ID   SPTC2_HUMAN             Reviewed;         562 AA.
AC   O15270; Q16685;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1998, sequence version 1.
DT   27-MAR-2024, entry version 203.
DE   RecName: Full=Serine palmitoyltransferase 2 {ECO:0000305};
DE            EC=2.3.1.50 {ECO:0000269|PubMed:19416851};
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 {ECO:0000303|PubMed:19416851};
DE   AltName: Full=Serine-palmitoyl-CoA transferase 2;
DE            Short=SPT 2;
GN   Name=SPTLC2 {ECO:0000312|HGNC:HGNC:11278}; Synonyms=KIAA0526, LCB2;
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 [MRNA].
RC   TISSUE=Pancreas;
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   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
RX   PubMed=9628581; DOI=10.1093/dnares/5.1.31;
RA   Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N.,
RA   Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. IX. The
RT   complete sequences of 100 new cDNA clones from brain which can code for
RT   large proteins in vitro.";
RL   DNA Res. 5:31-39(1998).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12508121; DOI=10.1038/nature01348;
RA   Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA   Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA   Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA   Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA   Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA   Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA   Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA   Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA   Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA   Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA   Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA   Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA   Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA   Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA   Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA   Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA   Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA   Waterston R., Hood L., Weissenbach J.;
RT   "The DNA sequence and analysis of human chromosome 14.";
RL   Nature 421:601-607(2003).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Lymph;
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   NUCLEOTIDE SEQUENCE [MRNA] OF 60-562.
RC   TISSUE=Pancreatic islet;
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   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 68-144.
RC   TISSUE=Pancreatic islet;
RX   PubMed=7506601; DOI=10.1093/hmg/2.11.1793;
RA   Takeda J., Yano H., Eng S., Zeng Y., Bell G.I.;
RT   "A molecular inventory of human pancreatic islets: sequence analysis of
RT   1000 cDNA clones.";
RL   Hum. Mol. Genet. 2:1793-1798(1993).
RN   [7]
RP   TISSUE SPECIFICITY.
RX   PubMed=17023427; DOI=10.1074/jbc.m608066200;
RA   Hornemann T., Richard S., Ruetti M.F., Wei Y., von Eckardstein A.;
RT   "Cloning and initial characterization of a new subunit for mammalian
RT   serine-palmitoyltransferase.";
RL   J. Biol. Chem. 281:37275-37281(2006).
RN   [8]
RP   FUNCTION.
RX   PubMed=19648650; DOI=10.1074/jbc.m109.023192;
RA   Hornemann T., Penno A., Ruetti M.F., Ernst D., Kivrak-Pfiffner F.,
RA   Rohrer L., von Eckardstein A.;
RT   "The SPTLC3 subunit of serine palmitoyltransferase generates short chain
RT   sphingoid bases.";
RL   J. Biol. Chem. 284:26322-26330(2009).
RN   [9]
RP   FUNCTION, CATALYTIC ACTIVITY, AND IDENTIFICATION IN THE SPT COMPLEX.
RX   PubMed=19416851; DOI=10.1073/pnas.0811269106;
RA   Han G., Gupta S.D., Gable K., Niranjanakumari S., Moitra P., Eichler F.,
RA   Brown R.H. Jr., Harmon J.M., Dunn T.M.;
RT   "Identification of small subunits of mammalian serine palmitoyltransferase
RT   that confer distinct acyl-CoA substrate specificities.";
RL   Proc. Natl. Acad. Sci. U.S.A. 106:8186-8191(2009).
RN   [10]
RP   FUNCTION, VARIANTS HSAN1C MET-359; VAL-382 AND PHE-504, AND
RP   CHARACTERIZATION OF VARIANTS HSAN1C MET-359; VAL-382 AND PHE-504.
RX   PubMed=20920666; DOI=10.1016/j.ajhg.2010.09.010;
RA   Rotthier A., Auer-Grumbach M., Janssens K., Baets J., Penno A.,
RA   Almeida-Souza L., Van Hoof K., Jacobs A., De Vriendt E.,
RA   Schlotter-Weigel B., Loscher W., Vondracek P., Seeman P., De Jonghe P.,
RA   Van Dijck P., Jordanova A., Hornemann T., Timmerman V.;
RT   "Mutations in the SPTLC2 subunit of serine palmitoyltransferase cause
RT   hereditary sensory and autonomic neuropathy type I.";
RL   Am. J. Hum. Genet. 87:513-522(2010).
