SPTLC2
entrez
9517
canonical
uniprot
O15270
canonical
ensembl
ENSG00000100596
resolver
ensp
ENSP00000216484
resolver
ensp
ENSP00000452189
resolver
enst
ENST00000216484
resolver
genesymbol
SPTLC2
resolver
genesymbol_syn
KIAA0526
resolver
genesymbol_syn
LCB2
resolver
hgnc
HGNC:11278
resolver
uniprot
Q16685
resolver
uniprot_entry
SPTC2_HUMAN
resolver
uniprot_sec
Q16685
resolver
activity_regulation
ACTIVITY REGULATION: SPT complex catalytic activity is negatively regulated by ORMDL proteins, including ORMDL3, in the presence of ceramides (PubMed:37308477). This mechanism allows to maintain ceramide levels at sufficient concentrations for the production of complex sphingolipids, but which prevents the accumulation of ceramides to levels that trigger apoptosis (Probable). {ECO:0000269|PubMed:37308477, ECO:0000305}.
uniprot
proteins
amino_acid_sequence
MRPEPGGCCCRRTVRANGCVANGEVRNGYVRSSAAAAAAAAAGQIHHVTQNGGLYKRPFNEAFEETPMLVAVLTYVGYGVLTLFGYLRDFLRYWRIEKCHHATEREEQKDFVSLYQDFENFYTRNLYMRIRDNWNRPICSVPGARVDIMERQSHDYNWSFKYTGNIIKGVINMGSYNYLGFARNTGSCQEAAAKVLEEYGAGVCSTRQEIGNLDKHEELEELVARFLGVEAAMAYGMGFATNSMNIPALVGKGCLILSDELNHASLVLGARLSGATIRIFKHNNMQSLEKLLKDAIVYGQPRTRRPWKKILILVEGIYSMEGSIVRLPEVIALKKKYKAYLYLDEAHSIGALGPTGRGVVEYFGLDPEDVDVMMGTFTKSFGASGGYIGGKKELIDYLRTHSHSAVYATSLSPPVVEQIITSMKCIMGQDGTSLGKECVQQLAENTRYFRRRLKEMGFIIYGNEDSPVVPLMLYMPAKIGAFGREMLKRNIGVVVVGFPATPIIESRARFCLSAAHTKEILDTALKEIDEVGDLLQLKYSRHRLVPLLDRPFDETTYEETED
uniprot
proteins
disease_involvement
DISEASE: Neuropathy, hereditary sensory and autonomic, 1C (HSAN1C) [MIM:613640]: A form of hereditary sensory and autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by prominent sensory abnormalities with a variable degree of motor and autonomic dysfunction. The neurological phenotype is often complicated by severe infections, osteomyelitis, and amputations. HSAN1C symptoms include loss of touch and vibration in the feet, dysesthesia and severe panmodal sensory loss in the upper and lower limbs, distal lower limb sensory loss with ulceration and osteomyelitis, and distal muscle weakness. {ECO:0000269|PubMed:20920666, ECO:0000269|PubMed:23658386, ECO:0000269|PubMed:26573920}. Note=The disease is caused by variants affecting the gene represented in this entry. SPTLC2 disease mutations cause a shift in the substrate specificity of SPT resulting in the alternative use of L-alanine and L-glycine over its canonical substrate L-serine. This leads to the production of 1-deoxysphingolipids that cannot be correctly metabolized (PubMed:23658386). {ECO:0000269|PubMed:23658386, ECO:0000269|PubMed:26573920}.
uniprot
proteins
ec_number
2.3.1.50
uniprot
proteins
function
FUNCTION: Component of the serine palmitoyltransferase multisubunit enzyme (SPT) that catalyzes the initial and rate-limiting step in sphingolipid biosynthesis by condensing L-serine and activated acyl-CoA (most commonly palmitoyl-CoA) to form long-chain bases (PubMed:19416851, PubMed:19648650, PubMed:20504773, PubMed:20920666). The SPT complex is composed of SPTLC1, SPTLC2 or SPTLC3 and SPTSSA or SPTSSB. Within this complex, the heterodimer consisting of SPTLC1 and SPTLC2/SPTLC3 forms the catalytic core (PubMed:19416851). The composition of the serine palmitoyltransferase (SPT) complex determines the substrate preference (PubMed:19416851). The SPTLC1-SPTLC2-SPTSSA complex shows a strong preference for C16-CoA substrate, while the SPTLC1-SPTLC3-SPTSSA isozyme uses both C14-CoA and C16-CoA as substrates, with a slight preference for C14-CoA (PubMed:19416851, PubMed:19648650). The SPTLC1-SPTLC2-SPTSSB complex shows a strong preference for C18-CoA substrate, while the SPTLC1-SPTLC3-SPTSSB isozyme displays an ability to use a broader range of acyl-CoAs, without apparent preference (PubMed:19416851, PubMed:19648650). Crucial for adipogenesis (By similarity). {ECO:0000250|UniProtKB:P97363, ECO:0000269|PubMed:19416851, ECO:0000269|PubMed:19648650, ECO:0000269|PubMed:20504773, ECO:0000269|PubMed:20920666}.
