Reviewed, UniProtKB/Swiss-Prot P37287 (PIGA_HUMAN)

Names and origin

Protein names

Recommended name:
    Phosphatidylinositol N-acetylglucosaminyltransferase subunit A
    EC=2.4.1.198
Alternative name(s):
    GlcNAc-PI synthesis protein
    Phosphatidylinositol-glycan biosynthesis class A protein
      Short name=PIG-A

Gene names

Name:

PIGA

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	484 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Necessary for the synthesis of N-acetylglucosaminyl-phosphatidylinositol, the very early intermediate in GPI-anchor biosynthesis.
Catalytic activity	UDP-N-acetyl-D-glucosamine + 1-phosphatidyl-1D-myo-inositol = UDP + 6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol.
Pathway	Glycolipid biosynthesis; glycosylphosphatidylinositol-anchor biosynthesis.
Subunit structure	Associates with PIGC, PIGH, PIGP, PIGQ and DPM2. The latter is not essential for activity. Interacts directly with PIGY.
Subcellular location	Endoplasmic reticulum membrane; Single-pass membrane protein.
Involvement in disease	Defects in PIGA are the cause of paroxysmal nocturnal hemoglobinuria (PNH) [MIM:311770]. PNH is an acquired hemolytic blood disorder characterized by chronic hemolysis with hemoglobinuria, increased tendency to venous thrombosis, and variable degrees of bone marrow failure Biosynthesis of the GPI anchor is deficient in patients with PNH leading to deficient surface expression of GPI-anchored proteins such as DAF or CD59 which play roles in the protection of red cells from the action of complement.
Sequence similarities	Belongs to the glycosyltransferase 1 family.

Ontologies

Keywords
Biological process	GPI-anchor biosynthesis
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Alternative splicing
Disease	Disease mutation
Domain	Transmembrane
Molecular function	Glycosyltransferase Transferase
Gene Ontology (GO)
Biological process	positive regulation of metabolic process Ref.7 Traceable author statement. Source: HGNC preassembly of GPI anchor in ER membrane Inferred from Experiment. Source: Reactome
Cellular component	endoplasmic reticulum membrane Ref.7 Inferred from direct assay. Source: HGNC glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex Ref.7 Inferred from direct assay. Source: HGNC integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	phosphatidylinositol N-acetylglucosaminyltransferase activity Ref.7 Traceable author statement. Source: HGNC protein binding Ref.7 Inferred from physical interaction. Source: HGNC
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P37287-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P37287-2)

The sequence of this isoform differs from the canonical sequence as follows:
     115-283: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 484	484	Phosphatidylinositol N-acetylglucosaminyltransferase subunit A		PRO_0000080326
Regions
	Topological domain	1 – 421	421	Cytoplasmic Potential
	Transmembrane	422 – 442	21	Potential
	Topological domain	443 – 484	42	Lumenal Potential
Natural variations
	Alternative sequence	115 – 283	169	Missing in isoform 2.		VSP_001802
	Natural variant	19	1	R → W in PNH.		VAR_015442
	Natural variant	40	1	D → H in PNH.		VAR_015436
	Natural variant	48	1	G → A in PNH.		VAR_015437
	Natural variant	48	1	G → D in PNH.		VAR_015438
	Natural variant	48	1	G → V in PNH.		VAR_015439
	Natural variant	128	1	H → R in PNH.		VAR_015440
	Natural variant	155	1	S → F in PNH.		VAR_005531
	Natural variant	239	1	G → R in PNH.		VAR_015441
	Natural variant	297	1	N → D in PNH.		VAR_005532

