ID   CGT_HUMAN               Reviewed;         541 AA.
AC   Q16880; B3KXU7; O00196;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   18-MAY-2010, sequence version 2.
DT   27-MAR-2024, entry version 170.
DE   RecName: Full=2-hydroxyacylsphingosine 1-beta-galactosyltransferase {ECO:0000305};
DE            EC=2.4.1.47 {ECO:0000250|UniProtKB:Q09426};
DE   AltName: Full=Ceramide UDP-galactosyltransferase;
DE   AltName: Full=Cerebroside synthase;
DE   AltName: Full=UDP-galactose-ceramide galactosyltransferase;
DE   Flags: Precursor;
GN   Name=UGT8 {ECO:0000312|HGNC:HGNC:12555}; Synonyms=CGT, UGT4;
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], AND VARIANT MET-368.
RX   PubMed=8661025; DOI=10.1006/geno.1996.0242;
RA   Bosio A., Binczek E., Lebeau M.M., Fernald A.A., Stoffel W.;
RT   "The human gene CGT encoding the UDP-galactose ceramide galactosyl
RT   transferase (cerebroside synthase): cloning, characterization, and
RT   assignment to human chromosome 4, band q26.";
RL   Genomics 34:69-75(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], VARIANT MET-368, CATALYTIC ACTIVITY, AND
RP   FUNCTION.
RX   PubMed=9125199; DOI=10.1006/bbrc.1997.6240;
RA   Kapitonov D.E., Yu R.K.;
RT   "Cloning, characterization, and expression of human ceramide
RT   galactosyltransferase cDNA.";
RL   Biochem. Biophys. Res. Commun. 232:449-453(1997).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT MET-368.
RC   TISSUE=Testis;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA   Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA   Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA   Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA   Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA   Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA   Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA   Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA   Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA   Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA   Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA   Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA   Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA   Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA   Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA   Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT   4.";
RL   Nature 434:724-731(2005).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT MET-368.
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   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT MET-368.
RC   TISSUE=Brain;
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).
CC   -!- FUNCTION: Catalyzes the transfer of galactose to ceramide, a key
CC       enzymatic step in the biosynthesis of galactocerebrosides, which are
CC       abundant sphingolipids of the myelin membrane of the central nervous
CC       system and peripheral nervous system (PubMed:9125199). Galactosylates
CC       both hydroxy- and non-hydroxy fatty acid-containing ceramides and
CC       diglycerides (By similarity). {ECO:0000250|UniProtKB:Q09426,
CC       ECO:0000269|PubMed:9125199}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=an N-acylsphing-4-enine + UDP-alpha-D-galactose = a beta-D-
CC         galactosyl-(1<->1')-N-acylsphing-4-enine + H(+) + UDP;
CC         Xref=Rhea:RHEA:13093, ChEBI:CHEBI:15378, ChEBI:CHEBI:18390,
CC         ChEBI:CHEBI:52639, ChEBI:CHEBI:58223, ChEBI:CHEBI:66914; EC=2.4.1.47;
CC         Evidence={ECO:0000250|UniProtKB:Q09426};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13094;
CC         Evidence={ECO:0000250|UniProtKB:Q09426};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=an N-acyl-sphingoid base + UDP-alpha-D-galactose = a D-
CC         galactosylceramide + H(+) + UDP; Xref=Rhea:RHEA:48344,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:36498, ChEBI:CHEBI:58223,
CC         ChEBI:CHEBI:66914, ChEBI:CHEBI:83273;
CC         Evidence={ECO:0000269|PubMed:9125199};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=N-(2-hydroxy-hexanoyl)-sphing-4-enine + UDP-alpha-D-galactose
CC         = H(+) + N-(2-hydroxy-hexanoyl)-beta-D-galactosyl-sphing-4-enine +
CC         UDP; Xref=Rhea:RHEA:43400, ChEBI:CHEBI:15378, ChEBI:CHEBI:58223,
CC         ChEBI:CHEBI:66914, ChEBI:CHEBI:83244, ChEBI:CHEBI:83246;
CC         Evidence={ECO:0000250|UniProtKB:Q09426};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43401;
CC         Evidence={ECO:0000250|UniProtKB:Q09426};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=N-(2-hydroxy-hexanoyl)-sphinganine + UDP-alpha-D-galactose =
CC         H(+) + N-(2-hydroxyhexanoyl)-beta-D-galactosylsphinganine + UDP;
CC         Xref=Rhea:RHEA:43404, ChEBI:CHEBI:15378, ChEBI:CHEBI:58223,
CC         ChEBI:CHEBI:66914, ChEBI:CHEBI:83248, ChEBI:CHEBI:83257;
CC         Evidence={ECO:0000250|UniProtKB:Q09426};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43405;
CC         Evidence={ECO:0000250|UniProtKB:Q09426};
CC   -!- PATHWAY: Sphingolipid metabolism; galactosylceramide biosynthesis.
CC       {ECO:0000269|PubMed:9125199}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass membrane
CC       protein {ECO:0000305}. Endoplasmic reticulum
CC       {ECO:0000250|UniProtKB:Q09426}.
CC   -!- SIMILARITY: Belongs to the UDP-glycosyltransferase family.
CC       {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Functional Glycomics Gateway - GTase;
CC       Note=2-hydroxyacylsphingosine 1-beta-galactosyltransferase precursor;
CC       URL="http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_hum_449";
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DR   EMBL; U30930; AAC50565.1; -; mRNA.
DR   EMBL; U32370; AAC50815.1; -; Genomic_DNA.
DR   EMBL; U31353; AAC50815.1; JOINED; Genomic_DNA.
DR   EMBL; U31461; AAC50815.1; JOINED; Genomic_DNA.
DR   EMBL; U31658; AAC50815.1; JOINED; Genomic_DNA.
DR   EMBL; U31861; AAC50815.1; JOINED; Genomic_DNA.
DR   EMBL; U62899; AAC51187.1; -; mRNA.
DR   EMBL; AK127970; BAG54609.1; -; mRNA.
DR   EMBL; AC122938; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471057; EAX06307.1; -; Genomic_DNA.
DR   EMBL; BC075069; AAH75069.1; -; mRNA.
DR   CCDS; CCDS3705.1; -.
DR   PIR; JC5423; JC5423.
DR   RefSeq; NP_001121646.1; NM_001128174.2.
DR   RefSeq; NP_001309041.1; NM_001322112.1.
DR   RefSeq; NP_001309042.1; NM_001322113.1.
DR   RefSeq; NP_001309043.1; NM_001322114.1.
DR   RefSeq; NP_003351.2; NM_003360.4.
DR   AlphaFoldDB; Q16880; -.
DR   SMR; Q16880; -.
DR   BioGRID; 113215; 120.
DR   IntAct; Q16880; 26.
DR   MINT; Q16880; -.
DR   STRING; 9606.ENSP00000311648; -.
DR   BindingDB; Q16880; -.
DR   ChEMBL; CHEMBL4739855; -.
DR   SwissLipids; SLP:000001432; -.
DR   CAZy; GT1; Glycosyltransferase Family 1.
DR   GlyConnect; 980; 10 N-Linked glycans (3 sites).
DR   GlyCosmos; Q16880; 3 sites, 10 glycans.
DR   GlyGen; Q16880; 5 sites, 10 N-linked glycans (3 sites), 1 O-linked glycan (2 sites).
DR   iPTMnet; Q16880; -.
DR   PhosphoSitePlus; Q16880; -.
DR   BioMuta; UGT8; -.
DR   DMDM; 296434442; -.
DR   EPD; Q16880; -.
DR   jPOST; Q16880; -.
DR   MassIVE; Q16880; -.
DR   MaxQB; Q16880; -.
DR   PaxDb; 9606-ENSP00000311648; -.
DR   PeptideAtlas; Q16880; -.
DR   ProteomicsDB; 61118; -.
DR   Pumba; Q16880; -.
DR   Antibodypedia; 2809; 237 antibodies from 31 providers.
DR   DNASU; 7368; -.
DR   Ensembl; ENST00000310836.11; ENSP00000311648.6; ENSG00000174607.11.
DR   Ensembl; ENST00000394511.3; ENSP00000378019.3; ENSG00000174607.11.
DR   GeneID; 7368; -.
DR   KEGG; hsa:7368; -.
DR   MANE-Select; ENST00000310836.11; ENSP00000311648.6; NM_001128174.3; NP_001121646.2.
DR   UCSC; uc003ibs.3; human.
DR   AGR; HGNC:12555; -.
DR   CTD; 7368; -.
DR   DisGeNET; 7368; -.
DR   GeneCards; UGT8; -.
DR   HGNC; HGNC:12555; UGT8.
DR   HPA; ENSG00000174607; Tissue enriched (brain).
DR   MIM; 601291; gene.
DR   neXtProt; NX_Q16880; -.
DR   OpenTargets; ENSG00000174607; -.
DR   PharmGKB; PA37195; -.
DR   VEuPathDB; HostDB:ENSG00000174607; -.
DR   eggNOG; KOG1192; Eukaryota.
DR   GeneTree; ENSGT00940000156545; -.
DR   HOGENOM; CLU_012949_3_1_1; -.
DR   InParanoid; Q16880; -.
DR   OMA; TKNCDMI; -.
DR   OrthoDB; 382054at2759; -.
DR   PhylomeDB; Q16880; -.
DR   TreeFam; TF315472; -.
DR   BioCyc; MetaCyc:HS10812-MONOMER; -.
DR   BRENDA; 2.4.1.47; 2681.
DR   PathwayCommons; Q16880; -.
DR   Reactome; R-HSA-9840309; Glycosphingolipid biosynthesis.
DR   SignaLink; Q16880; -.
DR   SIGNOR; Q16880; -.
DR   UniPathway; UPA00787; -.
DR   BioGRID-ORCS; 7368; 12 hits in 1157 CRISPR screens.
DR   ChiTaRS; UGT8; human.
DR   GeneWiki; UGT8; -.
DR   GenomeRNAi; 7368; -.
DR   Pharos; Q16880; Tchem.
DR   PRO; PR:Q16880; -.
