ID PIGG_HUMAN Reviewed; 983 AA. AC Q5H8A4; B4DKC7; Q2TAK5; Q6UX31; Q7L5Y4; Q8N866; Q8NCC9; Q96SY9; Q9BVT7; AC Q9NXG5; DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2005, sequence version 1. DT 27-MAR-2024, entry version 149. DE RecName: Full=GPI ethanolamine phosphate transferase 2; DE EC=2.-.-.-; DE AltName: Full=GPI7 homolog; DE Short=hGPI7; DE AltName: Full=Phosphatidylinositol-glycan biosynthesis class G protein; DE Short=PIG-G; GN Name=PIGG; Synonyms=GPI7; ORFNames=UNQ1930/PRO4405; 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), FUNCTION, SUBCELLULAR LOCATION, AND RP INTERACTION WITH PIGF. RX PubMed=15632136; DOI=10.1074/jbc.m413755200; RA Shishioh N., Hong Y., Ohishi K., Ashida H., Maeda Y., Kinoshita T.; RT "GPI7 is the second partner of PIG-F and involved in modification of RT glycosylphosphatidylinositol."; RL J. Biol. Chem. 280:9728-9734(2005). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale effort to RT identify novel human secreted and transmembrane proteins: a bioinformatics RT assessment."; RL Genome Res. 13:2265-2270(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RX PubMed=16303743; DOI=10.1093/dnares/12.2.117; RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J., RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S., RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y., RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S., RA Isogai T.; RT "Signal sequence and keyword trap in silico for selection of full-length RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA RT libraries."; RL DNA Res. 12:117-126(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 5 AND 6), NUCLEOTIDE RP SEQUENCE [LARGE SCALE MRNA] OF 367-983 (ISOFORM 1), AND VARIANT ILE-699. RC TISSUE=Cervix, Colon mucosa, Teratocarcinoma, and Thalamus; 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]. 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANTS HIS-458; RP ARG-610 AND ILE-699. RC TISSUE=Lung, and Placenta; 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 INVOLVEMENT IN NEDHSCA, VARIANTS NEDHSCA 310-GLN--SER-983 DEL AND CYS-669, RP AND CHARACTERIZATION OF VARIANTS NEDHSCA 310-GLN--SER-983 DEL AND CYS-669. RX PubMed=26996948; DOI=10.1016/j.ajhg.2016.02.007; RA Makrythanasis P., Kato M., Zaki M.S., Saitsu H., Nakamura K., Santoni F.A., RA Miyatake S., Nakashima M., Issa M.Y., Guipponi M., Letourneau A., RA Logan C.V., Roberts N., Parry D.A., Johnson C.A., Matsumoto N., Hamamy H., RA Sheridan E., Kinoshita T., Antonarakis S.E., Murakami Y.; RT "Pathogenic variants in PIGG cause intellectual disability with seizures RT and hypotonia."; RL Am. J. Hum. Genet. 98:615-626(2016). RN [8] RP VARIANT NEDHSCA 547-TRP--SER-983 DEL, AND CHARACTERIZATION OF VARIANT RP NEDHSCA 547-TRP--SER-983 DEL. RX PubMed=28581210; DOI=10.1002/humu.23268; RA Zhao J.J., Halvardson J., Knaus A., Georgii-Hemming P., Baeck P., RA Krawitz P.M., Thuresson A.C., Feuk L.; RT "Reduced cell surface levels of GPI-linked markers in a new case with PIGG RT loss of function."; RL Hum. Mutat. 38:1394-1401(2017). RN [9] RP VARIANT NEDHSCA TYR-214, CHARACTERIZATION OF VARIANT NEDHSCA TYR-214, AND RP POLYMORPHISM. RX PubMed=33763700; DOI=10.1182/blood.2020009810; RA Duval R., Nicolas G., Willemetz A., Murakami Y., Mikdar M., Vrignaud C., RA Megahed H., Cartron J.P., Masson C., Wehbi S., Koehl B., Hully M., RA Siquier K., Chemlay N., Rotig A., Lyonnet S., Colin Y., Barcia G., RA Cantagrel V., Le Van Kim C., Hermine O., Kinoshita T., Peyrard T., RA Azouzi S.; RT "Inherited glycosylphosphatidylinositol defects cause the rare Emm-negative RT blood phenotype and developmental disorders."; RL Blood 137:3660-3669(2021). RN [10] RP VARIANTS NEDHSCA MET-124; SER-138; ASP-270; ARG-271; ARG-278; RP 304-ARG--SER-983 DEL; LEU-344; LEU-497; 505-TRP--SER-983 DEL; MET-531; RP TRP-681; ASP-696; PRO-851; 934-TYR--SER-983 DEL AND 957-TYR--SER-983 DEL, RP CHARACTERIZATION OF VARIANTS NEDHSCA TRP-681 AND ASP-696, AND FUNCTION. RX PubMed=34113002; DOI=10.1038/s41436-021-01215-9; RA Tremblay-Laganiere C., Maroofian R., Nguyen T.T.M., Karimiani E.G., RA Kirmani S., Akbar F., Ibrahim S., Afroze B., Doosti M., Ashrafzadeh F., RA Babaei M., Efthymiou S., Christoforou M., Sultan T., Ladda R.L., RA McLaughlin H.M., Truty R., Mahida S., Cohen J.S., Baranano K., Ismail F.Y., RA Patel M.S., Lehman A., Edmondson A.C., Nagy A., Walker M.A., RA Mercimek-Andrews S., Maki Y., Sachdev R., Macintosh R., Palmer E.E., RA Mancini G.M.S., Barakat T.S., Steinfeld R., Ruesch C.T., Stettner G.M., RA Wagner M., Wortmann S.B., Kini U., Brady A.F., Stals K.L., Ismayilova N., RA Ellard S., Bernardo D., Nugent K., McLean S.D., Antonarakis S.E., RA Houlden H., Kinoshita T., Campeau P.M., Murakami Y.; RT "PIGG variant pathogenicity assessment reveals characteristic features RT within 19 families."; RL Genet. Med. 23:1873-1881(2021). RN [11] RP POLYMORPHISM, AND INVOLVEMENT IN EMM-NUL PHENOTYPE. RX PubMed=34535746; DOI=10.1038/s41598-021-98090-w; RA Lane W.J., Aeschlimann J., Vege S., Lomas-Francis C., Burgos A., Mah H.H., RA Halls J.B.L., Baeck P., Ligthart P.C., Veldhuisen B., Shah R.J., RA Joshi S.R., Westhoff C.M.; RT "PIGG defines the Emm blood group system."; RL Sci. Rep. 11:18545-18545(2021). CC -!- FUNCTION: Ethanolamine phosphate transferase involved in CC glycosylphosphatidylinositol-anchor biosynthesis. Transfers CC ethanolamine phosphate to the GPI second mannose. CC {ECO:0000269|PubMed:15632136, ECO:0000269|PubMed:34113002}. CC -!- PATHWAY: Glycolipid biosynthesis; glycosylphosphatidylinositol-anchor CC biosynthesis. CC -!- SUBUNIT: Forms a complex with PIGF. PIGF is required to stabilize it. CC Competes with PIGO for the binding of PIGF. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:15632136}; Multi-pass membrane protein CC {ECO:0000269|PubMed:15632136}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=6; CC Name=1; CC IsoId=Q5H8A4-1; Sequence=Displayed; CC Name=2; CC IsoId=Q5H8A4-2; Sequence=VSP_019832; CC Name=3; CC IsoId=Q5H8A4-3; Sequence=VSP_019828; CC Name=4; CC IsoId=Q5H8A4-4; Sequence=VSP_019831, VSP_019833; CC Name=5; CC IsoId=Q5H8A4-5; Sequence=VSP_019827, VSP_019829, VSP_019830; CC Name=6; CC IsoId=Q5H8A4-6; Sequence=VSP_054387, VSP_054388, VSP_019833; CC -!- POLYMORPHISM: Genetic variations in PIGG define the Emm blood group CC system [MIM:619812]. {ECO:0000269|PubMed:33763700, CC ECO:0000269|PubMed:34535746}. CC -!- DISEASE: Neurodevelopmental disorder with or without hypotonia, CC seizures, and cerebellar atrophy (NEDHSCA) [MIM:616917]: An autosomal CC recessive disorder characterized by delayed psychomotor development, CC hypotonia, and early-onset seizures in most patients. Additional CC variable features are cerebellar atrophy, ataxia, and non-specific CC dysmorphic features. Some patients may have the Emm-null blood group CC phenotype. {ECO:0000269|PubMed:26996948, ECO:0000269|PubMed:28581210, CC ECO:0000269|PubMed:33763700, ECO:0000269|PubMed:34113002}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- MISCELLANEOUS: [Isoform 4]: May be produced at very low levels due to a CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA CC decay. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the PIGG/PIGN/PIGO family. PIGG subfamily. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAQ88902.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; CC Sequence=BAA91046.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAB55130.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB162713; BAD89023.1; -; mRNA. DR EMBL; AY358538; AAQ88902.1; ALT_SEQ; mRNA. DR EMBL; AK074815; BAC11227.1; -; mRNA. DR EMBL; AK000272; BAA91046.1; ALT_INIT; mRNA. DR EMBL; AK027465; BAB55130.1; ALT_INIT; mRNA. DR EMBL; AK097244; BAC04984.1; -; mRNA. DR EMBL; AK296507; BAG59139.1; -; mRNA. DR EMBL; AC092574; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC116565; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC000937; AAH00937.2; -; mRNA. DR EMBL; BC001249; AAH01249.2; -; mRNA. DR EMBL; BC110878; AAI10879.1; -; mRNA. DR CCDS; CCDS3336.1; -. [Q5H8A4-2] DR CCDS; CCDS46992.1; -. [Q5H8A4-1] DR CCDS; CCDS75080.1; -. [Q5H8A4-3] DR CCDS; CCDS75083.1; -. [Q5H8A4-5] DR RefSeq; NP_001120650.1; NM_001127178.2. [Q5H8A4-1] DR RefSeq; NP_001275980.1; NM_001289051.1. DR RefSeq; NP_001275981.1; NM_001289052.1. [Q5H8A4-3] DR RefSeq; NP_001275984.1; NM_001289055.1. [Q5H8A4-6] DR RefSeq; NP_001275986.1; NM_001289057.1. [Q5H8A4-5] DR RefSeq; NP_060203.3; NM_017733.4. [Q5H8A4-2] DR AlphaFoldDB; Q5H8A4; -. DR SMR; Q5H8A4; -. DR BioGRID; 120220; 118. DR ComplexPortal; CPX-2677; Glycosylphosphatidylinsitol ethanolamine-phosphate transferase II complex. DR IntAct; Q5H8A4; 11. DR MINT; Q5H8A4; -. DR STRING; 9606.ENSP00000415203; -. DR GlyCosmos; Q5H8A4; 1 site, No reported glycans. DR GlyGen; Q5H8A4; 1 site. DR iPTMnet; Q5H8A4; -. DR PhosphoSitePlus; Q5H8A4; -. DR SwissPalm; Q5H8A4; -. DR BioMuta; PIGG; -. DR DMDM; 74707851; -. DR EPD; Q5H8A4; -. DR jPOST; Q5H8A4; -. DR MassIVE; Q5H8A4; -. DR MaxQB; Q5H8A4; -. DR PaxDb; 9606-ENSP00000415203; -. DR PeptideAtlas; Q5H8A4; -. DR ProteomicsDB; 4448; -. DR ProteomicsDB; 62844; -. [Q5H8A4-1] DR ProteomicsDB; 62845; -. [Q5H8A4-2] DR ProteomicsDB; 62846; -. [Q5H8A4-3] DR ProteomicsDB; 62847; -. [Q5H8A4-4] DR ProteomicsDB; 62848; -. [Q5H8A4-5] DR Pumba; Q5H8A4; -. DR Antibodypedia; 3105; 10 antibodies from 9 providers. DR DNASU; 54872; -. DR Ensembl; ENST00000310340.9; ENSP00000311750.5; ENSG00000174227.16. [Q5H8A4-2] DR Ensembl; ENST00000383028.8; ENSP00000372494.4; ENSG00000174227.16. [Q5H8A4-3] DR Ensembl; ENST00000453061.7; ENSP00000415203.2; ENSG00000174227.16. [Q5H8A4-1] DR Ensembl; ENST00000503111.5; ENSP00000426002.1; ENSG00000174227.16. [Q5H8A4-5] DR GeneID; 54872; -. DR KEGG; hsa:54872; -. DR MANE-Select; ENST00000453061.7; ENSP00000415203.2; NM_001127178.3; NP_001120650.1. DR UCSC; uc003gaj.6; human. [Q5H8A4-1] DR AGR; HGNC:25985; -. DR CTD; 54872; -. DR DisGeNET; 54872; -. DR GeneCards; PIGG; -. DR HGNC; HGNC:25985; PIGG. DR HPA; ENSG00000174227; Low tissue specificity. DR MalaCards; PIGG; -. DR MIM; 616917; phenotype. DR MIM; 616918; gene. DR MIM; 619812; phenotype. DR neXtProt; NX_Q5H8A4; -. DR OpenTargets; ENSG00000174227; -. DR Orphanet; 488635; Early-onset epilepsy-intellectual disability-brain anomalies syndrome. DR Orphanet; 280; Wolf-Hirschhorn syndrome. DR PharmGKB; PA143485575; -. DR VEuPathDB; HostDB:ENSG00000174227; -. DR eggNOG; KOG2125; Eukaryota. DR GeneTree; ENSGT00910000144269; -. DR HOGENOM; CLU_055386_0_0_1; -. DR InParanoid; Q5H8A4; -. DR OMA; RVKFGHD; -. DR OrthoDB; 5479199at2759; -. DR PhylomeDB; Q5H8A4; -. DR TreeFam; TF300609; -. DR PathwayCommons; Q5H8A4; -. DR Reactome; R-HSA-162710; Synthesis of glycosylphosphatidylinositol (GPI). DR SignaLink; Q5H8A4; -. DR SIGNOR; Q5H8A4; -. DR UniPathway; UPA00196; -. DR BioGRID-ORCS; 54872; 11 hits in 1156 CRISPR screens. DR ChiTaRS; PIGG; human. DR GenomeRNAi; 54872; -. DR Pharos; Q5H8A4; Tbio. DR PRO; PR:Q5H8A4; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; Q5H8A4; Protein. DR Bgee; ENSG00000174227; Expressed in right uterine tube and 186 other cell types or tissues. DR ExpressionAtlas; Q5H8A4; baseline and differential. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0051267; F:CP2 mannose-ethanolamine phosphotransferase activity; IDA:MGI. DR GO; GO:0016780; F:phosphotransferase activity, for other substituted phosphate groups; TAS:Reactome. DR GO; GO:0016740; F:transferase activity; IMP:UniProtKB. DR GO; GO:0006506; P:GPI anchor biosynthetic process; IDA:MGI. DR GO; GO:0016254; P:preassembly of GPI anchor in ER membrane; TAS:Reactome. DR CDD; cd16024; GPI_EPT_2; 1. DR Gene3D; 3.40.720.10; Alkaline Phosphatase, subunit A; 1. DR InterPro; IPR017850; Alkaline_phosphatase_core_sf. DR InterPro; IPR002591; Phosphodiest/P_Trfase. DR InterPro; IPR037674; PIG-G_N. DR InterPro; IPR039527; PIGG/GPI7. DR InterPro; IPR045687; PIGG/GPI7_C. DR PANTHER; PTHR23072:SF0; GPI ETHANOLAMINE PHOSPHATE TRANSFERASE 2; 1. DR PANTHER; PTHR23072; PHOSPHATIDYLINOSITOL GLYCAN-RELATED; 1. DR Pfam; PF01663; Phosphodiest; 1. DR Pfam; PF19316; PIGO_PIGG; 1. DR SUPFAM; SSF53649; Alkaline phosphatase-like; 1. DR Genevisible; Q5H8A4; HS. PE 1: Evidence at protein level; KW Alternative splicing; Disease variant; Endoplasmic reticulum; Glycoprotein; KW GPI-anchor biosynthesis; Intellectual disability; Membrane; KW Reference proteome; Transferase; Transmembrane; Transmembrane helix. FT CHAIN 1..983 FT /note="GPI ethanolamine phosphate transferase 2" FT /id="PRO_0000246185" FT TOPO_DOM 1..431 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 432..452 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 471..491 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 506..526 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 552..572 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 699..719 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 721..741 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 752..772 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 789..809 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 812..832 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 879..899 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 919..939 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 955..975 FT /note="Helical" FT /evidence="ECO:0000255" FT CARBOHYD 194 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VAR_SEQ 1..122 FT /note="Missing (in isoform 6)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_054387" FT VAR_SEQ 1..89 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_019827" FT VAR_SEQ 120..252 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_019828" FT VAR_SEQ 372..388 FT /note="DPGFEQFKMSERLHGNW -> GSHPAPAQRPTGTAQKG (in isoform FT 5)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_019829" FT VAR_SEQ 389..983 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_019830" FT VAR_SEQ 430..463 FT /note="YDIYSMMVGTVVVLEVLTLLLLSVPQALRRKAEL -> FSPCSCSASHRHCT FT ERLSWKSHCHLLGFLCSFIW (in isoform 4)" FT /evidence="ECO:0000303|PubMed:12975309" FT /id="VSP_019831" FT VAR_SEQ 430..463 FT /note="YDIYSMMVGTVVVLEVLTLLLLSVPQALRRKAEL -> FSPCSCSASHRHCA FT ERLSWKSHCHLLGFLCSFIW (in isoform 6)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_054388" FT VAR_SEQ 437..444 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:16303743" FT /id="VSP_019832" FT VAR_SEQ 464..983 FT /note="Missing (in isoform 4 and isoform 6)" FT /evidence="ECO:0000303|PubMed:12975309, FT ECO:0000303|PubMed:14702039" FT /id="VSP_019833" FT VARIANT 55 FT /note="S -> Y (in dbSNP:rs34120878)" FT /id="VAR_057680" FT VARIANT 124 FT /note="T -> M (in NEDHSCA; uncertain significance; FT dbSNP:rs370385328)" FT /evidence="ECO:0000269|PubMed:34113002" FT /id="VAR_087224" FT VARIANT 138 FT /note="N -> S (in NEDHSCA; dbSNP:rs148712954)" FT /evidence="ECO:0000269|PubMed:34113002" FT /id="VAR_087225" FT VARIANT 214 FT /note="H -> Y (in NEDHSCA; unable to rescue surface FT expression of Emm in PIGG-null cells)" FT /evidence="ECO:0000269|PubMed:33763700" FT /id="VAR_087226" FT VARIANT 270 FT /note="G -> D (in NEDHSCA)" FT /evidence="ECO:0000269|PubMed:34113002" FT /id="VAR_087227" FT VARIANT 271 FT /note="M -> R (in NEDHSCA; dbSNP:rs1406989563)" FT /evidence="ECO:0000269|PubMed:34113002" FT /id="VAR_087228" FT VARIANT 278 FT /note="G -> R (in NEDHSCA; dbSNP:rs552500897)" FT /evidence="ECO:0000269|PubMed:34113002" FT /id="VAR_087229" FT VARIANT 304..983 FT /note="Missing (in NEDHSCA)" FT /evidence="ECO:0000269|PubMed:34113002" FT /id="VAR_087230" FT VARIANT 310..983 FT /note="Missing (in NEDHSCA; loss of ethanolamine phosphate FT transferase activity as evidenced by abnormal accumulation FT of the GPI precursors H7 and H7' and absence of mature GPI FT precursor H8 in patient lymphoblasts)" FT /evidence="ECO:0000269|PubMed:26996948" FT /id="VAR_087231" FT VARIANT 344 FT /note="M -> L (in NEDHSCA; uncertain significance)" FT /evidence="ECO:0000269|PubMed:34113002" FT /id="VAR_087232" FT VARIANT 458 FT /note="R -> H (in dbSNP:rs13115344)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_027022" FT VARIANT 497 FT /note="S -> L (in NEDHSCA; uncertain significance; FT dbSNP:rs755547556)" FT /evidence="ECO:0000269|PubMed:34113002" FT /id="VAR_087233" FT VARIANT 505..983 FT /note="Missing (in NEDHSCA)" FT /evidence="ECO:0000269|PubMed:34113002" FT /id="VAR_087234" FT VARIANT 531 FT /note="V -> M (in NEDHSCA; uncertain significance; FT dbSNP:rs143362968)" FT /evidence="ECO:0000269|PubMed:34113002" FT /id="VAR_087235" FT VARIANT 547..983 FT /note="Missing (in NEDHSCA; decreased protein abundance)" FT /evidence="ECO:0000269|PubMed:28581210" FT /id="VAR_087236" FT VARIANT 610 FT /note="C -> R (in dbSNP:rs7666425)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_027023" FT VARIANT 669 FT /note="R -> C (in NEDHSCA; almost complete loss of FT ethanolamine phosphate transferase activity as evidenced by FT abnormal accumulation of the GPI precursors H7 and H7' and FT absence of mature GPI precursor H8 in patient lymphoblasts; FT does not affect protein expression levels in transfected FT HEK293 cells; dbSNP:rs372392424)" FT /evidence="ECO:0000269|PubMed:26996948" FT /id="VAR_076775" FT VARIANT 681 FT /note="R -> W (in NEDHSCA; uncertain significance; shows a FT mild decrease in phosphotransferase activity; FT dbSNP:rs899791968)" FT /evidence="ECO:0000269|PubMed:34113002" FT /id="VAR_087237" FT VARIANT 696 FT /note="E -> D (in NEDHSCA; uncertain significance; shows a FT mild decrease in phosphotransferase activity)" FT /evidence="ECO:0000269|PubMed:34113002" FT /id="VAR_087238" FT VARIANT 699 FT /note="V -> I (in dbSNP:rs13114026)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334" FT /id="VAR_027024" FT VARIANT 731 FT /note="V -> I (in dbSNP:rs34916638)" FT /id="VAR_060086" FT VARIANT 851 FT /note="Q -> P (in NEDHSCA; dbSNP:rs150802299)" FT /evidence="ECO:0000269|PubMed:34113002" FT /id="VAR_087239" FT VARIANT 881 FT /note="I -> T (in dbSNP:rs34623004)" FT /id="VAR_060087" FT VARIANT 932 FT /note="F -> S (in dbSNP:rs1127410)" FT /id="VAR_027025" FT VARIANT 934..983 FT /note="Missing (in NEDHSCA)" FT /evidence="ECO:0000269|PubMed:34113002" FT /id="VAR_087240" FT VARIANT 957..983 FT /note="Missing (in NEDHSCA)" FT /evidence="ECO:0000269|PubMed:34113002" FT /id="VAR_087241" FT CONFLICT 624 FT /note="D -> G (in Ref. 3; BAC11227)" FT /evidence="ECO:0000305" FT CONFLICT 889 FT /note="F -> L (in Ref. 3; BAC11227)" FT /evidence="ECO:0000305" SQ SEQUENCE 983 AA; 108173 MW; 18D5DF737B000D2D CRC64; MRLGSGTFAT CCVAIEVLGI AVFLRGFFPA PVRSSARAEH GAEPPAPEPS AGASSNWTTL PPPLFSKVVI VLIDALRDDF VFGSKGVKFM PYTTYLVEKG ASHSFVAEAK PPTVTMPRIK ALMTGSLPGF VDVIRNLNSP ALLEDSVIRQ AKAAGKRIVF YGDETWVKLF PKHFVEYDGT TSFFVSDYTE VDNNVTRHLD KVLKRGDWDI LILHYLGLDH IGHISGPNSP LIGQKLSEMD SVLMKIHTSL QSKERETPLP NLLVLCGDHG MSETGSHGAS STEEVNTPLI LISSAFERKP GDIRHPKHVQ QTDVAATLAI ALGLPIPKDS VGSLLFPVVE GRPMREQLRF LHLNTVQLSK LLQENVPSYE KDPGFEQFKM SERLHGNWIR LYLEEKHSEV LFNLGSKVLR QYLDALKTLS LSLSAQVAQY DIYSMMVGTV VVLEVLTLLL LSVPQALRRK AELEVPLSSP GFSLLFYLVI LVLSAVHVIV CTSAESSCYF CGLSWLAAGG VMVLASALLC VIVSVLTNVL VGGNTPRKNP MHPSSRWSEL DLLILLGTAG HVLSLGASSF VEEEHQTWYF LVNTLCLALS QETYRNYFLG DDGEPPCGLC VEQGHDGATA AWQDGPGCDV LERDKGHGSP STSEVLRGRE KWMVLASPWL ILACCRLLRS LNQTGVQWAH RPDLGHWLTS SDHKAELSVL AALSLLVVFV LVQRGCSPVS KAALALGLLG VYCYRAAIGS VRFPWRPDSK DISKGIIEAR FVYVFVLGIL FTGTKDLLKS QVIAADFKLK TVGLWEIYSG LVLLAALLFR PHNLPVLAFS LLIQTLMTKF IWKPLRHDAA EITVMHYWFG QAFFYFQGNS NNIATVDISA GFVGLDTYVE IPAVLLTAFG TYAGPVLWAS HLVHFLSSET RSGSALSHAC FCYALICSIP VFTYIVLVTS LRYHLFIWSV FSPKLLYEGM HLLITAAVCV FFTAMDQTRL TQS //