Reviewed, UniProtKB/Swiss-Prot Q9H553 (ALG2_HUMAN)

Names and origin

Protein names

Recommended name:
    Alpha-1,3-mannosyltransferase ALG2
    EC=2.4.1.-
Alternative name(s):
    GDP-Man:Man(1)GlcNAc(2)-PP-dolichol mannosyltransferase
    Asparagine-linked glycosylation protein 2

Gene names

Name:	ALG2
ORF Names:	UNQ666/PRO1298

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	416 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at transcript level.

General annotation (Comments)

Function	Mannosylates Man(2)GlcNAc(2)-dolichol diphosphate and Man(1)GlcNAc(2)-dolichol diphosphate to form Man(3)GlcNAc(2)-dolichol diphosphate.
Pathway	Protein modification; protein glycosylation.
Subcellular location	Membrane; Single-pass membrane proteinPotential.
Involvement in disease	Defects in ALG2 are the cause of congenital disorder of glycosylation type 1I (CDG1I) [MIM:607906]. 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.
Sequence similarities	Belongs to the glycosyltransferase 1 family.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Alternative splicing
Disease	Congenital disorder of glycosylation
Domain	Transmembrane
Molecular function	Glycosyltransferase Transferase
Gene Ontology (GO)
Biological process	dolichol-linked oligosaccharide biosynthetic process Ref.6 Inferred from genetic interaction. Source: UniProtKB protein amino acid glycosylation in endoplasmic reticulum Ref.6 Inferred from genetic interaction. Source: UniProtKB protein localization Inferred from mutant phenotype. Source: UniProtKB response to calcium ion Inferred from direct assay. Source: UniProtKB
Cellular component	membrane fraction Inferred from direct assay. Source: UniProtKB nucleus Inferred from direct assay. Source: UniProtKB perinuclear region of cytoplasm Inferred from direct assay. Source: UniProtKB
Molecular function	alpha-1,3-mannosyltransferase activity Ref.6 Inferred from direct assay. Source: UniProtKB calcium-dependent protein binding Inferred from mutant phenotype. Source: UniProtKB protein C-terminus binding Inferred from physical interaction. Source: UniProtKB protein N-terminus binding Inferred from physical interaction. Source: UniProtKB protein anchor Inferred from mutant phenotype. Source: UniProtKB protein heterodimerization activity Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9H553-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9H553-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-91: Missing.
     92-116: VRMVFLALYVLFLADEEFDVVVCDQ → MPLLKLVHGSPLVFGEKFKLFTL

