SPTC1_RAT
ID SPTC1_RAT Reviewed; 473 AA.
AC D4A2H2;
DT 13-FEB-2019, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 1.
DT 03-AUG-2022, entry version 83.
DE RecName: Full=Serine palmitoyltransferase 1 {ECO:0000305};
DE EC=2.3.1.50 {ECO:0000250|UniProtKB:O15269};
DE AltName: Full=Long chain base biosynthesis protein 1;
DE Short=LCB 1;
DE AltName: Full=Serine-palmitoyl-CoA transferase 1;
DE Short=SPT 1;
DE Short=SPT1;
GN Name=Sptlc1 {ECO:0000312|RGD:1307140}; Synonyms=Lcb1; ORFNames=rCG_44191;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP INDUCTION BY MIRNA, AND TISSUE SPECIFICITY.
RX PubMed=21994399; DOI=10.1523/jneurosci.3883-11.2011;
RA Geekiyanage H., Chan C.;
RT "MicroRNA-137/181c regulates serine palmitoyltransferase and in turn
RT amyloid beta, novel targets in sporadic Alzheimer's disease.";
RL J. Neurosci. 31:14820-14830(2011).
CC -!- FUNCTION: Serine palmitoyltransferase (SPT). The heterodimer formed
CC with SPTLC2 or SPTLC3 constitutes the catalytic core. The composition
CC of the serine palmitoyltransferase (SPT) complex determines the
CC substrate preference. The SPTLC1-SPTLC2-SPTSSA complex shows a strong
CC preference for C16-CoA substrate, while the SPTLC1-SPTLC3-SPTSSA
CC isozyme uses both C14-CoA and C16-CoA as substrates, with a slight
CC preference for C14-CoA. The SPTLC1-SPTLC2-SPTSSB complex shows a strong
CC preference for C18-CoA substrate, while the SPTLC1-SPTLC3-SPTSSB
CC isozyme displays an ability to use a broader range of acyl-CoAs,
CC without apparent preference (By similarity). Required for adipocyte
CC cell viability and metabolic homeostasis (By similarity).
CC {ECO:0000250|UniProtKB:O15269, ECO:0000250|UniProtKB:O35704}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + hexadecanoyl-CoA + L-serine = 3-oxosphinganine + CO2 +
CC CoA; Xref=Rhea:RHEA:14761, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:33384, ChEBI:CHEBI:57287, ChEBI:CHEBI:57379,
CC ChEBI:CHEBI:58299; EC=2.3.1.50;
CC Evidence={ECO:0000250|UniProtKB:O15269};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14762;
CC Evidence={ECO:0000250|UniProtKB:O15269};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + L-serine + octadecanoyl-CoA = 3-oxoeicosasphinganine +
CC CO2 + CoA; Xref=Rhea:RHEA:33683, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:33384, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57394, ChEBI:CHEBI:65073;
CC Evidence={ECO:0000250|UniProtKB:O15269};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33684;
CC Evidence={ECO:0000250|UniProtKB:O15269};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + L-serine + tetradecanoyl-CoA = 3-oxohexadecasphinganine
CC + CO2 + CoA; Xref=Rhea:RHEA:35675, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:33384, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57385, ChEBI:CHEBI:71007;
CC Evidence={ECO:0000250|UniProtKB:O15269};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35676;
CC Evidence={ECO:0000250|UniProtKB:O15269};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dodecanoyl-CoA + H(+) + L-serine = 3-oxotetradecasphinganine +
CC CO2 + CoA; Xref=Rhea:RHEA:35679, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:33384, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57375, ChEBI:CHEBI:71008;
CC Evidence={ECO:0000250|UniProtKB:O15269};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35680;
CC Evidence={ECO:0000250|UniProtKB:O15269};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000250};
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC {ECO:0000250|UniProtKB:O15269}.
CC -!- SUBUNIT: Heterodimer with SPTLC2 or SPTLC3. Component of the serine
CC palmitoyltransferase (SPT) complex, composed of SPTLC1, either SPTLC2
CC or SPTLC3, and either SPTSSA or SPTSSB. The composition of the complex
CC will define the substrate specificity. Interacts with SPTSSA and
CC SPTSSB; the interaction is direct. Interacts with ORMDL3 (By
CC similarity). Interacts with RTN4 (isoform B) (By similarity).
CC {ECO:0000250|UniProtKB:O15269, ECO:0000250|UniProtKB:O35704}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:O35704}; Single-pass membrane protein
CC {ECO:0000250|UniProtKB:O35704}.
CC -!- TISSUE SPECIFICITY: Expressed in astrocytes.
CC {ECO:0000269|PubMed:21994399}.
CC -!- INDUCTION: Expression in increased by palmitate at protein level but
CC not mRNA level (PubMed:21994399). Expression is down-regulated by
CC microRNA miR-137 and miR-181c (at protein level) (PubMed:21994399).
CC {ECO:0000269|PubMed:21994399}.
