SPTC2_MOUSE
ID SPTC2_MOUSE Reviewed; 560 AA.
AC P97363; P97356;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Serine palmitoyltransferase 2 {ECO:0000305};
DE EC=2.3.1.50 {ECO:0000250|UniProtKB:O15270};
DE AltName: Full=Long chain base biosynthesis protein 2;
DE Short=LCB 2;
DE AltName: Full=Long chain base biosynthesis protein 2a;
DE Short=LCB2a;
DE AltName: Full=Serine-palmitoyl-CoA transferase 2;
DE Short=SPT 2;
GN Name=Sptlc2 {ECO:0000312|MGI:MGI:108074}; Synonyms=Lcb2;
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 [MRNA].
RC TISSUE=Kidney, and Testis;
RX PubMed=8921873; DOI=10.1016/0378-1119(96)00309-5;
RA Nagiec M.M., Lester R.L., Dickson R.C.;
RT "Sphingolipid synthesis: identification and characterization of mammalian
RT cDNAs encoding the Lcb2 subunit of serine palmitoyltransferase.";
RL Gene 177:237-241(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Nagiec M.M., Lester R.L., Dickson R.C.;
RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ; TISSUE=Kidney, and Liver;
RX PubMed=9363775; DOI=10.1111/j.1432-1033.1997.00239.x;
RA Weiss B., Stoffel W.;
RT "Human and murine serine-palmitoyl-CoA transferase. Cloning, expression and
RT characterization of the key enzyme in sphingolipid synthesis.";
RL Eur. J. Biochem. 249:239-247(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Mammary gland;
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 [5]
RP SUBCELLULAR LOCATION.
RC TISSUE=Liver;
RX PubMed=1317856; DOI=10.1016/s0021-9258(19)49887-6;
RA Mandon E.C., Ehses I., Rother J., van Echten G., Sandhoff K.;
RT "Subcellular localization and membrane topology of serine
RT palmitoyltransferase, 3-dehydrosphinganine reductase, and sphinganine N-
RT acyltransferase in mouse liver.";
RL J. Biol. Chem. 267:11144-11148(1992).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP INDUCTION BY HIGH FAT DIET, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
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).
RN [8]
RP DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND PATHWAY.
RX PubMed=27818258; DOI=10.1016/j.cmet.2016.10.002;
RA Chaurasia B., Kaddai V.A., Lancaster G.I., Henstridge D.C., Sriram S.,
RA Galam D.L., Gopalan V., Prakash K.N., Velan S.S., Bulchand S., Tsong T.J.,
RA Wang M., Siddique M.M., Yuguang G., Sigmundsson K., Mellet N.A., Weir J.M.,
RA Meikle P.J., Bin M Yassin M.S., Shabbir A., Shayman J.A., Hirabayashi Y.,
RA Shiow S.T., Sugii S., Summers S.A.;
RT "Adipocyte Ceramides Regulate Subcutaneous Adipose Browning, Inflammation,
RT and Metabolism.";
RL Cell Metab. 24:820-834(2016).
RN [9]
RP FUNCTION, DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE, INDUCTION BY HIGH FAT
RP DIET, TISSUE SPECIFICITY, AND PATHWAY.
RX PubMed=28698261; DOI=10.2337/db16-1232;
RA Lee S.Y., Lee H.Y., Song J.H., Kim G.T., Jeon S., Song Y.J., Lee J.S.,
RA Hur J.H., Oh H.H., Park S.Y., Shim S.M., Yoo H.J., Lee B.C., Jiang X.C.,
RA Choi C.S., Park T.S.;
RT "Adipocyte-Specific Deficiency of De Novo Sphingolipid Biosynthesis Leads
RT to Lipodystrophy and Insulin Resistance.";
RL Diabetes 66:2596-2609(2017).