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 1994. Version 1. Checksum: 34DCD074A3920852	FASTA	484	54,127
	10 20 30 40 50 60 MACRGGAGNG HRASATLSRV SPGSLYTCRT RTHNICMVSD FFYPNMGGVE SHIYQLSQCL 70 80 90 100 110 120 IERGHKVIIV THAYGNRKGI RYLTSGLKVY YLPLKVMYNQ STATTLFHSL PLLRYIFVRE 130 140 150 160 170 180 RVTIIHSHSS FSAMAHDALF HAKTMGLQTV FTDHSLFGFA DVSSVLTNKL LTVSLCDTNH 190 200 210 220 230 240 IICVSYTSKE NTVLRAALNP EIVSVIPNAV DPTDFTPDPF RRHDSITIVV VSRLVYRKGI 250 260 270 280 290 300 DLLSGIIPEL CQKYPDLNFI IGGEGPKRII LEEVRERYQL HDRVRLLGAL EHKDVRNVLV 310 320 330 340 350 360 QGHIFLNTSL TEAFCMAIVE AASCGLQVVS TRVGGIPEVL PENLIILCEP SVKSLCEGLE 370 380 390 400 410 420 KAIFQLKSGT LPAPENIHNI VKTFYTWRNV AERTEKVYDR VSVEAVLPMD KRLDRLISHC 430 440 450 460 470 480 GPVTGYIFAL LAVFNFLFLI FLRWMTPDSI IDVAIDATGP RGAWTNNYSH SKRGGENNEI SETR
	Isoform 2 [UniParc]. Checksum: 3F443EA94F271865		315	35,078
	10 20 30 40 50 60 MACRGGAGNG HRASATLSRV SPGSLYTCRT RTHNICMVSD FFYPNMGGVE SHIYQLSQCL 70 80 90 100 110 120 IERGHKVIIV THAYGNRKGI RYLTSGLKVY YLPLKVMYNQ STATTLFHSL PLLRVRLLGA 130 140 150 160 170 180 LEHKDVRNVL VQGHIFLNTS LTEAFCMAIV EAASCGLQVV STRVGGIPEV LPENLIILCE 190 200 210 220 230 240 PSVKSLCEGL EKAIFQLKSG TLPAPENIHN IVKTFYTWRN VAERTEKVYD RVSVEAVLPM 250 260 270 280 290 300 DKRLDRLISH CGPVTGYIFA LLAVFNFLFL IFLRWMTPDS IIDVAIDATG PRGAWTNNYS 310 HSKRGGENNE ISETR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The cloning of PIG-A, a component in the early step of GPI-anchor biosynthesis." Miyata T., Takeda J., Iida Y., Yamada N., Inoue N., Takahashi M., Maeda K., Kitani T., Kinoshita T. Science 259:1318-1320(1993) [PubMed: 7680492] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Genomic organization of the X-linked gene (PIG-A) that is mutated in paroxysmal nocturnal haemoglobinuria and of a related autosomal pseudogene mapped to 12q21." Bessler M., Hillmen P., Longo L., Luzzatto L., Mason P.J. Hum. Mol. Genet. 3:751-757(1994) [PubMed: 8081362] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[3]	"Characterization of genomic PIG-A gene: a gene for glycosylphosphatidylinositol-anchor biosynthesis and paroxysmal nocturnal hemoglobinuria." Iida Y., Takeda J., Miyata T., Inoue N., Nishimura J., Kitani T., Maeda K., Kinoshita T. Blood 83:3126-3131(1994) [PubMed: 8193350] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[4]	"Characterization of alternatively spliced PIG-A transcripts in normal and paroxysmal nocturnal hemoglobinuria cells." Yu J., Nagarajan S., Ueda E., Knez J.J., Petersen R.B., Medof M.E. Braz. J. Med. Biol. Res. 27:195-201(1994) [PubMed: 8081230] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[6]	"Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria." Takeda J., Miyata T., Kawagoe K., Iida Y., Endo Y., Fujita T., Takahashi M., Kitani T., Kinoshita T. Cell 73:703-711(1993) [PubMed: 8500164] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 301-420, DISEASE.
[7]	"The initial enzyme for glycosylphosphatidylinositol biosynthesis requires PIG-Y, a seventh component." Murakami Y., Siripanyaphinyo U., Hong Y., Tashima Y., Maeda Y., Kinoshita T. Mol. Biol. Cell 16:5236-5246(2005) [PubMed: 16162815] [Abstract] Cited for: INTERACTION WITH PIGY.
[8]	"Paroxysmal nocturnal haemoglobinuria (PNH) is caused by somatic mutations in the PIG-A gene." Bessler M., Mason P.J., Hilmen P., Miyata T., Yamada N., Takeda J., Luzzato L., Kinoshita T. EMBO J. 13:110-117(1994) [PubMed: 8306954] [Abstract] Cited for: VARIANT PNH PHE-155.
[9]	"Mutations within the Piga gene in patients with paroxysmal nocturnal hemoglobinuria." Ware R.E., Rosse W.F., Howard T.A. Blood 83:2418-2422(1994) [PubMed: 8167330] [Abstract] Cited for: VARIANT PNH ASP-297.
[10]	"The spectrum of somatic mutations in the PIG-A gene in paroxysmal nocturnal hemoglobinuria includes large deletions and small duplications." Nafa K., Bessler M., Castro-Malaspina H., Jhanwar S., Luzzatto L. Blood Cells Mol. Dis. 24:370-384(1998) [PubMed: 10087994] [Abstract] Cited for: VARIANTS PNH TRP-19; HIS-40; ALA-48; ASP-48; ARG-128 AND ARG-239.
[11]	"Mutation analysis of the PIG-A gene in Korean patients with paroxysmal nocturnal haemoglobinuria." Yoon J.H., Cho H.I., Park S.S., Chang Y.H., Kim B.K. J. Clin. Pathol. 55:410-413(2002) [PubMed: 12037021] [Abstract] Cited for: VARIANT PNH VAL-48.
+	Additional computationally mapped references.

