Q9H3S5 (PIGM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
GPI mannosyltransferase 1
EC=2.4.1.-

Alternative name(s):
GPI mannosyltransferase I
Short name=GPI-MT-I
Phosphatidylinositol-glycan biosynthesis class M protein
Short name=PIG-M

Gene names

Name:

PIGM

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	423 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Mannosyltransferase involved in glycosylphosphatidylinositol-anchor biosynthesis. Transfers the first alpha-1,4-mannose to GlcN-acyl-PI during GPI precursor assembly. Ref.1
Pathway	Glycolipid biosynthesis; glycosylphosphatidylinositol-anchor biosynthesis.
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein Ref.1.
Involvement in disease	Defects in PIGM are the cause of glycosylphosphatidylinositol deficiency (GPID) [MIM:610293]. GPID is an autosomal recessive trait that results in a propensity to venous thrombosis and seizures. Deficiency is due to a point mutation in the regulatory sequences of PIGM that disrupts binding of the transcription factor SP1 to its cognate promoter motif, leading to a strong reduction of expression.
Sequence similarities	Belongs to the PIGM family.

Ontologies

Keywords
Biological process	GPI-anchor biosynthesis
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Molecular function	Glycosyltransferase Transferase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	C-terminal protein lipidation Traceable author statement. Source: Reactome preassembly of GPI anchor in ER membrane Traceable author statement. Source: Reactome
Cellular component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 423	423	GPI mannosyltransferase 1		PRO_0000246213
Regions
	Topological domain	1 – 17	17	Cytoplasmic Potential
	Transmembrane	18 – 38	21	Helical; Potential
	Topological domain	39 – 79	41	Lumenal Potential
	Transmembrane	80 – 100	21	Helical; Potential
	Topological domain	101 – 138	38	Cytoplasmic Potential
	Transmembrane	139 – 161	23	Helical; Potential
	Topological domain	162 – 169	8	Lumenal Potential
	Transmembrane	170 – 190	21	Helical; Potential
	Topological domain	191 – 225	35	Cytoplasmic Potential
	Transmembrane	226 – 246	21	Helical; Potential
	Topological domain	247 – 287	41	Lumenal Potential
	Transmembrane	288 – 308	21	Helical; Potential
	Topological domain	309 – 314	6	Cytoplasmic Potential
	Transmembrane	315 – 337	23	Helical; Potential
	Topological domain	338	1	Lumenal Potential
	Transmembrane	339 – 350	12	Helical; Potential
	Topological domain	351 – 357	7	Cytoplasmic Potential
	Transmembrane	358 – 378	21	Helical; Potential
	Topological domain	379 – 384	6	Lumenal Potential
	Transmembrane	385 – 405	21	Helical; Potential
	Topological domain	406 – 423	18	Cytoplasmic Potential
Natural variations
	Natural variant	365	1	F → L. Corresponds to variant rs12409352 [ dbSNP | Ensembl ].		VAR_027026
Experimental info
	Mutagenesis	49	1	D → A: Almost abolishes enzyme activity. Ref.1
	Mutagenesis	51	1	D → A: Abolishes enzyme activity. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9H3S5 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: E17DCD8252E28EF0	FASTA	423	49,460