CC -!- FUNCTION: Serine palmitoyltransferase (SPT). The heterodimer formed
CC with LCB1/SPTLC1 constitutes the catalytic core. The composition of the
CC serine palmitoyltransferase (SPT) complex determines the substrate
CC preference. The SPTLC1-SPTLC2-SPTSSA complex shows a strong preference
CC for C16-CoA substrate, while the SPTLC1-SPTLC2-SPTSSB complex displays
CC a preference for C18-CoA substrate (By similarity). Plays an important
CC role in de novo sphyngolipid biosynthesis which is crucial for
CC adipogenesis (PubMed:28698261). {ECO:0000250|UniProtKB:O15270,
CC ECO:0000269|PubMed:28698261}.
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:O15270};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14762;
CC Evidence={ECO:0000250|UniProtKB:O15270};
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:O15270};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000250};
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC {ECO:0000269|PubMed:27818258, ECO:0000269|PubMed:28698261}.
CC -!- SUBUNIT: Heterodimer with SPTLC1. Component of the serine
CC palmitoyltransferase (SPT) complex, composed of LCB1/SPTLC1, LCB2
CC (SPTLC2 or SPTLC3) and ssPT (SPTSSA or SPTSSB) (By similarity).
CC {ECO:0000250|UniProtKB:O15270}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:1317856}; Single-pass membrane protein
CC {ECO:0000269|PubMed:1317856}.
CC -!- TISSUE SPECIFICITY: Expressed in a variety of tissues. Expressed in
CC brains cortices (at protein level) (PubMed:21994399). Expressed in
CC brown and white adipose tissues (PubMed:28698261, PubMed:27818258).
CC Expressed in liver (PubMed:27818258). {ECO:0000269|PubMed:21994399,
CC ECO:0000269|PubMed:27818258, ECO:0000269|PubMed:28698261}.
CC -!- DEVELOPMENTAL STAGE: In brains, expressed at low levels after birth,
CC expression highly increases at 2 weeks after birth to decrease and be
CC maintained at 4 weeks after birth until, at least, 18 months
CC (PubMed:21994399). Expression increases in differentiated adipocytes
CC (PubMed:28698261). {ECO:0000269|PubMed:21994399,
CC ECO:0000269|PubMed:28698261}.
CC -!- INDUCTION: Expression levels increase upon high-fat diet (at protein
CC level). {ECO:0000269|PubMed:21994399, ECO:0000269|PubMed:28698261}.
CC -!- DISRUPTION PHENOTYPE: Adipocyte-specific knockout mice have reduced
CC adipose tissue mass and develop hepatosteatosis with insulin resistance
CC and hyperglycemia. {ECO:0000269|PubMed:27818258,
CC ECO:0000269|PubMed:28698261}.
CC -!- SIMILARITY: Belongs to the class-II pyridoxal-phosphate-dependent
CC aminotransferase family. {ECO:0000305}.
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DR EMBL; U27455; AAC53310.1; -; mRNA.
DR EMBL; X95642; CAA64898.1; -; mRNA.
DR EMBL; BC003227; AAH03227.1; -; mRNA.
DR CCDS; CCDS26076.1; -.
DR PIR; JC5180; JC5180.
DR RefSeq; NP_035609.1; NM_011479.4.
DR AlphaFoldDB; P97363; -.
DR SMR; P97363; -.
DR BioGRID; 203487; 15.
DR IntAct; P97363; 12.
DR STRING; 10090.ENSMUSP00000021424; -.
DR iPTMnet; P97363; -.
DR PhosphoSitePlus; P97363; -.
DR EPD; P97363; -.
DR jPOST; P97363; -.
DR PaxDb; P97363; -.
DR PeptideAtlas; P97363; -.
DR PRIDE; P97363; -.
DR ProteomicsDB; 257059; -.
DR Antibodypedia; 26092; 278 antibodies from 29 providers.
DR DNASU; 20773; -.
DR Ensembl; ENSMUST00000021424; ENSMUSP00000021424; ENSMUSG00000021036.
DR GeneID; 20773; -.
DR KEGG; mmu:20773; -.
DR UCSC; uc007oiw.1; mouse.
DR CTD; 9517; -.
DR MGI; MGI:108074; Sptlc2.