uniprot
proteins
mass_dalton
62924
uniprot
proteins
mutagenesis
MUTAGEN 122; /note="Y->A: Decreased catalytic activity with L-serine and palmitoyl-CoA as substrates. Does not affect the negative regulation by OMRDL3 and ceramides."; /evidence="ECO:0000269|PubMed:33558762, ECO:0000269|PubMed:37308477"; MUTAGEN 126; /note="L->W: Some decrease in catalytic activity with L-serine and palmitoyl-CoA as substrates."; /evidence="ECO:0000269|PubMed:33558762"; MUTAGEN 130; /note="I->W: Loss of catalytic activity with L-serine and palmitoyl-CoA as substrates."; /evidence="ECO:0000269|PubMed:33558762"; MUTAGEN 134; /note="W->A: Loss of catalytic activity with L-serine and palmitoyl-CoA as substrates."; /evidence="ECO:0000269|PubMed:33558762"; MUTAGEN 176; /note="Y->A: Loss of catalytic activity with L-serine and palmitoyl-CoA as substrates."; /evidence="ECO:0000269|PubMed:33558762"; MUTAGEN 258; /note="S->R: Loss of catalytic activity with L-serine and palmitoyl-CoA as substrates."; /evidence="ECO:0000269|PubMed:33558762"; MUTAGEN 302; /note="R->A: Reduces the dimerization propensity with SPTLC1; reduces the dimerization propensity with SPTLC1; when associated with A-305. Does not impair enzymatic activity; when associated with A-304 and A-305."; /evidence="ECO:0000269|PubMed:33558761"; MUTAGEN 304; /note="R->A: Reduces the dimerization propensity with SPTLC1; when associated with A-302 and A-304. Does not impair enzymatic activity; when associated with A-302 and A-304."; /evidence="ECO:0000269|PubMed:33558761"; MUTAGEN 305; /note="R->A: Reduces the dimerization propensity with SPTLC1; when associated with A-302 and A-304. Does not impair enzymatic activity; when associated with A-302 and A-304."; /evidence="ECO:0000269|PubMed:33558761"; MUTAGEN 320; /note="M->Q: Decreased catalytic activity with L-serine and palmitoyl-CoA as substrates."; /evidence="ECO:0000269|PubMed:33558762"; MUTAGEN 378; /note="T->A: Decreased catalytic activity with L-serine and palmitoyl-CoA as substrates."; /evidence="ECO:0000269|PubMed:33558762"; MUTAGEN 379; /note="K->A: Loss of catalytic activity with L-serine and palmitoyl-CoA as substrates."; /evidence="ECO:0000269|PubMed:33558762"; MUTAGEN 479; /note="I->W: Loss of catalytic activity with L-serine and palmitoyl-CoA as substrates."; /evidence="ECO:0000269|PubMed:33558762"; MUTAGEN 503; /note="I->R: Loss of negative regulation by OMRDL3 and ceramides."; /evidence="ECO:0000269|PubMed:37308477"; MUTAGEN 509; /note="R->A: Loss of catalytic activity with L-serine and palmitoyl-CoA as substrates."; /evidence="ECO:0000269|PubMed:33558762
uniprot
proteins
pathway_participation
PATHWAY: Lipid metabolism; sphingolipid metabolism.
uniprot
proteins
protein_family
Class-II pyridoxal-phosphate-dependent aminotransferase family
uniprot
proteins
pubmed
12508121
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
17023427
uniprot
proteins
pubmed
19416851
uniprot
proteins
pubmed
19648650
uniprot
proteins
pubmed
20504773
uniprot
proteins
pubmed
20920666
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21994399
uniprot
proteins
pubmed
23658386
uniprot
proteins
pubmed
26573920
uniprot
proteins
pubmed
30700557
uniprot
proteins
pubmed
33558761
uniprot
proteins
pubmed
33558762
uniprot
proteins
pubmed
37308477
uniprot
proteins
pubmed
7506601
uniprot
proteins
pubmed
8921873
uniprot
proteins
pubmed
9363775
uniprot
proteins
pubmed
9628581
uniprot
proteins
sequence_length
562
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P97363}; Single-pass membrane protein {ECO:0000250|UniProtKB:P97363}.
uniprot
proteins
transmembrane_region
TRANSMEM 67..87; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins