PIGK
entrez
10026
canonical
uniprot
Q92643
canonical
ensembl
ENSG00000142892
resolver
ensp
ENSP00000359848
resolver
genesymbol
PIGK
resolver
genesymbol_syn
GPI8
resolver
hgnc
HGNC:8965
resolver
uniprot
B2R7K3
resolver
uniprot
B4E2M3
resolver
uniprot
O14822
resolver
uniprot
Q5TG77
resolver
uniprot_entry
GPI8_HUMAN
resolver
uniprot_sec
B2R7K3
resolver
uniprot_sec
B4E2M3
resolver
uniprot_sec
O14822
resolver
uniprot_sec
Q5TG77
resolver
activity_regulation
ACTIVITY REGULATION: In the absence of proproteins substrates, exists in an inactive state with a disrupted catalytic site by an autoinhibitory loop (PubMed:37684232). The binding of proprotein substrates, particularly the CSP region, to GPI-T triggers concerted conformational changes that alleviate the inhibition by the autoinhibitory loop (PubMed:37684232). Meanwhile, proprotein residues near the omega- site induce the formation of a catalytic cleft for catalysis, following which the products are released and GPI-T reverts to the inactive state (PubMed:37684232). {ECO:0000269|PubMed:37684232}.
uniprot
proteins
amino_acid_sequence
MAVTDSLSRAATVLATVLLLSFGSVAASHIEDQAEQFFRSGHTNNWAVLVCTSRFWFNYRHVANTLSVYRSVKRLGIPDSHIVLMLADDMACNPRNPKPATVFSHKNMELNVYGDDVEVDYRSYEVTVENFLRVLTGRIPPSTPRSKRLLSDDRSNILIYMTGHGGNGFLKFQDSEEITNIELADAFEQMWQKRRYNELLFIIDTCQGASMYERFYSPNIMALASSQVGEDSLSHQPDPAIGVHLMDRYTFYVLEFLEEINPASQTNMNDLFQVCPKSLCVSTPGHRTDLFQRDPKNVLITDFFGSVRKVEITTETIKLQQDSEIMESSYKEDQMDEKLMEPLKYAEQLPVAQIIHQKPKLKDWHPPGGFILGLWALIIMVFFKTYGIKHMKFIF
uniprot
proteins
disease_involvement
DISEASE: Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures (NEDHCAS) [MIM:618879]: An autosomal recessive neurodevelopmental disorder characterized by global developmental delay, intellectual disability, hypotonia, cerebellar ataxia, cerebellar atrophy, delayed motor skills, poor or absent speech, and epilepsy in most patients. Some patients manifest facial dysmorphism. Disease onset is in infancy. {ECO:0000269|PubMed:32220290}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.6.1.-
uniprot
proteins
function
FUNCTION: Catalytic subunit of the glycosylphosphatidylinositol-anchor (GPI-anchor) transamidase (GPI-T) complex that catalyzes the formation of the linkage between a proprotein and a GPI-anchor and participates in GPI anchored protein biosynthesis (PubMed:10793132, PubMed:11483512, PubMed:12582175, PubMed:34576938, PubMed:35165458, PubMed:35551457, PubMed:37684232, PubMed:9356492). Recognizes diverse proproteins at a C-terminal signal peptide (CSP) region that lacks consensus sequence and replaces it with a GPI-anchor via a transamidation reaction (PubMed:35165458, PubMed:35551457, PubMed:37684232). Transamidation catalysis reaction follows a two-phase mechanism (PubMed:37684232). In the acyl-enzyme phase, the carbonyl group of the proproteins's omega-site undergoes a nucleophilic attack forming an enzyme-substrate thioester bond (PubMed:37684232). Followed by a general acid catalysis that allows CSP releasing, regenerating the carbonyl, and forming the acyl-enzyme intermediate (PubMed:37684232). In the GPI-anchor attachment phase, the amino group of the GPI-anchor's ethanolamine phosphate, the one on third mannose (EtNP3), mediates a nucleophilic attack on the carbonyl of the acyl-enzyme intermediate, replacing the CSP, allowing GPI-anchor attachment to the omega-residue, therefore forming the product and freeing the enzyme (PubMed:37684232). {ECO:0000269|PubMed:10793132, ECO:0000269|PubMed:11483512, ECO:0000269|PubMed:12582175, ECO:0000269|PubMed:34576938, ECO:0000269|PubMed:35165458, ECO:0000269|PubMed:35551457, ECO:0000269|PubMed:37684232, ECO:0000269|PubMed:9356492}.
