TLC3B_MOUSE
ID TLC3B_MOUSE Reviewed; 275 AA.
AC Q7TNV1; Q3V2R2; Q561N3; Q9CW26;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2006, sequence version 2.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=Ceramide synthase {ECO:0000305|PubMed:23275342};
DE EC=2.3.1.- {ECO:0000269|PubMed:23275342};
DE AltName: Full=Protein FAM57B;
DE AltName: Full=TLC domain-containing protein 3B;
GN Name=Tlcd3b; Synonyms=Fam57b;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Cerebellum;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC STRAIN=C57BL/6J; TISSUE=Retina;
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 [3]
RP FUNCTION, ALTERNATIVE PROMOTER USAGE, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, DEVELOPMENTAL STAGE, AND CATALYTIC ACTIVITY.
RX PubMed=23275342; DOI=10.1074/jbc.m112.440792;
RA Yamashita-Sugahara Y., Tokuzawa Y., Nakachi Y., Kanesaki-Yatsuka Y.,
RA Matsumoto M., Mizuno Y., Okazaki Y.;
RT "Fam57b (family with sequence similarity 57, member B), a novel peroxisome
RT proliferator-activated receptor gamma target gene that regulates
RT adipogenesis through ceramide synthesis.";
RL J. Biol. Chem. 288:4522-4537(2013).
RN [4]
RP DISRUPTION PHENOTYPE.
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. In vitro, isoform 3
CC stimulates the production of C16-, C18- and C20-ceramides, isoform 1
CC slightly increases the levels of C18- and C20-ceramides, while isoform
CC 2 exhibits only minimal activity. May interfere with adipogenesis by
CC stimulating ceramide synthesis. {ECO:0000269|PubMed:23275342}.
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:0000269|PubMed:23275342};
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:0000269|PubMed:23275342};
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:0000269|PubMed:23275342};
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Golgi apparatus membrane
CC {ECO:0000269|PubMed:23275342}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:23275342}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:23275342}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage; Named isoforms=3;
CC Name=1;
CC IsoId=Q7TNV1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7TNV1-2; Sequence=VSP_021637;
CC Name=3;
CC IsoId=Q7TNV1-3; Sequence=VSP_021636;
CC -!- TISSUE SPECIFICITY: Each isoform has a distinct expression pattern.
CC Isoform 1 is highly expressed in brain. Isoform 2 is expressed at low
CC levels, if any, in all analyzed tissues, with slightly higher levels in
CC testis. Isoform 3 is expressed at very high levels in testis and, at
CC lower levels, in white adipose tissue. In epididymal fat, isoform 3 is
CC expressed at higher levels in obese mice compared with lean mice. By
CC contrast, isoform 1 and 2 levels are significantly lower in obese mice
CC compared with lean mice. {ECO:0000269|PubMed:23275342}.
CC -!- DEVELOPMENTAL STAGE: Up-regulated during adipogenesis.
CC {ECO:0000269|PubMed:23275342}.
CC -!- INDUCTION: [Isoform 3]: Strongly up-regulated by PPARG.
CC -!- DISRUPTION PHENOTYPE: Knockout mice exhibit a significant reduction of
CC the cone photoreceptor light responses, thinning of the outer nuclear
CC layer, and loss of cone photoreceptors across the retina compared with
CC wild-type animals (PubMed:33077892). Knockout male mice are fertile
CC (PubMed:33077892). {ECO:0000269|PubMed:33077892}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB23923.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK005271; BAB23923.1; ALT_FRAME; mRNA.
DR EMBL; AK131642; BAE20735.1; -; mRNA.
DR EMBL; BC055444; AAH55444.1; -; mRNA.
DR EMBL; BC093505; AAH93505.2; -; mRNA.
DR CCDS; CCDS52400.1; -. [Q7TNV1-3]
DR CCDS; CCDS52401.1; -. [Q7TNV1-1]
DR CCDS; CCDS85415.1; -. [Q7TNV1-2]
DR RefSeq; NP_001139819.1; NM_001146347.1. [Q7TNV1-2]
DR RefSeq; NP_081160.1; NM_026884.1. [Q7TNV1-3]
DR RefSeq; NP_084254.1; NM_029978.1. [Q7TNV1-1]
DR RefSeq; XP_006508227.1; XM_006508164.2. [Q7TNV1-3]
DR RefSeq; XP_006508229.1; XM_006508166.1. [Q7TNV1-2]
DR AlphaFoldDB; Q7TNV1; -.
