Reviewed, UniProtKB/Swiss-Prot Q9BV10 (ALG12_HUMAN)

Names and origin

Protein names

Recommended name:
    Dolichyl-P-Man:Man(7)GlcNAc(2)-PP-dolichyl-alpha-1,6-mannosyltransferase
    EC=2.4.1.-
Alternative name(s):
    Mannosyltransferase ALG12 homolog
      Short name=hALG12
    Membrane protein SB87

Gene names

Name:	ALG12
ORF Names:	PP14673

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

General annotation (Comments)

Function	Adds the eighth mannose residue in an alpha-1,6 linkage onto the dolichol-PP-oligosaccharide precursor (dolichol-PP-Man7GlcNAc2) required for protein glycosylation.
Pathway	Protein modification; protein glycosylation.
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein Probable.
Tissue specificity	Expressed in fibroblasts.
Involvement in disease	Defects in ALG12 are the cause of congenital disorder of glycosylation type 1G (CDG1G) [MIM:607143]. 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.1 Ref.8 Ref.9 Ref.10 Ref.11
Sequence similarities	Belongs to the glycosyltransferase 22 family.
Sequence caution	The sequence AAM94900.1 differs from that shown. Reason: Frameshift at position 468.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Polymorphism
Disease	Congenital disorder of glycosylation Disease mutation
Domain	Transmembrane
Molecular function	Glycosyltransferase Transferase
Gene Ontology (GO)
Biological process	GPI anchor biosynthetic process Inferred from electronic annotation. Source: InterPro protein amino acid N-linked glycosylation Ref.8 Inferred from genetic interaction. Source: UniProtKB protein folding Ref.8 Non-traceable author statement. Source: UniProtKB
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW intrinsic to endoplasmic reticulum membrane Inferred from electronic annotation. Source: InterPro
Molecular function	alpha-1,6-mannosyltransferase activity Ref.8 Inferred by curator. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 488	488	Dolichyl-P-Man:Man(7)GlcNAc(2)-PP-dolichyl-alpha-1,6-mannosyltransferase		PRO_0000215781
Regions
	Transmembrane	11 – 31	21	Potential
	Transmembrane	68 – 88	21	Potential
	Transmembrane	93 – 113	21	Potential
	Transmembrane	122 – 142	21	Potential
	Transmembrane	145 – 165	21	Potential
	Transmembrane	177 – 197	21	Potential
	Transmembrane	212 – 232	21	Potential
	Transmembrane	264 – 284	21	Potential
	Transmembrane	290 – 310	21	Potential
	Transmembrane	312 – 332	21	Potential
	Transmembrane	346 – 366	21	Potential
	Transmembrane	423 – 443	21	Potential
Natural variations
	Natural variant	67	1	T → M in CDG1G. Ref.8		VAR_017904
	Natural variant	101	1	G → R in CDG1G. Ref.11		VAR_038428
	Natural variant	142	1	F → V in CDG1G. dbSNP rs28942090. Ref.1		VAR_017905
	Natural variant	146	1	R → Q in CDG1G. Ref.8 Ref.11		VAR_017906
	Natural variant	158	1	L → P in CDG1G. Ref.9		VAR_017907
	Natural variant	393	1	I → V: dbSNP rs3922872. Ref.7		VAR_024466
Experimental info
	Sequence conflict	267	1	A → T in AAM94900. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q9BV10-1 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 8D4F921C21CBC8B6	FASTA	488	54,655
	10 20 30 40 50 60 MAGKGSSGRR PLLLGLLVAV ATVHLVICPY TKVEESFNLQ ATHDLLYHWQ DLEQYDHLEF 70 80 90 100 110 120 PGVVPRTFLG PVVIAVFSSP AVYVLSLLEM SKFYSQLIVR GVLGLGVIFG LWTLQKEVRR 130 140 150 160 170 180 HFGAMVATMF CWVTAMQFHL MFYCTRTLPN VLALPVVLLA LAAWLRHEWA RFIWLSAFAI 190 200 210 220 230 240 IVFRVELCLF LGLLLLLALG NRKVSVVRAL RHAVPAGILC LGLTVAVDSY FWRQLTWPEG 250 260 270 280 290 300 KVLWYNTVLN KSSNWGTSPL LWYFYSALPR GLGCSLLFIP LGLVDRRTHA PTVLALGFMA 310 320 330 340 350 360 LYSLLPHKEL RFIIYAFPML NITAARGCSY LLNNYKKSWL YKAGSLLVIG HLVVNAAYSA 370 380 390 400 410 420 TALYVSHFNY PGGVAMQRLH QLVPPQTDVL LHIDVAAAQT GVSRFLQVNS AWRYDKREDV 430 440 450 460 470 480 QPGTGMLAYT HILMEAAPGL LALYRDTHRV LASVVGTTGV SLNLTQLPPF NVHLQTKLVL LERLPRPS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Congenital disorders of glycosylation type Ig is defined by a deficiency in dolichyl-P-mannose:Man7GlcNAc2-PP-dolichyl mannosyltransferase." Chantret I., Dupre T., Delenda C., Bucher S., Dancourt J., Barnier A., Charollais A., Heron D., Bader-Meunier B., Danos O., Seta N., Durand G., Oriol R., Codogno P., Moore S.E.H. J. Biol. Chem. 277:25815-25822(2002) [PubMed: 11983712] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT CDG1G VAL-142. Tissue: Skin.
[2]	"Identification of novel membrane proteins." Zhang W., Li N., Wan T., Cao X. Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Large-scale cDNA transfection screening for genes related to cancer development and progression." Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X. , Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J. Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004) [PubMed: 15498874] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"A genome annotation-driven approach to cloning the human ORFeome." Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I. Genome Biol. 5:RESEARCH84.1-RESEARCH84.11(2004) [PubMed: 15461802] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"The DNA sequence of human chromosome 22." Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H. Nature 402:489-495(1999) [PubMed: 10591208] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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-393. Tissue: Eye.
[8]	"ALG12 mannosyltransferase defect in congenital disorder of glycosylation type Ig." Grubenmann C.E., Frank C.G., Kjaergaard S., Berger E.G., Aebi M., Hennet T. Hum. Mol. Genet. 11:2331-2339(2002) [PubMed: 12217961] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS CDG1G MET-67 AND GLN-146.
[9]	"Deficiency of dolichyl-P-Man:Man7GlcNAc2-PP-dolichyl mannosyltransferase causes congenital disorder of glycosylation type Ig." Thiel C., Schwarz M., Hasilik M., Grieben U., Hanefeld F., Lehle L., von Figura K., Koerner C. Biochem. J. 367:195-201(2002) [PubMed: 12093361] [Abstract] Cited for: CHARACTERIZATION OF VARIANT CDG1G PRO-158.
[10]	"Abnormal glycosylation of red cell membrane band 3 in the congenital disorder of glycosylation Ig." Zdebska E., Bader-Meunier B., Schischmanoff P.-O., Dupre T., Seta N., Tchernia G., Koscielak J., Delaunay J. Pediatr. Res. 54:224-229(2003) [PubMed: 12736397] [Abstract] Cited for: INVOLVEMENT IN CDG1G.
[11]	"Expanding spectrum of congenital disorder of glycosylation Ig (CDG-Ig): sibs with a unique skeletal dysplasia, hypogammaglobulinemia, cardiomyopathy, genital malformations, and early lethality." Kranz C., Basinger A.A., Guecsavas-Calikoglu M., Sun L., Powell C.M., Henderson F.W., Aylsworth A.S., Freeze H.H. Am. J. Med. Genet. A 143:1371-1378(2007) [PubMed: 17506107] [Abstract] Cited for: VARIANTS CDG1G ARG-101 AND GLN-146.

