TLC3B_HUMAN
ID TLC3B_HUMAN Reviewed; 274 AA.
AC Q71RH2; Q9H0J1;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Ceramide synthase {ECO:0000250|UniProtKB:Q7TNV1};
DE EC=2.3.1.- {ECO:0000250|UniProtKB:Q7TNV1};
DE AltName: Full=Protein FAM57B;
DE AltName: Full=TLC domain-containing protein 3B {ECO:0000305};
GN Name=TLCD3B {ECO:0000312|HGNC:HGNC:25295}; Synonyms=FAM57B;
GN ORFNames=FP1188;
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 [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15498874; DOI=10.1073/pnas.0404089101;
RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X.,
RA Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X.,
RA Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.;
RT "Large-scale cDNA transfection screening for genes related to cancer
RT development and progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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).
RN [4]
RP INVOLVEMENT IN CORD22, VARIANT CORD22 SER-56, AND TISSUE SPECIFICITY.
RX PubMed=33077892; DOI=10.1038/s41436-020-01003-x;
RA Bertrand R.E., Wang J., Xiong K.H., Thangavel C., Qian X., Ba-Abbad R.,
RA Liang Q., Simoes R.T., Sampaio S.A.M., Carss K.J., Lucy Raymond F.,
RA Robson A.G., Webster A.R., Arno G., Porto F.B.O., Chen R.;
RT "Ceramide synthase TLCD3B is a novel gene associated with human recessive
RT retinal dystrophy.";
RL Genet. Med. 23:488-497(2021).
CC -!- FUNCTION: Involved in ceramide synthesis. {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=octadecanoyl-CoA + sphing-4-enine = CoA + H(+) + N-
CC octadecanoylsphing-4-enine; Xref=Rhea:RHEA:36691, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57394, ChEBI:CHEBI:57756,
CC ChEBI:CHEBI:72961; Evidence={ECO:0000250|UniProtKB:Q7TNV1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=eicosanoyl-CoA + sphing-4-enine = CoA + H(+) + N-eicosanoyl-
CC sphing-4-enine; Xref=Rhea:RHEA:45284, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57380, ChEBI:CHEBI:57756,
CC ChEBI:CHEBI:72962; Evidence={ECO:0000250|UniProtKB:Q7TNV1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexadecanoyl-CoA + sphing-4-enine = CoA + H(+) + N-
CC hexadecanoylsphing-4-enine; Xref=Rhea:RHEA:36687, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57379, ChEBI:CHEBI:57756,
CC ChEBI:CHEBI:72959; Evidence={ECO:0000250|UniProtKB:Q7TNV1};
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:Q7TNV1}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q7TNV1}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage; Named isoforms=2;
CC Name=1;
CC IsoId=Q71RH2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q71RH2-2; Sequence=VSP_013343;
CC -!- TISSUE SPECIFICITY: Expressed in testis (PubMed:33077892). Expressed in
CC the retina with higher expression levels in the macular than in the
CC peripheral region (PubMed:33077892). {ECO:0000269|PubMed:33077892}.
CC -!- DISEASE: Cone-rod dystrophy 22 (CORD22) [MIM:619531]: An autosomal
CC recessive form of cone-rod dystrophy, an inherited retinal dystrophy
CC characterized by retinal pigment deposits visible on fundus
CC examination, predominantly in the macular region, and initial loss of
CC cone photoreceptors followed by rod degeneration. This leads to
CC decreased visual acuity and sensitivity in the central visual field,
CC followed by loss of peripheral vision. Severe loss of vision occurs
CC earlier than in retinitis pigmentosa, due to cone photoreceptors
CC degenerating at a higher rate than rod photoreceptors.
CC {ECO:0000269|PubMed:33077892}. Note=The disease may be caused by
CC variants affecting distinct genetic loci, including the gene
CC represented in this entry.
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DR EMBL; AL136777; CAB66711.1; -; mRNA.
DR EMBL; AF370365; AAQ15201.1; -; mRNA.
DR EMBL; BC007892; AAH07892.2; -; mRNA.
DR CCDS; CCDS10667.2; -. [Q71RH2-1]
DR CCDS; CCDS81967.1; -. [Q71RH2-2]
DR RefSeq; NP_001305433.1; NM_001318504.1. [Q71RH2-2]
DR RefSeq; NP_113666.2; NM_031478.5. [Q71RH2-1]
DR RefSeq; XP_016879242.1; XM_017023753.1.
DR RefSeq; XP_016879243.1; XM_017023754.1. [Q71RH2-2]
DR AlphaFoldDB; Q71RH2; -.
DR BioGRID; 123741; 4.
DR STRING; 9606.ENSP00000369863; -.
