Reviewed, UniProtKB/Swiss-Prot Q9BT22 (ALG1_HUMAN)

Names and origin

Protein names

Recommended name:
    Chitobiosyldiphosphodolichol beta-mannosyltransferase
    EC=2.4.1.142
Alternative name(s):
    GDP-mannose-dolichol diphosphochitobiose mannosyltransferase
    GDP-Man:GlcNAc2-PP-dolichol mannosyltransferase
    Beta-1,4-mannosyltransferase
    Mannosyltransferase-1
    Hmat-1
      Short name=MT-1
    Asparagine-linked glycosylation protein 1 homolog

Gene names

Name:	ALG1
Synonyms:	HMAT1, HMT1
ORF Names:	PSEC0061, UNQ861/PRO1870

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

General annotation (Comments)

Function	Participates in the formation of the lipid-linked precursor oligosaccharide for N-glycosylation. Involved in assembling the dolichol-pyrophosphate-GlcNAc(2)-Man5 intermediate on the cytoplasmic surface of the ER. Ref.1
Catalytic activity	GDP-mannose + chitobiosyldiphosphodolichol = GDP + beta-1,4-D-mannosylchitobiosyldiphosphodolichol.
Pathway	Protein modification; protein glycosylation.
Subcellular location	Endoplasmic reticulum membrane; Single-pass type II membrane protein Probable.
Involvement in disease	Defects in ALG1 are the cause of congenital disorder of glycosylation type 1K (CDG1K) [MIM:608540]. CDGs are a family of severe inherited diseases caused by a defect in protein N-glycosylation. They are characterized by under-glycosylated serum proteins. These multisystem disorders present with a wide variety of clinical features, such as disorders of the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. Ref.7 Ref.8 Ref.9
Sequence similarities	Belongs to the glycosyltransferase 1 family.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Polymorphism
Disease	Congenital disorder of glycosylation Disease mutation
Domain	Signal-anchor Transmembrane
Molecular function	Glycosyltransferase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	lipopolysaccharide biosynthetic process Ref.1 Traceable author statement. Source: ProtInc protein amino acid glycosylation Ref.1 Traceable author statement. Source: ProtInc
Cellular component	endoplasmic reticulum Ref.1 Traceable author statement. Source: ProtInc integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	chitobiosyldiphosphodolichol beta-mannosyltransferase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 464	464	Chitobiosyldiphosphodolichol beta-mannosyltransferase		PRO_0000080249
Regions
	Topological domain	1 – 2	2	Cytoplasmic Potential
	Transmembrane	3 – 23	21	Signal-anchor for type II membrane protein Potential
	Topological domain	24 – 464	441	Lumenal Potential
Amino acid modifications
	Modified residue	242	1	Phosphoserine Ref.5
Natural variations
	Natural variant	150	1	S → R in CDG1K; impairs activity. Ref.9		VAR_023364
	Natural variant	258	1	S → L in CDG1K; impairs activity. dbSNP rs28939378. Ref.7 Ref.8 Ref.9		VAR_023365
	Natural variant	267	1	S → N: dbSNP rs17849848. Ref.3		VAR_038425
	Natural variant	325	1	L → M: dbSNP rs17852920. Ref.3		VAR_038426
	Natural variant	342	1	Q → P in CDG1K; impairs activity. Ref.8		VAR_023366
	Natural variant	429	1	D → E No effect on activity. dbSNP rs9745522. Ref.9		VAR_023367
	Natural variant	438	1	R → W: dbSNP rs16835020.		VAR_049350
	Natural variant	455	1	Q → R: dbSNP rs17856919. Ref.3		VAR_038427