DR   Proteomes; UP000005640; Chromosome 4.
DR   RNAct; Q16880; Protein.
DR   Bgee; ENSG00000174607; Expressed in inferior vagus X ganglion and 165 other cell types or tissues.
DR   ExpressionAtlas; Q16880; baseline and differential.
DR   GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0003851; F:2-hydroxyacylsphingosine 1-beta-galactosyltransferase activity; ISS:UniProtKB.
DR   GO; GO:0047263; F:N-acylsphingosine galactosyltransferase activity; TAS:Reactome.
DR   GO; GO:0008489; F:UDP-galactose:glucosylceramide beta-1,4-galactosyltransferase activity; TAS:ProtInc.
DR   GO; GO:0007417; P:central nervous system development; TAS:ProtInc.
DR   GO; GO:0007010; P:cytoskeleton organization; IEA:Ensembl.
DR   GO; GO:0006682; P:galactosylceramide biosynthetic process; ISS:UniProtKB.
DR   GO; GO:0006688; P:glycosphingolipid biosynthetic process; TAS:Reactome.
DR   GO; GO:0048812; P:neuron projection morphogenesis; IEA:Ensembl.
DR   GO; GO:0030913; P:paranodal junction assembly; IEA:Ensembl.
DR   GO; GO:0007422; P:peripheral nervous system development; TAS:ProtInc.
DR   GO; GO:0002175; P:protein localization to paranode region of axon; IEA:Ensembl.
DR   GO; GO:0035902; P:response to immobilization stress; IEA:Ensembl.
DR   CDD; cd03784; GT1_Gtf-like; 1.
DR   Gene3D; 3.40.50.2000; Glycogen Phosphorylase B; 2.
DR   InterPro; IPR002213; UDP_glucos_trans.
DR   InterPro; IPR035595; UDP_glycos_trans_CS.
DR   PANTHER; PTHR48043:SF161; 2-HYDROXYACYLSPHINGOSINE 1-BETA-GALACTOSYLTRANSFERASE; 1.
DR   PANTHER; PTHR48043; EG:EG0003.4 PROTEIN-RELATED; 1.
DR   Pfam; PF00201; UDPGT; 1.
DR   SUPFAM; SSF53756; UDP-Glycosyltransferase/glycogen phosphorylase; 1.
DR   PROSITE; PS00375; UDPGT; 1.
DR   Genevisible; Q16880; HS.
PE   1: Evidence at protein level;
KW   Endoplasmic reticulum; Glycoprotein; Glycosyltransferase; Lipid metabolism;
KW   Membrane; Reference proteome; Signal; Sphingolipid metabolism; Transferase;
KW   Transmembrane; Transmembrane helix.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   CHAIN           21..541
FT                   /note="2-hydroxyacylsphingosine 1-beta-
FT                   galactosyltransferase"
FT                   /id="PRO_0000036064"
FT   TRANSMEM        472..492
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        78
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        333
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        442
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VARIANT         226
FT                   /note="P -> L (in dbSNP:rs4148254)"
FT                   /id="VAR_052466"
FT   VARIANT         368
FT                   /note="I -> M (in dbSNP:rs11098261)"
FT                   /evidence="ECO:0000269|PubMed:14702039,
FT                   ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:8661025,
FT                   ECO:0000269|PubMed:9125199, ECO:0000269|Ref.5"
FT                   /id="VAR_052467"
FT   CONFLICT        99
FT                   /note="T -> P (in Ref. 2; AAC51187)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        116
FT                   /note="L -> M (in Ref. 2; AAC51187)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        356
FT                   /note="L -> V (in Ref. 2; AAC51187)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        379
FT                   /note="L -> V (in Ref. 2; AAC51187)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   541 AA;  61438 MW;  02FA965FEC8EB788 CRC64;
     MKSYTPYFIL LWSAVGIAKA AKIIIVPPIM FESHMYIFKT LASALHERGH HTVFLLSEGR
     DIAPSNHYSL QRYPGIFNST TSDAFLQSKM RNIFSGRLTA IELFDILDHY TKNCDLMVGN
     HALIQGLKKE KFDLLLVDPN DMCGFVIAHL LGVKYAVFST GLWYPAEVGA PAPLAYVPEF
     NSLLTDRMNL LQRMKNTGVY LISRLGVSFL VLPKYERIMQ KYNLLPEKSM YDLVHGSSLW
     MLCTDVALEF PRPTLPNVVY VGGILTKPAS PLPEDLQRWV NGANEHGFVL VSFGAGVKYL
     SEDIANKLAG ALGRLPQKVI WRFSGPKPKN LGNNTKLIEW LPQNDLLGHS KIKAFLSHGG
     LNSIFETIYH GVPVVGIPLF GDHYDTMTRV QAKGMGILLE WKTVTEKELY EALVKVINNP
     SYRQRAQKLS EIHKDQPGHP VNRTIYWIDY IIRHNGAHHL RAAVHQISFC QYFLLDIAFV
     LLLGAALLYF LLSWVTKFIY RKIKSLWSRN KHSTVNGHYH NGILNGKYKR NGHIKHEKKV
     K
//