Q92643 (GPI8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
GPI-anchor transamidase
Short name=GPI transamidase
EC=3.-.-.-

Alternative name(s):
GPI8 homolog
Short name=hGPI8
Phosphatidylinositol-glycan biosynthesis class K protein
Short name=PIG-K

Gene names

Name:	PIGK
Synonyms:	GPI8

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	395 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Mediates GPI anchoring in the endoplasmic reticulum, by replacing a protein's C-terminal GPI attachment signal peptide with a pre-assembled GPI. During this transamidation reaction, the GPI transamidase forms a carbonyl intermediate with the substrate protein.
Pathway	Glycolipid biosynthesis; glycosylphosphatidylinositol-anchor biosynthesis.
Subunit structure	Forms a complex with PIGT, PIGS, PIGU and GAA1. Ref.7 Ref.8
Subcellular location	Endoplasmic reticulum membrane; Single-pass type I membrane protein Ref.8.
Post-translational modification	The disulfide bond between PIGK/GPI8 and PIGT is important for normal enzyme activity.
Sequence similarities	Belongs to the peptidase C13 family.

Ontologies

Keywords
Biological process	GPI-anchor biosynthesis
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Hydrolase Protease Thiol protease
PTM	Disulfide bond
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	C-terminal protein lipidation Traceable author statement. Source: Reactome attachment of GPI anchor to protein Traceable author statement Ref.8. Source: UniProtKB protein thiol-disulfide exchange Traceable author statement Ref.9. Source: UniProtKB proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	GPI-anchor transamidase complex Inferred from mutant phenotype Ref.7. Source: UniProtKB
Molecular function	GPI-anchor transamidase activity Inferred from mutant phenotype Ref.7. Source: UniProtKB cysteine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro protein binding Inferred from physical interaction Ref.7Ref.8. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 27	27	Ref.8
	Chain	28 – 395	368	GPI-anchor transamidase		PRO_0000026529
Regions
	Topological domain	28 – 367	340	Lumenal Potential
	Transmembrane	368 – 388	21	Helical; Potential
	Topological domain	389 – 395	7	Cytoplasmic Potential
	Region	311 – 321	11	Essential for GPI attachment
Sites
	Active site	164	1	Ref.7
	Active site	206	1	Ref.7
Amino acid modifications
	Disulfide bond	92		Interchain (with C-182 in PIGT) Ref.9
Natural variations
	Natural variant	16	1	T → A. Corresponds to variant rs12723684 [ dbSNP | Ensembl ].		VAR_051518
Experimental info
	Mutagenesis	92	1	C → A: Partial loss of activity. Ref.7 Ref.9
	Mutagenesis	92	1	C → S: Decrease in activity. Ref.7 Ref.9
	Mutagenesis	164	1	H → A: Loss of activity. Ref.7
	Mutagenesis	206	1	C → A: Loss of activity. Ref.7
	Mutagenesis	311 – 395	85	Missing: Loss of activity. Ref.7
	Sequence conflict	1 – 4	4	MAVT → SLHEA Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q92643 [UniParc]. Last modified July 11, 2002. Version 2. Checksum: AF706DDDAD13EFB2	FASTA	395	45,252
	10 20 30 40 50 60 MAVTDSLSRA ATVLATVLLL SFGSVAASHI EDQAEQFFRS GHTNNWAVLV CTSRFWFNYR 70 80 90 100 110 120 HVANTLSVYR SVKRLGIPDS HIVLMLADDM ACNPRNPKPA TVFSHKNMEL NVYGDDVEVD 130 140 150 160 170 180 YRSYEVTVEN FLRVLTGRIP PSTPRSKRLL SDDRSNILIY MTGHGGNGFL KFQDSEEITN 190 200 210 220 230 240 IELADAFEQM WQKRRYNELL FIIDTCQGAS MYERFYSPNI MALASSQVGE DSLSHQPDPA 250 260 270 280 290 300 IGVHLMDRYT FYVLEFLEEI NPASQTNMND LFQVCPKSLC VSTPGHRTDL FQRDPKNVLI 310 320 330 340 350 360 TDFFGSVRKV EITTETIKLQ QDSEIMESSY KEDQMDEKLM EPLKYAEQLP VAQIIHQKPK 370 380 390 LKDWHPPGGF ILGLWALIIM VFFKTYGIKH MKFIF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Yeast Gpi8p is essential for GPI anchor attachment onto proteins." Benghezal M., Benachour A., Rusconi S., Aebi M., Conzelmann A. EMBO J. 15:6575-6583(1996) [PubMed: 8978684] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The affected gene underlying the class K glycosylphosphatidylinositol (GPI) surface protein defect codes for the GPI transamidase." Yu J., Nagarajan S., Knez J.J., Udenfriend S., Chen R., Medof M.E. Proc. Natl. Acad. Sci. U.S.A. 94:12580-12585(1997) [PubMed: 9356492] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Cerebellum.
