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   27-MAR-2024, entry version 180.
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: Component of the serine palmitoyltransferase multisubunit
CC       enzyme (SPT) that catalyzes the initial and rate-limiting step in
CC       sphingolipid biosynthesis by condensing L-serine and activated acyl-CoA
CC       (most commonly palmitoyl-CoA) to form long-chain bases. The SPT complex
CC       is composed of SPTLC1, SPTLC2 or SPTLC3 and SPTSSA or SPTSSB. Within
CC       this complex, the heterodimer consisting of SPTLC1 and SPTLC2/SPTLC3
CC       forms the catalytic core. The composition of the serine
CC       palmitoyltransferase (SPT) complex determines the substrate preference.
CC       The SPTLC1-SPTLC2-SPTSSA complex shows a strong preference for C16-CoA
CC       substrate, while the SPTLC1-SPTLC3-SPTSSA isozyme uses both C14-CoA and
CC       C16-CoA as substrates, with a slight preference for C14-CoA. The
CC       SPTLC1-SPTLC2-SPTSSB complex shows a strong preference for C18-CoA
CC       substrate, while the SPTLC1-SPTLC3-SPTSSB isozyme displays an ability
CC       to use a broader range of acyl-CoAs, without apparent preference (By
CC       similarity). Crucial for adipogenesis (PubMed:28698261).
CC       {ECO:0000250|UniProtKB:O15270, 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   -!- ACTIVITY REGULATION: SPT complex catalytic activity is negatively
CC       regulated by ORMDL proteins, including ORMDL3, in the presence of
CC       ceramides. This mechanism allows to maintain ceramide levels at
CC       sufficient concentrations for the production of complex sphingolipids,
CC       but which prevents the accumulation of ceramides to levels that trigger
CC       apoptosis. {ECO:0000250|UniProtKB:O15270}.
CC   -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC       {ECO:0000269|PubMed:27818258, ECO:0000269|PubMed:28698261}.
CC   -!- SUBUNIT: Component of the serine palmitoyltransferase (SPT) complex,
CC       which is composed of SPTLC1, SPTLC2 or SPTLC3 and SPTSSA or SPTSSB. The
CC       heterodimer consisting of SPTLC1 and SPTLC2/SPTLC3 forms the catalytic
CC       core of the enzyme, while SPTSSA or SPTSSB subunits determine substrate
CC       specificity. SPT also interacts with ORMDL proteins, especially ORMDL3,
CC       which negatively regulate SPT activity in the presence of ceramides.
CC       Forms dimers of heterodimers with SPTLC1.
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; 16.
DR   IntAct; P97363; 12.
DR   STRING; 10090.ENSMUSP00000021424; -.
DR   GlyGen; P97363; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P97363; -.
DR   PhosphoSitePlus; P97363; -.
DR   SwissPalm; P97363; -.
DR   EPD; P97363; -.
DR   jPOST; P97363; -.
DR   PaxDb; 10090-ENSMUSP00000021424; -.
DR   PeptideAtlas; P97363; -.
DR   ProteomicsDB; 257059; -.
DR   Pumba; P97363; -.
DR   Antibodypedia; 26092; 306 antibodies from 29 providers.
DR   DNASU; 20773; -.
DR   Ensembl; ENSMUST00000021424.5; ENSMUSP00000021424.5; ENSMUSG00000021036.11.
DR   GeneID; 20773; -.
DR   KEGG; mmu:20773; -.
DR   UCSC; uc007oiw.1; mouse.
DR   AGR; MGI:108074; -.
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; NDCFSRP; -.
DR   OrthoDB; 9643at2759; -.
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; 26 hits in 81 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 275 other cell types or tissues.
DR   ExpressionAtlas; P97363; baseline and differential.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
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; IEA:UniProtKB-EC.
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   CDD; cd06454; KBL_like; 1.
DR   Gene3D; 3.90.1150.10; Aspartate Aminotransferase, domain 1; 1.
DR   Gene3D; 3.40.640.10; Type I PLP-dependent aspartate aminotransferase-like (Major domain); 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   PANTHER; PTHR13693; CLASS II AMINOTRANSFERASE/8-AMINO-7-OXONONANOATE SYNTHASE; 1.
DR   PANTHER; PTHR13693:SF79; SERINE PALMITOYLTRANSFERASE 2; 1.
DR   Pfam; PF00155; Aminotran_1_2; 1.
DR   SUPFAM; SSF53383; PLP-dependent transferases; 1.
DR   PROSITE; PS00599; AA_TRANSFER_CLASS_2; 1.
DR   Genevisible; P97363; MM.
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
//