Web resources

GeneReviews

GGDB

GlycoGene database

Cross-references

Sequence databases
EMBLGenBankDDBJ	AJ290427 mRNA. Translation: CAC83681.1. AJ303120 mRNA. Translation: CAC67488.1. AF311904 mRNA. Translation: AAM94900.1. Frameshift. AF318343 mRNA. Translation: AAL55850.1. CR456369 mRNA. Translation: CAG30255.1. AL671710 Genomic DNA. Translation: CAO72064.1. CH471138 Genomic DNA. Translation: EAW73480.1. BC001729 mRNA. Translation: AAH01729.1. BC098562 mRNA. Translation: AAH98562.1.
IPI	IPI00012208.
RefSeq	NP_077010.1.
UniGene	Hs.526711
3D structure databases
ModBase	Search...
Protein family/group databases
CAZy	GT22. Glycosyltransferase Family 22.
Proteomic databases
PRIDE	Q9BV10.
Genome annotation databases
Ensembl	ENSG00000182858. Homo sapiens. [Contig view]
GeneID	79087.
KEGG	hsa:79087.
Organism-specific databases
GeneCards	GC22M048682.
H-InvDB	HIX0018816.
HGNC	HGNC:19358. ALG12.
MIM	607143. phenotype. 607144. gene.
Orphanet	137. CDG syndrome. 79324. CDG syndrome, type Ig.
PharmGKB	PA134987771.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q9BV10.
HOVERGEN	Q9BV10.
OMA	Q9BV10. TSPLLWY.
Enzyme and pathway databases
BRENDA	2.4.1.130. 247.
Gene expression databases
Bgee	Q9BV10.
CleanEx	HS_ALG12.
GermOnline	ENSG00000182858. Homo sapiens.
Family and domain databases
InterPro	IPR005599. Alg9_trans. [Graphical view]
PANTHER	PTHR22760. Alg9_trans. 1 hit.
Pfam	PF03901. Glyco_transf_22. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	67909.
SOURCE	Search...

Entry information

Entry name

ALG12_HUMAN

Accession

Primary (citable) accession number: Q9BV10
Secondary accession number(s): A6PWM1 , Q4KMH4, Q8NG10, Q96AA4

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2004
Last sequence update:	June 1, 2001
Last modified:	June 16, 2009
This is version 68 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)