ID   CHST8_HUMAN             Reviewed;         424 AA.
AC   Q9H2A9; Q9H3N2;
DT   15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT   15-MAR-2005, sequence version 2.
DT   05-FEB-2025, entry version 154.
DE   RecName: Full=Carbohydrate sulfotransferase 8;
DE            EC=2.8.2.-;
DE   AltName: Full=GalNAc-4-O-sulfotransferase 1;
DE            Short=GalNAc-4-ST1;
DE            Short=GalNAc4ST-1;
DE   AltName: Full=N-acetylgalactosamine-4-O-sulfotransferase 1;
GN   Name=CHST8;
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 [MRNA], ENZYME ACTIVITY, FUNCTION, AND TISSUE
RP   SPECIFICITY.
RC   TISSUE=Fetal brain;
RX   PubMed=10988300; DOI=10.1074/jbc.m007821200;
RA   Xia G., Evers M.R., Kang H.-G., Schachner M., Baenziger J.U.;
RT   "Molecular cloning and expression of the pituitary glycoprotein hormone N-
RT   acetylgalactosamine-4-O-sulfotransferase.";
RL   J. Biol. Chem. 275:38402-38409(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], ENZYME ACTIVITY, TISSUE SPECIFICITY, AND
RP   BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=11001942; DOI=10.1074/jbc.m007983200;
RA   Okuda T., Mita S., Yamauchi S., Fukuta M., Nakano H., Sawada T.,
RA   Habuchi O.;
RT   "Molecular cloning and characterization of GalNAc 4-sulfotransferase
RT   expressed in human pituitary gland.";
RL   J. Biol. Chem. 275:40605-40613(2000).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA], ENZYME ACTIVITY, FUNCTION, AND TISSUE
RP   SPECIFICITY.
RX   PubMed=11445554; DOI=10.1093/glycob/11.6.495;
RA   Hiraoka N., Misra A., Belot F., Hindsgaul O., Fukuda M.;
RT   "Molecular cloning and expression of two distinct human N-
RT   acetylgalactosamine 4-O-sulfotransferases that transfer sulfate to GalNAc
RT   beta 1->4GlcNAc beta 1->R in both N- and O-glycans.";
RL   Glycobiology 11:495-504(2001).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Muscle;
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   [5]
RP   INDUCTION.
RX   PubMed=15632154; DOI=10.1074/jbc.m412635200;
RA   Barret A., Forestier L., Deslys J.-P., Julien R., Gallet P.F.;
RT   "Glycosylation-related gene expression in prion diseases: PrPSc
RT   accumulation in scrapie infected GT1 cells depends on beta-1,4-linked
RT   GalNAc-4-SO4 hyposulfation.";
RL   J. Biol. Chem. 280:10516-10523(2005).
RN   [6]
RP   TISSUE SPECIFICITY, VARIANT TRP-77, AND CHARACTERIZATION OF VARIANT TRP-77.
RX   PubMed=22289416; DOI=10.1016/j.ygeno.2012.01.005;
RA   Cabral R.M., Kurban M., Wajid M., Shimomura Y., Petukhova L.,
RA   Christiano A.M.;
RT   "Whole-exome sequencing in a single proband reveals a mutation in the CHST8
RT   gene in autosomal recessive peeling skin syndrome.";
RL   Genomics 99:202-208(2012).
RN   [7]
RP   VARIANT [LARGE SCALE ANALYSIS] HIS-247.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA   Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA   Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA   Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA   Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal cancers.";
RL   Science 314:268-274(2006).
CC   -!- FUNCTION: Catalyzes the transfer of sulfate to position 4 of non-
CC       reducing N-acetylgalactosamine (GalNAc) residues in both N-glycans and
CC       O-glycans. Required for biosynthesis of glycoprotein hormones lutropin
CC       and thyrotropin, by mediating sulfation of their carbohydrate
CC       structures. Only active against terminal GalNAcbeta1,GalNAcbeta. Not
CC       active toward chondroitin. {ECO:0000269|PubMed:10988300,
CC       ECO:0000269|PubMed:11445554}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=10 uM for carbonic anhydrase VI {ECO:0000269|PubMed:11001942};
CC       pH dependence:
CC         Optimum pH is 7.2. {ECO:0000269|PubMed:11001942};
CC   -!- INTERACTION:
CC       Q9H2A9; P28329-3: CHAT; NbExp=3; IntAct=EBI-21642354, EBI-25837549;
CC       Q9H2A9; P22607: FGFR3; NbExp=3; IntAct=EBI-21642354, EBI-348399;
CC       Q9H2A9; P06396: GSN; NbExp=3; IntAct=EBI-21642354, EBI-351506;
CC   -!- SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000250}; Single-
CC       pass type II membrane protein {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Predominantly expressed in pituitary gland. In
CC       brain, it is expressed in pituitary gland, cerebellum, medulla
CC       oblongata, pons, thalamus and spinal cord. Expressed in the epidermis.
