CHST8_HUMAN
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 03-AUG-2022, entry version 141.
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, INVOLVEMENT IN PSS3, VARIANT PSS3 TRP-77, AND
RP CHARACTERIZATION OF VARIANT PSS3 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 -!- DISEASE: Peeling skin syndrome 3 (PSS3) [MIM:616265]: A form of peeling
CC skin syndrome, a genodermatosis characterized by generalized,
CC continuous shedding of the outer layers of the epidermis. Two main PSS
CC subtypes have been suggested. Patients with non-inflammatory PSS (type
CC A) manifest white scaling, with painless and easy removal of the skin,
CC irritation when in contact with water, dust and sand, and no history of
CC erythema, pruritis or atopy. Inflammatory PSS (type B) is associated
CC with generalized erythema, pruritus and atopy. It is an ichthyosiform
CC erythroderma characterized by lifelong patchy peeling of the entire
CC skin with onset at birth or shortly after. Several patients have been
CC reported with high IgE levels. PSS3 is characterized by generalized
CC white scaling occurring over the upper and lower extremities. Symptoms
CC start during the second half of the first decade of life.
CC {ECO:0000269|PubMed:22289416}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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; 28.
DR STRING; 9606.ENSP00000262622; -.
DR GlyGen; Q9H2A9; 4 sites.
DR iPTMnet; Q9H2A9; -.
DR PhosphoSitePlus; Q9H2A9; -.
DR BioMuta; CHST8; -.
DR DMDM; 61212124; -.
DR MassIVE; Q9H2A9; -.
DR PaxDb; Q9H2A9; -.
DR PeptideAtlas; Q9H2A9; -.
DR PRIDE; Q9H2A9; -.
DR ProteomicsDB; 80521; -.
DR TopDownProteomics; Q9H2A9; -.
DR Antibodypedia; 2401; 144 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 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 MIM; 616265; phenotype.
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; KYEDRNN; -.
DR OrthoDB; 1330889at2759; -.
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; 28 hits in 1057 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 pituitary gland and 135 other tissues.
DR ExpressionAtlas; Q9H2A9; baseline and differential.
DR Genevisible; Q9H2A9; HS.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of 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; PTHR12137; 1.
DR Pfam; PF03567; Sulfotransfer_2; 1.
PE 1: Evidence at protein level;
KW Carbohydrate metabolism; Disease variant; Glycoprotein; Golgi apparatus;
KW Membrane; Reference proteome; Signal-anchor; Transferase; Transmembrane;
KW 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 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 (in PSS3; results in decreased enzyme
FT activity; the mutant protein shows reduced glycosylation;
FT 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