DR STRING; 10090.ENSMUSP00000078392; -.
DR SwissLipids; SLP:000001109; -. [Q7TNV1-1]
DR SwissLipids; SLP:000001110; -. [Q7TNV1-3]
DR iPTMnet; Q7TNV1; -.
DR PhosphoSitePlus; Q7TNV1; -.
DR MaxQB; Q7TNV1; -.
DR PaxDb; Q7TNV1; -.
DR PRIDE; Q7TNV1; -.
DR ProteomicsDB; 271845; -. [Q7TNV1-1]
DR ProteomicsDB; 271846; -. [Q7TNV1-2]
DR ProteomicsDB; 271847; -. [Q7TNV1-3]
DR Antibodypedia; 26964; 33 antibodies from 16 providers.
DR Ensembl; ENSMUST00000079423; ENSMUSP00000078392; ENSMUSG00000058966. [Q7TNV1-1]
DR Ensembl; ENSMUST00000098032; ENSMUSP00000095640; ENSMUSG00000058966. [Q7TNV1-3]
DR Ensembl; ENSMUST00000205324; ENSMUSP00000145837; ENSMUSG00000058966. [Q7TNV1-3]
DR Ensembl; ENSMUST00000207020; ENSMUSP00000145721; ENSMUSG00000058966. [Q7TNV1-2]
DR GeneID; 68952; -.
DR KEGG; mmu:68952; -.
DR UCSC; uc009jsy.2; mouse. [Q7TNV1-1]
DR UCSC; uc012ftv.1; mouse. [Q7TNV1-3]
DR CTD; 83723; -.
DR MGI; MGI:1916202; Tlcd3b.
DR VEuPathDB; HostDB:ENSMUSG00000058966; -.
DR eggNOG; KOG4561; Eukaryota.
DR GeneTree; ENSGT01010000222313; -.
DR HOGENOM; CLU_049796_0_0_1; -.
DR InParanoid; Q7TNV1; -.
DR OMA; CKHIIND; -.
DR OrthoDB; 1354968at2759; -.
DR PhylomeDB; Q7TNV1; -.
DR TreeFam; TF350344; -.
DR BioGRID-ORCS; 68952; 0 hits in 73 CRISPR screens.
DR ChiTaRS; Fam57b; mouse.
DR PRO; PR:Q7TNV1; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q7TNV1; protein.
DR Bgee; ENSMUSG00000058966; Expressed in retinal neural layer and 178 other tissues.
DR ExpressionAtlas; Q7TNV1; baseline and differential.
DR Genevisible; Q7TNV1; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
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; IDA:MGI.
DR GO; GO:0046513; P:ceramide biosynthetic process; IDA:MGI.
DR GO; GO:0055088; P:lipid homeostasis; IBA:GO_Central.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IMP:MGI.
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; Endoplasmic reticulum; Golgi apparatus;
KW Lipid biosynthesis; Lipid metabolism; Membrane; Reference proteome;
KW Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..275
FT /note="Ceramide synthase"
FT /id="PRO_0000185543"
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 232..252
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:15489334"
FT /id="VSP_021637"
FT VAR_SEQ 1..42
FT /note="MLTPMVAGGVVFPGLFLLSKNTLQRLPQLRWEEADAVIVSAR -> MALLFL
FT LGCVFFPLCFVVLRWGLQNRTSLRMERQEAVLVASK (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_021636"
SQ SEQUENCE 275 AA; 30778 MW; F6BABA980959A8AC CRC64;
MLTPMVAGGV VFPGLFLLSK NTLQRLPQLR WEEADAVIVS ARLVSSVQAI MASTAGYIVS
TSCKHIIDDQ HWLSSAYTQF AVPYFIYDIY AMFLCHWHKH QVKGHGGEDG TPRALGSTWA
VVRGYLHKEF LMVLHHAAMV LVCFPLSVVW RQGKGDFFLG CMLMAEVSTP FVCLGKILIQ
YKQQHTLLHK VNGALMLLSF LCCRVLLFPY LYWAYGRHAG LPLLSVPMAI PAHVNLGAAL
LLAPQLYWFF LICRGACRLF RPRGSPPPSP CQTQD