Sequences

	Sequence		Length	Mass (Da)
	Q9BT22-1 [UniParc]. Last modified August 30, 2005. Version 2. Checksum: 83F55FD12CFDDBE9	FASTA	464	52,518
	10 20 30 40 50 60 MAASCLVLLA LCLLLPLLLL GGWKRWRRGR AARHVVAVVL GDVGRSPRMQ YHALSLAMHG 70 80 90 100 110 120 FSVTLLGFCN SKPHDELLQN NRIQIVGLTE LQSLAVGPRV FQYGVKVVLQ AMYLLWKLMW 130 140 150 160 170 180 REPGAYIFLQ NPPGLPSIAV CWFVGCLCGS KLVIDWHNYG YSIMGLVHGP NHPLVLLAKW 190 200 210 220 230 240 YEKFFGRLSH LNLCVTNAMR EDLADNWHIR AVTVYDKPAS FFKETPLDLQ HRLFMKLGSM 250 260 270 280 290 300 HSPFRARSEP EDPVTERSAF TERDAGSGLV TRLRERPALL VSSTSWTEDE DFSILLAALE 310 320 330 340 350 360 KFEQLTLDGH NLPSLVCVIT GKGPLREYYS RLIHQKHFQH IQVCTPWLEA EDYPLLLGSA 370 380 390 400 410 420 DLGVCLHTSS SGLDLPMKVV DMFGCCLPVC AVNFKCLHEL VKHEENGLVF EDSEELAAQL 430 440 450 460 QMLFSNFPDP AGKLNQFRKN LRESQQLRWD ESWVQTVLPL VMDT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of the human cDNA which can complement the defect of the yeast mannosyltransferase I-deficient mutant alg 1." Takahashi T., Honda R., Nishikawa Y. Glycobiology 10:321-327(2000) [PubMed: 10704531] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION. Tissue: Fetal brain.
[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: Teratocarcinoma.
[3]	"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], VARIANTS ASN-267; MET-325 AND ARG-455. Tissue: Brain.
[4]	"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] OF 2-464.
[5]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-242, MASS SPECTROMETRY.
[6]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[7]	"Deficiency of GDP-Man:GlcNAc2-PP-dolichol mannosyltransferase causes congenital disorder of glycosylation type Ik." Schwarz M., Thiel C., Luebbehusen J., Dorland B., de Koning T., von Figura K., Lehle L., Koerner C. Am. J. Hum. Genet. 74:472-481(2004) [PubMed: 14973778] [Abstract] Cited for: VARIANT CDG1K LEU-258.
[8]	"Congenital disorder of glycosylation type Ik (CDG-Ik): a defect of mannosyltransferase I." Kranz C., Denecke J., Lehle L., Sohlbach K., Jeske S., Meinhardt F., Rossi R., Gudowius S., Marquardt T. Am. J. Hum. Genet. 74:545-551(2004) [PubMed: 14973782] [Abstract] Cited for: VARIANTS CDG1K LEU-258 AND PRO-342.
[9]	"Deficiency of the first mannosylation step in the N-glycosylation pathway causes congenital disorder of glycosylation type Ik." Grubenmann C.E., Frank C.G., Huelsmeier A.J., Schollen E., Matthijs G., Mayatepek E., Berger E.G., Aebi M., Hennet T. Hum. Mol. Genet. 13:535-542(2004) [PubMed: 14709599] [Abstract] Cited for: VARIANTS CDG1K ARG-150 AND LEU-258, VARIANT GLU-429.

Web resources

GGDB

GlycoGene database

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB019038 mRNA. Translation: BAA90748.1. AK075373 mRNA. Translation: BAC11576.1. BC004402 mRNA. Translation: AAH04402.1. BC031095 mRNA. Translation: AAH31095.1. AY359073 mRNA. Translation: AAQ89432.1. Different initiation.
IPI	IPI00549761.
RefSeq	NP_061982.3.
UniGene	Hs.592086
3D structure databases
SMR	Q9BT22. Positions 144-451.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9BT22.
Protein family/group databases
CAZy	GT33. Glycosyltransferase Family 33.
Proteomic databases
PRIDE	Q9BT22.
Genome annotation databases
Ensembl	ENST00000262374; ENSP00000262374; ENSG00000033011; Homo sapiens. [Genome view]
GeneID	56052.
KEGG	hsa:56052.
UCSC	uc002cyj.1. human.
Organism-specific databases
CTD	56052.
GeneCards	GC16P005061.
H-InvDB	HIX0009871. HIX0030848.
HGNC	HGNC:18294. ALG1.
MIM	605907. gene. 608540. phenotype.
Orphanet	79327. CDG syndrome, type Ik.
PharmGKB	PA134979319.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG07228.
HOGENOM	HBG319770.
HOVERGEN	Q9BT22.
InParanoid	Q9BT22.
OMA	LQNPPGL.
OrthoDB	EOG90KBJ0.
PhylomeDB	Q9BT22.
Enzyme and pathway databases
BRENDA	2.4.1.142. 247.
Gene expression databases
ArrayExpress	Q9BT22.
Bgee	Q9BT22.
CleanEx	HS_ALG1.
Genevestigator	Q9BT22.
GermOnline	ENSG00000033011. Homo sapiens.
Family and domain databases
InterPro	IPR001296. Glyco_trans_1. [Graphical view]
Pfam	PF00534. Glycos_transf_1. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	61475.
SOURCE	Search...

Entry information

Entry name

ALG1_HUMAN

Accession

Primary (citable) accession number: Q9BT22
Secondary accession number(s): Q6UVZ9, Q8N5Y4, Q9P2Y2

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 30, 2005
Last sequence update:	August 30, 2005
Last modified:	February 9, 2010
This is version 75 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.