uniprot
proteins
mass_dalton
45252
uniprot
proteins
mutagenesis
MUTAGEN 54; /note="R->A: No effect on function in GPI-anchor attachment to protein."; /evidence="ECO:0000269|PubMed:34576938"; MUTAGEN 58; /note="N->A: Decreased function in GPI-anchor attachment to protein. Substantially decreases GPI-anchor transamidase activity."; /evidence="ECO:0000269|PubMed:34576938, ECO:0000269|PubMed:35165458"; MUTAGEN 60; /note="R->A: Decreased function in GPI-anchor attachment to protein. Reduces by 25% the GPI-anchor transamidase activity."; /evidence="ECO:0000269|PubMed:34576938, ECO:0000269|PubMed:35551457"; MUTAGEN 60; /note="R->E: Reduces by 90% the GPI-anchor transamidase activity."; /evidence="ECO:0000269|PubMed:35551457"; MUTAGEN 60; /note="R->K: Reduces by 60% the GPI-anchor transamidase activity."; /evidence="ECO:0000269|PubMed:35551457"; MUTAGEN 60; /note="R->L: Reduces by 40% the GPI-anchor transamidase activity."; /evidence="ECO:0000269|PubMed:35551457"; MUTAGEN 61; /note="H->A: Decreased function in GPI-anchor attachment to protein."; /evidence="ECO:0000269|PubMed:34576938"; MUTAGEN 74; /note="R->A: No effect on function in GPI-anchor attachment to protein."; /evidence="ECO:0000269|PubMed:34576938"; MUTAGEN 79; /note="D->A: No effect on function in GPI-anchor attachment to protein."; /evidence="ECO:0000269|PubMed:34576938"; MUTAGEN 92; /note="C->A: Decreased function in GPI-anchor attachment to protein. Decreases GPI-anchor transamidase activity by approximately 40%."; /evidence="ECO:0000269|PubMed:10793132, ECO:0000269|PubMed:12582175, ECO:0000269|PubMed:35551457"; MUTAGEN 92; /note="C->S: Decreased function in GPI-anchor attachment to protein."; /evidence="ECO:0000269|PubMed:10793132, ECO:0000269|PubMed:12582175, ECO:0000269|PubMed:34576938"; MUTAGEN 118; /note="E->A: No effect on function in GPI-anchor attachment to protein."; /evidence="ECO:0000269|PubMed:34576938"; MUTAGEN 120; /note="D->N: Does not affect GPI-anchor transamidase activity."; /evidence="ECO:0000269|PubMed:35165458"; MUTAGEN 125; /note="E->A: No effect on function in GPI-anchor attachment to protein."; /evidence="ECO:0000269|PubMed:34576938"; MUTAGEN 129; /note="E->A: No effect on function in GPI-anchor attachment to protein."; /evidence="ECO:0000269|PubMed:34576938"; MUTAGEN 160; /note="Y->A: No effect on function in GPI-anchor attachment to protein."; /evidence="ECO:0000269|PubMed:34576938"; MUTAGEN 164; /note="H->A: Loss of function in GPI-anchor attachment to protein. Abolishes GPI-anchor transamidase activity."; /evidence="ECO:0000269|PubMed:10793132, ECO:0000269|PubMed:34576938, ECO:0000269|PubMed:35165458, ECO:0000269|PubMed:35551457"; MUTAGEN 174; /note="D->A: No effect on function in GPI-anchor attachment to protein."; /evidence="ECO:0000269|PubMed:34576938"; MUTAGEN 198; /note="E->A: No effect on function in GPI-anchor attachment to protein."; /evidence="ECO:0000269|PubMed:34576938"; MUTAGEN 204; /note="D->A: Decreased function in GPI-anchor attachment to protein."; /evidence="ECO:0000269|PubMed:34576938"; MUTAGEN 204; /note="D->K: Reduces by 60% the GPI-anchor transamidase activity."; /evidence="ECO:0000269|PubMed:35551457"; MUTAGEN 206; /note="C->A: Loss of function in GPI-anchor attachment to protein. Abolishes GPI-anchor transamidase activity."; /evidence="ECO:0000269|PubMed:10793132, ECO:0000269|PubMed:35165458, ECO:0000269|PubMed:35551457"; MUTAGEN 206; /note="C->S: Loss of function in GPI-anchor attachment to protein."; /evidence="ECO:0000269|PubMed:34576938"; MUTAGEN 230; /note="E->A: No effect on function in GPI-anchor attachment to protein."; /evidence="ECO:0000269|PubMed:34576938"; MUTAGEN 231; /note="D->A: No effect on function in GPI-anchor attachment to protein."; /evidence="ECO:0000269|PubMed:34576938"; MUTAGEN 232; /note="S->A: No effect on function in GPI-anchor attachment to protein."; /evidence="ECO:0000269|PubMed:34576938"; MUTAGEN 238; /note="D->A: No effect on function in GPI-anchor attachment to protein."; /evidence="ECO:0000269|PubMed:34576938"; MUTAGEN 244; /note="H->A: No effect on function in GPI-anchor attachment to protein."; /evidence="ECO:0000269|PubMed:34576938"; MUTAGEN 247; /note="D->A: No effect on function in GPI-anchor attachment to protein."; /evidence="ECO:0000269|PubMed:34576938"; MUTAGEN 247; /note="D->K: Almost abolishes the GPI-anchor transamidase activity."; /evidence="ECO:0000269|PubMed:35551457"; MUTAGEN 289; /note="D->A: No effect on function in GPI-anchor attachment to protein."; /evidence="ECO:0000269|PubMed:34576938"; MUTAGEN 302; /note="D->A: No effect on function in GPI-anchor attachment to protein."; /evidence="ECO:0000269|PubMed:34576938"; MUTAGEN 311..395; /note="Missing: Loss of activity."; /evidence="ECO:0000269|PubMed:10793132
uniprot
proteins
pathway_participation
PATHWAY: Glycolipid biosynthesis; glycosylphosphatidylinositol-anchor biosynthesis. {ECO:0000269|PubMed:10793132, ECO:0000269|PubMed:11483512, ECO:0000269|PubMed:12582175, ECO:0000269|PubMed:35165458, ECO:0000269|PubMed:35551457, ECO:0000269|PubMed:9356492}.
uniprot
proteins
post_translational_modification
PTM: The disulfide bond between PIGK/GPI8 and PIGT is important for normal enzyme activity. {ECO:0000269|PubMed:12582175, ECO:0000269|PubMed:35551457}.
uniprot
proteins
protein_family
Peptidase C13 family
uniprot
proteins
pubmed
10793132
uniprot
proteins
pubmed
11483512
uniprot
proteins
pubmed
12582175
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
32220290
uniprot
proteins
pubmed
34576938
uniprot
proteins
pubmed
35165458
uniprot
proteins
pubmed
35551457
uniprot
proteins
pubmed
37684232
uniprot
proteins
pubmed
8978684
uniprot
proteins
pubmed
9356492
uniprot
proteins
sequence_length
395
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000269|PubMed:11483512}; Single-pass type I membrane protein {ECO:0000269|PubMed:35165458, ECO:0000269|PubMed:35551457}.
uniprot
proteins
transmembrane_region
TRANSMEM 369..385; /note="Helical"; /evidence="ECO:0000269|PubMed:35165458, ECO:0000269|PubMed:35551457, ECO:0000312|PDB:7W72, ECO:0000312|PDB:7WLD
uniprot
proteins