RN   [11]
RP   FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=20504773; DOI=10.1074/jbc.m110.122259;
RA   Gable K., Gupta S.D., Han G., Niranjanakumari S., Harmon J.M., Dunn T.M.;
RT   "A disease-causing mutation in the active site of serine
RT   palmitoyltransferase causes catalytic promiscuity.";
RL   J. Biol. Chem. 285:22846-22852(2010).
RN   [12]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [13]
RP   INDUCTION IN ALZHEIMER DISEASE.
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   [14]
RP   REGULATION OF SPT COMPLEX ACTIVITY BY ORMDL PROTEINS IN THE PRESENCE OF
RP   CERAMIDES.
RX   PubMed=30700557; DOI=10.1074/jbc.ra118.007291;
RA   Davis D.L., Gable K., Suemitsu J., Dunn T.M., Wattenberg B.W.;
RT   "The ORMDL/Orm-serine palmitoyltransferase (SPT) complex is directly
RT   regulated by ceramide: Reconstitution of SPT regulation in isolated
RT   membranes.";
RL   J. Biol. Chem. 294:5146-5156(2019).
RN   [15] {ECO:0007744|PDB:7K0I, ECO:0007744|PDB:7K0J, ECO:0007744|PDB:7K0K, ECO:0007744|PDB:7K0L, ECO:0007744|PDB:7K0M, ECO:0007744|PDB:7K0N, ECO:0007744|PDB:7K0O, ECO:0007744|PDB:7K0P, ECO:0007744|PDB:7K0Q}
RP   STRUCTURE BY ELECTRON MICROSCOPY (2.60 ANGSTROMS) IN COMPLEX WITH SPTLC1;
RP   SPTSSA AND ORMDL3, AND MUTAGENESIS OF ARG-302; ARG-304 AND ARG-305.
RX   PubMed=33558761; DOI=10.1038/s41594-020-00551-9;
RA   Wang Y., Niu Y., Zhang Z., Gable K., Gupta S.D., Somashekarappa N., Han G.,
RA   Zhao H., Myasnikov A.G., Kalathur R.C., Dunn T.M., Lee C.H.;
RT   "Structural insights into the regulation of human serine
RT   palmitoyltransferase complexes.";
RL   Nat. Struct. Mol. Biol. 28:240-248(2021).
RN   [16] {ECO:0007744|PDB:6M4N, ECO:0007744|PDB:6M4O, ECO:0007744|PDB:7CQI, ECO:0007744|PDB:7CQK}
RP   STRUCTURE BY ELECTRON MICROSCOPY (3.20 ANGSTROMS) IN COMPLEX WITH SPTLC1;
RP   SPTSSA AND ORMDL3, MUTAGENESIS OF TYR-122; LEU-126; ILE-130; TRP-134;
RP   TYR-176; SER-258; MET-320; THR-378; LYS-379; ILE-479 AND ARG-509, AND
RP   BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=33558762; DOI=10.1038/s41594-020-00553-7;
RA   Li S., Xie T., Liu P., Wang L., Gong X.;
RT   "Structural insights into the assembly and substrate selectivity of human
RT   SPT-ORMDL3 complex.";
RL   Nat. Struct. Mol. Biol. 28:249-257(2021).
RN   [17] {ECO:0007744|PDB:7YIU, ECO:0007744|PDB:7YIY, ECO:0007744|PDB:7YJ1, ECO:0007744|PDB:7YJ2}
RP   STRUCTURE BY ELECTRON MICROSCOPY (2.70 ANGSTROMS) IN COMPLEX WITH SPTLC1;
RP   SPTSSA AND ORMDL3, AND MUTAGENESIS OF TYR-122 AND ILE-503.
RX   PubMed=37308477; DOI=10.1038/s41467-023-39274-y;
RA   Xie T., Liu P., Wu X., Dong F., Zhang Z., Yue J., Mahawar U., Farooq F.,
RA   Vohra H., Fang Q., Liu W., Wattenberg B.W., Gong X.;
RT   "Ceramide sensing by human SPT-ORMDL complex for establishing sphingolipid
RT   homeostasis.";
RL   Nat. Commun. 14:3475-3475(2023).
