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   24-JUL-2024, entry version 179.
DE   RecName: Full=Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 1 {ECO:0000305};
DE            EC=2.4.3.3 {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=2.4.3.3;
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   -!- INTERACTION:
CC       Q9NSC7; P13569: CFTR; NbExp=5; IntAct=EBI-2854712, EBI-349854;
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="https://atlasgeneticsoncology.org/gene/44087/ST6GALNAC1";
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";
CC   -!- WEB RESOURCE: Name=Protein Spotlight; Note=The slime inside us - Issue
CC       257 of April 2023;
CC       URL="https://www.proteinspotlight.org/back_issues/257/";
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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; 8.
DR   IntAct; Q9NSC7; 3.
DR   STRING; 9606.ENSP00000156626; -.
DR   CAZy; GT29; Glycosyltransferase Family 29.
DR   GlyCosmos; Q9NSC7; 5 sites, No reported glycans.
DR   GlyGen; Q9NSC7; 7 sites, 1 O-linked glycan (2 sites).
DR   iPTMnet; Q9NSC7; -.
DR   PhosphoSitePlus; Q9NSC7; -.
DR   SwissPalm; Q9NSC7; -.
DR   BioMuta; ST6GALNAC1; -.
DR   DMDM; 21759444; -.
DR   jPOST; Q9NSC7; -.
DR   MassIVE; Q9NSC7; -.
DR   PaxDb; 9606-ENSP00000156626; -.
DR   PeptideAtlas; Q9NSC7; -.
DR   ProteomicsDB; 82533; -.
DR   Antibodypedia; 2230; 143 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   AGR; HGNC:23614; -.
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; 5348004at2759; -.
DR   PhylomeDB; Q9NSC7; -.
DR   TreeFam; TF354325; -.
DR   BioCyc; MetaCyc:HS00998-MONOMER; -.
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; 10 hits in 1145 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 133 other cell types or tissues.
DR   ExpressionAtlas; Q9NSC7; baseline and differential.
DR   GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB.
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: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; Glycosyl transferase family 29; 1.
DR   InterPro; IPR001675; Glyco_trans_29.
DR   InterPro; IPR038578; GT29-like_sf.
DR   PANTHER; PTHR45941; -; 1.
DR   PANTHER; PTHR45941:SF1; ALPHA-N-ACETYLGALACTOSAMINIDE ALPHA-2,6-SIALYLTRANSFERASE 1; 1.
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; uncertain significance; does dot affect protein
FT                   sialyltransferase activity; dbSNP:rs146032525)"
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; uncertain significance; reduced protein
FT                   sialyltransferase activity; dbSNP:rs548273650)"
FT                   /evidence="ECO:0000269|PubMed:35303419"
FT                   /id="VAR_086493"
FT   VARIANT         391
FT                   /note="R -> Q (found in patients with inflammatory bowel
FT                   disease; likely pathogenic; impaired localization to the
FT                   Golgi apparatus; abolished protein sialyltransferase
FT                   activity; dbSNP:rs755904228)"
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; uncertain significance; reduced protein
FT                   sialyltransferase activity; dbSNP:rs150096642)"
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
//