PIGL_HUMAN
ID PIGL_HUMAN Reviewed; 252 AA.
AC Q9Y2B2; A8KA67; B4DYN4;
DT 11-JUL-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=N-acetylglucosaminyl-phosphatidylinositol de-N-acetylase;
DE EC=3.5.1.89;
DE AltName: Full=Phosphatidylinositol-glycan biosynthesis class L protein;
DE Short=PIG-L;
GN Name=PIGL;
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] (ISOFORM 1).
RX PubMed=10085243; DOI=10.1042/bj3390185;
RA Watanabe R., Ohishi K., Maeda Y., Nakamura N., Kinoshita T.;
RT "Mammalian PIG-L and its yeast homologue Gpi12p are N-
RT acetylglucosaminylphosphatidylinositol de-N-acetylases essential in
RT glycosylphosphatidylinositol biosynthesis.";
RL Biochem. J. 339:185-192(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Testis, and Trachea;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [4]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [6]
RP VARIANT CHIME PRO-167.
RX PubMed=22444671; DOI=10.1016/j.ajhg.2012.02.010;
RA Ng B.G., Hackmann K., Jones M.A., Eroshkin A.M., He P., Wiliams R.,
RA Bhide S., Cantagrel V., Gleeson J.G., Paller A.S., Schnur R.E.,
RA Tinschert S., Zunich J., Hegde M.R., Freeze H.H.;
RT "Mutations in the glycosylphosphatidylinositol gene PIGL cause CHIME
RT syndrome.";
RL Am. J. Hum. Genet. 90:685-688(2012).
CC -!- FUNCTION: Involved in the second step of GPI biosynthesis. De-N-
CC acetylation of N-acetylglucosaminyl-phosphatidylinositol.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-
CC inositol + H2O = acetate + an alpha-D-GlcN-(1->6)-(1,2-diacyl-sn-
CC glycero-3-phospho)-1D-myo-inositol; Xref=Rhea:RHEA:11660,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:30089, ChEBI:CHEBI:57265,
CC ChEBI:CHEBI:57997; EC=3.5.1.89;
CC -!- PATHWAY: Glycolipid biosynthesis; glycosylphosphatidylinositol-anchor
CC biosynthesis.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250};
CC Single-pass membrane protein {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Y2B2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y2B2-2; Sequence=VSP_056886;
CC -!- DISEASE: Coloboma, congenital heart disease, ichthyosiform dermatosis,
CC intellectual disability and ear anomalies syndrome (CHIME)
CC [MIM:280000]: An extremely rare autosomal recessive multisystem
CC disorder clinically characterized by colobomas, congenital heart
CC defects, migratory ichthyosiform dermatosis, intellectual disability,
CC and ear anomalies including conductive hearing loss. Other clinical
CC features include distinctive facial features, abnormal growth,
CC genitourinary abnormalities, seizures, and feeding difficulties.
CC {ECO:0000269|PubMed:22444671}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the PIGL family. {ECO:0000305}.
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DR EMBL; AB017165; BAA74775.1; -; mRNA.
DR EMBL; AK292932; BAF85621.1; -; mRNA.
DR EMBL; AK302523; BAG63796.1; -; mRNA.
DR EMBL; AC005971; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471222; EAX04498.1; -; Genomic_DNA.
DR EMBL; BC068197; AAH68197.1; -; mRNA.
DR CCDS; CCDS11176.1; -. [Q9Y2B2-1]
DR RefSeq; NP_004269.1; NM_004278.3. [Q9Y2B2-1]
DR RefSeq; XP_016880841.1; XM_017025352.1. [Q9Y2B2-1]
DR RefSeq; XP_016880842.1; XM_017025353.1. [Q9Y2B2-1]
DR RefSeq; XP_016880845.1; XM_017025356.1. [Q9Y2B2-2]
DR AlphaFoldDB; Q9Y2B2; -.
DR SMR; Q9Y2B2; -.
DR BioGRID; 114869; 3.
DR IntAct; Q9Y2B2; 2.
DR STRING; 9606.ENSP00000225609; -.
DR SwissLipids; SLP:000001964; -.
DR iPTMnet; Q9Y2B2; -.
DR PhosphoSitePlus; Q9Y2B2; -.
DR BioMuta; PIGL; -.
DR DMDM; 14916637; -.
DR EPD; Q9Y2B2; -.
DR jPOST; Q9Y2B2; -.
DR MassIVE; Q9Y2B2; -.
DR MaxQB; Q9Y2B2; -.
DR PaxDb; Q9Y2B2; -.
DR PeptideAtlas; Q9Y2B2; -.
DR PRIDE; Q9Y2B2; -.
DR ProteomicsDB; 85718; -. [Q9Y2B2-1]
DR Antibodypedia; 2335; 120 antibodies from 19 providers.
DR DNASU; 9487; -.
DR Ensembl; ENST00000225609.10; ENSP00000225609.5; ENSG00000108474.17. [Q9Y2B2-1]
DR GeneID; 9487; -.
DR KEGG; hsa:9487; -.
DR MANE-Select; ENST00000225609.10; ENSP00000225609.5; NM_004278.4; NP_004269.1.
DR UCSC; uc002gpv.4; human. [Q9Y2B2-1]
DR CTD; 9487; -.
DR DisGeNET; 9487; -.
DR GeneCards; PIGL; -.
DR HGNC; HGNC:8966; PIGL.
DR HPA; ENSG00000108474; Low tissue specificity.
DR MalaCards; PIGL; -.
DR MIM; 280000; phenotype.
DR MIM; 605947; gene.
DR neXtProt; NX_Q9Y2B2; -.
DR OpenTargets; ENSG00000108474; -.
DR Orphanet; 3474; CHIME syndrome.
DR Orphanet; 247262; Hyperphosphatasia-intellectual disability syndrome.
DR PharmGKB; PA33297; -.
DR VEuPathDB; HostDB:ENSG00000108474; -.
DR eggNOG; KOG3332; Eukaryota.
DR GeneTree; ENSGT00390000018434; -.
DR HOGENOM; CLU_034979_1_0_1; -.
DR InParanoid; Q9Y2B2; -.
DR OMA; RWGWITI; -.
DR OrthoDB; 1454301at2759; -.
DR PhylomeDB; Q9Y2B2; -.
DR TreeFam; TF315150; -.
DR BRENDA; 3.5.1.89; 2681.
DR PathwayCommons; Q9Y2B2; -.
DR Reactome; R-HSA-162710; Synthesis of glycosylphosphatidylinositol (GPI).
DR SignaLink; Q9Y2B2; -.
DR UniPathway; UPA00196; -.
DR BioGRID-ORCS; 9487; 36 hits in 1085 CRISPR screens.
DR ChiTaRS; PIGL; human.
DR GenomeRNAi; 9487; -.
DR Pharos; Q9Y2B2; Tbio.
DR PRO; PR:Q9Y2B2; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q9Y2B2; protein.
DR Bgee; ENSG00000108474; Expressed in mucosa of stomach and 152 other tissues.
DR ExpressionAtlas; Q9Y2B2; baseline and differential.
DR Genevisible; Q9Y2B2; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016811; F:hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides; IBA:GO_Central.
DR GO; GO:0000225; F:N-acetylglucosaminylphosphatidylinositol deacetylase activity; IBA:GO_Central.
DR GO; GO:0006506; P:GPI anchor biosynthetic process; IBA:GO_Central.
DR GO; GO:0016254; P:preassembly of GPI anchor in ER membrane; TAS:Reactome.
DR Gene3D; 3.40.50.10320; -; 1.
DR InterPro; IPR003737; GlcNAc_PI_deacetylase-related.
DR InterPro; IPR039516; GPI12.
DR InterPro; IPR024078; LmbE-like_dom_sf.
DR PANTHER; PTHR12993; PTHR12993; 1.
DR PANTHER; PTHR12993:SF11; PTHR12993:SF11; 1.
DR Pfam; PF02585; PIG-L; 1.
DR SUPFAM; SSF102588; SSF102588; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Deafness; Disease variant; Endoplasmic reticulum;
KW GPI-anchor biosynthesis; Hydrolase; Ichthyosis; Intellectual disability;
KW Lipid metabolism; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..252
FT /note="N-acetylglucosaminyl-phosphatidylinositol de-N-
FT acetylase"
FT /id="PRO_0000207167"
FT TRANSMEM 2..22
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 23..252
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT VAR_SEQ 177..251
FT /note="CSVLTLQSVNVLRKYISLLDLPLSLLHTQDVLFVLNSKEVAQAKKAMSCHRS
FT QLLWFRRLYIIFSRYMRINSLSF -> KACSFCKGPQDTVPLRN (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056886"
FT VARIANT 167
FT /note="L -> P (in CHIME; dbSNP:rs145303331)"
FT /evidence="ECO:0000269|PubMed:22444671"
FT /id="VAR_068221"
SQ SEQUENCE 252 AA; 28531 MW; 420454DCA51704FB CRC64;
MEAMWLLCVA LAVLAWGFLW VWDSSERMKS REQGGRLGAE SRTLLVIAHP DDEAMFFAPT
VLGLARLRHW VYLLCFSAGN YYNQGETRKK ELLQSCDVLG IPLSSVMIID NRDFPDDPGM
QWDTEHVARV LLQHIEVNGI NLVVTFDAGG VSGHSNHIAL YAAVRALHSE GKLPKGCSVL
TLQSVNVLRK YISLLDLPLS LLHTQDVLFV LNSKEVAQAK KAMSCHRSQL LWFRRLYIIF
SRYMRINSLS FL