[4]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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]. Tissue: Liver.
[7]	"Gaa1p and gpi8p are components of a glycosylphosphatidylinositol (GPI) transamidase that mediates attachment of GPI to proteins." Ohishi K., Inoue N., Maeda Y., Takeda J., Riezman H., Kinoshita T. Mol. Biol. Cell 11:1523-1533(2000) [PubMed: 10793132] [Abstract] Cited for: SUBUNIT, ACTIVE SITE, MUTAGENESIS OF CYS-92; HIS-164; CYS-206 AND 311-GLU--PHE-395.
[8]	"PIG-S and PIG-T, essential for GPI anchor attachment to proteins, form a complex with GAA1 and GPI8." Ohishi K., Inoue N., Kinoshita T. EMBO J. 20:4088-4098(2001) [PubMed: 11483512] [Abstract] Cited for: PROTEIN SEQUENCE OF 28-47, SUBUNIT, SUBCELLULAR LOCATION, MEMBRANE TOPOLOGY.
[9]	"Two subunits of glycosylphosphatidylinositol transamidase, GPI8 and PIG-T, form a functionally important intermolecular disulfide bridge." Ohishi K., Nagamune K., Maeda Y., Kinoshita T. J. Biol. Chem. 278:13959-13967(2003) [PubMed: 12582175] [Abstract] Cited for: DISULFIDE BOND FORMATION WITH PIGT, MUTAGENESIS OF CYS-92.
[10]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	Y07596 mRNA. Translation: CAA68871.1. AF022913 mRNA. Translation: AAB81597.1. AK313015 mRNA. Translation: BAG35850.1. AL035409, AC093433, AC113935 Genomic DNA. Translation: CAI21819.1. CH471059 Genomic DNA. Translation: EAX06380.1. BC020737 mRNA. Translation: AAH20737.1.
IPI	IPI00022543.
RefSeq	NP_005473.1. NM_005482.2.
UniGene	Hs.178305.
3D structure databases
ProteinModelPortal	Q92643.
ModBase	Search...
Protein-protein interaction databases
STRING	Q92643.
Protein family/group databases
MEROPS	C13.005.
Polymorphism databases
DMDM	22001630.
Proteomic databases
PRIDE	Q92643.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000370812; ENSP00000359848; ENSG00000142892.
GeneID	10026.
KEGG	hsa:10026.
UCSC	uc001dhk.1. human.
Organism-specific databases
CTD	10026.
GeneCards	GC01M077554.
H-InvDB	HIX0000713.
HGNC	HGNC:8965. PIGK.
MIM	605087. gene.
neXtProt	NX_Q92643.
PharmGKB	PA33296.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG19257.
GeneTree	ENSGT00530000063391.
HOGENOM	HBG561734.
HOVERGEN	HBG027488.
InParanoid	Q92643.
OMA	FNYRHMA.
OrthoDB	EOG4HX518.
PhylomeDB	Q92643.
Enzyme and pathway databases
Reactome	REACT_17015. Metabolism of proteins.
Gene expression databases
ArrayExpress	Q92643.
Bgee	Q92643.
CleanEx	HS_PIGK.
Genevestigator	Q92643.
GermOnline	ENSG00000142892. Homo sapiens.
Family and domain databases
InterPro	IPR001096. Peptidase_C13. [Graphical view]
KO	K05290.
PANTHER	PTHR12000. Peptidase_C13. 1 hit.
Pfam	PF01650. Peptidase_C13. 1 hit. [Graphical view]
PIRSF	PIRSF019663. Legumain. 1 hit.
PRINTS	PR00776. HEMOGLOBNASE.
ProtoNet	Search...
Other
NextBio	37889.
SOURCE	Search...

Entry information

Entry name

GPI8_HUMAN

Accession

Primary (citable) accession number: Q92643
Secondary accession number(s): B2R7K3, O14822, Q5TG77

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 11, 2002
Last sequence update:	July 11, 2002
Last modified:	January 25, 2012
This is version 96 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.