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Chain	1 – 416	416	Alpha-1,3-mannosyltransferase ALG2
Regions
	Transmembrane	85 – 105	21	Potential
Natural variations
	Alternative sequence	1 – 91	91	Missing in isoform 2.
	Alternative sequence	92 – 116	25	VRMVF…VVCDQ → MPLLKLVHGSPLVFGEKFKL FTL in isoform 2.
Experimental info
	Sequence conflict	178	1	Q → R in BAC11449. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 778DB1FD069E7F29	FASTA	416	47,092
	10 20 30 40 50 60 MAEEQGRERD SVPKPSVLFL HPDLGVGGAE RLVLDAALAL QARGCSVKIW TAHYDPGHCF 70 80 90 100 110 120 AESRELPVRC AGDWLPRGLG WGGRGAAVCA YVRMVFLALY VLFLADEEFD VVVCDQVSAC 130 140 150 160 170 180 IPVFRLARRR KKILFYCHFP DLLLTKRDSF LKRLYRAPID WIEEYTTGMA DCILVNSQFT 190 200 210 220 230 240 AAVFKETFKS LSHIDPDVLY PSLNVTSFDS VVPEKLDDLV PKGKKFLLLS INRYERKKNL 250 260 270 280 290 300 TLALEALVQL RGRLTSQDWE RVHLIVAGGY DERVLENVEH YQELKKMVQQ SDLGQYVTFL 310 320 330 340 350 360 RSFSDKQKIS LLHSCTCVLY TPSNEHFGIV PLEAMYMQCP VIAVNSGGPL ESIDHSVTGF 370 380 390 400 410 LCEPDPVHFS EAIEKFIREP SLKATMGLAG RARVKEKFSP EAFTEQLYRY VTKLLV
	Isoform 2 [UniParc]. Checksum: C8506E37A7E15848		323	37,017
	10 20 30 40 50 60 MPLLKLVHGS PLVFGEKFKL FTLVSACIPV FRLARRRKKI LFYCHFPDLL LTKRDSFLKR 70 80 90 100 110 120 LYRAPIDWIE EYTTGMADCI LVNSQFTAAV FKETFKSLSH IDPDVLYPSL NVTSFDSVVP 130 140 150 160 170 180 EKLDDLVPKG KKFLLLSINR YERKKNLTLA LEALVQLRGR LTSQDWERVH LIVAGGYDER 190 200 210 220 230 240 VLENVEHYQE LKKMVQQSDL GQYVTFLRSF SDKQKISLLH SCTCVLYTPS NEHFGIVPLE 250 260 270 280 290 300 AMYMQCPVIA VNSGGPLESI DHSVTGFLCE PDPVHFSEAI EKFIREPSLK ATMGLAGRAR 310 320 VKEKFSPEAF TEQLYRYVTK LLV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of the mammalian genes which complement the defect of the yeast alg2 mutation." Takahashi T., Katoh R., Okutomi S., Suzuki Y., Mori H., Takizawa Y., Nishikawa Y. Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"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] (ISOFORM 2).
[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] (ISOFORMS 1 AND 2). Tissue: Placenta.
[4]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] (ISOFORM 1). Tissue: Embryonic testis carcinoma.
[6]	"A new type of congenital disorders of glycosylation (CDG-Ii) provides new insights into the early steps of dolichol-linked oligosaccharide biosynthesis." Thiel C., Schwarz M., Peng J., Grzmil M., Hasilik M., Braulke T., Kohlschuetter A., von Figura K., Lehle L., Koerner C. J. Biol. Chem. 278:22498-22505(2003) [PubMed: 12684507] [Abstract] Cited for: FUNCTION, DISEASE.
+	Additional computationally mapped references.

Web resources

GeneReviews

GGDB

GlycoGene database

Cross-references

Sequence databases
EMBLGenBankDDBJ	AB161356 mRNA. Translation: BAD11905.1. AY358697 mRNA. Translation: AAQ89060.1. AK027417 mRNA. Translation: BAB55099.1. AK074704 mRNA. Translation: BAC11150.1. AK074988 mRNA. Translation: BAC11337.1. AK075172 mRNA. Translation: BAC11449.1. AL137067 Genomic DNA. Translation: CAC07999.1. BC017876 mRNA. Translation: AAH17876.1.
RefSeq	NP_149078.1.
UniGene	Hs.40919
3D structure databases
ModBase	Search...
Genome annotation databases
Ensembl	ENSG00000119523. Homo sapiens. [Contig view]
GeneID	85365.
KEGG	hsa:85365.
Organism-specific databases
H-InvDB	HIX0019474.
HGNC	HGNC:23159. ALG2.
MIM	607905. gene. 607906. phenotype.
Orphanet	79326. CDG syndrome type Ii.
PharmGKB	PA134956849.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	Q9H553.
HOVERGEN	Q9H553.
Gene expression databases
ArrayExpress	Q9H553.
CleanEx	HS_ALG2.
GermOnline	ENSG00000119523. Homo sapiens.
Family and domain databases
InterPro	IPR001296. Glyco_trans_1. [Graphical view]
Pfam	PF00534. Glycos_transf_1. 1 hit. [Graphical view]
ProDom	Q9H553. [Graphical view] [Entries sharing at least one domain]
BLOCKS	Search...
Other Resources
SOURCE	Search...
ProtoNet	Search...

Entry information

Entry name

ALG2_HUMAN

Accession

Primary (citable) accession number: Q9H553
Secondary accession number(s): A2A2Y0, Q8NBX2, Q8NC39

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 13, 2004
Last sequence update:	March 1, 2001
Last modified:	July 22, 2008
This is version 56 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)