SIA7A_HUMAN
ID SIA7A_HUMAN Reviewed; 600 AA.
AC Q9NSC7; Q6UW90; Q9NSC6;
DT 11-JUL-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 1 {ECO:0000305};
DE EC=2.4.99.3 {ECO:0000269|PubMed:16319059, ECO:0000269|PubMed:35303419};
DE AltName: Full=GalNAc alpha-2,6-sialyltransferase I {ECO:0000303|PubMed:10536037, ECO:0000303|PubMed:12820722};
DE AltName: Full=ST6GalNAc I {ECO:0000303|PubMed:10536037, ECO:0000303|PubMed:12820722};
DE Short=ST6GalNAc-I {ECO:0000303|PubMed:16319059};
DE Short=ST6GalNAcI {ECO:0000303|PubMed:10536037, ECO:0000303|PubMed:12820722};
DE Short=hST6GalNAc-I {ECO:0000303|PubMed:16319059};
DE AltName: Full=Sialyltransferase 7A;
DE Short=SIAT7-A;
GN Name=ST6GALNAC1 {ECO:0000312|HGNC:HGNC:23614}; Synonyms=SIAT7A;
GN ORFNames=UNQ543/PRO848 {ECO:0000303|PubMed:12975309};
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 / MRNA].
RX PubMed=10536037; DOI=10.1093/glycob/9.11.1213;
RA Ikehara Y., Kojima N., Kurosawa N., Kudo T., Kono M., Nishihara S.,
RA Issiki S., Morozumi K., Itzkowitz S., Tsuda T., Nishimura S., Tsuji S.,
RA Narimatsu H.;
RT "Cloning and expression of a human gene encoding an N-acetylgalactosamine-
RT alpha2,6-sialyltransferase (ST6GalNac I); a candidate for synthesis of
RT cancer-associated sialyl-Tnantigens.";
RL Glycobiology 9:1213-1224(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=12820722; DOI=10.1023/a:1022200525695;
RA Julien S., Krzewinski-Recchi M.A., Harduin-Lepers A., Gouyer V., Huet G.,
RA Le Bourhis X., Delannoy P.;
RT "Expression of sialyl-Tn antigen in breast cancer cells transfected with
RT the human CMP-Neu5Ac: GalNAc alpha2,6-sialyltransferase (ST6GalNac I)
RT cDNA.";
RL Glycoconj. J. 18:883-893(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-80.
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=16319059; DOI=10.1074/jbc.m511826200;
RA Sewell R., Baeckstroem M., Dalziel M., Gschmeissner S., Karlsson H.,
RA Noll T., Gaetgens J., Clausen H., Hansson G.C., Burchell J.,
RA Taylor-Papadimitriou J.;
RT "The ST6GalNAc-I sialyltransferase localizes throughout the Golgi and is
RT responsible for the synthesis of the tumor-associated sialyl-Tn O-glycan in
RT human breast cancer.";
RL J. Biol. Chem. 281:3586-3594(2006).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, GLYCOSYLATION, INVOLVEMENT IN INFLAMMATORY BOWEL DISEASE,
RP VARIANTS PRO-207; CYS-341; GLN-391 AND MET-462, AND CHARACTERIZATION OF
RP VARIANTS PRO-207; CYS-341; GLN-391 AND MET-462.
RX PubMed=35303419; DOI=10.1016/j.cell.2022.02.013;
RA Yao Y., Kim G., Shafer S., Chen Z., Kubo S., Ji Y., Luo J., Yang W.,
RA Perner S.P., Kanellopoulou C., Park A.Y., Jiang P., Li J., Baris S.,
RA Aydiner E.K., Ertem D., Mulder D.J., Warner N., Griffiths A.M.,
RA Topf-Olivestone C., Kori M., Werner L., Ouahed J., Field M., Liu C.,
RA Schwarz B., Bosio C.M., Ganesan S., Song J., Urlaub H., Oellerich T.,
RA Malaker S.A., Zheng L., Bertozzi C.R., Zhang Y., Matthews H.,
RA Montgomery W., Shih H.Y., Jiang J., Jones M., Baras A., Shuldiner A.,
RA Gonzaga-Jauregui C., Snapper S.B., Muise A.M., Shouval D.S., Ozen A.,
RA Pan K.T., Wu C., Lenardo M.J.;
RT "Mucus sialylation determines intestinal host-commensal homeostasis.";
RL Cell 0:0-0(2022).