CC -!- PTM: Phosphorylation at Tyr-164 inhibits activity and promotes cell
CC survival. {ECO:0000250|UniProtKB:O15269}.
CC -!- SIMILARITY: Belongs to the class-II pyridoxal-phosphate-dependent
CC aminotransferase family. {ECO:0000305}.
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DR EMBL; AABR07027039; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH473977; EDL98057.1; -; Genomic_DNA.
DR RefSeq; NP_001101876.1; NM_001108406.1.
DR AlphaFoldDB; D4A2H2; -.
DR SMR; D4A2H2; -.
DR STRING; 10116.ENSRNOP00000014546; -.
DR PhosphoSitePlus; D4A2H2; -.
DR jPOST; D4A2H2; -.
DR PaxDb; D4A2H2; -.
DR PeptideAtlas; D4A2H2; -.
DR Ensembl; ENSRNOT00000014546; ENSRNOP00000014546; ENSRNOG00000010882.
DR GeneID; 361213; -.
DR KEGG; rno:361213; -.
DR CTD; 10558; -.
DR RGD; 1307140; Sptlc1.
DR eggNOG; KOG1358; Eukaryota.
DR GeneTree; ENSGT00550000074872; -.
DR HOGENOM; CLU_015846_0_1_1; -.
DR InParanoid; D4A2H2; -.
DR OMA; RNTPTFA; -.
DR OrthoDB; 438936at2759; -.
DR PhylomeDB; D4A2H2; -.
DR TreeFam; TF314877; -.
DR BRENDA; 2.3.1.50; 5301.
DR Reactome; R-RNO-1660661; Sphingolipid de novo biosynthesis.
DR UniPathway; UPA00222; -.
DR PRO; PR:D4A2H2; -.
DR Proteomes; UP000002494; Chromosome 17.
DR Proteomes; UP000234681; Chromosome 17.
DR Bgee; ENSRNOG00000010882; Expressed in ovary and 20 other tissues.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISO:RGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0017059; C:serine C-palmitoyltransferase complex; ISO:RGD.
DR GO; GO:0035339; C:SPOTS complex; ISO:RGD.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR GO; GO:0004758; F:serine C-palmitoyltransferase activity; ISO:RGD.
DR GO; GO:0046513; P:ceramide biosynthetic process; ISO:RGD.
DR GO; GO:1904504; P:positive regulation of lipophagy; ISO:RGD.
DR GO; GO:1904649; P:regulation of fat cell apoptotic process; ISO:RGD.
DR GO; GO:0046511; P:sphinganine biosynthetic process; ISO:RGD.
DR GO; GO:0030148; P:sphingolipid biosynthetic process; ISO:RGD.
DR GO; GO:0006665; P:sphingolipid metabolic process; ISO:RGD.
DR GO; GO:0006686; P:sphingomyelin biosynthetic process; ISO:RGD.
DR GO; GO:0046512; P:sphingosine biosynthetic process; ISO:RGD.
DR Gene3D; 3.40.640.10; -; 1.
DR Gene3D; 3.90.1150.10; -; 1.
DR InterPro; IPR004839; Aminotransferase_I/II.
DR InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR InterPro; IPR015422; PyrdxlP-dep_Trfase_small.
DR Pfam; PF00155; Aminotran_1_2; 1.
DR SUPFAM; SSF53383; SSF53383; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Coiled coil; Endoplasmic reticulum; Lipid metabolism;
KW Membrane; Phosphoprotein; Pyridoxal phosphate; Reference proteome;
KW Sphingolipid metabolism; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..473
FT /note="Serine palmitoyltransferase 1"
FT /id="PRO_0000446338"
FT TOPO_DOM 1..15
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 16..36
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 37..473
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOD_RES 164
FT /note="Phosphotyrosine; by ABL"
FT /evidence="ECO:0000250|UniProtKB:O15269"
SQ SEQUENCE 473 AA; 52549 MW; 6AE8F5E60D373B2E CRC64;
MATVAEQWVL VEMVQALYEA PAYHLILEGI LILWIIRLVF SKTYKLQERS DLTAKEKEEL
IEEWQPEPLV PPVSRNHPAL NYNIVSGPPT HNIVVNGKEC VNFASFNFLG LLANPRVKAA
AFASLKKYGV GTCGPRGFYG TFDVHLDLEE RLAKFMKTEE AIIYSYGFST IASAIPAYSK
RGDIVFVDSA ACFAIQKGLQ ASRSDIKLFK HNDVADLERL LKEQEIEDQK NPRKARVTRR
FIVAEGLYMN TGTICPLPEL VRLKYKYKAR IFLEESLSFG VLGEHGRGVT EHYGISIDDI
DLISANMENA LASVGGFCCG RSFVVDHQRL SGQGYCFSAS LPPLLAAAAI EALNIMEENP
GIFAVLKKKC QTIHKSLQGV SGLKVVGESL CPALHLQLEE STGSRERDMK LLQEIVEQCM
NKGIALTQAR YLDKEEKCLP PPSIRVVVTV EQTDEELQRA AATIREAAQA VLL