CC       Expressed at lower level in lung, spleen, adrenal gland, placenta,
CC       prostate, testis, mammary gland and trachea.
CC       {ECO:0000269|PubMed:10988300, ECO:0000269|PubMed:11001942,
CC       ECO:0000269|PubMed:11445554, ECO:0000269|PubMed:22289416}.
CC   -!- INDUCTION: Down-regulated (17-fold) in prion-infected cells.
CC       {ECO:0000269|PubMed:15632154}.
CC   -!- SIMILARITY: Belongs to the sulfotransferase 2 family. {ECO:0000305}.
CC   -!- CAUTION: PubMed:10988300 reports the possible existence of a secreted
CC       isoform starting at Met-119. However, they do not provide any
CC       experimental evidence. {ECO:0000305}.
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DR   EMBL; AF300612; AAG39444.1; -; mRNA.
DR   EMBL; AB047801; BAB19806.1; -; mRNA.
DR   EMBL; AF305781; AAL09373.1; -; mRNA.
DR   EMBL; BC011380; AAH11380.1; -; mRNA.
DR   EMBL; BC014250; AAH14250.1; -; mRNA.
DR   EMBL; BC018723; AAH18723.1; -; mRNA.
DR   CCDS; CCDS12433.1; -.
DR   RefSeq; NP_001121367.1; NM_001127895.1.
DR   RefSeq; NP_001121368.1; NM_001127896.1.
DR   RefSeq; NP_071912.2; NM_022467.3.
DR   RefSeq; XP_011525524.1; XM_011527222.1.
DR   RefSeq; XP_011525526.1; XM_011527224.1.
DR   RefSeq; XP_016882632.1; XM_017027143.1.
DR   AlphaFoldDB; Q9H2A9; -.
DR   BioGRID; 122148; 95.
DR   IntAct; Q9H2A9; 80.
DR   STRING; 9606.ENSP00000262622; -.
DR   GlyCosmos; Q9H2A9; 4 sites, No reported glycans.
DR   GlyGen; Q9H2A9; 8 sites, 1 O-linked glycan (4 sites).
DR   iPTMnet; Q9H2A9; -.
DR   PhosphoSitePlus; Q9H2A9; -.
DR   BioMuta; CHST8; -.
DR   DMDM; 61212124; -.
DR   jPOST; Q9H2A9; -.
DR   MassIVE; Q9H2A9; -.
DR   PaxDb; 9606-ENSP00000262622; -.
DR   PeptideAtlas; Q9H2A9; -.
DR   ProteomicsDB; 80521; -.
DR   TopDownProteomics; Q9H2A9; -.
DR   Antibodypedia; 2401; 177 antibodies from 27 providers.
DR   DNASU; 64377; -.
DR   Ensembl; ENST00000262622.4; ENSP00000262622.3; ENSG00000124302.13.
DR   Ensembl; ENST00000434302.5; ENSP00000392604.1; ENSG00000124302.13.
DR   Ensembl; ENST00000438847.7; ENSP00000393879.1; ENSG00000124302.13.
DR   Ensembl; ENST00000650847.1; ENSP00000499084.1; ENSG00000124302.13.
DR   GeneID; 64377; -.
DR   KEGG; hsa:64377; -.
DR   MANE-Select; ENST00000650847.1; ENSP00000499084.1; NM_001127895.2; NP_001121367.1.
DR   UCSC; uc002nus.5; human.
DR   AGR; HGNC:15993; -.
DR   CTD; 64377; -.
DR   DisGeNET; 64377; -.
DR   GeneCards; CHST8; -.
DR   HGNC; HGNC:15993; CHST8.
DR   HPA; ENSG00000124302; Group enriched (brain, pituitary gland).
DR   MalaCards; CHST8; -.
DR   MIM; 610190; gene.
DR   neXtProt; NX_Q9H2A9; -.
DR   OpenTargets; ENSG00000124302; -.
DR   Orphanet; 263548; Peeling skin syndrome type A.
DR   PharmGKB; PA26508; -.
DR   VEuPathDB; HostDB:ENSG00000124302; -.
DR   eggNOG; KOG4651; Eukaryota.
DR   GeneTree; ENSGT00940000159100; -.
DR   HOGENOM; CLU_043398_5_1_1; -.
DR   InParanoid; Q9H2A9; -.
DR   OMA; RHHVKHL; -.
DR   OrthoDB; 2019940at2759; -.
DR   PhylomeDB; Q9H2A9; -.
DR   TreeFam; TF325581; -.
DR   PathwayCommons; Q9H2A9; -.
DR   Reactome; R-HSA-975578; Reactions specific to the complex N-glycan synthesis pathway.
DR   SABIO-RK; Q9H2A9; -.
DR   SignaLink; Q9H2A9; -.
DR   BioGRID-ORCS; 64377; 37 hits in 1135 CRISPR screens.
DR   ChiTaRS; CHST8; human.
DR   GenomeRNAi; 64377; -.
DR   Pharos; Q9H2A9; Tbio.
DR   PRO; PR:Q9H2A9; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   RNAct; Q9H2A9; protein.
DR   Bgee; ENSG00000124302; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 137 other cell types or tissues.
DR   ExpressionAtlas; Q9H2A9; baseline and differential.
DR   GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR   GO; GO:0016020; C:membrane; NAS:UniProtKB.
DR   GO; GO:0001537; F:N-acetylgalactosamine 4-O-sulfotransferase activity; IDA:UniProtKB.
DR   GO; GO:0008146; F:sulfotransferase activity; IBA:GO_Central.
DR   GO; GO:0016051; P:carbohydrate biosynthetic process; IEA:InterPro.
DR   GO; GO:0007417; P:central nervous system development; NAS:UniProtKB.
DR   GO; GO:0042446; P:hormone biosynthetic process; IEP:UniProtKB.
DR   GO; GO:0030166; P:proteoglycan biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0006790; P:sulfur compound metabolic process; IDA:UniProtKB.
DR   InterPro; IPR018011; Carb_sulfotrans_8-10.
DR   InterPro; IPR005331; Sulfotransferase.
DR   PANTHER; PTHR12137; CARBOHYDRATE SULFOTRANSFERASE; 1.
DR   PANTHER; PTHR12137:SF7; CARBOHYDRATE SULFOTRANSFERASE 8; 1.
DR   Pfam; PF03567; Sulfotransfer_2; 1.
PE   1: Evidence at protein level;
KW   Carbohydrate metabolism; Glycoprotein; Golgi apparatus; Membrane;
KW   Proteomics identification; Reference proteome; Signal-anchor; Transferase;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN           1..424
FT                   /note="Carbohydrate sulfotransferase 8"
FT                   /id="PRO_0000189653"
FT   TOPO_DOM        1..10
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        11..31
FT                   /note="Helical; Signal-anchor for type II membrane protein"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        32..424
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   REGION          47..107
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        66..77
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         198..204
FT                   /ligand="3'-phosphoadenylyl sulfate"
FT                   /ligand_id="ChEBI:CHEBI:58339"
FT                   /evidence="ECO:0000250"
FT   BINDING         258..266
FT                   /ligand="3'-phosphoadenylyl sulfate"
FT                   /ligand_id="ChEBI:CHEBI:58339"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        128
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        294
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        367
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        415
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VARIANT         77
FT                   /note="R -> W (found in a family showing features of non-
FT                   inflammatory peeling skin syndrome segregating as a
FT                   recessive trait; uncertain significance; results in
FT                   decreased enzyme activity; the mutant protein shows reduced
FT                   glycosylation; dbSNP:rs149660944)"
FT                   /evidence="ECO:0000269|PubMed:22289416"
FT                   /id="VAR_067723"
FT   VARIANT         247
FT                   /note="R -> H (in a colorectal cancer sample; somatic
FT                   mutation; dbSNP:rs1261984908)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_036538"
FT   CONFLICT        326
FT                   /note="I -> T (in Ref. 1; AAG39444)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   424 AA;  48834 MW;  D4CEF1E7287D6102 CRC64;
     MTLRPGTMRL ACMFSSILLF GAAGLLLFIS LQDPTELAPQ QVPGIKFNIR PRQPHHDLPP
     GGSQDGDLKE PTERVTRDLS SGAPRGRNLP APDQPQPPLQ RGTRLRLRQR RRRLLIKKMP
     AAATIPANSS DAPFIRPGPG TLDGRWVSLH RSQQERKRVM QEACAKYRAS SSRRAVTPRH
     VSRIFVEDRH RVLYCEVPKA GCSNWKRVLM VLAGLASSTA DIQHNTVHYG SALKRLDTFD
     RQGILHRLST YTKMLFVREP FERLVSAFRD KFEHPNSYYH PVFGKAILAR YRANASREAL
     RTGSGVRFPE FVQYLLDVHR PVGMDIHWDH VSRLCSPCLI DYDFVGKFES MEDDANFFLS
     LIRAPRNLTF PRFKDRHSQE ARTTARIAHQ YFAQLSALQR QRTYDFYYMD YLMFNYSKPF
     ADLY
//