GPAA1_HUMAN
ID GPAA1_HUMAN Reviewed; 621 AA.
AC O43292; Q9NSS0; Q9UQ31;
DT 01-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Glycosylphosphatidylinositol anchor attachment 1 protein;
DE Short=GPI anchor attachment protein 1;
DE AltName: Full=GAA1 protein homolog;
DE Short=hGAA1;
GN Name=GPAA1; Synonyms=GAA1;
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, AND TISSUE SPECIFICITY.
RC TISSUE=Heart;
RX PubMed=9468317; DOI=10.1016/s0014-5793(97)01576-7;
RA Hiroi Y., Komuro I., Chen R., Hosoda T., Mizuno T., Kudoh S.,
RA Georgescu S.P., Medof M.E., Yazaki Y.;
RT "Molecular cloning of human homolog of yeast GAA1 which is required for
RT attachment of glycosylphosphatidylinositols to proteins.";
RL FEBS Lett. 421:252-258(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RC TISSUE=Lung;
RX PubMed=10393431; DOI=10.1159/000015258;
RA Inoue N., Ohishi K., Endo Y., Fujita T., Takeda J., Kinoshita T.;
RT "Human and mouse GPAA1 (glycosylphosphatidylinositol anchor attachment 1)
RT genes: genomic structures, chromosome loci and the presence of a minor
RT class intron.";
RL Cytogenet. Cell Genet. 84:199-205(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Muscle, Placenta, and Skin;
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 [5]
RP PROTEIN SEQUENCE OF 2-21, SUBUNIT, SUBCELLULAR LOCATION, AND MEMBRANE
RP TOPOLOGY.
RX PubMed=11483512; DOI=10.1093/emboj/20.15.4088;
RA Ohishi K., Inoue N., Kinoshita T.;
RT "PIG-S and PIG-T, essential for GPI anchor attachment to proteins, form a
RT complex with GAA1 and GPI8.";
RL EMBO J. 20:4088-4098(2001).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [7]
RP FUNCTION, INVOLVEMENT IN GPIBD15, VARIANTS GPIBD15 LEU-51; ASN-54; SER-176;
RP PRO-290; PRO-291 AND PRO-389, AND CHARACTERIZATION OF VARIANTS GPIBD15
RP LEU-51; SER-176 AND PRO-291.
RX PubMed=29100095; DOI=10.1016/j.ajhg.2017.09.020;
RA Nguyen T.T.M., Murakami Y., Sheridan E., Ehresmann S., Rousseau J.,
RA St-Denis A., Chai G., Ajeawung N.F., Fairbrother L., Reimschisel T.,
RA Bateman A., Berry-Kravis E., Xia F., Tardif J., Parry D.A., Logan C.V.,
RA Diggle C., Bennett C.P., Hattingh L., Rosenfeld J.A., Perry M.S.,
RA Parker M.J., Le Deist F., Zaki M.S., Ignatius E., Isohanni P.,
RA Loennqvist T., Carroll C.J., Johnson C.A., Gleeson J.G., Kinoshita T.,
RA Campeau P.M.;
RT "Mutations in GPAA1, encoding a GPI transamidase complex protein, cause
RT developmental delay, epilepsy, cerebellar atrophy, and osteopenia.";
RL Am. J. Hum. Genet. 101:856-865(2017).
CC -!- FUNCTION: Essential for GPI-anchoring of precursor proteins but not for
CC GPI synthesis. Acts before or during formation of the carbonyl
CC intermediate. {ECO:0000269|PubMed:29100095,
CC ECO:0000269|PubMed:9468317}.
CC -!- PATHWAY: Glycolipid biosynthesis; glycosylphosphatidylinositol-anchor
CC biosynthesis.
CC -!- SUBUNIT: Forms a complex with PIGK/GPI8, PIGT, PIGU and PIGS.
CC {ECO:0000269|PubMed:11483512}.
CC -!- INTERACTION:
CC O43292; Q92643: PIGK; NbExp=11; IntAct=EBI-720225, EBI-8617711;
CC O43292; Q969N2: PIGT; NbExp=11; IntAct=EBI-720225, EBI-726383;
CC O43292-2; Q92993: KAT5; NbExp=3; IntAct=EBI-25884370, EBI-399080;
CC O43292-2; Q8TAP4-4: LMO3; NbExp=3; IntAct=EBI-25884370, EBI-11742507;
CC O43292-2; P23284: PPIB; NbExp=3; IntAct=EBI-25884370, EBI-359252;
CC O43292-2; Q15047-2: SETDB1; NbExp=3; IntAct=EBI-25884370, EBI-9090795;
CC O43292-2; P61981: YWHAG; NbExp=3; IntAct=EBI-25884370, EBI-359832;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:11483512}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:11483512}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O43292-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O43292-2; Sequence=VSP_009542;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed in fetal and adult tissues.
CC Expressed at higher levels in fetal tissues than adult tissues.
CC {ECO:0000269|PubMed:9468317}.
CC -!- DISEASE: Glycosylphosphatidylinositol biosynthesis defect 15 (GPIBD15)
CC [MIM:617810]: An autosomal recessive disorder characterized by delayed
CC psychomotor development, variable intellectual disability, hypotonia,
CC early-onset seizures in most patients, and cerebellar atrophy,
CC resulting in cerebellar signs including gait ataxia and dysarthria.
CC {ECO:0000269|PubMed:29100095}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAB75660.2; Type=Erroneous gene model prediction; Note=Erroneous prediction from an unspliced cDNA.; Evidence={ECO:0000305};
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DR EMBL; AB006969; BAA24035.1; -; mRNA.
DR EMBL; AB002135; BAA82588.1; -; mRNA.
DR EMBL; AB002137; BAA82590.1; -; Genomic_DNA.
DR EMBL; AB017267; BAA82587.1; -; Genomic_DNA.
DR EMBL; AL157437; CAB75660.2; ALT_SEQ; mRNA.
DR EMBL; BC003171; AAH03171.1; -; mRNA.
DR EMBL; BC004129; AAH04129.1; -; mRNA.
DR EMBL; BC006383; AAH06383.2; -; mRNA.
DR CCDS; CCDS43776.1; -. [O43292-1]
DR PIR; T46923; T46923.
DR RefSeq; NP_003792.1; NM_003801.3. [O43292-1]
DR PDB; 7W72; EM; 3.10 A; A=1-621.
DR PDBsum; 7W72; -.
DR AlphaFoldDB; O43292; -.
DR SMR; O43292; -.
DR BioGRID; 114271; 116.
DR ComplexPortal; CPX-6503; GPI-anchor transamidase complex.
DR CORUM; O43292; -.
DR IntAct; O43292; 39.
DR MINT; O43292; -.
DR STRING; 9606.ENSP00000347206; -.
DR GlyGen; O43292; 2 sites.
DR iPTMnet; O43292; -.
DR PhosphoSitePlus; O43292; -.
DR SwissPalm; O43292; -.
DR BioMuta; GPAA1; -.
DR EPD; O43292; -.
DR jPOST; O43292; -.
DR MassIVE; O43292; -.
DR MaxQB; O43292; -.
DR PaxDb; O43292; -.
DR PeptideAtlas; O43292; -.
DR PRIDE; O43292; -.
DR ProteomicsDB; 48861; -. [O43292-1]
DR ProteomicsDB; 48862; -. [O43292-2]
DR Antibodypedia; 28266; 156 antibodies from 24 providers.
DR DNASU; 8733; -.
DR Ensembl; ENST00000355091.9; ENSP00000347206.4; ENSG00000197858.11. [O43292-1]
DR Ensembl; ENST00000361036.10; ENSP00000354316.6; ENSG00000197858.11. [O43292-2]
DR GeneID; 8733; -.
DR KEGG; hsa:8733; -.
DR MANE-Select; ENST00000355091.9; ENSP00000347206.4; NM_003801.4; NP_003792.1.
DR UCSC; uc003zax.4; human. [O43292-1]
DR CTD; 8733; -.
DR DisGeNET; 8733; -.
DR GeneCards; GPAA1; -.
DR HGNC; HGNC:4446; GPAA1.
DR HPA; ENSG00000197858; Low tissue specificity.
DR MalaCards; GPAA1; -.
DR MIM; 603048; gene.
DR MIM; 617810; phenotype.
DR neXtProt; NX_O43292; -.
DR OpenTargets; ENSG00000197858; -.
DR Orphanet; 529665; Neurodevelopmental delay-seizures-ophthalmic anomalies-osteopenia-cerebellar atrophy syndrome.
DR PharmGKB; PA28827; -.
DR VEuPathDB; HostDB:ENSG00000197858; -.
DR eggNOG; KOG3566; Eukaryota.
DR GeneTree; ENSGT00390000013685; -.
DR HOGENOM; CLU_007442_2_1_1; -.
DR InParanoid; O43292; -.
DR OMA; MAIALWM; -.
DR OrthoDB; 1486030at2759; -.
DR PhylomeDB; O43292; -.
DR TreeFam; TF313030; -.
DR PathwayCommons; O43292; -.
DR Reactome; R-HSA-162791; Attachment of GPI anchor to uPAR.
DR SignaLink; O43292; -.
DR SIGNOR; O43292; -.
DR UniPathway; UPA00196; -.
DR BioGRID-ORCS; 8733; 28 hits in 1079 CRISPR screens.
DR ChiTaRS; GPAA1; human.
DR GeneWiki; GPAA1; -.
DR GenomeRNAi; 8733; -.
DR Pharos; O43292; Tbio.
