Reviewed, UniProtKB/Swiss-Prot Q8WZA1 (PMGT1_HUMAN)

Names and origin

Protein names

Recommended name:
    Protein O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase 1
      Short name=POMGnT1
    EC=2.4.1.-
Alternative name(s):
    UDP-GlcNAc:alpha-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I.2
      Short name=GnT I.2

Gene names

Name:	POMGNT1
Synonyms:	MGAT1.2
ORF Names:	UNQ746/PRO1475

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	660 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Participates in O-mannosyl glycosylation. May be responsible for the synthesis of the GlcNAc(beta1-2)Man(alpha1-)O-Ser/Thr moiety on alpha-dystroglycan and other O-mannosylated proteins. Is specific for alpha linked terminal mannose and does not have MGAT3, MGAT4, MGAT5, MGAT7 or MGAT8 activity.
Catalytic activity	UDP-N-acetyl-D-glucosamine + Man-R = N-acetyl-D-glucosamine-beta-1,2-Man-R + UDP.
Cofactor	Manganese.
Pathway	Protein modification; protein glycosylation.
Subcellular location	Golgi apparatus membrane; Single-pass type II membrane protein Potential.
Tissue specificity	Constitutively expressed. An additional weaker band is also detected in spinal cord, lymph node, and trachea. Expressed especially in astrocytes. Also expressed in immature and mature neurons. Ref.1 Ref.7
Domain	Amino acid residues between 299-311 are important for both protein expression and enzymatic activity. The minimal catalytic domain is located between positions 299-651. Single amino acid substitutions in the stem domain from MEB patients abolished the activity of the membrane-bound form but not the soluble form. This suggests that the stem domain of the soluble form is unnecessary for activity, but that some amino acids play a crucial role in the membrane-bound form. Ref.10
Involvement in disease	Defects in POMGNT1 are the cause of muscle-eye-brain disease (MEB) [MIM:253280]. MEB is an autosomal recessive disorder characterized by congenital muscular dystrophy, ocular abnormalities, cobblestone lissencephaly and cerebellar hypoplasia. MEB patients present severe congenital myopia, congenital glaucoma, pallor of the optic disks, retinal hypoplasia, mental retardation, hydrocephalus, abnormal electroencephalograms, generalized muscle weakness and myoclonic jerks. Ref.1 Ref.10 Ref.2 Ref.9 Ref.11 Ref.12 Defects in POMGNT1 are a cause of Walker-Warburg syndrome (WWS) [MIM:236670]; also known as hydrocephalus-agyria-retinal dysplasia or HARD syndrome. WWS is an autosomal recessive disorder characterized by cobblestone lissencephaly, hydrocephalus, agyria, retinal displasia, with or without encephalocele. It is often associated with congenital muscular dystrophy and usually lethal within the first few months of life. Ref.2
Sequence similarities	Belongs to the glycosyltransferase 13 family.
Biophysicochemical properties	Kinetic parameters: KM=1.85 mM for mannosylpeptide KM=0.73 mM for UDP-GlcNAc KM=30 mM for Man(alpha1-)O-benzyl KM=12 mM for CYA[Man(alpha1-)O-T]AV pH dependence: Optimum pH is 6.0.

Ontologies

Keywords
Cellular component	Golgi apparatus Membrane
Coding sequence diversity	Polymorphism
Disease	Congenital muscular dystrophy Disease mutation Lissencephaly
Domain	Signal-anchor Transmembrane
Ligand	Manganese
Molecular function	Glycosyltransferase Transferase
PTM	Isopeptide bond Ubl conjugation
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	protein amino acid N-linked glycosylation Inferred from electronic annotation. Source: InterPro protein amino acid O-linked glycosylation Ref.1 Inferred from direct assay. Source: MGI
Cellular component	Golgi membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW microsome Ref.1 Inferred from direct assay. Source: MGI
Molecular function	alpha-1,3-mannosylglycoprotein 2-beta-N-acetylglucosaminyltransferase activity Inferred from electronic annotation. Source: InterPro beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,3-N-acetylglucosaminyltransferase activity Ref.7 Inferred from direct assay. Source: MGI manganese ion binding 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 – 660	660	Protein O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase 1		PRO_0000191390
Regions
	Topological domain	1 – 37	37	Cytoplasmic Potential
	Transmembrane	38 – 58	21	Signal-anchor for type II membrane protein Potential
	Topological domain	59 – 660	602	Lumenal Potential
	Compositional bias	263 – 267	5	Poly-Arg
Amino acid modifications
	Cross-link	537		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.8
	Cross-link	538		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.8
Natural variations
	Natural variant	223	1	E → K in MEB; specific activity abolished in the membrane bound form but not the soluble form. Ref.10 Ref.2 Ref.9		VAR_023101
	Natural variant	250	1	E → V: dbSNP rs17855359. Ref.6		VAR_030645
	Natural variant	265	1	R → H in MEB; found on the same allele as Q-311; could be a polymorphism. Ref.11		VAR_023102
	Natural variant	269	1	C → Y in MEB; specific activity abolished of the membrane bound form but not the soluble form. Ref.10 Ref.2 Ref.9		VAR_023103
	Natural variant	311	1	R → Q in MEB; found on the same allele as H-265; could be a polymorphism. Ref.11		VAR_023104
	Natural variant	425	1	W → S in MEB. Ref.12		VAR_023105
	Natural variant	442	1	R → C in MEB. dbSNP rs28940869. Ref.11		VAR_023106
	Natural variant	490	1	C → Y in MEB. Ref.12		VAR_023107
	Natural variant	493	1	P → R in MEB; specific activity abolished. Ref.1 Ref.9		VAR_023108
	Natural variant	504	1	V → I: dbSNP rs17102066.		VAR_030646
	Natural variant	550	1	S → N in MEB. Ref.1		VAR_023109
	Natural variant	623	1	V → M: dbSNP rs6659553. Ref.5		VAR_023110

Sequences

	Sequence		Length	Mass (Da)
	Q8WZA1-1 [UniParc]. Last modified March 1, 2002. Version 1. Checksum: B28D0E543E162B46	FASTA	660	75,220
	10 20 30 40 50 60 MDDWKPSPLI KPFGARKKRS WYLTWKYKLT NQRALRRFCQ TGAVLFLLVT VIVNIKLILD 70 80 90 100 110 120 TRRAISEANE DPEPEQDYDE ALGRLEPPRR RGSGPRRVLD VEVYSSRSKV YVAVDGTTVL 130 140 150 160 170 180 EDEAREQGRG IHVIVLNQAT GHVMAKRVFD TYSPHEDEAM VLFLNMVAPG RVLICTVKDE 190 200 210 220 230 240 GSFHLKDTAK ALLRSLGSQA GPALGWRDTW AFVGRKGGPV FGEKHSKSPA LSSWGDPVLL 250 260 270 280 290 300 KTDVPLSSAE EAECHWADTE LNRRRRRFCS KVEGYGSVCS CKDPTPIEFS PDPLPDNKVL 310 320 330 340 350 360 NVPVAVIAGN RPNYLYRMLR SLLSAQGVSP QMITVFIDGY YEEPMDVVAL FGLRGIQHTP 370 380 390 400 410 420 ISIKNARVSQ HYKASLTATF NLFPEAKFAV VLEEDLDIAV DFFSFLSQSI HLLEEDDSLY 430 440 450 460 470 480 CISAWNDQGY EHTAEDPALL YRVETMPGLG WVLRRSLYKE ELEPKWPTPE KLWDWDMWMR 490 500 510 520 530 540 MPEQRRGREC IIPDVSRSYH FGIVGLNMNG YFHEAYFKKH KFNTVPGVQL RNVDSLKKEA 550 560 570 580 590 600 YEVEVHRLLS EAEVLDHSKN PCEDSFLPDT EGHTYVAFIR MEKDDDFTTW TQLAKCLHIW 610 620 630 640 650 660 DLDVRGNHRG LWRLFRKKNH FLVVGVPASP YSVKKPPSVT PIFLEPPPKE EGAPGAPEQT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Muscular dystrophy and neuronal migration disorder caused by mutations in a glycosyltransferase, POMGnT1." Yoshida A., Kobayashi K., Manya H., Taniguchi K., Kano H., Mizuno M., Inazu T., Mitsuhashi H., Takahashi S., Takeuchi M., Herrmann R., Straub V., Talim B., Voit T., Topaloglu H., Toda T., Endo T. Dev. Cell 1:717-724(2001) [PubMed: 11709191] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES, VARIANTS MEB ARG-493 AND ASN-550. Tissue: Brain.
[2]	"Worldwide distribution and broader clinical spectrum of muscle-eye-brain disease." Taniguchi K., Kobayashi K., Saito K., Yamanouchi H., Ohnuma A., Hayashi Y.K., Manya H., Jin D.K., Lee M., Parano E., Falsaperla R., Pavone P., Coster R.V., Talim B., Steinbrecher A., Straub V., Nishino I., Topaloglu H. , Voit T., Endo T., Toda T. Hum. Mol. Genet. 12:527-534(2003) [PubMed: 12588800] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INVOLVEMENT IN WWS, VARIANTS MEB LYS-223 AND TYR-269. Tissue: Brain.
[3]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"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].
[5]	"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], VARIANT MET-623.
[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], VARIANT VAL-250. Tissue: Placenta.
[7]	"Cloning and expression of a novel UDP-GlcNAc:alpha-D-mannoside beta-1,2-N-acetylglucosaminyltransferase homologous to UDP-GlcNAc:alpha-3-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I." Zhang W., Betel D., Schachter H. Biochem. J. 361:153-162(2002) [PubMed: 11742540] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 84-660, TISSUE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES. Tissue: Brain.
[8]	"Tryptic digestion of ubiquitin standards reveals an improved strategy for identifying ubiquitinated proteins by mass spectrometry." Denis N.J., Vasilescu J., Lambert J.-P., Smith J.C., Figeys D. Proteomics 7:868-874(2007) [PubMed: 17370265] [Abstract] Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-537 AND LYS-538, MASS SPECTROMETRY.
[9]	"Loss-of-function of an N-acetylglucosaminyltransferase, POMGnT1, in muscle-eye-brain disease." Manya H., Sakai K., Kobayashi K., Taniguchi K., Kawakita M., Toda T., Endo T. Biochem. Biophys. Res. Commun. 306:93-97(2003) [PubMed: 12788071] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS MEB LYS-223; TYR-269 AND ARG-493.
[10]	"Structure-function analysis of human protein O-linked mannose beta1,2-N-acetylglucosaminyltransferase 1, POMGnT1." Akasaka-Manya K., Manya H., Kobayashi K., Toda T., Endo T. Biochem. Biophys. Res. Commun. 320:39-44(2004) [PubMed: 15207699] [Abstract] Cited for: IDENTIFICATION OF CATALYTIC DOMAIN, CHARACTERIZATION OF VARIANTS MEB LYS-223 AND TYR-269.
[11]	"POMGnT1 gene alterations in a family with neurological abnormalities." Vervoort V.S., Holden K.R., Ukadike K.C., Collins J.S., Saul R.A., Srivastava A.K. Ann. Neurol. 56:143-148(2004) [PubMed: 15236414] [Abstract] Cited for: VARIANTS MEB HIS-265; GLN-311 AND CYS-442.
[12]	"POMGnT1 mutation and phenotypic spectrum in muscle-eye-brain disease." Diesen C., Saarinen A., Pihko H., Rosenlew C., Cormand B., Dobyns W.B., Dieguez J., Valanne L., Joensuu T., Lehesjoki A.-E. J. Med. Genet. 41:E115-E115(2004) [PubMed: 15466003] [Abstract] Cited for: VARIANTS MEB SER-425 AND TYR-490.
+	Additional computationally mapped references.