	10 20 30 40 50 60 MGSTKHWGEW LLNLKVAPAG VFGVAFLARV ALVFYGVFQD RTLHVRYTDI DYQVFTDAAR 70 80 90 100 110 120 FVTEGRSPYL RATYRYTPLL GWLLTPNIYL SELFGKFLFI SCDLLTAFLL YRLLLLKGLG 130 140 150 160 170 180 RRQACGYCVF WLLNPLPMAV SSRGNADSIV ASLVLMVLYL IKKRLVACAA VFYGFAVHMK 190 200 210 220 230 240 IYPVTYILPI TLHLLPDRDN DKSLRQFRYT FQACLYELLK RLCNRAVLLF VAVAGLTFFA 250 260 270 280 290 300 LSFGFYYEYG WEFLEHTYFY HLTRRDIRHN FSPYFYMLYL TAESKWSFSL GIAAFLPQLI 310 320 330 340 350 360 LLSAVSFAYY RDLVFCCFLH TSIFVTFNKV CTSQYFLWYL CLLPLVMPLV RMPWKRAVVL 370 380 390 400 410 420 LMLWFIGQAM WLAPAYVLEF QGKNTFLFIW LAGLFFLLIN CSILIQIISH YKEEPLTERI KYD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"PIG-M transfers the first mannose to glycosylphosphatidylinositol on the lumenal side of the ER." Maeda Y., Watanabe R., Harris C.L., Hong Y., Ohishi K., Kinoshita K., Kinoshita T. EMBO J. 20:250-261(2001) [PubMed: 11226175] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, MUTAGENESIS OF ASP-49 AND ASP-51.
[2]	"Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries." Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J., Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S., Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y. , Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S., Isogai T. DNA Res. 12:117-126(2005) [PubMed: 16303743] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Mammary gland.
[3]	"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].
[4]	"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: Brain and Eye.
[5]	"Hypomorphic promoter mutation in PIGM causes inherited glycosylphosphatidylinositol deficiency." Almeida A.M., Murakami Y., Layton D.M., Hillmen P., Sellick G.S., Maeda Y., Richards S., Patterson S., Kotsianidis I., Mollica L., Crawford D.H., Baker A., Ferguson M., Roberts I., Houlston R., Kinoshita T., Karadimitris A. Nat. Med. 12:846-851(2006) [PubMed: 16767100] [Abstract] Cited for: INVOLVEMENT IN GLYCOSYLPHOSPHATIDYLINOSITOL DEFICIENCY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB028127 mRNA. Translation: BAB18567.1. AK074655 mRNA. Translation: BAC11116.1. AL513302 Genomic DNA. Translation: CAH71492.1. BC001803 mRNA. Translation: AAH01803.1. BC019865 mRNA. Translation: AAH19865.1.
IPI	IPI00024023.
RefSeq	NP_660150.1. NM_145167.2.
UniGene	Hs.552810.
3D structure databases
ProteinModelPortal	Q9H3S5.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9H3S5. 1 interaction.
STRING	Q9H3S5.
Protein family/group databases
CAZy	GT50. Glycosyltransferase Family 50.
PTM databases
PhosphoSite	Q9H3S5.
Polymorphism databases
DMDM	74752622.
Proteomic databases
PRIDE	Q9H3S5.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000368090; ENSP00000357069; ENSG00000143315.
GeneID	93183.
KEGG	hsa:93183.
UCSC	uc001fuv.1. human.
Organism-specific databases
CTD	93183.
GeneCards	GC01M159997.
H-InvDB	HIX0001206.
HGNC	HGNC:18858. PIGM.
MIM	610273. gene. 610293. phenotype.
neXtProt	NX_Q9H3S5.
Orphanet	83639. Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency.
PharmGKB	PA38718.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG07935.
GeneTree	ENSGT00390000017728.
HOGENOM	HBG559139.
HOVERGEN	HBG082137.
InParanoid	Q9H3S5.
OMA	EFLEHTY.
OrthoDB	EOG4Q2DG6.
PhylomeDB	Q9H3S5.
Enzyme and pathway databases
Reactome	REACT_17015. Metabolism of proteins.
Gene expression databases
ArrayExpress	Q9H3S5.
Bgee	Q9H3S5.
CleanEx	HS_PIGM.
Genevestigator	Q9H3S5.
GermOnline	ENSG00000143315. Homo sapiens.
Family and domain databases
InterPro	IPR007704. Mannosyltransferase_DXD. [Graphical view]
KO	K05284.
PANTHER	PTHR12886. Mannos_trans_DXD. 1 hit.
Pfam	PF05007. Mannosyl_trans. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	78019.
SOURCE	Search...

Entry information

Entry name

PIGM_HUMAN

Accession

Primary (citable) accession number: Q9H3S5

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 25, 2006
Last sequence update:	March 1, 2001
Last modified:	January 25, 2012
This is version 85 of the entry and version 1 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.