and
CC       neurons (at protein level).
CC   -!- DEVELOPMENTAL STAGE: Detected in fetal epidermis from 49 to 135
CC       days estimated gestational age (at protein level).
CC   -!- INDUCTION: Up-regulated upon keratinocyte differentiation (at
CC       protein level).
CC   -!- DOMAIN: The HXXXXD motif is essential for acyltransferase activity
CC       and may constitute the binding site for the phosphate moiety of
CC       the glycerol-3-phosphate (By similarity).
CC   -!- DISEASE: Defects in ABHD5 are the cause of Chanarin-Dorfman
CC       syndrome (CDS) [MIM:275630]; also called triglyceride storage
CC       disease with impaired long-chain fatty acid oxidation or neutral
CC       lipid storage disease with ichthyosis. CDS is an autosomal
CC       recessive inborn error of lipid metabolism with multisystemic
CC       accumulation of triglycerides although plasma concentrations are
CC       normal. Clinical characteristics are congenital generalized
CC       ichthyosis, vacuolated leukocytes, hepatomegaly, myopathy,
CC       cataracts, neurosensory hearing loss and developmental delay. The
CC       disorder presents at birth with generalized, fine, white scaling
CC       of the skin and a variable degree of erythema resembling non-
CC       bullous congenital ichthyosiform erythroderma.
CC   -!- SIMILARITY: Belongs to the peptidase S33 family. ABHD4/ABHD5
CC       subfamily.
CC   -!- WEB RESOURCE: Name=GeneReviews;
CC       URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/ABHD5";
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DR   EMBL; AL606838; CAD12731.1; -; Genomic_DNA.
DR   EMBL; AF151816; AAD34053.1; -; mRNA.
DR   EMBL; AK313811; BAG36547.1; -; mRNA.
DR   EMBL; AC105903; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471055; EAW64699.1; -; Genomic_DNA.
DR   EMBL; BC021958; AAH21958.1; -; mRNA.
DR   IPI; IPI00290979; -.
DR   RefSeq; NP_057090.2; -.
DR   UniGene; Hs.19385; -.
DR   STRING; Q8WTS1; -.
DR   MEROPS; S33.975; -.
DR   PeptideAtlas; Q8WTS1; -.
DR   PRIDE; Q8WTS1; -.
DR   Ensembl; ENST00000013894; ENSP00000013894; ENSG00000011198; Homo sapiens.
DR   Ensembl; ENST00000413300; ENSP00000392159; ENSG00000011198; Homo sapiens.
DR   Ensembl; ENST00000454293; ENSP00000412014; ENSG00000011198; Homo sapiens.
DR   Ensembl; ENST00000456453; ENSP00000391582; ENSG00000011198; Homo sapiens.
DR   Ensembl; ENST00000458276; ENSP00000390849; ENSG00000011198; Homo sapiens.
DR   GeneID; 51099; -.
DR   KEGG; hsa:51099; -.
DR   UCSC; uc003cmx.1; human.
DR   CTD; 51099; -.
DR   GeneCards; GC03P043707; -.
DR   HGNC; HGNC:21396; ABHD5.
DR   HPA; CAB020685; -.
DR   MIM; 275630; phenotype.
DR   MIM; 604780; gene.
DR   Orphanet; 98907; Dorfman-Chanarin disease.
DR   Orphanet; 79394; Erythroderma, congenital ichthyosiform, nonbullous.
DR   Orphanet; 313; Ichthyosis, lamellar.
DR   Orphanet; 165; Neutral lipid storage disease.
DR   PharmGKB; PA134891622; -.
DR   HOGENOM; Q8WTS1; -.
DR   HOVERGEN; Q8WTS1; -.
DR   OMA; VENQFVE; -.
DR   Reactome; REACT_602; Metabolism of lipids and lipoproteins.
DR   NextBio; 53805; -.
DR   ArrayExpress; Q8WTS1; -.
DR   Bgee; Q8WTS1; -.
DR   CleanEx; HS_ABHD5; -.
DR   Genevestigator; Q8WTS1; -.
DR   GermOnline; ENSG00000011198; Homo sapiens.
DR   GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR   GO; GO:0012511; C:monolayer-surrounded lipid storage body; IEA:UniProtKB-SubCell.
DR   GO; GO:0003841; F:1-acylglycerol-3-phosphate O-acyltransferas...; IEA:EC.
DR   GO; GO:0016787; F:hydrolase activity; IEA:InterPro.
DR   GO; GO:0042171; F:lysophosphatidic acid acyltransferase activity; IDA:UniProtKB.
DR   GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR   GO; GO:0006631; P:fatty acid metabolic process; IEA:UniProtKB-KW.
DR   GO; GO:0010891; P:negative regulation of sequestering of trig...; IDA:UniProtKB.
DR   GO; GO:0006654; P:phosphatidic acid biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0010898; P:positive regulation of triglyceride catabol...; IDA:UniProtKB.
DR   InterPro; IPR000073; AB_hydrolase_1.
DR   Pfam; PF00561; Abhydrolase_1; 1.
PE   1: Evidence at protein level;
KW   Acyltransferase; Cataract; Complete proteome; Cytoplasm; Deafness;
KW   Differentiation; Disease mutation; Fatty acid metabolism; Ichthyosis;
KW   Lipid droplet; Lipid metabolism; Phospholipid biosynthesis;
KW   Transferase.
FT   CHAIN         1    349       1-acylglycerol-3-phosphate O-
FT                                acyltransferase ABHD5.
FT                                /FTId=PRO_0000080866.
FT   MOTIF       327    332       HXXXXD motif.
FT   VARIANT       7      7       E -> K (in CDS).
FT                                /FTId=VAR_023387.
FT   VARIANT      72     72       I -> T (in dbSNP:rs2302349).
FT                                /FTId=VAR_037574.
FT   VARIANT      82     82       H -> R (found in a patient with CDS but
FT                                without evidence it may cause the
FT                                disease).
FT                                /FTId=VAR_057953.
FT   VARIANT     115    115       S -> G (in CDS).
FT                                /FTId=VAR_057954.
FT   VARIANT     130    130       Q -> P (in CDS; loss of PNPLA2-dependent
FT                                triacylclycerol hydrolysis but no effect
FT                                on LPA acyltransferase activity;
FT                                dbSNP:rs28939077).
FT                                /FTId=VAR_023388.
FT   VARIANT     260    260       E -> K (in CDS; loss of PNPLA2-dependent
FT                                triacylclycerol hydrolysis but no effect
FT                                on LPA acyltransferase activity).
FT                                /FTId=VAR_023389.
FT   CONFLICT    263    263       F -> S (in Ref. 2; AAD34053).
SQ   SEQUENCE   349 AA;  39096 MW;  85958A2DEC169C82 CRC64;
     MAAEEEEVDS ADTGERSGWL TGWLPTWCPT SISHLKEAEE KMLKCVPCTY KKEPVRISNG
     NKIWTLKFSH NISNKTPLVL LHGFGGGLGL WALNFGDLCT NRPVYAFDLL GFGRSSRPRF
     DSDAEEVENQ FVESIEEWRC ALGLDKMILL GHNLGGFLAA AYSLKYPSRV NHLILVEPWG
     FPERPDLADQ DRPIPVWIRA LGAALTPFNP LAGLRIAGPF GLSLVQRLRP DFKRKYSSMF
     EDDTVTEYIY HCNVQTPSGE TAFKNMTIPY GWAKRPMLQR IGKMHPDIPV SVIFGARSCI
     DGNSGTSIQS LRPHSYVKTI AILGAGHYVY ADQPEEFNQK VKEICDTVD
//