Web resources

GeneReviews

GGDB

GlycoGene database

Functional Glycomics Gateway - GTase

Protein O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase 1

Cross-references

Sequence databases
EMBLGenBankDDBJ	AB057356 mRNA. Translation: BAB71960.1. AY358592 mRNA. Translation: AAQ88955.1. AK000284 mRNA. Translation: BAA91053.1. AK022727 mRNA. Translation: BAB14207.1. Different initiation. AL672043 Genomic DNA. Translation: CAH72470.1. BC001471 mRNA. Translation: AAH01471.1. AF250859 mRNA. Translation: AAF71270.2.
IPI	IPI00550558.
RefSeq	NP_060209.3.
UniGene	Hs.525134
3D structure databases
HSSP	HSSP built from PDB template 1FO8 based on UniProtKB P27115.
ModBase	Search...
Protein family/group databases
CAZy	GT13. Glycosyltransferase Family 13.
PTM databases
PhosphoSite	Q8WZA1.
Proteomic databases
PRIDE	Q8WZA1.
Genome annotation databases
Ensembl	ENSG00000085998. Homo sapiens. [Contig view]
GeneID	55624.
KEGG	hsa:55624.
UCSC	uc001cpe.1. human.
Organism-specific databases
GeneCards	GC01M046367.
H-InvDB	HIX0000544.
HGNC	HGNC:19139. POMGNT1.
MIM	236670. phenotype. 253280. phenotype. 606822. gene.
Orphanet	588. Muscle eye brain disease. 899. Walker-Warburg syndrome.
PharmGKB	PA142671161.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q8WZA1.
Gene expression databases
ArrayExpress	Q8WZA1.
Bgee	Q8WZA1.
CleanEx	HS_POMGNT1.
GermOnline	ENSG00000085998. Homo sapiens.
Family and domain databases
InterPro	IPR004139. Glyco_trans_13. [Graphical view]
PANTHER	PTHR10468. Glyco_trans_13. 1 hit.
Pfam	PF03071. GNT-I. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	60240.
SOURCE	Search...

Entry information

Entry name

PMGT1_HUMAN

Accession

Primary (citable) accession number: Q8WZA1
Secondary accession number(s): Q5VST2 , Q9BV55, Q9H9L8, Q9NXF9, Q9NYF7

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 16, 2005
Last sequence update:	March 1, 2002
Last modified:	July 7, 2009
This is version 61 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)