DR iPTMnet; Q71RH2; -.
DR PhosphoSitePlus; Q71RH2; -.
DR BioMuta; FAM57B; -.
DR DMDM; 62510682; -.
DR EPD; Q71RH2; -.
DR MassIVE; Q71RH2; -.
DR PaxDb; Q71RH2; -.
DR PeptideAtlas; Q71RH2; -.
DR PRIDE; Q71RH2; -.
DR ProteomicsDB; 68621; -. [Q71RH2-1]
DR ProteomicsDB; 68622; -. [Q71RH2-2]
DR Antibodypedia; 26964; 33 antibodies from 16 providers.
DR DNASU; 83723; -.
DR Ensembl; ENST00000279389.8; ENSP00000279389.4; ENSG00000149926.14. [Q71RH2-2]
DR Ensembl; ENST00000380495.9; ENSP00000369863.4; ENSG00000149926.14. [Q71RH2-1]
DR GeneID; 83723; -.
DR KEGG; hsa:83723; -.
DR MANE-Select; ENST00000380495.9; ENSP00000369863.4; NM_031478.6; NP_113666.2.
DR UCSC; uc002dvt.4; human. [Q71RH2-1]
DR CTD; 83723; -.
DR DisGeNET; 83723; -.
DR GeneCards; TLCD3B; -.
DR HGNC; HGNC:25295; TLCD3B.
DR HPA; ENSG00000149926; Tissue enhanced (brain, retina, testis).
DR MIM; 615175; gene.
DR MIM; 619531; phenotype.
DR neXtProt; NX_Q71RH2; -.
DR OpenTargets; ENSG00000149926; -.
DR Orphanet; 1872; Cone rod dystrophy.
DR VEuPathDB; HostDB:ENSG00000149926; -.
DR eggNOG; KOG4561; Eukaryota.
DR GeneTree; ENSGT01010000222313; -.
DR HOGENOM; CLU_049796_0_0_1; -.
DR InParanoid; Q71RH2; -.
DR OMA; CKHIIND; -.
DR OrthoDB; 1354968at2759; -.
DR PhylomeDB; Q71RH2; -.
DR TreeFam; TF350344; -.
DR PathwayCommons; Q71RH2; -.
DR BioGRID-ORCS; 83723; 33 hits in 1087 CRISPR screens.
DR GeneWiki; FAM57B; -.
DR GenomeRNAi; 83723; -.
DR Pharos; Q71RH2; Tdark.
DR PRO; PR:Q71RH2; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q71RH2; protein.
DR Bgee; ENSG00000149926; Expressed in left testis and 150 other tissues.
DR ExpressionAtlas; Q71RH2; baseline and differential.
DR Genevisible; Q71RH2; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:LIFEdb.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0050291; F:sphingosine N-acyltransferase activity; IBA:GO_Central.
DR GO; GO:0046513; P:ceramide biosynthetic process; IBA:GO_Central.
DR GO; GO:0055088; P:lipid homeostasis; IBA:GO_Central.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IEA:Ensembl.
DR InterPro; IPR006634; TLC-dom.
DR Pfam; PF03798; TRAM_LAG1_CLN8; 1.
DR SMART; SM00724; TLC; 1.
DR PROSITE; PS50922; TLC; 1.
PE 1: Evidence at protein level;
KW Alternative promoter usage; Cone-rod dystrophy; Disease variant;
KW Endoplasmic reticulum; Golgi apparatus; Lipid biosynthesis;
KW Lipid metabolism; Membrane; Reference proteome; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..274
FT /note="Ceramide synthase"
FT /id="PRO_0000185542"
FT TRANSMEM 130..150
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 159..179
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 194..214
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 223..243
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 34..261
FT /note="TLC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00205"
FT VAR_SEQ 1..50
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11230166"
FT /id="VSP_013343"
FT VARIANT 56
FT /note="G -> S (in CORD22; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:33077892"
FT /id="VAR_086272"
SQ SEQUENCE 274 AA; 30629 MW; FB1CF6E96102EC54 CRC64;
MLTPMVAGGV VFPGLFLLSK NTLQRLPQLR WEEADAVIVS ARLVSSVQAI MASTAGYIVS
TSCKHIIDDQ HWLSSAYTQF AVPYFIYDIY AMFLCHWHKH QVKGHGGDDG AARAPGSTWA
IARGYLHKEF LMVLHHAAMV LVCFPLSVVW RQGKGDFFLG CMLMAEVSTP FVCLGKILIQ
YKQQHTLLHK VNGALMLLSF LCCRVLLFPY LYWAYGRHAG LPLLAVPLAI PAHVNLGAAL
LLAPQLYWFF LICRGACRLF WPRSRPPPAC QAQD