DR PRO; PR:O43292; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; O43292; protein.
DR Bgee; ENSG00000197858; Expressed in stromal cell of endometrium and 203 other tissues.
DR ExpressionAtlas; O43292; baseline and differential.
DR Genevisible; O43292; HS.
DR GO; GO:0005813; C:centrosome; IDA:HPA.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0042765; C:GPI-anchor transamidase complex; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0015631; F:tubulin binding; NAS:UniProtKB.
DR GO; GO:0016255; P:attachment of GPI anchor to protein; IBA:GO_Central.
DR GO; GO:0006621; P:protein retention in ER lumen; NAS:UniProtKB.
DR GO; GO:0065003; P:protein-containing complex assembly; IMP:UniProtKB.
DR InterPro; IPR007246; Gaa1.
DR PANTHER; PTHR13304; PTHR13304; 1.
DR Pfam; PF04114; Gaa1; 1.
DR PIRSF; PIRSF036762; GAA1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Direct protein sequencing;
KW Disease variant; Endoplasmic reticulum; Glycoprotein;
KW GPI-anchor biosynthesis; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:11483512"
FT CHAIN 2..621
FT /note="Glycosylphosphatidylinositol anchor attachment 1
FT protein"
FT /id="PRO_0000087554"
FT TOPO_DOM 2..24
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 25..45
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 46..368
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 369..389
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 390..427
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 428..448
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 449..458
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 459..479
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 480..495
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 496..516
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 517..543
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 544..564
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 565..599
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 600..620
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 621
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT CARBOHYD 203
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 517
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 25..85
FT /note="CVLSYVAGIAWFLALVFPPLTQRTYMSENAMGSTMVEEQFAGGDRARAFARD
FT FAAHRKKSG -> W (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_009542"
FT VARIANT 51
FT /note="S -> L (in GPIBD15; results in low amounts of GPI-
FT anchored proteins on cell surface; dbSNP:rs1554763770)"
FT /evidence="ECO:0000269|PubMed:29100095"
FT /id="VAR_080543"
FT VARIANT 54
FT /note="A -> N (in GPIBD15; unknown pathological
FT significance; requires 2 nucleotide substitutions;
FT dbSNP:rs1554763777)"
FT /evidence="ECO:0000269|PubMed:29100095"
FT /id="VAR_080544"
FT VARIANT 176
FT /note="W -> S (in GPIBD15; results in low amounts of GPI-
FT anchored proteins on cell surface; dbSNP:rs782220208)"
FT /evidence="ECO:0000269|PubMed:29100095"
FT /id="VAR_080545"
FT VARIANT 290
FT /note="L -> P (in GPIBD15; dbSNP:rs1554764058)"
FT /evidence="ECO:0000269|PubMed:29100095"
FT /id="VAR_080546"
FT VARIANT 291
FT /note="L -> P (in GPIBD15; results in low amounts of GPI-
FT anchored proteins on cell surface; dbSNP:rs1010907740)"
FT /evidence="ECO:0000269|PubMed:29100095"
FT /id="VAR_080547"
FT VARIANT 389
FT /note="A -> P (in GPIBD15; dbSNP:rs782768127)"
FT /evidence="ECO:0000269|PubMed:29100095"
FT /id="VAR_080548"
SQ SEQUENCE 621 AA; 67623 MW; A70AC8758A919A98 CRC64;
MGLLSDPVRR RALARLVLRL NAPLCVLSYV AGIAWFLALV FPPLTQRTYM SENAMGSTMV
EEQFAGGDRA RAFARDFAAH RKKSGALPVA WLERTMRSVG LEVYTQSFSR KLPFPDETHE
RYMVSGTNVY GILRAPRAAS TESLVLTVPC GSDSTNSQAV GLLLALAAHF RGQIYWAKDI
VFLVTEHDLL GTEAWLEAYH DVNVTGMQSS PLQGRAGAIQ AAVALELSSD VVTSLDVAVE
GLNGQLPNLD LLNLFQTFCQ KGGLLCTLQG KLQPEDWTSL DGPLQGLQTL LLMVLRQASG
RPHGSHGLFL RYRVEALTLR GINSFRQYKY DLVAVGKALE GMFRKLNHLL ERLHQSFFLY
LLPGLSRFVS IGLYMPAVGF LLLVLGLKAL ELWMQLHEAG MGLEEPGGAP GPSVPLPPSQ
GVGLASLVAP LLISQAMGLA LYVLPVLGQH VATQHFPVAE AEAVVLTLLA IYAAGLALPH
NTHRVVSTQA PDRGWMALKL VALIYLALQL GCIALTNFSL GFLLATTMVP TAALAKPHGP
RTLYAALLVL TSPAATLLGS LFLWRELQEA PLSLAEGWQL FLAALAQGVL EHHTYGALLF
PLLSLGLYPC WLLFWNVLFW K
