ALG12_HUMAN
ID ALG12_HUMAN Reviewed; 488 AA.
AC Q9BV10; A6PWM1; Q4KMH4; Q8NG10; Q96AA4;
DT 15-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Dol-P-Man:Man(7)GlcNAc(2)-PP-Dol alpha-1,6-mannosyltransferase;
DE EC=2.4.1.260;
DE AltName: Full=Asparagine-linked glycosylation protein 12 homolog;
DE Short=hALG12;
DE AltName: Full=Dolichyl-P-Man:Man(7)GlcNAc(2)-PP-dolichyl-alpha-1,6-mannosyltransferase;
DE AltName: Full=Mannosyltransferase ALG12 homolog;
DE AltName: Full=Membrane protein SB87;
GN Name=ALG12; ORFNames=PP14673;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT CDG1G VAL-142.
RC TISSUE=Skin;
RX PubMed=11983712; DOI=10.1074/jbc.m203285200;
RA Chantret I., Dupre T., Delenda C., Bucher S., Dancourt J., Barnier A.,
RA Charollais A., Heron D., Bader-Meunier B., Danos O., Seta N., Durand G.,
RA Oriol R., Codogno P., Moore S.E.H.;
RT "Congenital disorders of glycosylation type Ig is defined by a deficiency
RT in dolichyl-P-mannose:Man7GlcNAc2-PP-dolichyl mannosyltransferase.";
RL J. Biol. Chem. 277:25815-25822(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Zhang W., Li N., Wan T., Cao X.;
RT "Identification of novel membrane proteins.";
RL Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15498874; DOI=10.1073/pnas.0404089101;
RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X.,
RA Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X.,
RA Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.;
RT "Large-scale cDNA transfection screening for genes related to cancer
RT development and progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-393.
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP CHARACTERIZATION OF VARIANTS CDG1G MET-67 AND GLN-146.
RX PubMed=12217961; DOI=10.1093/hmg/11.19.2331;
RA Grubenmann C.E., Frank C.G., Kjaergaard S., Berger E.G., Aebi M.,
RA Hennet T.;
RT "ALG12 mannosyltransferase defect in congenital disorder of glycosylation
RT type Ig.";
RL Hum. Mol. Genet. 11:2331-2339(2002).
RN [9]
RP CHARACTERIZATION OF VARIANT CDG1G PRO-158.
RX PubMed=12093361; DOI=10.1042/bj20020794;
RA Thiel C., Schwarz M., Hasilik M., Grieben U., Hanefeld F., Lehle L.,
RA von Figura K., Koerner C.;
RT "Deficiency of dolichyl-P-Man:Man7GlcNAc2-PP-dolichyl mannosyltransferase
RT causes congenital disorder of glycosylation type Ig.";
RL Biochem. J. 367:195-201(2002).
RN [10]
RP INVOLVEMENT IN CDG1G.
RX PubMed=12736397; DOI=10.1203/01.pdr.0000072327.55955.f7;
RA Zdebska E., Bader-Meunier B., Schischmanoff P.-O., Dupre T., Seta N.,
RA Tchernia G., Koscielak J., Delaunay J.;
RT "Abnormal glycosylation of red cell membrane band 3 in the congenital
RT disorder of glycosylation Ig.";
RL Pediatr. Res. 54:224-229(2003).
RN [11]
RP VARIANTS CDG1G ARG-101 AND GLN-146.
RX PubMed=17506107; DOI=10.1002/ajmg.a.31791;
RA Kranz C., Basinger A.A., Guecsavas-Calikoglu M., Sun L., Powell C.M.,
RA Henderson F.W., Aylsworth A.S., Freeze H.H.;
RT "Expanding spectrum of congenital disorder of glycosylation Ig (CDG-Ig):
RT sibs with a unique skeletal dysplasia, hypogammaglobulinemia,
RT cardiomyopathy, genital malformations, and early lethality.";
RL Am. J. Med. Genet. A 143:1371-1378(2007).
CC -!- FUNCTION: Adds the eighth mannose residue in an alpha-1,6 linkage onto
CC the dolichol-PP-oligosaccharide precursor (dolichol-PP-Man(7)GlcNAc(2))
CC required for protein glycosylation.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a dolichyl beta-D-mannosyl phosphate + alpha-D-Man-(1->2)-
CC alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)-alpha-D-
CC Man-(1->3)-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-
CC (1->4)-alpha-D-GlcNAc-diphosphodolichol = a dolichyl phosphate +
CC alpha-D-Man-(1->2)-alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-
CC Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->6)]-alpha-D-Man-
CC (1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-alpha-D-GlcNAc-
CC diphosphodolichol + H(+); Xref=Rhea:RHEA:29535, Rhea:RHEA-COMP:9517,
CC Rhea:RHEA-COMP:9527, Rhea:RHEA-COMP:12629, Rhea:RHEA-COMP:12630,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57683, ChEBI:CHEBI:58211,
CC ChEBI:CHEBI:132517, ChEBI:CHEBI:132519; EC=2.4.1.260;
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305};
CC Multi-pass membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in fibroblasts.