DR VEuPathDB; HostDB:ENSMUSG00000021036; -.
DR eggNOG; KOG1357; Eukaryota.
DR GeneTree; ENSGT00940000155786; -.
DR HOGENOM; CLU_015846_7_1_1; -.
DR InParanoid; P97363; -.
DR OMA; IEDEPPY; -.
DR OrthoDB; 438936at2759; -.
DR PhylomeDB; P97363; -.
DR TreeFam; TF300452; -.
DR BRENDA; 2.3.1.50; 3474.
DR Reactome; R-MMU-1660661; Sphingolipid de novo biosynthesis.
DR UniPathway; UPA00222; -.
DR BioGRID-ORCS; 20773; 25 hits in 76 CRISPR screens.
DR ChiTaRS; Sptlc2; mouse.
DR PRO; PR:P97363; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; P97363; protein.
DR Bgee; ENSMUSG00000021036; Expressed in decidua and 272 other tissues.
DR ExpressionAtlas; P97363; baseline and differential.
DR Genevisible; P97363; MM.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0017059; C:serine C-palmitoyltransferase complex; ISA:MGI.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR GO; GO:0004758; F:serine C-palmitoyltransferase activity; IDA:MGI.
DR GO; GO:0060612; P:adipose tissue development; IMP:UniProtKB.
DR GO; GO:0046513; P:ceramide biosynthetic process; IMP:MGI.
DR GO; GO:0061724; P:lipophagy; ISO:MGI.
DR GO; GO:1904504; P:positive regulation of lipophagy; ISO:MGI.
DR GO; GO:0046511; P:sphinganine biosynthetic process; IDA:MGI.
DR GO; GO:0030148; P:sphingolipid biosynthetic process; IMP:UniProtKB.
DR GO; GO:0006686; P:sphingomyelin biosynthetic process; IMP:MGI.
DR GO; GO:0046512; P:sphingosine biosynthetic process; IMP:MGI.
DR Gene3D; 3.40.640.10; -; 1.
DR Gene3D; 3.90.1150.10; -; 1.
DR InterPro; IPR001917; Aminotrans_II_pyridoxalP_BS.
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.
DR PROSITE; PS00599; AA_TRANSFER_CLASS_2; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Endoplasmic reticulum; Lipid metabolism; Membrane;
KW Pyridoxal phosphate; Reference proteome; Sphingolipid metabolism;
KW Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..560
FT /note="Serine palmitoyltransferase 2"
FT /id="PRO_0000163859"
FT TRANSMEM 65..85
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MOD_RES 377
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250"
SQ SEQUENCE 560 AA; 62982 MW; 6429566979B18D1C CRC64;
MRPEPGGCCC RRPMRANGCV KNGEVRNGYL RSSTATVAAA GQIHHVTENG GLYKRPFNEA
FEETPMLVAV LTYVGYGVLT LFGYLRDFLR HWRIEKCHHA TEREEQKDFV SLYQDFENFY
TRNLYMRIRD NWNRPICSVP GAKVDIMERK SHDYNWSFKY TGNIIKGVIN MGSYNYLGFA
RNTGSCQEAA AEVLKEYGAG VCSTRQEIGN LDKHEELEKL VARFLGVEAA MTYGMGFATN
SMNIPALVGK GCLILSDELN HASLVLGARL SGATIRIFKH NNMQSLEKLL KDAIVYGQPR
TRRPWKKILI LVEGIYSMEG SIVRLPEVIA LKKKYKAYLY LDEAHSIGAL GPSGRGVVDY
FGLDPEDVDV MMGTFTKSFG ASGGYIGGKK ELIDYLRTHS HSAVYATSMS PPVMEQIITS
MKCIMGQDGT SLGKECIQQL AENTRYFRRR LKEMGFIIYG NEDSPVVPLM LYMPAKIGAF
GREMLKRNIG VVVVGFPATP IIESRARFCL SAAHTKEILD TALKEIDEVG DLLQLKYSRH
RLVPLLDRPF DETTYEETED