CC -!- FUNCTION: Protein sialyltransferase specifically expressed in goblet
CC cells that plays a key role in intestinal host-commensal homeostasis
CC (PubMed:35303419). Conjugates sialic acid with an alpha-2-6 linkage to
CC N-acetylgalactosamine (GalNAc) glycan chains linked to serine or
CC threonine in glycoproteins (PubMed:16319059, PubMed:35303419).
CC Catalyzes the formation of the sialyl-Tn (S-Tn) antigen, an antigen
CC found in intestinal goblet cells, as well as ulcerative colitis (UC)
CC and various cancers (PubMed:16319059, PubMed:35303419). Protein
CC sialylation in globlet cells is essential for mucus integrity and is
CC required to protect the intestinal mucus against excessive bacterial
CC proteolytic degradation (PubMed:35303419).
CC {ECO:0000269|PubMed:16319059, ECO:0000269|PubMed:35303419}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a beta-D-galactosyl-(1->3)-N-acetyl-alpha-D-galactosaminyl
CC derivative + CMP-N-acetyl-beta-neuraminate = a beta-D-galactosyl-
CC (1->3)-[N-acetyl-alpha-neuraminyl-(2->6)]-N-acetyl-alpha-D-
CC galactosaminyl derivative + CMP + H(+); Xref=Rhea:RHEA:11136,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57812, ChEBI:CHEBI:60377,
CC ChEBI:CHEBI:133470, ChEBI:CHEBI:140764; EC=2.4.99.3;
CC Evidence={ECO:0000269|PubMed:16319059, ECO:0000269|PubMed:35303419};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11137;
CC Evidence={ECO:0000269|PubMed:16319059, ECO:0000269|PubMed:35303419};
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC {ECO:0000269|PubMed:16319059, ECO:0000269|PubMed:35303419}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:16319059, ECO:0000269|PubMed:35303419}; Single-pass
CC type II membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expression is restricted to the gastrointestinal
CC tract (PubMed:16319059). Highly expressed in goblet cells
CC (PubMed:35303419). Also expressed in various tumor cells
CC (PubMed:16319059). {ECO:0000269|PubMed:16319059,
CC ECO:0000269|PubMed:35303419}.
CC -!- PTM: Glycosylated; autosialylated. {ECO:0000269|PubMed:35303419}.
CC -!- DISEASE: Note=Inflammatory bowel disease (PubMed:35303419). A chronic,
CC relapsing inflammation of the gastrointestinal tract with a complex
CC etiology (PubMed:35303419). It is subdivided into Crohn disease and
CC ulcerative colitis phenotypes (PubMed:35303419). Crohn disease may
CC affect any part of the gastrointestinal tract from the mouth to the
CC anus, but most frequently it involves the terminal ileum and colon
CC (PubMed:35303419). Bowel inflammation is transmural and discontinuous;
CC it may contain granulomas or be associated with intestinal or perianal
CC fistulas (PubMed:35303419). In contrast, in ulcerative colitis, the
CC inflammation is continuous and limited to rectal and colonic mucosal
CC layers; fistulas and granulomas are not observed (PubMed:35303419).
CC Both diseases include extraintestinal inflammation of the skin, eyes,
CC or joints (PubMed:35303419). Disease susceptibility is associated with
CC variants affecting the gene represented in this entry
CC (PubMed:35303419). {ECO:0000269|PubMed:35303419}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 29 family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/ST6GALNAC1ID44087ch17q25.html";
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - GTase; Note=ST6GalNAc
CC I;
CC URL="http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_hum_630";
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DR EMBL; Y11339; CAA72179.2; -; mRNA.
DR EMBL; Y11340; CAA72180.1; -; Genomic_DNA.