CC -!- DISEASE: Congenital disorder of glycosylation 1G (CDG1G) [MIM:607143]:
CC A form of congenital disorder of glycosylation, a multisystem disorder
CC caused by a defect in glycoprotein biosynthesis and characterized by
CC under-glycosylated serum glycoproteins. Congenital disorders of
CC glycosylation result in a wide variety of clinical features, such as
CC defects in the nervous system development, psychomotor retardation,
CC dysmorphic features, hypotonia, coagulation disorders, and
CC immunodeficiency. The broad spectrum of features reflects the critical
CC role of N-glycoproteins during embryonic development, differentiation,
CC and maintenance of cell functions. {ECO:0000269|PubMed:11983712,
CC ECO:0000269|PubMed:12093361, ECO:0000269|PubMed:12217961,
CC ECO:0000269|PubMed:12736397, ECO:0000269|PubMed:17506107}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 22 family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAM94900.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AJ290427; CAC83681.1; -; mRNA.
DR EMBL; AJ303120; CAC67488.1; -; mRNA.
DR EMBL; AF311904; AAM94900.1; ALT_FRAME; mRNA.
DR EMBL; AF318343; AAL55850.1; -; mRNA.
DR EMBL; CR456369; CAG30255.1; -; mRNA.
DR EMBL; AL671710; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471138; EAW73480.1; -; Genomic_DNA.
DR EMBL; BC001729; AAH01729.1; -; mRNA.
DR EMBL; BC098562; AAH98562.1; -; mRNA.
DR CCDS; CCDS14081.1; -.
DR RefSeq; NP_077010.1; NM_024105.3.
DR AlphaFoldDB; Q9BV10; -.
DR BioGRID; 122535; 22.
DR IntAct; Q9BV10; 9.
DR STRING; 9606.ENSP00000333813; -.
DR CAZy; GT22; Glycosyltransferase Family 22.
DR iPTMnet; Q9BV10; -.
DR PhosphoSitePlus; Q9BV10; -.
DR BioMuta; ALG12; -.
DR DMDM; 45476971; -.
DR EPD; Q9BV10; -.
DR jPOST; Q9BV10; -.
DR MassIVE; Q9BV10; -.
DR MaxQB; Q9BV10; -.
DR PaxDb; Q9BV10; -.
DR PeptideAtlas; Q9BV10; -.
DR PRIDE; Q9BV10; -.
DR ProteomicsDB; 79150; -.
DR Antibodypedia; 28215; 99 antibodies from 22 providers.
DR DNASU; 79087; -.
DR Ensembl; ENST00000330817.11; ENSP00000333813.5; ENSG00000182858.14.
DR GeneID; 79087; -.
DR KEGG; hsa:79087; -.
DR MANE-Select; ENST00000330817.11; ENSP00000333813.5; NM_024105.4; NP_077010.1.
DR UCSC; uc003biy.4; human.
DR CTD; 79087; -.
DR DisGeNET; 79087; -.
DR GeneCards; ALG12; -.
DR GeneReviews; ALG12; -.
DR HGNC; HGNC:19358; ALG12.
DR HPA; ENSG00000182858; Low tissue specificity.
DR MalaCards; ALG12; -.
DR MIM; 607143; phenotype.
DR MIM; 607144; gene.
DR neXtProt; NX_Q9BV10; -.
DR OpenTargets; ENSG00000182858; -.
DR Orphanet; 79324; ALG12-CDG.
DR PharmGKB; PA134987771; -.
DR VEuPathDB; HostDB:ENSG00000182858; -.
DR eggNOG; KOG2516; Eukaryota.
DR GeneTree; ENSGT00950000183090; -.
DR HOGENOM; CLU_008917_0_0_1; -.
DR InParanoid; Q9BV10; -.
DR OMA; FTQYDHH; -.
DR PhylomeDB; Q9BV10; -.
DR TreeFam; TF314453; -.
DR BRENDA; 2.4.1.260; 2681.
DR PathwayCommons; Q9BV10; -.
DR Reactome; R-HSA-446193; Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein.
DR Reactome; R-HSA-4720489; Defective ALG12 causes CDG-1g.
DR SignaLink; Q9BV10; -.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 79087; 81 hits in 1073 CRISPR screens.
DR ChiTaRS; ALG12; human.
DR GeneWiki; ALG12; -.
DR GenomeRNAi; 79087; -.
DR Pharos; Q9BV10; Tbio.
DR PRO; PR:Q9BV10; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; Q9BV10; protein.
DR Bgee; ENSG00000182858; Expressed in right lobe of thyroid gland and 150 other tissues.
DR ExpressionAtlas; Q9BV10; baseline and differential.
DR Genevisible; Q9BV10; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; NAS:UniProtKB.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IEA:InterPro.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0000009; F:alpha-1,6-mannosyltransferase activity; IBA:GO_Central.
DR GO; GO:0052917; F:dolichyl-P-Man:Man(7)GlcNAc(2)-PP-dolichol alpha-1,6-mannosyltransferase; IEA:UniProtKB-EC.
DR GO; GO:0000030; F:mannosyltransferase activity; IBA:GO_Central.
DR GO; GO:0006488; P:dolichol-linked oligosaccharide biosynthetic process; IDA:MGI.
DR GO; GO:0006457; P:protein folding; NAS:UniProtKB.
DR GO; GO:0006487; P:protein N-linked glycosylation; IBA:GO_Central.
DR InterPro; IPR039485; ALG12.
DR InterPro; IPR005599; GPI_mannosylTrfase.
DR PANTHER; PTHR22760; PTHR22760; 1.
DR PANTHER; PTHR22760:SF1; PTHR22760:SF1; 1.
DR Pfam; PF03901; Glyco_transf_22; 1.
PE 1: Evidence at protein level;
KW Congenital disorder of glycosylation; Disease variant;
KW Endoplasmic reticulum; Glycosyltransferase; Membrane; Reference proteome;
KW Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..488
FT /note="Dol-P-Man:Man(7)GlcNAc(2)-PP-Dol alpha-1,6-
FT mannosyltransferase"
FT /id="PRO_0000215781"
FT TRANSMEM 11..31
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 68..88
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 93..113
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 122..142
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 145..165
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 177..197
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 212..232
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 264..284
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 290..310
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 312..332
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 346..366
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 423..443
FT /note="Helical"
FT /evidence="ECO:0000255"
FT VARIANT 67
FT /note="T -> M (in CDG1G; dbSNP:rs121907931)"
FT /evidence="ECO:0000269|PubMed:12217961"
FT /id="VAR_017904"
FT VARIANT 101
FT /note="G -> R (in CDG1G; dbSNP:rs121907933)"
FT /evidence="ECO:0000269|PubMed:17506107"
FT /id="VAR_038428"
FT VARIANT 142
FT /note="F -> V (in CDG1G; dbSNP:rs28942090)"
FT /evidence="ECO:0000269|PubMed:11983712"
FT /id="VAR_017905"
FT VARIANT 146
FT /note="R -> Q (in CDG1G; dbSNP:rs121907932)"
FT /evidence="ECO:0000269|PubMed:12217961,
FT ECO:0000269|PubMed:17506107"
FT /id="VAR_017906"
FT VARIANT 158
FT /note="L -> P (in CDG1G; dbSNP:rs121907934)"
FT /evidence="ECO:0000269|PubMed:12093361"
FT /id="VAR_017907"
FT VARIANT 393
FT /note="I -> V (in dbSNP:rs3922872)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_024466"
FT CONFLICT 267
FT /note="A -> T (in Ref. 2; AAM94900)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 488 AA; 54655 MW; 8D4F921C21CBC8B6 CRC64;
MAGKGSSGRR PLLLGLLVAV ATVHLVICPY TKVEESFNLQ ATHDLLYHWQ DLEQYDHLEF
PGVVPRTFLG PVVIAVFSSP AVYVLSLLEM SKFYSQLIVR GVLGLGVIFG LWTLQKEVRR
HFGAMVATMF CWVTAMQFHL MFYCTRTLPN VLALPVVLLA LAAWLRHEWA RFIWLSAFAI
IVFRVELCLF LGLLLLLALG NRKVSVVRAL RHAVPAGILC LGLTVAVDSY FWRQLTWPEG
KVLWYNTVLN KSSNWGTSPL LWYFYSALPR GLGCSLLFIP LGLVDRRTHA PTVLALGFMA
LYSLLPHKEL RFIIYAFPML NITAARGCSY LLNNYKKSWL YKAGSLLVIG HLVVNAAYSA
TALYVSHFNY PGGVAMQRLH QLVPPQTDVL LHIDVAAAQT GVSRFLQVNS AWRYDKREDV
QPGTGMLAYT HILMEAAPGL LALYRDTHRV LASVVGTTGV SLNLTQLPPF NVHLQTKLVL
LERLPRPS