RN   [18]
RP   VARIANT HSAN1C PRO-182, CHARACTERIZATION OF VARIANT HSAN1C PRO-182, AND
RP   PATHOLOGICAL MECHANISM.
RX   PubMed=23658386; DOI=10.1212/wnl.0b013e318295d789;
RA   Murphy S.M., Ernst D., Wei Y., Laura M., Liu Y.T., Polke J., Blake J.,
RA   Winer J., Houlden H., Hornemann T., Reilly M.M.;
RT   "Hereditary sensory and autonomic neuropathy type 1 (HSANI) caused by a
RT   novel mutation in SPTLC2.";
RL   Neurology 80:2106-2111(2013).
RN   [19]
RP   VARIANT HSAN1C TRP-183, AND CHARACTERIZATION OF VARIANT HSAN1C TRP-183.
RX   PubMed=26573920; DOI=10.1007/s12017-015-8379-1;
RA   Suriyanarayanan S., Auranen M., Toppila J., Paetau A., Shcherbii M.,
RA   Palin E., Wei Y., Lohioja T., Schlotter-Weigel B., Schoen U., Abicht A.,
RA   Rautenstrauss B., Tyynismaa H., Walter M.C., Hornemann T., Ylikallio E.;
RT   "The Variant p.(Arg183Trp) in SPTLC2 Causes Late-Onset Hereditary Sensory
RT   Neuropathy.";
RL   NeuroMolecular Med. 18:81-90(2016).
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
CC       (PubMed:19648650, PubMed:19416851, PubMed:20920666, PubMed:20504773).
CC       The SPT complex is composed of SPTLC1, SPTLC2 or SPTLC3 and SPTSSA or
CC       SPTSSB. Within this complex, the heterodimer consisting of SPTLC1 and
CC       SPTLC2/SPTLC3 forms the catalytic core (PubMed:19416851). The
CC       composition of the serine palmitoyltransferase (SPT) complex determines
CC       the substrate preference (PubMed:19416851). The SPTLC1-SPTLC2-SPTSSA
CC       complex shows a strong preference for C16-CoA substrate, while the
CC       SPTLC1-SPTLC3-SPTSSA isozyme uses both C14-CoA and C16-CoA as
CC       substrates, with a slight preference for C14-CoA (PubMed:19648650,
CC       PubMed:19416851). 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 (PubMed:19648650, PubMed:19416851). Crucial
CC       for adipogenesis (By similarity). {ECO:0000250|UniProtKB:P97363,
CC       ECO:0000269|PubMed:19416851, ECO:0000269|PubMed:19648650,
CC       ECO:0000269|PubMed:20504773, ECO:0000269|PubMed:20920666}.
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:0000269|PubMed:19416851};
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:0000269|PubMed:19416851};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33684;
CC         Evidence={ECO:0000269|PubMed:19416851};
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 (PubMed:37308477). This mechanism allows to maintain ceramide
CC       levels at sufficient concentrations for the production of complex
CC       sphingolipids, but which prevents the accumulation of ceramides to
CC       levels that trigger apoptosis (Probable). {ECO:0000269|PubMed:37308477,
CC       ECO:0000305}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.75 mM for L-serine {ECO:0000269|PubMed:20504773};
CC         KM=0.3 mM for L-serine {ECO:0000269|PubMed:33558761};
CC         Vmax=1350 pmol/min/mg enzyme {ECO:0000269|PubMed:20504773};
CC   -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC   -!- SUBUNIT: Component of the serine palmitoyltransferase (SPT) complex,
CC       which is composed of SPTLC1, SPTLC2 or SPTLC3 and SPTSSA or SPTSSB
CC       (PubMed:19416851). The heterodimer consisting of SPTLC1 and
CC       SPTLC2/SPTLC3 forms the catalytic core of the enzyme, while SPTSSA or
CC       SPTSSB subunits determine substrate specificity (PubMed:33558762,
CC       PubMed:37308477). SPT also interacts with ORMDL proteins, especially
CC       ORMDL3, which negatively regulate SPT activity in the presence of
CC       ceramides (PubMed:30700557, PubMed:33558762, PubMed:37308477). Forms
CC       dimers of heterodimers with SPTLC1 (PubMed:33558761, PubMed:33558762).
CC       {ECO:0000269|PubMed:19416851, ECO:0000269|PubMed:30700557,
CC       ECO:0000269|PubMed:33558761, ECO:0000269|PubMed:33558762,
CC       ECO:0000269|PubMed:37308477}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000250|UniProtKB:P97363}; Single-pass membrane protein
CC       {ECO:0000250|UniProtKB:P97363}.
CC   -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:17023427}.
CC   -!- INDUCTION: Expression at protein level is highly increased in brains of
CC       patients with Alzheimer disease. No changes are observed at mRNA level.
CC       {ECO:0000269|PubMed:21994399}.
CC   -!- DISEASE: Neuropathy, hereditary sensory and autonomic, 1C (HSAN1C)
CC       [MIM:613640]: A form of hereditary sensory and autonomic neuropathy, a
CC       genetically and clinically heterogeneous group of disorders
CC       characterized by degeneration of dorsal root and autonomic ganglion
CC       cells, and by prominent sensory abnormalities with a variable degree of
CC       motor and autonomic dysfunction. The neurological phenotype is often
CC       complicated by severe infections, osteomyelitis, and amputations.
CC       HSAN1C symptoms include loss of touch and vibration in the feet,
CC       dysesthesia and severe panmodal sensory loss in the upper and lower
CC       limbs, distal lower limb sensory loss with ulceration and
CC       osteomyelitis, and distal muscle weakness.
CC       {ECO:0000269|PubMed:20920666, ECO:0000269|PubMed:23658386,
CC       ECO:0000269|PubMed:26573920}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry. SPTLC2 disease mutations
CC       cause a shift in the substrate specificity of SPT resulting in the
CC       alternative use of L-alanine and L-glycine over its canonical substrate
CC       L-serine. This leads to the production of 1-deoxysphingolipids that
CC       cannot be correctly metabolized (PubMed:23658386).
CC       {ECO:0000269|PubMed:23658386, ECO:0000269|PubMed:26573920}.
CC   -!- SIMILARITY: Belongs to the class-II pyridoxal-phosphate-dependent
CC       aminotransferase family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAA25452.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; Y08686; CAA69942.1; -; mRNA.
DR   EMBL; AB011098; BAA25452.2; ALT_INIT; mRNA.
DR   EMBL; AF111168; AAD09621.1; -; Genomic_DNA.
DR   EMBL; BC005123; AAH05123.1; -; mRNA.
DR   EMBL; U15555; AAC50871.1; -; mRNA.
DR   CCDS; CCDS9865.1; -.
DR   PIR; I38873; I38873.
DR   RefSeq; NP_004854.1; NM_004863.3.
DR   PDB; 6M4N; EM; 3.80 A; B/F=1-562.
DR   PDB; 6M4O; EM; 3.40 A; T=1-562.
DR   PDB; 7CQI; EM; 3.20 A; T=1-562.
DR   PDB; 7CQK; EM; 3.30 A; T=1-562.
DR   PDB; 7K0I; EM; 3.30 A; B/E=1-544.
DR   PDB; 7K0J; EM; 3.10 A; B=1-562.
DR   PDB; 7K0K; EM; 2.60 A; B=1-562.
DR   PDB; 7K0L; EM; 3.40 A; B=1-562.
DR   PDB; 7K0M; EM; 2.90 A; B/F=1-544.
DR   PDB; 7K0N; EM; 3.10 A; B/F=1-562.
DR   PDB; 7K0O; EM; 3.10 A; B/F=1-544.
DR   PDB; 7K0P; EM; 3.10 A; B/F=1-544.
DR   PDB; 7K0Q; EM; 3.30 A; B=1-562.
DR   PDB; 7YIU; EM; 2.90 A; B=1-562.
DR   PDB; 7YIY; EM; 2.70 A; B=1-562.
DR   PDB; 7YJ1; EM; 3.10 A; B=1-562.
DR   PDB; 7YJ2; EM; 2.90 A; B=1-562.
DR   PDBsum; 6M4N; -.
DR   PDBsum; 6M4O; -.
DR   PDBsum; 7CQI; -.
DR   PDBsum; 7CQK; -.
DR   PDBsum; 7K0I; -.
DR   PDBsum; 7K0J; -.
DR   PDBsum; 7K0K; -.
DR   PDBsum; 7K0L; -.
DR   PDBsum; 7K0M; -.
DR   PDBsum; 7K0N; -.
DR   PDBsum; 7K0O; -.
DR   PDBsum; 7K0P; -.
DR   PDBsum; 7K0Q; -.
DR   PDBsum; 7YIU; -.
DR   PDBsum; 7YIY; -.
DR   PDBsum; 7YJ1; -.
DR   PDBsum; 7YJ2; -.
DR   AlphaFoldDB; O15270; -.
DR   EMDB; EMD-30081; -.
DR   EMDB; EMD-30082; -.
DR   EMDB; EMD-33864; -.
DR   EMDB; EMD-33866; -.
DR   EMDB; EMD-33868; -.
DR   EMDB; EMD-33869; -.
DR   SMR; O15270; -.
DR   BioGRID; 114894; 129.
DR   ComplexPortal; CPX-6663; Serine palmitoyltransferase complex, SPTLC1-SPTLC2-SPTSSA variant.
DR   ComplexPortal; CPX-6664; Serine palmitoyltransferase complex, SPTLC1-SPTLC2-SPTSSB variant.
DR   CORUM; O15270; -.
DR   DIP; DIP-34604N; -.
DR   IntAct; O15270; 31.
DR   MINT; O15270; -.
DR   STRING; 9606.ENSP00000216484; -.
DR   BindingDB; O15270; -.
DR   ChEMBL; CHEMBL1250344; -.
DR   DrugBank; DB00114; Pyridoxal phosphate.
DR   DrugBank; DB00133; Serine.
DR   iPTMnet; O15270; -.
DR   PhosphoSitePlus; O15270; -.
DR   SwissPalm; O15270; -.
DR   BioMuta; SPTLC2; -.
DR   EPD; O15270; -.
DR   jPOST; O15270; -.
DR   MassIVE; O15270; -.
DR   MaxQB; O15270; -.
DR   PaxDb; 9606-ENSP00000216484; -.
DR   PeptideAtlas; O15270; -.
DR   ProteomicsDB; 48559; -.
DR   Pumba; O15270; -.
DR   Antibodypedia; 26092; 306 antibodies from 29 providers.
DR   DNASU; 9517; -.
DR   Ensembl; ENST00000216484.7; ENSP00000216484.2; ENSG00000100596.8.
DR   GeneID; 9517; -.
DR   KEGG; hsa:9517; -.
DR   MANE-Select; ENST00000216484.7; ENSP00000216484.2; NM_004863.4; NP_004854.1.
DR   UCSC; uc001xub.4; human.
DR   AGR; HGNC:11278; -.
DR   CTD; 9517; -.
DR   DisGeNET; 9517; -.
DR   GeneCards; SPTLC2; -.
DR   HGNC; HGNC:11278; SPTLC2.
DR   HPA; ENSG00000100596; Low tissue specificity.
DR   MalaCards; SPTLC2; -.
DR   MIM; 605713; gene.
DR   MIM; 613640; phenotype.
DR   neXtProt; NX_O15270; -.
DR   OpenTargets; ENSG00000100596; -.
DR   Orphanet; 36386; Hereditary sensory and autonomic neuropathy type 1.
DR   PharmGKB; PA36107; -.
DR   VEuPathDB; HostDB:ENSG00000100596; -.
DR   eggNOG; KOG1357; Eukaryota.
DR   GeneTree; ENSGT00940000155786; -.
DR   HOGENOM; CLU_015846_7_1_1; -.
DR   InParanoid; O15270; -.
DR   OMA; NDCFSRP; -.
DR   OrthoDB; 9643at2759; -.
DR   PhylomeDB; O15270; -.
DR   TreeFam; TF300452; -.
DR   BioCyc; MetaCyc:HS02117-MONOMER; -.
DR   BRENDA; 2.3.1.50; 2681.
DR   PathwayCommons; O15270; -.
DR   Reactome; R-HSA-1660661; Sphingolipid de novo biosynthesis.
DR   SABIO-RK; O15270; -.
