SPTLC1
entrez
10558
canonical
uniprot
O15269
canonical
ensembl
ENSG00000090054
resolver
ensp
ENSP00000262554
resolver
ensp
ENSP00000337635
resolver
ensp
ENSP00000745913
resolver
genesymbol
SPTLC1
resolver
genesymbol_syn
LCB1
resolver
hgnc
HGNC:11277
resolver
uniprot
A8K681
resolver
uniprot
Q5VWB4
resolver
uniprot
Q6NUL7
resolver
uniprot
Q96IX6
resolver
uniprot_entry
Q6NUL7_HUMAN
resolver
uniprot_entry
SPTC1_HUMAN
resolver
uniprot_sec
A8K681
resolver
uniprot_sec
Q5VWB4
resolver
uniprot_sec
Q96IX6
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
MATATEQWVLVEMVQALYEAPAYHLILEGILILWIIRLLFSKTYKLQERSDLTVKEKEELIEEWQPEPLVPPVPKDHPALNYNIVSGPPSHKTVVNGKECINFASFNFLGLLDNPRVKAAALASLKKYGVGTCGPRGFYGTFDVHLDLEDRLAKFMKTEEAIIYSYGFATIASAIPAYSKRGDIVFVDRAACFAIQKGLQASRSDIKLFKHNDMADLERLLKEQEIEDQKNPRKARVTRRFIVVEGLYMNTGTICPLPELVKLKYKYKARIFLEESLSFGVLGEHGRGVTEHYGINIDDIDLISANMENALASIGGFCCGRSFVIDHQRLSGQGYCFSASLPPLLAAAAIEALNIMEENPGIFAVLKEKCGQIHKALQGISGLKVVGESLSPAFHLQLEESTGSREQDVRLLQEIVDQCMNRSIALTQARYLEKEEKCLPPPSIRVVVTVEQTEEELERAASTIKEVAQAVLL
uniprot
proteins
disease_involvement
DISEASE: Amyotrophic lateral sclerosis 27, juvenile (ALS27) [MIM:620285]: A form of amyotrophic lateral sclerosis, a neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. ALS27 is an autosomal dominant form manifesting as toe walking and gait abnormalities in early childhood. {ECO:0000269|PubMed:34059824, ECO:0000269|PubMed:34459874, ECO:0000269|PubMed:36204986, ECO:0000269|PubMed:37308477}. Note=The disease is caused by variants affecting the gene represented in this entry. Variants associated with ALS27 tend to disrupt the normal homeostatic regulation of serine palmitoyltransferase (SPT) by ORMDL proteins, resulting in up-regulated SPT activity and elevated levels of canonical SPT products. {ECO:0000269|PubMed:34059824}.; DISEASE: Neuropathy, hereditary sensory and autonomic, 1A (HSAN1A) [MIM:162400]: 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. HSAN1A is an autosomal dominant axonal form with onset in the second or third decades. Initial symptoms are loss of pain, touch, heat, and cold sensation over the feet, followed by distal muscle wasting and weakness. Loss of pain sensation leads to chronic skin ulcers and distal amputations. {ECO:0000269|PubMed:11242114, ECO:0000269|PubMed:19132419, ECO:0000269|PubMed:19651702, ECO:0000269|PubMed:20504773, ECO:0000269|PubMed:21618344, ECO:0000269|PubMed:22302274, ECO:0000269|PubMed:23454272, ECO:0000269|PubMed:24247255, ECO:0000269|PubMed:30420926}. Note=The disease is caused by variants affecting the gene represented in this entry. Variants associated with HSAN1A tend to increase serine palmitoyltransferase (SPT) usage of alanine or glycine rather than serine, resulting in deoxysphingolipid synthesis. Deoxysphingolipids cannot be efficiently degraded by the cell machinery and cause cell toxicity. {ECO:0000305|PubMed:34059824}.
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. The SPT complex is also composed of SPTLC2 or SPTLC3 and SPTSSA or SPTSSB. Within this complex, the heterodimer with SPTLC2 or SPTLC3 forms the catalytic core (PubMed:19416851, PubMed:33558762, PubMed:36170811). The composition of the serine palmitoyltransferase (SPT) complex determines the substrate preference (PubMed:19416851, PubMed:33558762). 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, PubMed:33558761, PubMed:33558762). Required for adipocyte cell viability and metabolic homeostasis (By similarity). {ECO:0000250|UniProtKB:O35704, ECO:0000269|PubMed:19416851, ECO:0000269|PubMed:19648650, ECO:0000269|PubMed:33558761, ECO:0000269|PubMed:33558762, ECO:0000269|PubMed:36170811}.
uniprot
proteins
mass_dalton
52744
uniprot
proteins
mutagenesis
MUTAGEN 138; /note="F->A: Decreased catalytic activity with L-serine and palmitoyl-CoA as substrates."; /evidence="ECO:0000269|PubMed:33558762"; MUTAGEN 164; /note="Y->F: Increased serine palmitoyltransferase activity and sphingolipid content."; /evidence="ECO:0000269|PubMed:23629659"; MUTAGEN 337; /note="F->A: Strongly decreased catalytic activity with L-serine and palmitoyl-CoA as substrates."; /evidence="ECO:0000269|PubMed:33558762"; MUTAGEN 338; /note="S->A: Decreased catalytic activity with L-serine and palmitoyl-CoA as substrates."; /evidence="ECO:0000269|PubMed:33558762
uniprot
proteins
pathway_participation
PATHWAY: Lipid metabolism; sphingolipid metabolism. {ECO:0000269|PubMed:19416851}.
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Tyr-164 inhibits activity and promotes cell survival. {ECO:0000269|PubMed:23629659}.
uniprot
proteins
protein_family
Class-II pyridoxal-phosphate-dependent aminotransferase family
uniprot
proteins
pubmed
11242114
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15037712
uniprot
proteins
pubmed
15164053
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
17023427
uniprot
proteins
pubmed
17060578
uniprot
proteins
pubmed
19132419
uniprot
proteins
pubmed
19416851
uniprot
proteins
pubmed
19648650
uniprot
proteins
pubmed
19651702
uniprot
proteins
pubmed
20182505
uniprot
proteins
pubmed
20504773
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21618344
uniprot
proteins
pubmed
21994399
uniprot
proteins
pubmed
22302274
uniprot
proteins
pubmed
23454272
uniprot
proteins
pubmed
23629659
uniprot
proteins
pubmed
24247255
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
30420926
uniprot
proteins
pubmed
30700557
uniprot
proteins
pubmed
33558761
uniprot
proteins
pubmed
33558762
uniprot
proteins
pubmed
34059824
uniprot
proteins
pubmed
34459874
uniprot
proteins
pubmed
36170811
uniprot
proteins
pubmed
36204986
uniprot
proteins
pubmed
37308477
uniprot
proteins
pubmed
9363775
uniprot
proteins
sequence_length
473
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000269|PubMed:21618344}; Single-pass membrane protein {ECO:0000250|UniProtKB:O35704}.
uniprot
proteins
transmembrane_region
TRANSMEM 16..36; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins