PIGW_HUMAN
ID PIGW_HUMAN Reviewed; 504 AA.
AC Q7Z7B1; Q8N9G3;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Phosphatidylinositol-glycan biosynthesis class W protein {ECO:0000305};
DE Short=PIG-W {ECO:0000303|PubMed:14517336};
DE EC=2.3.-.- {ECO:0000250|UniProtKB:Q7TSN4};
GN Name=PIGW {ECO:0000312|HGNC:HGNC:23213};
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].
RX PubMed=14517336; DOI=10.1091/mbc.e03-03-0193;
RA Murakami Y., Siripanyapinyo U., Hong Y., Kang J.Y., Ishihara S.,
RA Nakakuma H., Maeda Y., Kinoshita T.;
RT "PIG-W is critical for inositol acylation but not for flipping of
RT glycosylphosphatidylinositol-anchor.";
RL Mol. Biol. Cell 14:4285-4295(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-416, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [4]
RP INVOLVEMENT IN GPIBD11, VARIANTS GPIBD11 PRO-71 AND VAL-167,
RP CHARACTERIZATION OF VARIANTS GPIBD11 PRO-71 AND VAL-167, AND FUNCTION.
RX PubMed=24367057; DOI=10.1136/jmedgenet-2013-102156;
RA Chiyonobu T., Inoue N., Morimoto M., Kinoshita T., Murakami Y.;
RT "Glycosylphosphatidylinositol (GPI) anchor deficiency caused by mutations
RT in PIGW is associated with West syndrome and hyperphosphatasia with mental
RT retardation syndrome.";
RL J. Med. Genet. 51:203-207(2014).
CC -!- FUNCTION: Required for the transport of GPI-anchored proteins to the
CC plasma membrane (PubMed:24367057). Probable acetyltransferase, which
CC acetylates the inositol ring of phosphatidylinositol during
CC biosynthesis of GPI-anchor. Acetylation during GPI-anchor biosynthesis
CC is not essential for the subsequent mannosylation and is usually
CC removed soon after the attachment of GPIs to proteins (By similarity).
CC {ECO:0000250|UniProtKB:Q7TSN4, ECO:0000269|PubMed:24367057}.
CC -!- PATHWAY: Glycolipid biosynthesis; glycosylphosphatidylinositol-anchor
CC biosynthesis. {ECO:0000250|UniProtKB:Q7TSN4}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q7TSN4}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q7TSN4}.
CC -!- DISEASE: Glycosylphosphatidylinositol biosynthesis defect 11 (GPIBD11)
CC [MIM:616025]: An autosomal recessive neurologic disorder characterized
CC by developmental delay, intellectual disability, tonic seizures
CC associated with hypsarrhythmia, dysmorphic facial features, and
CC elevated serum alkaline phosphatase. {ECO:0000269|PubMed:24367057}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the PIGW family. {ECO:0000305}.
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DR EMBL; AB097818; BAC77021.1; -; mRNA.
DR EMBL; AK094752; BAC04413.1; -; mRNA.
DR CCDS; CCDS11313.1; -.
DR RefSeq; NP_001333683.1; NM_001346754.1.
DR RefSeq; NP_001333684.1; NM_001346755.1.
DR RefSeq; NP_848612.2; NM_178517.4.
DR AlphaFoldDB; Q7Z7B1; -.
DR BioGRID; 129756; 24.
DR IntAct; Q7Z7B1; 9.
DR STRING; 9606.ENSP00000482202; -.
DR ChEMBL; CHEMBL4523365; -.
DR GlyGen; Q7Z7B1; 1 site.
DR iPTMnet; Q7Z7B1; -.
DR PhosphoSitePlus; Q7Z7B1; -.
DR BioMuta; PIGW; -.
DR DMDM; 74713752; -.
DR jPOST; Q7Z7B1; -.
DR MassIVE; Q7Z7B1; -.
DR MaxQB; Q7Z7B1; -.
DR PaxDb; Q7Z7B1; -.
DR PeptideAtlas; Q7Z7B1; -.
DR PRIDE; Q7Z7B1; -.
DR ProteomicsDB; 69510; -.
DR Antibodypedia; 74148; 100 antibodies from 23 providers.
DR DNASU; 284098; -.
DR Ensembl; ENST00000614443.2; ENSP00000482202.1; ENSG00000277161.2.
DR Ensembl; ENST00000616581.2; ENSP00000481144.1; ENSG00000275600.2.
DR Ensembl; ENST00000620233.1; ENSP00000480021.1; ENSG00000277161.2.
DR Ensembl; ENST00000631508.1; ENSP00000488033.1; ENSG00000275600.2.
DR GeneID; 284098; -.
DR KEGG; hsa:284098; -.
DR MANE-Select; ENST00000614443.2; ENSP00000482202.1; NM_001346754.2; NP_001333683.1.
DR UCSC; uc002hmz.2; human.
DR CTD; 284098; -.
DR DisGeNET; 284098; -.
DR GeneCards; PIGW; -.
DR HGNC; HGNC:23213; PIGW.
DR HPA; ENSG00000277161; Low tissue specificity.
DR MalaCards; PIGW; -.
DR MIM; 610275; gene.
DR MIM; 616025; phenotype.
DR neXtProt; NX_Q7Z7B1; -.
DR OpenTargets; ENSG00000277161; -.
DR Orphanet; 83639; Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency.
DR Orphanet; 247262; Hyperphosphatasia-intellectual disability syndrome.
DR PharmGKB; PA134894412; -.
DR VEuPathDB; HostDB:ENSG00000277161; -.
DR eggNOG; KOG0411; Eukaryota.
DR GeneTree; ENSGT00390000013520; -.
DR HOGENOM; CLU_020802_2_1_1; -.
DR InParanoid; Q7Z7B1; -.
DR OMA; GLYVMQP; -.
DR OrthoDB; 1202772at2759; -.
DR PhylomeDB; Q7Z7B1; -.
DR PathwayCommons; Q7Z7B1; -.
DR Reactome; R-HSA-162710; Synthesis of glycosylphosphatidylinositol (GPI).
DR SignaLink; Q7Z7B1; -.
DR UniPathway; UPA00196; -.
DR BioGRID-ORCS; 284098; 80 hits in 1076 CRISPR screens.
DR ChiTaRS; PIGW; human.
DR GenomeRNAi; 284098; -.
DR Pharos; Q7Z7B1; Tbio.
DR PRO; PR:Q7Z7B1; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q7Z7B1; protein.
DR Bgee; ENSG00000277161; Expressed in islet of Langerhans and 100 other tissues.
DR ExpressionAtlas; Q7Z7B1; baseline and differential.
DR Genevisible; Q7Z7B1; HS.
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:0032216; F:glucosaminyl-phosphatidylinositol O-acyltransferase activity; IBA:GO_Central.
DR GO; GO:0008374; F:O-acyltransferase activity; TAS:Reactome.
DR GO; GO:0006506; P:GPI anchor biosynthetic process; IBA:GO_Central.
DR GO; GO:0006505; P:GPI anchor metabolic process; IC:UniProtKB.
DR GO; GO:0016254; P:preassembly of GPI anchor in ER membrane; TAS:Reactome.
DR GO; GO:0072659; P:protein localization to plasma membrane; IMP:UniProtKB.
DR InterPro; IPR009447; PIGW/GWT1.
DR PANTHER; PTHR20661; PTHR20661; 1.
DR Pfam; PF06423; GWT1; 1.
DR PIRSF; PIRSF017321; GWT1; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Disease variant; Endoplasmic reticulum; Glycoprotein;
KW GPI-anchor biosynthesis; Intellectual disability; Membrane; Phosphoprotein;
KW Reference proteome; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..504
FT /note="Phosphatidylinositol-glycan biosynthesis class W
FT protein"
FT /id="PRO_0000246282"
FT TOPO_DOM 1..21
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 22..42
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 74..94
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 132..152
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 163..183
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 203..223
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 238..258
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 261..281
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 306..326
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 339..359
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 371..391
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 449..469
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 474..494
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MOD_RES 416
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CARBOHYD 15
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 71
FT /note="T -> P (in GPIBD11; reduced protein abundance;
FT decreased function in GPI-anchored protein transport;
FT dbSNP:rs587777733)"
FT /evidence="ECO:0000269|PubMed:24367057"
FT /id="VAR_071933"
FT VARIANT 167
FT /note="M -> V (in GPIBD11; no effect on protein abundance;
FT loss of function in GPI-anchored protein transport;
FT dbSNP:rs200024253)"
FT /evidence="ECO:0000269|PubMed:24367057"
FT /id="VAR_071934"
FT CONFLICT 126
FT /note="N -> D (in Ref. 2; BAC04413)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 504 AA; 56882 MW; 6CACD6EFD154DDE2 CRC64;
MSEKQMKEAF VSNLNGTTVL EITQGLCFPA FCILCRGFLI IFSQYLCSFS PTWKTRFLTD
FVVLIVPMVA TLTIWASFIL LELLGVIIFG AGLLYQIYRR RTCYARLPFL KILEKFLNIS
LESEYNPAIS CFRVITSAFT AIAILAVDFP LFPRRFAKTE LYGTGAMDFG VGGFVFGSAM
VCLEVRRRKY MEGSKLHYFT NSLYSVWPLV FLGIGRLAII KSIGYQEHLT EYGVHWNFFF
TIIVVKLITP LLLIIFPLNK SWIIALGITV LYQLALDFTS LKRLILYGTD GSGTRVGLLN
ANREGIISTL GYVAIHMAGV QTGLYMHKNR SHIKDLIKVA CFLLLAAISL FISLYVVQVN
VEAVSRRMAN LAFCIWIVAS SLILLSSLLL GDIILSFAKF LIKGALVPCS WKLIQSPVTN
KKHSESLVPE AERMEPSLCL ITALNRKQLI FFLLSNITTG LINLMVDTLH SSTLWALFVV
NLYMFSNCLI VYVLYLQDKT VQFW