DR   SignaLink; O15270; -.
DR   UniPathway; UPA00222; -.
DR   BioGRID-ORCS; 9517; 105 hits in 1178 CRISPR screens.
DR   ChiTaRS; SPTLC2; human.
DR   GeneWiki; SPTLC2; -.
DR   GenomeRNAi; 9517; -.
DR   Pharos; O15270; Tchem.
DR   PRO; PR:O15270; -.
DR   Proteomes; UP000005640; Chromosome 14.
DR   RNAct; O15270; Protein.
DR   Bgee; ENSG00000100596; Expressed in corpus callosum and 194 other cell types or tissues.
DR   ExpressionAtlas; O15270; baseline and differential.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR   GO; GO:0017059; C:serine C-palmitoyltransferase complex; IDA:UniProtKB.
DR   GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR   GO; GO:0004758; F:serine C-palmitoyltransferase activity; IDA:UniProtKB.
DR   GO; GO:0060612; P:adipose tissue development; ISS:UniProtKB.
DR   GO; GO:0046513; P:ceramide biosynthetic process; IDA:MGI.
DR   GO; GO:1904504; P:positive regulation of lipophagy; IDA:MGI.
DR   GO; GO:0046511; P:sphinganine biosynthetic process; IEA:Ensembl.
DR   GO; GO:0030148; P:sphingolipid biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0006686; P:sphingomyelin biosynthetic process; IEA:Ensembl.
DR   GO; GO:0046512; P:sphingosine biosynthetic process; IDA:ComplexPortal.
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; O15270; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Acyltransferase; Disease variant; Endoplasmic reticulum;
KW   Lipid metabolism; Membrane; Neurodegeneration; Neuropathy;
KW   Pyridoxal phosphate; Reference proteome; Sphingolipid metabolism;
KW   Transferase; Transmembrane; Transmembrane helix.
FT   CHAIN           1..562
FT                   /note="Serine palmitoyltransferase 2"
FT                   /id="PRO_0000163858"
FT   TRANSMEM        67..87
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         379
FT                   /note="N6-(pyridoxal phosphate)lysine"
FT                   /evidence="ECO:0000250"
FT   VARIANT         182
FT                   /note="A -> P (in HSAN1C; reduced activity with L-serine as
FT                   substrate; increased activity toward L-alanine resulting in
FT                   the accumulation of 1-deoxy-sphinganine;
FT                   dbSNP:rs864621998)"
FT                   /evidence="ECO:0000269|PubMed:23658386"
FT                   /id="VAR_069525"
FT   VARIANT         183
FT                   /note="R -> W (in HSAN1C; late onset; slightly increased
FT                   activity with L-serine as substrate; highly increased
FT                   activity toward L-alanine resulting in the accumulation of
FT                   1-deoxy-sphinganine; dbSNP:rs775437084)"
FT                   /evidence="ECO:0000269|PubMed:26573920"
FT                   /id="VAR_081286"
FT   VARIANT         359
FT                   /note="V -> M (in HSAN1C; partial loss of normal activity
FT                   as measured by reduced formation of sphinganine; affects
FT                   enzymatic affinity resulting in the accumulation of the
FT                   alternative metabolite 1-deoxy-sphinganine;
FT                   dbSNP:rs267607090)"
FT                   /evidence="ECO:0000269|PubMed:20920666"
FT                   /id="VAR_064798"
FT   VARIANT         382
FT                   /note="G -> V (in HSAN1C; complete loss of normal activity
FT                   as measured by lack of formation of sphinganine; affects
FT                   enzymatic affinity resulting in the accumulation of the
FT                   alternative metabolite 1-deoxy-sphinganine;
FT                   dbSNP:rs267607089)"
FT                   /evidence="ECO:0000269|PubMed:20920666"
FT                   /id="VAR_064799"
FT   VARIANT         504
FT                   /note="I -> F (in HSAN1C; partial loss of normal activity
FT                   as measured by reduced formation of sphinganine; affects
FT                   enzymatic affinity resulting in the accumulation of the
FT                   alternative metabolite 1-deoxy-sphinganine;
FT                   dbSNP:rs267607091)"
FT                   /evidence="ECO:0000269|PubMed:20920666"
FT                   /id="VAR_064800"
FT   MUTAGEN         122
FT                   /note="Y->A: Decreased catalytic activity with L-serine and
FT                   palmitoyl-CoA as substrates. Does not affect the negative
FT                   regulation by OMRDL3 and ceramides."
FT                   /evidence="ECO:0000269|PubMed:33558762,
FT                   ECO:0000269|PubMed:37308477"
FT   MUTAGEN         126
FT                   /note="L->W: Some decrease in catalytic activity with
FT                   L-serine and palmitoyl-CoA as substrates."
FT                   /evidence="ECO:0000269|PubMed:33558762"
FT   MUTAGEN         130
FT                   /note="I->W: Loss of catalytic activity with L-serine and
FT                   palmitoyl-CoA as substrates."
FT                   /evidence="ECO:0000269|PubMed:33558762"
FT   MUTAGEN         134
FT                   /note="W->A: Loss of catalytic activity with L-serine and
FT                   palmitoyl-CoA as substrates."
FT                   /evidence="ECO:0000269|PubMed:33558762"
FT   MUTAGEN         176
FT                   /note="Y->A: Loss of catalytic activity with L-serine and
FT                   palmitoyl-CoA as substrates."
FT                   /evidence="ECO:0000269|PubMed:33558762"
FT   MUTAGEN         258
FT                   /note="S->R: Loss of catalytic activity with L-serine and
FT                   palmitoyl-CoA as substrates."
FT                   /evidence="ECO:0000269|PubMed:33558762"
FT   MUTAGEN         302
FT                   /note="R->A: Reduces the dimerization propensity with
FT                   SPTLC1; reduces the dimerization propensity with SPTLC1;
FT                   when associated with A-305. Does not impair enzymatic
FT                   activity; when associated with A-304 and A-305."
FT                   /evidence="ECO:0000269|PubMed:33558761"
FT   MUTAGEN         304
FT                   /note="R->A: Reduces the dimerization propensity with
FT                   SPTLC1; when associated with A-302 and A-304. Does not
FT                   impair enzymatic activity; when associated with A-302 and
FT                   A-304."
FT                   /evidence="ECO:0000269|PubMed:33558761"
FT   MUTAGEN         305
FT                   /note="R->A: Reduces the dimerization propensity with
FT                   SPTLC1; when associated with A-302 and A-304. Does not
FT                   impair enzymatic activity; when associated with A-302 and
FT                   A-304."
FT                   /evidence="ECO:0000269|PubMed:33558761"
FT   MUTAGEN         320
FT                   /note="M->Q: Decreased catalytic activity with L-serine and
FT                   palmitoyl-CoA as substrates."
FT                   /evidence="ECO:0000269|PubMed:33558762"
FT   MUTAGEN         378
FT                   /note="T->A: Decreased catalytic activity with L-serine and
FT                   palmitoyl-CoA as substrates."
FT                   /evidence="ECO:0000269|PubMed:33558762"
FT   MUTAGEN         379
FT                   /note="K->A: Loss of catalytic activity with L-serine and
FT                   palmitoyl-CoA as substrates."
FT                   /evidence="ECO:0000269|PubMed:33558762"
FT   MUTAGEN         479
FT                   /note="I->W: Loss of catalytic activity with L-serine and
FT                   palmitoyl-CoA as substrates."
FT                   /evidence="ECO:0000269|PubMed:33558762"
FT   MUTAGEN         503
FT                   /note="I->R: Loss of negative regulation by OMRDL3 and
FT                   ceramides."
FT                   /evidence="ECO:0000269|PubMed:37308477"
FT   MUTAGEN         509
FT                   /note="R->A: Loss of catalytic activity with L-serine and
FT                   palmitoyl-CoA as substrates."
FT                   /evidence="ECO:0000269|PubMed:33558762"
FT   CONFLICT        61..64
FT                   /note="EAFE -> TLAR (in Ref. 5; AAC50871)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        436..562
FT                   /note="KECVQQLAENTRYFRRRLKEMGFIIYGNEDSPVVPLMLYMPAKIGAFGREML
FT                   KRNIGVVVVGFPATPIIESRARFCLSAAHTKEILDTALKEIDEVGDLLQLKYSRHRLVP
FT                   LLDRPFDETTYEETED -> NGITIHEVVQTRNTYHRFSPLSPVFSHQCLWIMLP (in
FT                   Ref. 5; AAC50871)"
FT                   /evidence="ECO:0000305"
FT   STRAND          50..52
FT                   /evidence="ECO:0007829|PDB:6M4O"
FT   STRAND          54..57
FT                   /evidence="ECO:0007829|PDB:7CQI"
FT   HELIX           68..93
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   STRAND          100..102
FT                   /evidence="ECO:0007829|PDB:7CQI"
FT   HELIX           106..108
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   STRAND          109..111
FT                   /evidence="ECO:0007829|PDB:7K0J"
FT   HELIX           117..120
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   HELIX           121..125
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   HELIX           128..133
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   STRAND          137..140
FT                   /evidence="ECO:0007829|PDB:7CQI"
FT   STRAND          143..152
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   STRAND          154..159
FT                   /evidence="ECO:0007829|PDB:7K0N"
FT   STRAND          161..172
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   HELIX           178..180
FT                   /evidence="ECO:0007829|PDB:7CQI"
FT   STRAND          184..186
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   HELIX           187..199
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   STRAND          204..206
FT                   /evidence="ECO:0007829|PDB:7K0N"
FT   TURN            207..211
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   HELIX           214..227
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   STRAND          229..236
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   HELIX           238..249
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   STRAND          255..259
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   HELIX           264..272
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   STRAND          275..280
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   HELIX           285..298
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   STRAND          300..303
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   STRAND          310..318
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   TURN            319..322
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   HELIX           327..337
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   STRAND          340..344
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   TURN            346..351
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   STRAND          352..356
FT                   /evidence="ECO:0007829|PDB:7K0N"
FT   HELIX           359..363
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   HELIX           367..369
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   STRAND          370..377
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   TURN            378..381
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   STRAND          386..390
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   HELIX           392..401
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   HELIX           403..407
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   HELIX           413..426
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   TURN            427..430
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   STRAND          431..433
FT                   /evidence="ECO:0007829|PDB:7K0N"
FT   HELIX           434..456
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   STRAND          462..465
FT                   /evidence="ECO:0007829|PDB:7K0M"
FT   STRAND          467..472
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   HELIX           476..488
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   STRAND          494..496
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   TURN            498..500
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   TURN            503..505
FT                   /evidence="ECO:0007829|PDB:6M4O"
FT   STRAND          507..511
FT                   /evidence="ECO:0007829|PDB:7K0K"
FT   STRAND          513..515
FT                   /evidence="ECO:0007829|PDB:7CQI"
FT   HELIX           518..535
FT                   /evidence="ECO:0007829|PDB:7K0K"
SQ   SEQUENCE   562 AA;  62924 MW;  0C1AA1E233DE36F1 CRC64;
     MRPEPGGCCC RRTVRANGCV ANGEVRNGYV RSSAAAAAAA AAGQIHHVTQ NGGLYKRPFN
     EAFEETPMLV AVLTYVGYGV LTLFGYLRDF LRYWRIEKCH HATEREEQKD FVSLYQDFEN
     FYTRNLYMRI RDNWNRPICS VPGARVDIME RQSHDYNWSF KYTGNIIKGV INMGSYNYLG
     FARNTGSCQE AAAKVLEEYG AGVCSTRQEI GNLDKHEELE ELVARFLGVE AAMAYGMGFA
     TNSMNIPALV GKGCLILSDE LNHASLVLGA RLSGATIRIF KHNNMQSLEK LLKDAIVYGQ
     PRTRRPWKKI LILVEGIYSM EGSIVRLPEV IALKKKYKAY LYLDEAHSIG ALGPTGRGVV
     EYFGLDPEDV DVMMGTFTKS FGASGGYIGG KKELIDYLRT HSHSAVYATS LSPPVVEQII
     TSMKCIMGQD GTSLGKECVQ QLAENTRYFR RRLKEMGFII YGNEDSPVVP LMLYMPAKIG
     AFGREMLKRN IGVVVVGFPA TPIIESRARF CLSAAHTKEI LDTALKEIDE VGDLLQLKYS
     RHRLVPLLDR PFDETTYEET ED
//