Q8WTS1 (ABHD5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
1-acylglycerol-3-phosphate O-acyltransferase ABHD5
EC=2.3.1.51

Alternative name(s):
Abhydrolase domain-containing protein 5
Lipid droplet-binding protein CGI-58

Gene names

Name:	ABHD5
Synonyms:	NCIE2
ORF Names:	CGI-58

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	349 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Lysophosphatidic acid acyltransferase which functions in phosphatidic acid biosynthesis. May regulate the cellular storage of triacylglycerol through activation of the phospholipase PNPLA2. Involved in keratinocyte differentiation. Ref.7 Ref.8 Ref.9
Catalytic activity	Acyl-CoA + 1-acyl-sn-glycerol 3-phosphate = CoA + 1,2-diacyl-sn-glycerol 3-phosphate. Ref.9
Subunit structure	Interacts with ADRP, PLIN and PNPLA2 By similarity.
Subcellular location	Cytoplasm. Lipid droplet By similarity. Note: Colocalized with PLIN and ADRP on the surface of lipid droplets. The localization is dependent upon the metabolic status of the adipocytes and the activity of PKA By similarity. Ref.8
Tissue specificity	Widely expressed in various tissues, including lymphocytes, liver, skeletal muscle and brain. Expressed by upper epidermal layers and dermal fibroblasts in skin, hepatocytes and neurons (at protein level). Ref.1 Ref.8
Developmental stage	Detected in fetal epidermis from 49 to 135 days estimated gestational age (at protein level). Ref.8
Induction	Up-regulated upon keratinocyte differentiation (at protein level). Ref.8
Domain	The HXXXXD motif is essential for acyltransferase activity and may constitute the binding site for the phosphate moiety of the glycerol-3-phosphate By similarity.
Involvement in disease	Chanarin-Dorfman syndrome (CDS) [MIM:275630]: An autosomal recessive inborn error of lipid metabolism with multisystemic accumulation of triglycerides although plasma concentrations are normal. Clinical characteristics are congenital generalized ichthyosis, vacuolated leukocytes, hepatomegaly, myopathy, cataracts, neurosensory hearing loss and developmental delay. The disorder presents at birth with generalized, fine, white scaling of the skin and a variable degree of erythema resembling non-bullous congenital ichthyosiform erythroderma. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.7 Ref.9 Ref.11
Sequence similarities	Belongs to the peptidase S33 family. ABHD4/ABHD5 subfamily.

Ontologies

Keywords
Biological process	Differentiation Fatty acid metabolism Lipid biosynthesis Lipid metabolism Phospholipid biosynthesis Phospholipid metabolism
Cellular component	Cytoplasm Lipid droplet
Disease	Cataract Deafness Disease mutation Ichthyosis
Molecular function	Acyltransferase Transferase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW fatty acid metabolic process Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of sequestering of triglyceride Inferred from direct assay Ref.7. Source: UniProtKB phosphatidic acid biosynthetic process Inferred from direct assay Ref.9. Source: UniProtKB positive regulation of lipoprotein lipase activity Inferred from electronic annotation. Source: Compara positive regulation of triglyceride catabolic process Inferred from direct assay Ref.7. Source: UniProtKB small molecule metabolic process Traceable author statement. Source: Reactome triglyceride catabolic process Traceable author statement. Source: Reactome
Cellular_component	cytosol Inferred from sequence or structural similarity. Source: UniProtKB lipid particle Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	1-acylglycerol-3-phosphate O-acyltransferase activity Inferred from electronic annotation. Source: EC lysophosphatidic acid acyltransferase activity Inferred from direct assay Ref.9. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 349	349	1-acylglycerol-3-phosphate O-acyltransferase ABHD5		PRO_0000080866
Regions
	Motif	327 – 332	6	HXXXXD motif
Natural variations
	Natural variant	7	1	E → K in CDS. Ref.1		VAR_023387
	Natural variant	72	1	I → T. Corresponds to variant rs2302349 [ dbSNP | Ensembl ].		VAR_037574
	Natural variant	82	1	H → R Found in a patient with CDS but without evidence it may cause the disease. Ref.10		VAR_057953
	Natural variant	115	1	S → G in CDS. Ref.11		VAR_057954
	Natural variant	130	1	Q → P in CDS; loss of PNPLA2-dependent triacylclycerol hydrolysis but no effect on LPA acyltransferase activity. Ref.1 Ref.7 Ref.9 Corresponds to variant rs28939077 [ dbSNP | Ensembl ].		VAR_023388
	Natural variant	260	1	E → K in CDS; loss of PNPLA2-dependent triacylclycerol hydrolysis but no effect on LPA acyltransferase activity. Ref.1 Ref.7 Ref.9 Corresponds to variant rs28939078 [ dbSNP | Ensembl ].		VAR_023389
Experimental info
	Sequence conflict	263	1	F → S in AAD34053. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q8WTS1 [UniParc]. Last modified March 1, 2002. Version 1. Checksum: 85958A2DEC169C82	FASTA	349	39,096
	10 20 30 40 50 60 MAAEEEEVDS ADTGERSGWL TGWLPTWCPT SISHLKEAEE KMLKCVPCTY KKEPVRISNG 70 80 90 100 110 120 NKIWTLKFSH NISNKTPLVL LHGFGGGLGL WALNFGDLCT NRPVYAFDLL GFGRSSRPRF 130 140 150 160 170 180 DSDAEEVENQ FVESIEEWRC ALGLDKMILL GHNLGGFLAA AYSLKYPSRV NHLILVEPWG 190 200 210 220 230 240 FPERPDLADQ DRPIPVWIRA LGAALTPFNP LAGLRIAGPF GLSLVQRLRP DFKRKYSSMF 250 260 270 280 290 300 EDDTVTEYIY HCNVQTPSGE TAFKNMTIPY GWAKRPMLQR IGKMHPDIPV SVIFGARSCI 310 320 330 340 DGNSGTSIQS LRPHSYVKTI AILGAGHYVY ADQPEEFNQK VKEICDTVD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mutations in CGI-58, the gene encoding a new protein of the esterase/lipase/thioesterase subfamily, in Chanarin-Dorfman syndrome." Lefevre C., Jobard F., Caux F., Bouadjar B., Karaduman A., Heilig R., Lakhdar H., Wollenberg A., Verret J.-L., Weissenbach J., Oezguec M., Lathrop M., Prud'homme J.-F., Fischer J. Am. J. Hum. Genet. 69:1002-1012(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY, VARIANTS CDS LYS-7; PRO-130 AND LYS-260.
[2]	"Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics." Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C. Genome Res. 10:703-713(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Substantia nigra.
[4]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Skin.
[7]	"Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is activated by CGI-58 and defective in Chanarin-Dorfman Syndrome." Lass A., Zimmermann R., Haemmerle G., Riederer M., Schoiswohl G., Schweiger M., Kienesberger P., Strauss J.G., Gorkiewicz G., Zechner R. Cell Metab. 3:309-319(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS CDS PRO-130 AND LYS-260.
[8]	"CGI-58 is an alpha/beta-hydrolase within lipid transporting lamellar granules of differentiated keratinocytes." Akiyama M., Sakai K., Takayama C., Yanagi T., Yamanaka Y., McMillan J.R., Shimizu H. Am. J. Pathol. 173:1349-1360(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INDUCTION.
[9]	"CGI-58, the causative gene for Chanarin-Dorfman syndrome, mediates acylation of lysophosphatidic acid." Ghosh A.K., Ramakrishnan G., Chandramohan C., Rajasekharan R. J. Biol. Chem. 283:24525-24533(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, CHARACTERIZATION OF VARIANTS CDS PRO-130 AND LYS-260.
[10]	"Two new mutations of the ABHD5 gene in a new adult case of Chanarin Dorfman syndrome: an uncommon lipid storage disease." Schleinitz N., Fischer J., Sanchez A., Veit V., Harle J.-R., Pelissier J.-F. Arch. Dermatol. 141:798-800(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ARG-82.
[11]	"A novel S115G mutation of CGI-58 in a Turkish patient with Dorfman-Chanarin syndrome." Ben Selma Z., Yilmaz S., Schischmanoff P.O., Blom A., Ozogul C., Laroche L., Caux F. J. Invest. Dermatol. 127:2273-2276(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CDS GLY-115.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AL606838 Genomic DNA. Translation: CAD12731.1. AF151816 mRNA. Translation: AAD34053.1. AK313811 mRNA. Translation: BAG36547.1. AC105903 Genomic DNA. No translation available. CH471055 Genomic DNA. Translation: EAW64699.1. BC021958 mRNA. Translation: AAH21958.1.
IPI	IPI00290979.
RefSeq	NP_057090.2. NM_016006.4.
UniGene	Hs.19385.
3D structure databases
ProteinModelPortal	Q8WTS1.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8WTS1. 2 interactions.
STRING	9606.ENSP00000390849.
Protein family/group databases
MEROPS	S33.975.
PTM databases
PhosphoSite	Q8WTS1.
Polymorphism databases
DMDM	73921640.
Proteomic databases
PaxDb	Q8WTS1.
PeptideAtlas	Q8WTS1.
PRIDE	Q8WTS1.
Protocols and materials databases
DNASU	51099.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000458276; ENSP00000390849; ENSG00000011198.
GeneID	51099.
KEGG	hsa:51099.
UCSC	uc003cmx.3. human.
Organism-specific databases
CTD	51099.
GeneCards	GC03P043707.
HGNC	HGNC:21396. ABHD5.
HPA	CAB020685. HPA035851. HPA035852.
MIM	275630. phenotype. 604780. gene.
neXtProt	NX_Q8WTS1.
Orphanet	98907. Dorfman-Chanarin disease.
PharmGKB	PA134891622.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0596.
HOGENOM	HOG000007445.
HOVERGEN	HBG054445.
InParanoid	Q8WTS1.
KO	K13699.
OMA	YHLNAQT.
PhylomeDB	Q8WTS1.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	Q8WTS1.
Bgee	Q8WTS1.
CleanEx	HS_ABHD5.
Genevestigator	Q8WTS1.
GermOnline	ENSG00000011198. Homo sapiens.
Family and domain databases
InterPro	IPR000073. AB_hydrolase_1. [Graphical view]
PRINTS	PR00111. ABHYDROLASE.
ProtoNet	Search...
Other
ChEMBL	CHEMBL1741206.
GenomeRNAi	51099.
NextBio	53805.
SOURCE	Search...

Entry information

Entry name

ABHD5_HUMAN

Accession

Primary (citable) accession number: Q8WTS1
Secondary accession number(s): B2R9K0, Q9Y369

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 30, 2005
Last sequence update:	March 1, 2002
Last modified:	May 1, 2013
This is version 105 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.