LIPH_HUMAN
ID LIPH_HUMAN Reviewed; 451 AA.
AC Q8WWY8; A2IBA7; Q8TEC7;
DT 23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Lipase member H;
DE Short=LIPH;
DE EC=3.1.1.- {ECO:0000269|PubMed:12963729};
DE AltName: Full=LPD lipase-related protein;
DE AltName: Full=Membrane-associated phosphatidic acid-selective phospholipase A1-alpha;
DE Short=mPA-PLA1 alpha;
DE AltName: Full=Phospholipase A1 member B;
DE Flags: Precursor;
GN Name=LIPH; Synonyms=LPDLR, MPAPLA1, PLA1B;
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 [MRNA], FUNCTION, ENZYME ACTIVITY, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF SER-154.
RX PubMed=12063250; DOI=10.1074/jbc.m201659200;
RA Sonoda H., Aoki J., Hiramatsu T., Ishida M., Bandoh K., Nagai Y.,
RA Taguchi R., Inoue K., Arai H.;
RT "A novel phosphatidic acid-selective phospholipase A1 that produces
RT lysophosphatidic acid.";
RL J. Biol. Chem. 277:34254-34263(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=12213196; DOI=10.1006/geno.2002.6837;
RA Jin W., Broedl U., Monajemi H., Glick J., Rader D.;
RT "Lipase h, a new member of the triglyceride lipase family synthesized by
RT the intestine.";
RL Genomics 80:268-273(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], VARIANT HYPT7 172-GLY--HIS-205 DEL, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Pancreas;
RX PubMed=17095700; DOI=10.1126/science.1133276;
RA Kazantseva A., Goltsov A., Zinchenko R., Grigorenko A.P., Abrukova A.V.,
RA Moliaka Y.K., Kirillov A.G., Guo Z., Lyle S., Ginter E.K., Rogaev E.I.;
RT "Human hair growth deficiency is linked to a genetic defect in the
RT phospholipase gene LIPH.";
RL Science 314:982-985(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
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 [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [7]
RP TISSUE SPECIFICITY.
RX PubMed=12719377; DOI=10.1093/hmg/ddg124;
RA Wen X.-Y., Hegele R.A., Wang J., Wang D.Y., Cheung J., Wilson M.,
RA Yahyapour M., Bai Y., Zhuang L., Skaug J., Young T.K., Connelly P.W.,
RA Koop B.F., Tsui L.-C., Stewart A.K.;
RT "Identification of a novel lipase gene mutated in lpd mice with
RT hypertriglyceridemia and associated with dyslipidemia in humans.";
RL Hum. Mol. Genet. 12:1131-1143(2003).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=12963729; DOI=10.1074/jbc.m213018200;
RA Hiramatsu T., Sonoda H., Takanezawa Y., Morikawa R., Ishida M.,
RA Kasahara K., Sanai Y., Taguchi R., Aoki J., Arai H.;
RT "Biochemical and molecular characterization of two phosphatidic acid-
RT selective phospholipase A1s, mPA-PLA1alpha and mPA-PLA1beta.";
RL J. Biol. Chem. 278:49438-49447(2003).
RN [9]
RP VARIANT HYPT7 ARG-108.
RX PubMed=19167195; DOI=10.1016/j.jdermsci.2008.12.001;
RA Naz G., Khan B., Ali G., Azeem Z., Wali A., Ansar M., Ahmad W.;
RT "Novel missense mutations in lipase H (LIPH) gene causing autosomal
RT recessive hypotrichosis (LAH2).";
RL J. Dermatol. Sci. 54:12-16(2009).
RN [10]
RP VARIANT ARWH2 ARG-108.
RX PubMed=18830268; DOI=10.1038/jid.2008.290;
RA Shimomura Y., Wajid M., Petukhova L., Shapiro L., Christiano A.M.;
RT "Mutations in the lipase H gene underlie autosomal recessive woolly
RT hair/hypotrichosis.";
RL J. Invest. Dermatol. 129:622-628(2009).
CC -!- FUNCTION: Hydrolyzes specifically phosphatidic acid (PA) to produce 2-
CC acyl lysophosphatidic acid (LPA; a potent bioactive lipid mediator) and
CC fatty acid. Does not hydrolyze other phospholipids, like
CC phosphatidylserine (PS), phosphatidylcholine (PC) and
CC phosphatidylethanolamine (PE) or triacylglycerol (TG).
CC {ECO:0000269|PubMed:12063250, ECO:0000269|PubMed:12963729}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphate +
CC H2O = 2-(9Z-octadecenoyl)-sn-glycero-3-phosphate + H(+) +
CC hexadecanoate; Xref=Rhea:RHEA:40943, ChEBI:CHEBI:7896,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:64839,
CC ChEBI:CHEBI:77593; Evidence={ECO:0000269|PubMed:12963729};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40944;
CC Evidence={ECO:0000305|PubMed:12963729};
CC -!- ACTIVITY REGULATION: Inhibited by sodium vanadate.
CC {ECO:0000269|PubMed:12963729}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12963729}. Cell
CC membrane {ECO:0000269|PubMed:12063250, ECO:0000269|PubMed:12963729};
CC Peripheral membrane protein.
CC -!- TISSUE SPECIFICITY: Present in intestine (at protein level). Expressed
CC in colon, prostate, kidney, pancreas, ovary, testis, intestine, lung
CC and pancreas. Expressed at lower level in brain, spleen and heart. In
CC hair, it is prominently expressed in hair follicles, including the stem
CC cell-rich bulge region. {ECO:0000269|PubMed:12063250,
CC ECO:0000269|PubMed:12213196, ECO:0000269|PubMed:12719377,
CC ECO:0000269|PubMed:17095700}.
CC -!- DISEASE: Hypotrichosis 7 (HYPT7) [MIM:604379]: A condition
CC characterized by the presence of less than the normal amount of hair.
CC Affected individuals have sparse or absent scalp, axillary and body
CC hair and sparse eyebrows and eyelashes. HYPT7 inheritance is autosomal
CC recessive. {ECO:0000269|PubMed:17095700, ECO:0000269|PubMed:19167195}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Woolly hair autosomal recessive 2 (ARWH2) [MIM:604379]: A hair
CC shaft disorder characterized by fine and tightly curled hair. Compared
CC to normal curly hair that is observed in some populations, woolly hair
CC grows slowly and stops growing after a few inches. Under light
CC microscopy, woolly hair shows some structural anomalies, including
CC trichorrhexis nodosa and tapered ends. Some individuals may present
CC with hypotrichosis. {ECO:0000269|PubMed:18830268}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. Lipase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB85023.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY036912; AAK63178.1; -; mRNA.
DR EMBL; AY093498; AAM18803.1; -; mRNA.
DR EMBL; EF186229; ABM67095.1; -; mRNA.
DR EMBL; AK074229; BAB85023.1; ALT_INIT; mRNA.
DR EMBL; AK122651; BAG53642.1; -; mRNA.
DR EMBL; CH471052; EAW78218.1; -; Genomic_DNA.
DR EMBL; BC064941; AAH64941.1; -; mRNA.
DR CCDS; CCDS3272.1; -.
DR RefSeq; NP_640341.1; NM_139248.2.
DR AlphaFoldDB; Q8WWY8; -.
DR SMR; Q8WWY8; -.
DR BioGRID; 128352; 98.
DR IntAct; Q8WWY8; 26.
DR STRING; 9606.ENSP00000296252; -.
DR SwissLipids; SLP:000000625; -.
DR ESTHER; human-LIPH; Phospholipase.
DR GlyGen; Q8WWY8; 3 sites.
DR iPTMnet; Q8WWY8; -.
DR PhosphoSitePlus; Q8WWY8; -.
DR BioMuta; LIPH; -.
DR DMDM; 74762634; -.
DR EPD; Q8WWY8; -.
DR MassIVE; Q8WWY8; -.
DR PaxDb; Q8WWY8; -.
DR PeptideAtlas; Q8WWY8; -.
DR PRIDE; Q8WWY8; -.
DR ProteomicsDB; 74960; -.
DR Antibodypedia; 33838; 93 antibodies from 23 providers.
DR DNASU; 200879; -.
DR Ensembl; ENST00000296252.9; ENSP00000296252.4; ENSG00000163898.10.
DR GeneID; 200879; -.
DR KEGG; hsa:200879; -.
DR MANE-Select; ENST00000296252.9; ENSP00000296252.4; NM_139248.3; NP_640341.1.
DR UCSC; uc003fpm.4; human.
DR CTD; 200879; -.
DR DisGeNET; 200879; -.
DR GeneCards; LIPH; -.
DR HGNC; HGNC:18483; LIPH.
DR HPA; ENSG00000163898; Tissue enhanced (intestine, stomach).
DR MalaCards; LIPH; -.
DR MIM; 604379; phenotype.
DR MIM; 607365; gene.
DR neXtProt; NX_Q8WWY8; -.
DR OpenTargets; ENSG00000163898; -.
DR Orphanet; 55654; Hypotrichosis simplex.
DR Orphanet; 170; Woolly hair.
DR PharmGKB; PA134934352; -.
DR VEuPathDB; HostDB:ENSG00000163898; -.
DR eggNOG; ENOG502QUQT; Eukaryota.
DR GeneTree; ENSGT00940000156285; -.
DR HOGENOM; CLU_027171_3_0_1; -.
DR InParanoid; Q8WWY8; -.
DR OMA; YPCSSYK; -.
DR OrthoDB; 534956at2759; -.
DR PhylomeDB; Q8WWY8; -.
DR TreeFam; TF324997; -.
DR BRENDA; 3.1.1.32; 2681.
DR PathwayCommons; Q8WWY8; -.
DR Reactome; R-HSA-1483166; Synthesis of PA.
DR SignaLink; Q8WWY8; -.
DR SIGNOR; Q8WWY8; -.
DR BioGRID-ORCS; 200879; 9 hits in 1073 CRISPR screens.
DR ChiTaRS; LIPH; human.
DR GeneWiki; LIPH; -.
DR GenomeRNAi; 200879; -.
DR Pharos; Q8WWY8; Tbio.
DR PRO; PR:Q8WWY8; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q8WWY8; protein.
DR Bgee; ENSG00000163898; Expressed in buccal mucosa cell and 131 other tissues.
DR ExpressionAtlas; Q8WWY8; baseline and differential.
DR Genevisible; Q8WWY8; HS.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0008201; F:heparin binding; IDA:UniProtKB.
DR GO; GO:0016298; F:lipase activity; IBA:GO_Central.
DR GO; GO:0004465; F:lipoprotein lipase activity; IBA:GO_Central.
DR GO; GO:0004620; F:phospholipase activity; IDA:UniProtKB.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IBA:GO_Central.
DR GO; GO:0016042; P:lipid catabolic process; IDA:UniProtKB.
DR GO; GO:0006654; P:phosphatidic acid biosynthetic process; TAS:Reactome.
DR GO; GO:0019433; P:triglyceride catabolic process; IBA:GO_Central.
DR CDD; cd00707; Pancreat_lipase_like; 1.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR013818; Lipase.
DR InterPro; IPR016272; Lipase_LIPH.
DR InterPro; IPR033906; Lipase_N.
DR InterPro; IPR000734; TAG_lipase.
DR PANTHER; PTHR11610; PTHR11610; 1.
DR Pfam; PF00151; Lipase; 1.
DR PIRSF; PIRSF000865; Lipoprotein_lipase_LIPH; 1.
DR PRINTS; PR00821; TAGLIPASE.
DR SUPFAM; SSF53474; SSF53474; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Disease variant; Disulfide bond; Glycoprotein;
KW Heparin-binding; Hydrolase; Hypotrichosis; Lipid degradation;
KW Lipid metabolism; Membrane; Reference proteome; Secreted; Signal.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..451
FT /note="Lipase member H"
FT /id="PRO_0000273321"
FT ACT_SITE 154
FT /note="Nucleophile"
FT ACT_SITE 178
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 248
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT CARBOHYD 50
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 66
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 357
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 233..246
FT /evidence="ECO:0000250"
FT DISULFID 270..281
FT /evidence="ECO:0000250"
FT DISULFID 284..292
FT /evidence="ECO:0000250"
FT DISULFID 427..446
FT /evidence="ECO:0000250"
FT VARIANT 108
FT /note="W -> R (in HYPT7 and ARWH2; dbSNP:rs267607219)"
FT /evidence="ECO:0000269|PubMed:18830268,
FT ECO:0000269|PubMed:19167195"
FT /id="VAR_059050"
FT VARIANT 172..205
FT /note="Missing (in HYPT7)"
FT /evidence="ECO:0000269|PubMed:17095700"
FT /id="VAR_030125"
FT MUTAGEN 154
FT /note="S->A: Loss of lipase activity."
FT /evidence="ECO:0000269|PubMed:12063250"
SQ SEQUENCE 451 AA; 50859 MW; 949CE32B0C15868B CRC64;
MLRFYLFISL LCLSRSDAEE TCPSFTRLSF HSAVVGTGLN VRLMLYTRKN LTCAQTINSS
AFGNLNVTKK TTFIVHGFRP TGSPPVWMDD LVKGLLSVED MNVVVVDWNR GATTLIYTHA
SSKTRKVAMV LKEFIDQMLA EGASLDDIYM IGVSLGAHIS GFVGEMYDGW LGRITGLDPA
GPLFNGKPHQ DRLDPSDAQF VDVIHSDTDA LGYKEPLGNI DFYPNGGLDQ PGCPKTILGG
FQYFKCDHQR SVYLYLSSLR ESCTITAYPC DSYQDYRNGK CVSCGTSQKE SCPLLGYYAD
NWKDHLRGKD PPMTKAFFDT AEESPFCMYH YFVDIITWNK NVRRGDITIK LRDKAGNTTE
SKINHEPTTF QKYHQVSLLA RFNQDLDKVA AISLMFSTGS LIGPRYKLRI LRMKLRSLAH
PERPQLCRYD LVLMENVETV FQPILCPELQ L
