LDAH_HUMAN
ID LDAH_HUMAN Reviewed; 325 AA.
AC Q9H6V9; B7ZA47; B7ZAJ5; D6W530; E7ESN0; Q53T37; Q53T58;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Lipid droplet-associated hydrolase {ECO:0000312|HGNC:HGNC:26145};
DE EC=3.1.1.- {ECO:0000250|UniProtKB:Q8BVA5};
DE AltName: Full=Lipid droplet-associated serine hydrolase {ECO:0000303|PubMed:24357060};
DE Short=hLDAH {ECO:0000303|PubMed:24357060};
GN Name=LDAH {ECO:0000303|PubMed:24357060, ECO:0000312|HGNC:HGNC:26145};
GN Synonyms=C2orf43 {ECO:0000312|HGNC:HGNC:26145};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 4), AND
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-184 (ISOFORM 2).
RC TISSUE=Brain, and Kidney;
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Pancreas;
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION.
RX PubMed=17135363; DOI=10.1096/fj.06-6711com;
RA Wan H.C., Melo R.C., Jin Z., Dvorak A.M., Weller P.F.;
RT "Roles and origins of leukocyte lipid bodies: proteomic and ultrastructural
RT studies.";
RL FASEB J. 21:167-178(2007).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=24357060; DOI=10.1161/atvbaha.113.302448;
RA Goo Y.H., Son S.H., Kreienberg P.B., Paul A.;
RT "Novel lipid droplet-associated serine hydrolase regulates macrophage
RT cholesterol mobilization.";
RL Arterioscler. Thromb. Vasc. Biol. 34:386-396(2014).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
CC -!- FUNCTION: Probable serine lipid hydrolase associated with lipid
CC droplets. Appears to lack cholesterol esterase activity. Appears to
CC lack triglyceride lipase activity. Highly expressed in macrophage-rich
CC areas in atherosclerotic lesions, suggesting that it could promote
CC cholesterol ester turnover in macrophages.
CC {ECO:0000250|UniProtKB:Q8BVA5}.
CC -!- SUBCELLULAR LOCATION: Lipid droplet {ECO:0000269|PubMed:17135363}.
CC Endoplasmic reticulum {ECO:0000250|UniProtKB:Q8BVA5}. Note=Localizes to
CC the endoplasmic reticulum in absence of lipid droplets and translocates
CC to lipid droplets upon lipid storage induction.
CC {ECO:0000250|UniProtKB:Q8BVA5}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q9H6V9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H6V9-2; Sequence=VSP_042202;
CC Name=3;
CC IsoId=Q9H6V9-3; Sequence=VSP_054624;
CC Name=4;
CC IsoId=Q9H6V9-4; Sequence=VSP_055283;
CC -!- TISSUE SPECIFICITY: Present in macrophage-rich areas in atherosclerotic
CC lesionsv(at protein level). {ECO:0000269|PubMed:24357060}.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. LDAH family.
CC {ECO:0000305}.
CC -!- CAUTION: The catalytic activity is unsure despite catalytic sites being
CC conserved. {ECO:0000250|UniProtKB:Q8BVA5}.
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DR EMBL; AK025473; BAB15142.1; -; mRNA.
DR EMBL; AK316162; BAH14533.1; -; mRNA.
DR EMBL; AK316204; BAH14575.1; -; mRNA.
DR EMBL; AK316310; BAH14681.1; -; mRNA.
DR EMBL; DC325170; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC012361; AAY14959.1; -; Genomic_DNA.
DR EMBL; AC012065; AAX93236.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00809.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00810.1; -; Genomic_DNA.
DR EMBL; BC017473; AAH17473.1; -; mRNA.
DR CCDS; CCDS1702.1; -. [Q9H6V9-1]
DR CCDS; CCDS62864.1; -. [Q9H6V9-4]
DR CCDS; CCDS62865.1; -. [Q9H6V9-3]
DR RefSeq; NP_001269649.1; NM_001282720.1. [Q9H6V9-3]
DR RefSeq; NP_001269650.1; NM_001282721.1. [Q9H6V9-4]
DR RefSeq; NP_001269651.1; NM_001282722.1. [Q9H6V9-4]
DR RefSeq; NP_068744.1; NM_021925.3. [Q9H6V9-1]
DR RefSeq; XP_011531316.1; XM_011533014.2. [Q9H6V9-2]
DR AlphaFoldDB; Q9H6V9; -.
DR BioGRID; 121936; 5.
DR IntAct; Q9H6V9; 2.
DR STRING; 9606.ENSP00000237822; -.
DR ESTHER; human-LDAH; LIDHydrolase.
DR iPTMnet; Q9H6V9; -.
DR PhosphoSitePlus; Q9H6V9; -.
DR SwissPalm; Q9H6V9; -.
DR BioMuta; LDAH; -.
DR DMDM; 74761484; -.
DR EPD; Q9H6V9; -.
DR jPOST; Q9H6V9; -.
DR MassIVE; Q9H6V9; -.
DR MaxQB; Q9H6V9; -.
DR PaxDb; Q9H6V9; -.
DR PeptideAtlas; Q9H6V9; -.
DR PRIDE; Q9H6V9; -.
DR ProteomicsDB; 7054; -.
DR ProteomicsDB; 7068; -.
DR ProteomicsDB; 81044; -. [Q9H6V9-1]
DR ProteomicsDB; 81045; -. [Q9H6V9-2]
DR Antibodypedia; 27316; 148 antibodies from 17 providers.
DR DNASU; 60526; -.
DR Ensembl; ENST00000237822.8; ENSP00000237822.3; ENSG00000118961.15. [Q9H6V9-1]
DR Ensembl; ENST00000541941.5; ENSP00000440570.1; ENSG00000118961.15. [Q9H6V9-4]
DR Ensembl; ENST00000619656.4; ENSP00000483067.1; ENSG00000118961.15. [Q9H6V9-4]
DR Ensembl; ENST00000626491.2; ENSP00000487592.1; ENSG00000118961.15. [Q9H6V9-3]
DR GeneID; 60526; -.
DR KEGG; hsa:60526; -.
DR MANE-Select; ENST00000237822.8; ENSP00000237822.3; NM_021925.4; NP_068744.1.
DR UCSC; uc002rec.5; human. [Q9H6V9-1]
DR CTD; 60526; -.
DR DisGeNET; 60526; -.
DR GeneCards; LDAH; -.
DR HGNC; HGNC:26145; LDAH.
DR HPA; ENSG00000118961; Low tissue specificity.
DR MIM; 613570; gene.
DR neXtProt; NX_Q9H6V9; -.
DR OpenTargets; ENSG00000118961; -.
DR PharmGKB; PA147358698; -.
DR VEuPathDB; HostDB:ENSG00000118961; -.
DR eggNOG; KOG3975; Eukaryota.
DR GeneTree; ENSGT00390000009688; -.
DR HOGENOM; CLU_018394_2_1_1; -.
DR InParanoid; Q9H6V9; -.
DR OMA; PVWVIGH; -.
DR OrthoDB; 1163030at2759; -.
DR PhylomeDB; Q9H6V9; -.
DR TreeFam; TF313050; -.
DR PathwayCommons; Q9H6V9; -.
DR SignaLink; Q9H6V9; -.
DR BioGRID-ORCS; 60526; 11 hits in 1049 CRISPR screens.
DR ChiTaRS; LDAH; human.
DR GenomeRNAi; 60526; -.
DR Pharos; Q9H6V9; Tbio.
DR PRO; PR:Q9H6V9; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9H6V9; protein.
DR Bgee; ENSG00000118961; Expressed in adrenal tissue and 171 other tissues.
DR ExpressionAtlas; Q9H6V9; baseline and differential.
DR Genevisible; Q9H6V9; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005811; C:lipid droplet; ISS:UniProtKB.
DR GO; GO:0004771; F:sterol esterase activity; ISS:UniProtKB.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0019915; P:lipid storage; IBA:GO_Central.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR019363; LDAH.
DR PANTHER; PTHR13390; PTHR13390; 1.
DR Pfam; PF10230; LIDHydrolase; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
DR PROSITE; PS00120; LIPASE_SER; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Endoplasmic reticulum; Hydrolase; Lipid degradation;
KW Lipid droplet; Lipid metabolism; Reference proteome.
FT CHAIN 1..325
FT /note="Lipid droplet-associated hydrolase"
FT /id="PRO_0000300124"
FT ACT_SITE 139
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10037"
FT ACT_SITE 271
FT /note="Charge relay system"
FT /evidence="ECO:0000305"
FT ACT_SITE 300
FT /note="Charge relay system"
FT /evidence="ECO:0000305"
FT VAR_SEQ 1..130
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055283"
FT VAR_SEQ 51
FT /note="P -> PGERKSL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042202"
FT VAR_SEQ 52..99
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054624"
SQ SEQUENCE 325 AA; 37319 MW; 6D5B414E60028DD1 CRC64;
MDSELKEEIP VHEEFILCGG AETQVLKCGP WTDLFHDQSV KRPKLLIFII PGNPGFSAFY
VPFAKALYSL TNRRFPVWTI SHAGHALAPK DKKILTTSED SNAQEIKDIY GLNGQIEHKL
AFLRTHVPKD MKLVLIGHSI GSYFTLQMLK RVPELPVIRA FLLFPTIERM SESPNGRIAT
PLLCWFRYVL YVTGYLLLKP CPETIKSLLI RRGLQVMNLE NEFSPLNILE PFCLANAAYL
GGQEMMEVVK RDDETIKEHL CKLTFYYGTI DPWCPKEYYE DIKKDFPEGD IRLCEKNIPH
AFITHFNQEM ADMIADSLKD DLSKM