Web resources

Functional Glycomics Gateway - GTase

Phosphatidylinositol N-acetylglucosaminyltransferase subunit A

Cross-references

Sequence databases
EMBLGenBankDDBJ	D11466 mRNA. Translation: BAA02019.1. X77725 , X77726, X77727, X77728 Genomic DNA. Translation: CAB57276.1. Sequence problems. D28791 Genomic DNA. Translation: BAA05966.1. S74936 mRNA. Translation: AAD14160.1. BC038236 mRNA. Translation: AAH38236.1. S61523 mRNA. Translation: AAD13929.1.
PIR	A46217.
RefSeq	NP_002632.1.
UniGene	Hs.137154
3D structure databases
ModBase	Search...
PTM databases
PhosphoSite	P37287.
Genome annotation databases
Ensembl	ENSG00000165195. Homo sapiens. [Contig view]
GeneID	5277.
KEGG	hsa:5277.
Organism-specific databases
H-InvDB	HIX0016667.
HGNC	HGNC:8957. PIGA.
MIM	311770. gene+phenotype.
Orphanet	447. Paroxysmal nocturnal haemoglobinuria.
PharmGKB	PA33288.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	P37287.
HOVERGEN	P37287.
Enzyme and pathway databases
Reactome	REACT_1069. Post-translational protein modification.
Gene expression databases
ArrayExpress	P37287.
CleanEx	HS_PIGA.
GermOnline	ENSG00000165195. Homo sapiens.
Family and domain databases
InterPro	IPR001296. Glyco_trans_1. IPR013234. PIGA_GPI_anchor. [Graphical view]
Pfam	PF00534. Glycos_transf_1. 1 hit. PF08288. PIGA. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
LinkHub	P37287.
NextBio	20392.
SOURCE	Search...

Entry information

Entry name

PIGA_HUMAN

Accession

Primary (citable) accession number: P37287
Secondary accession number(s): Q16025, Q16250

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1994
Last sequence update:	October 1, 1994
Last modified:	November 25, 2008
This is version 77 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)