CGT_HUMAN
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 03-AUG-2022, entry version 161.
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; Note=2-
CC 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; 113.
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 GlyGen; Q16880; 3 sites, 10 N-linked glycans (3 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; Q16880; -.
DR PeptideAtlas; Q16880; -.
DR PRIDE; Q16880; -.
DR ProteomicsDB; 61118; -.
DR Antibodypedia; 2809; 218 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 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; WKYEGSA; -.
DR OrthoDB; 508327at2759; -.
DR PhylomeDB; Q16880; -.
DR TreeFam; TF315472; -.
DR BioCyc; MetaCyc:HS10812-MON; -.
DR BRENDA; 2.4.1.47; 2681.
DR PathwayCommons; Q16880; -.
DR Reactome; R-HSA-1660662; Glycosphingolipid metabolism.
DR SignaLink; Q16880; -.
DR SIGNOR; Q16880; -.
DR UniPathway; UPA00787; -.
DR BioGRID-ORCS; 7368; 12 hits in 1075 CRISPR screens.
DR ChiTaRS; UGT8; human.
DR GeneWiki; UGT8; -.
DR GenomeRNAi; 7368; -.
DR Pharos; Q16880; Tbio.
DR PRO; PR:Q16880; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q16880; protein.
DR Bgee; ENSG00000174607; Expressed in inferior vagus X ganglion and 164 other tissues.
DR ExpressionAtlas; Q16880; baseline and differential.
DR Genevisible; Q16880; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:0006687; P:glycosphingolipid metabolic 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 CDD; cd03784; GT1_Gtf-like; 1.
DR InterPro; IPR002213; UDP_glucos_trans.
DR InterPro; IPR035595; UDP_glycos_trans_CS.
DR Pfam; PF00201; UDPGT; 1.
DR PROSITE; PS00375; UDPGT; 1.
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