DR EMBL; AY096001; AAM22800.1; -; mRNA.
DR EMBL; AY358918; AAQ89277.1; -; mRNA.
DR CCDS; CCDS11748.1; -.
DR RefSeq; NP_060884.1; NM_018414.4.
DR AlphaFoldDB; Q9NSC7; -.
DR SMR; Q9NSC7; -.
DR BioGRID; 120918; 7.
DR IntAct; Q9NSC7; 2.
DR STRING; 9606.ENSP00000156626; -.
DR CAZy; GT29; Glycosyltransferase Family 29.
DR GlyGen; Q9NSC7; 5 sites.
DR iPTMnet; Q9NSC7; -.
DR PhosphoSitePlus; Q9NSC7; -.
DR BioMuta; ST6GALNAC1; -.
DR DMDM; 21759444; -.
DR EPD; Q9NSC7; -.
DR jPOST; Q9NSC7; -.
DR MassIVE; Q9NSC7; -.
DR MaxQB; Q9NSC7; -.
DR PaxDb; Q9NSC7; -.
DR PeptideAtlas; Q9NSC7; -.
DR PRIDE; Q9NSC7; -.
DR ProteomicsDB; 82533; -.
DR Antibodypedia; 2230; 141 antibodies from 23 providers.
DR DNASU; 55808; -.
DR Ensembl; ENST00000156626.12; ENSP00000156626.6; ENSG00000070526.15.
DR GeneID; 55808; -.
DR KEGG; hsa:55808; -.
DR MANE-Select; ENST00000156626.12; ENSP00000156626.6; NM_018414.5; NP_060884.1.
DR UCSC; uc002jsh.5; human.
DR CTD; 55808; -.
DR DisGeNET; 55808; -.
DR GeneCards; ST6GALNAC1; -.
DR HGNC; HGNC:23614; ST6GALNAC1.
DR HPA; ENSG00000070526; Group enriched (cervix, intestine, stomach).
DR MIM; 610138; gene.
DR neXtProt; NX_Q9NSC7; -.
DR OpenTargets; ENSG00000070526; -.
DR PharmGKB; PA134935906; -.
DR VEuPathDB; HostDB:ENSG00000070526; -.
DR eggNOG; KOG2692; Eukaryota.
DR GeneTree; ENSGT00940000159930; -.
DR HOGENOM; CLU_032020_4_1_1; -.
DR InParanoid; Q9NSC7; -.
DR OMA; WDFEEQY; -.
DR OrthoDB; 891104at2759; -.
DR PhylomeDB; Q9NSC7; -.
DR TreeFam; TF354325; -.
DR BioCyc; MetaCyc:HS00998-MON; -.
DR BRENDA; 2.4.99.3; 2681.
DR PathwayCommons; Q9NSC7; -.
DR Reactome; R-HSA-4085001; Sialic acid metabolism.
DR SignaLink; Q9NSC7; -.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 55808; 6 hits in 1068 CRISPR screens.
DR ChiTaRS; ST6GALNAC1; human.
DR GeneWiki; ST6GALNAC1; -.
DR GenomeRNAi; 55808; -.
DR Pharos; Q9NSC7; Tbio.
DR PRO; PR:Q9NSC7; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q9NSC7; protein.
DR Bgee; ENSG00000070526; Expressed in mucosa of sigmoid colon and 132 other tissues.
DR ExpressionAtlas; Q9NSC7; baseline and differential.
DR Genevisible; Q9NSC7; HS.
DR GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0001665; F:alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase activity; IDA:UniProtKB.
DR GO; GO:0008373; F:sialyltransferase activity; NAS:UniProtKB.
DR GO; GO:0016740; F:transferase activity; IBA:GO_Central.
DR GO; GO:0048874; P:host-mediated regulation of intestinal microbiota composition; ISS:UniProtKB.
DR GO; GO:0009312; P:oligosaccharide biosynthetic process; IBA:GO_Central.
DR GO; GO:0006486; P:protein glycosylation; IDA:UniProtKB.
DR Gene3D; 3.90.1480.20; -; 1.
DR InterPro; IPR001675; Glyco_trans_29.
DR InterPro; IPR038578; GT29-like_sf.
DR Pfam; PF00777; Glyco_transf_29; 1.
PE 1: Evidence at protein level;
KW Disease variant; Disulfide bond; Glycoprotein; Glycosyltransferase;
KW Golgi apparatus; Membrane; Reference proteome; Signal-anchor; Transferase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..600
FT /note="Alpha-N-acetylgalactosaminide alpha-2,6-
FT sialyltransferase 1"
FT /id="PRO_0000149269"
FT TOPO_DOM 1..14
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 15..35
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 36..600
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 38..191
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 208..248
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 40..56
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 57..71
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 80..95
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 96..128
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 131..191
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 300
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 311
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 331
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 375
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 460
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 279..362
FT /evidence="ECO:0000250|UniProtKB:Q9UJ37"
FT DISULFID 365..533
FT /evidence="ECO:0000250|UniProtKB:Q9UJ37"
FT VARIANT 80
FT /note="V -> A (in dbSNP:rs8077382)"
FT /evidence="ECO:0000269|PubMed:12975309"
FT /id="VAR_021514"
FT VARIANT 207
FT /note="T -> P (found in patients with Inflammatory bowel
FT disease; unknown pathological significance; does dot affect
FT protein sialyltransferase activity)"
FT /evidence="ECO:0000269|PubMed:35303419"
FT /id="VAR_086492"
FT VARIANT 341
FT /note="R -> C (found in patients with Inflammatory bowel
FT disease; unknown pathological significance; reduced protein
FT sialyltransferase activity)"
FT /evidence="ECO:0000269|PubMed:35303419"
FT /id="VAR_086493"
FT VARIANT 391
FT /note="R -> Q (probable disease-associated variant found in
FT patients with Inflammatory bowel disease; impaired
FT localization to the Golgi apparatus; abolished protein
FT sialyltransferase activity)"
FT /evidence="ECO:0000269|PubMed:35303419"
FT /id="VAR_086494"
FT VARIANT 424
FT /note="I -> V (in dbSNP:rs35948039)"
FT /id="VAR_049226"
FT VARIANT 462
FT /note="T -> M (found in patients with Inflammatory bowel
FT disease; unknown pathological significance; reduced protein
FT sialyltransferase activity)"
FT /evidence="ECO:0000269|PubMed:35303419"
FT /id="VAR_086495"
SQ SEQUENCE 600 AA; 68564 MW; 9A28399A3DC8AB30 CRC64;
MRSCLWRCRH LSQGVQWSLL LAVLVFFLFA LPSFIKEPQT KPSRHQRTEN IKERSLQSLA
KPKSQAPTRA RRTTIYAEPV PENNALNTQT QPKAHTTGDR GKEANQAPPE EQDKVPHTAQ
RAAWKSPEKE KTMVNTLSPR GQDAGMASGR TEAQSWKSQD TKTTQGNGGQ TRKLTASRTV
SEKHQGKAAT TAKTLIPKSQ HRMLAPTGAV STRTRQKGVT TAVIPPKEKK PQATPPPAPF
QSPTTQRNQR LKAANFKSEP RWDFEEKYSF EIGGLQTTCP DSVKIKASKS LWLQKLFLPN
LTLFLDSRHF NQSEWDRLEH FAPPFGFMEL NYSLVQKVVT RFPPVPQQQL LLASLPAGSL
RCITCAVVGN GGILNNSHMG QEIDSHDYVF RLSGALIKGY EQDVGTRTSF YGFTAFSLTQ
SLLILGNRGF KNVPLGKDVR YLHFLEGTRD YEWLEALLMN QTVMSKNLFW FRHRPQEAFR
EALHMDRYLL LHPDFLRYMK NRFLRSKTLD GAHWRIYRPT TGALLLLTAL QLCDQVSAYG
FITEGHERFS DHYYDTSWKR LIFYINHDFK LEREVWKRLH DEGIIRLYQR PGPGTAKAKN
