PIGN_HUMAN
ID PIGN_HUMAN Reviewed; 931 AA.
AC O95427; Q7L8F8; Q8TC01; Q9NT05;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=GPI ethanolamine phosphate transferase 1;
DE EC=2.-.-.-;
DE AltName: Full=MCD4 homolog;
DE AltName: Full=Phosphatidylinositol-glycan biosynthesis class N protein;
DE Short=PIG-N;
GN Name=PIGN; Synonyms=MCD4;
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=10069808; DOI=10.1091/mbc.10.3.627;
RA Gaynor E.C., Mondesert G., Grimme S.J., Reed S.I., Orlean P., Emr S.D.;
RT "MCD4 encodes a conserved endoplasmic reticulum membrane protein essential
RT for glycosylphosphatidylinositol anchor synthesis in yeast.";
RL Mol. Biol. Cell 10:627-648(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASP-229.
RC TISSUE=Testis;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 107-931.
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP FUNCTION.
RX PubMed=23446422; DOI=10.1038/nature11935;
RA Burrell R.A., McClelland S.E., Endesfelder D., Groth P., Weller M.C.,
RA Shaikh N., Domingo E., Kanu N., Dewhurst S.M., Gronroos E., Chew S.K.,
RA Rowan A.J., Schenk A., Sheffer M., Howell M., Kschischo M., Behrens A.,
RA Helleday T., Bartek J., Tomlinson I.P., Swanton C.;
RT "Replication stress links structural and numerical cancer chromosomal
RT instability.";
RL Nature 494:492-496(2013).
RN [5]
RP VARIANT MCAHS1 GLN-709.
RX PubMed=21493957; DOI=10.1136/jmg.2010.087114;
RA Maydan G., Noyman I., Har-Zahav A., Neriah Z.B., Pasmanik-Chor M.,
RA Yeheskel A., Albin-Kaplanski A., Maya I., Magal N., Birk E., Simon A.J.,
RA Halevy A., Rechavi G., Shohat M., Straussberg R., Basel-Vanagaite L.;
RT "Multiple congenital anomalies-hypotonia-seizures syndrome is caused by a
RT mutation in PIGN.";
RL J. Med. Genet. 48:383-389(2011).
CC -!- FUNCTION: Ethanolamine phosphate transferase involved in
CC glycosylphosphatidylinositol-anchor biosynthesis. Transfers
CC ethanolamine phosphate to the first alpha-1,4-linked mannose of the
CC glycosylphosphatidylinositol precursor of GPI-anchor (By similarity).
CC May act as suppressor of replication stress and chromosome
CC missegregation. {ECO:0000250, ECO:0000269|PubMed:23446422}.
CC -!- PATHWAY: Glycolipid biosynthesis; glycosylphosphatidylinositol-anchor
CC biosynthesis.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250};
CC Multi-pass membrane protein {ECO:0000250}.
CC -!- DISEASE: Multiple congenital anomalies-hypotonia-seizures syndrome 1
CC (MCAHS1) [MIM:614080]: An autosomal recessive disorder characterized by
CC neonatal hypotonia, lack of psychomotor development, seizures,
CC dysmorphic features, and variable congenital anomalies involving the
CC cardiac, urinary, and gastrointestinal systems. Most affected
CC individuals die before 3 years of age. {ECO:0000269|PubMed:21493957}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the PIGG/PIGN/PIGO family. PIGN subfamily.
CC {ECO:0000305}.
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DR EMBL; AF109219; AAD11432.1; -; mRNA.
DR EMBL; BC028363; AAH28363.1; -; mRNA.
DR EMBL; AL137607; CAB70839.1; -; mRNA.
DR CCDS; CCDS45879.1; -.
DR PIR; T46311; T46311.
DR RefSeq; NP_036459.1; NM_012327.5.
DR RefSeq; NP_789744.1; NM_176787.4.
DR AlphaFoldDB; O95427; -.
DR SMR; O95427; -.
DR BioGRID; 117100; 70.
DR IntAct; O95427; 11.
DR STRING; 9606.ENSP00000350263; -.
DR GlyConnect; 1284; 2 N-Linked glycans (1 site).
DR GlyGen; O95427; 4 sites, 1 N-linked glycan (1 site).
DR iPTMnet; O95427; -.
DR PhosphoSitePlus; O95427; -.
DR SwissPalm; O95427; -.
DR BioMuta; PIGN; -.
DR EPD; O95427; -.
DR jPOST; O95427; -.
DR MassIVE; O95427; -.
DR MaxQB; O95427; -.
DR PaxDb; O95427; -.
DR PeptideAtlas; O95427; -.
DR PRIDE; O95427; -.
DR ProteomicsDB; 50868; -.
DR Antibodypedia; 48918; 70 antibodies from 16 providers.
DR DNASU; 23556; -.
DR Ensembl; ENST00000357637.10; ENSP00000350263.4; ENSG00000197563.11.
DR Ensembl; ENST00000400334.7; ENSP00000383188.2; ENSG00000197563.11.
DR Ensembl; ENST00000638936.1; ENSP00000492592.1; ENSG00000197563.11.
DR Ensembl; ENST00000640050.1; ENSP00000492051.1; ENSG00000197563.11.
DR Ensembl; ENST00000640145.1; ENSP00000491525.1; ENSG00000197563.11.
DR Ensembl; ENST00000640252.2; ENSP00000492233.1; ENSG00000197563.11.
DR Ensembl; ENST00000640876.1; ENSP00000491628.1; ENSG00000197563.11.
DR GeneID; 23556; -.
DR KEGG; hsa:23556; -.
DR MANE-Select; ENST00000640252.2; ENSP00000492233.1; NM_176787.5; NP_789744.1.
DR UCSC; uc021ulb.3; human.
DR CTD; 23556; -.
DR DisGeNET; 23556; -.
DR GeneCards; PIGN; -.
DR GeneReviews; PIGN; -.
DR HGNC; HGNC:8967; PIGN.
DR HPA; ENSG00000197563; Low tissue specificity.
DR MalaCards; PIGN; -.
DR MIM; 606097; gene.
DR MIM; 614080; phenotype.
DR neXtProt; NX_O95427; -.
DR OpenTargets; ENSG00000197563; -.
DR Orphanet; 2059; Fryns syndrome.
DR Orphanet; 280633; Multiple congenital anomalies-hypotonia-seizures syndrome.
DR PharmGKB; PA33298; -.
DR VEuPathDB; HostDB:ENSG00000197563; -.
DR eggNOG; KOG2124; Eukaryota.
DR GeneTree; ENSGT00390000017600; -.
DR HOGENOM; CLU_007676_0_0_1; -.
DR InParanoid; O95427; -.
DR PhylomeDB; O95427; -.
DR TreeFam; TF300506; -.
DR PathwayCommons; O95427; -.
DR Reactome; R-HSA-162710; Synthesis of glycosylphosphatidylinositol (GPI).
DR SignaLink; O95427; -.
DR UniPathway; UPA00196; -.
DR BioGRID-ORCS; 23556; 19 hits in 1072 CRISPR screens.
DR ChiTaRS; PIGN; human.
DR GenomeRNAi; 23556; -.
DR Pharos; O95427; Tbio.
DR PRO; PR:O95427; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; O95427; protein.
DR Bgee; ENSG00000197563; Expressed in buccal mucosa cell and 164 other tissues.
DR ExpressionAtlas; O95427; baseline and differential.
DR Genevisible; O95427; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0051377; F:mannose-ethanolamine phosphotransferase 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 CDD; cd16020; GPI_EPT_1; 1.
DR Gene3D; 3.40.720.10; -; 2.
DR InterPro; IPR017850; Alkaline_phosphatase_core_sf.
DR InterPro; IPR007070; GPI_EtnP_transferase_1.
DR InterPro; IPR017852; GPI_EtnP_transferase_1_C.
DR InterPro; IPR002591; Phosphodiest/P_Trfase.
DR InterPro; IPR037671; PIGN_N.
DR PANTHER; PTHR12250; PTHR12250; 1.
DR Pfam; PF01663; Phosphodiest; 1.
DR Pfam; PF04987; PigN; 1.
DR SUPFAM; SSF53649; SSF53649; 1.
PE 1: Evidence at protein level;
KW Disease variant; Endoplasmic reticulum; Epilepsy; Glycoprotein;
KW GPI-anchor biosynthesis; Membrane; Reference proteome; Transferase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..931
FT /note="GPI ethanolamine phosphate transferase 1"
FT /id="PRO_0000246198"
FT TOPO_DOM 1
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2..24
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 25..442
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 443..463
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 464..482
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 483..503
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 504..508
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 509..529
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 530..543
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 544..564
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 565
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 566..586
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 587..591
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 592..612
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 613..618
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 619..639
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 640..649
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 650..670
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 671..685
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 686..706
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 707..723
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 724..744
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 745..786
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 787..807
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 808..824
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 825..845
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 846..858
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 859..879
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 880..894
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 895..915
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 916..931
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT CARBOHYD 128
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 192
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 350
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 162
FT /note="K -> E (in dbSNP:rs17069506)"
FT /id="VAR_053573"
FT VARIANT 229
FT /note="H -> D (in dbSNP:rs9320001)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_053574"
FT VARIANT 469
FT /note="L -> F (in dbSNP:rs3862712)"
FT /id="VAR_053575"
FT VARIANT 470
FT /note="I -> L (in dbSNP:rs3862712)"
FT /id="VAR_053576"
FT VARIANT 709
FT /note="R -> Q (in MCAHS1; dbSNP:rs397514475)"
FT /evidence="ECO:0000269|PubMed:21493957"
FT /id="VAR_066402"
FT VARIANT 904
FT /note="F -> C (in dbSNP:rs34231046)"
FT /id="VAR_053577"
FT VARIANT 904
FT /note="F -> L (in dbSNP:rs34231046)"
FT /id="VAR_053578"
SQ SEQUENCE 931 AA; 105810 MW; D67B376EF7864C55 CRC64;
MLLFFTLGLL IHFVFFASIF DIYFTSPLVH GMTPQFTPLP PPARRLVLFV ADGLRADALY
ELDENGNSRA PFIRNIIMHE GSWGISHTRV PTESRPGHVA LIAGFYEDVS AVAKGWKENP
VEFDSLFNES KYTWSWGSPD ILPMFAKGAS GDHVYTYSYD AKREDFGAQD ATKLDTWVFD
NVKDFFHHAR NNQSLFSKIN EEKIVFFLHL LGIDTNGHAH RPSSRDYKHN IKKVDDGVKE
IVSMFNHFYG NDGKTTFIFT SDHGMTDWGS HGAGHPSETL TPLVTWGAGI KYPQRVSAQQ
FDDAFLKEWR LENWKRLDVN QADIAPLMTS LIGVPFPLNS VGILPVDYLN NTDLFKAESM
FTNAVQILEQ FKVKMTQKKE VTLPFLFTPF KLLSDSKQFN ILRKARSYIK HRKFDEVVSL
CKELIHLALK GLSYYHTYDR FFLGVNVVIG FVGWISYASL LIIKSHSNLI KGVSKEVKKP
SHLLPCSFVA IGILVAFFLL IQACPWTYYV YGLLPLPIWY AVLREFQVIQ DLVVSVLTYP
LSHFVGYLLA FTLGIEVLVL SFFYRYMLTA GLTAFAAWPF LTRLWTRAKM TSLSWTFFSL
LLAVFPLMPV VGRKPDISLV MGAGLLVLLL SLCVVTSLMK RKDSFIKEEL LVHLLQVLST
VLSMYVVYST QSSLLRKQGL PLMNQIISWA TLASSLVVPL LSSPVLFQRL FSILLSLMST
YLLLSTGYEA LFPLVLSCLM FVWINIEQET LQQSGVCCKQ KLTSIQFSYN TDITQFRQLY
LDDIRRAFFL VFFLVTAFFG TGNIASINSF DLASVYCFLT VFSPFMMGAL MMWKILIPFV
LVMCAFEAVQ LTTQLSSKSL FLIVLVISDI MALHFFFLVK DYGSWLDIGT SISHYVIVMS
MTIFLVFLNG LAQLLTTKKL RLCGKPKSHF M
