Reactome | UniProt:O15270 SPTLC2

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UniProt:O15270 SPTLC2 Show undefined attributes

chain	chain:1-562
checksum	0C1AA1E233DE36F1
comment	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).CATALYTIC ACTIVITY L-serine + hexadecanoyl-CoA + H(+) = 3-oxosphinganine + CO2 + CoACATALYTIC ACTIVITY octadecanoyl-CoA + L-serine + H(+) = 3-oxoeicosasphinganine + CO2 + CoACOFACTOR 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).BIOPHYSICOCHEMICAL PROPERTIES Lipid metabolism; sphingolipid metabolism.SUBUNIT Component of the serine palmitoyltransferase (SPT) complex, which is composed of SPTLC1, SPTLC2 or SPTLC3 and SPTSSA or SPTSSB (PubMed:19416851). The heterodimer consisting of SPTLC1 and SPTLC2/SPTLC3 forms the catalytic core of the enzyme, while SPTSSA or SPTSSB subunits determine substrate specificity (PubMed:33558762, PubMed:37308477). SPT also interacts with ORMDL proteins, especially ORMDL3, which negatively regulate SPT activity in the presence of ceramides (PubMed:30700557, PubMed:33558762, PubMed:37308477). Forms dimers of heterodimers with SPTLC1 (PubMed:33558761, PubMed:33558762).INTERACTION Widely expressed.INDUCTION Expression at protein level is highly increased in brains of patients with Alzheimer disease. No changes are observed at mRNA level.DISEASE 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).SIMILARITY Belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family.SEQUENCE CAUTION Extended N-terminus.
crossReference	[DatabaseIdentifier:12813723] ZINC - Substances:SPTC2_HUMAN [DatabaseIdentifier:12817147] ZINC target:O15270 [DatabaseIdentifier:11473958] ENSEMBL:ENSG00000100596 [DatabaseIdentifier:11572440] ENSEMBL:ENSP00000216484 [DatabaseIdentifier:11695139] ENSEMBL:ENST00000216484 [DatabaseIdentifier:11780427] Guide to Pharmacology - Targets:2510 [DatabaseIdentifier:11788731] GeneCards:SPTLC2 [DatabaseIdentifier:11833652] HMDB Protein:HMDBP00888 [DatabaseIdentifier:11841765] HPA:ENSG00000100596-SPTLC2 [DatabaseIdentifier:11851247] IntEnz:2.3.1.50 [DatabaseIdentifier:12126351] OpenTargets:ENSG00000100596 [DatabaseIdentifier:12137617] Orphanet:SPTLC2 [DatabaseIdentifier:12186930] PDB:6M4O [DatabaseIdentifier:12186927] PDB:7YIY [DatabaseIdentifier:12186926] PDB:7K0N [DatabaseIdentifier:12186925] PDB:6M4N [DatabaseIdentifier:12186938] PDB:7K0K [DatabaseIdentifier:12186933] PDB:7K0Q [DatabaseIdentifier:12186940] PDB:7CQK [DatabaseIdentifier:12186931] PDB:7K0M [DatabaseIdentifier:12186941] PDB:7CQI [DatabaseIdentifier:12186934] PDB:7YJ2 [DatabaseIdentifier:12186932] PDB:7K0P [DatabaseIdentifier:12186929] PDB:7K0L [DatabaseIdentifier:12186928] PDB:7K0O [DatabaseIdentifier:12186935] PDB:7YJ1 [DatabaseIdentifier:12186937] PDB:7YIU [DatabaseIdentifier:12186936] PDB:7K0J [DatabaseIdentifier:12186939] PDB:7K0I [DatabaseIdentifier:12266629] PRO:O15270 [DatabaseIdentifier:12286611] Pharos - Targets:O15270 [DatabaseIdentifier:12372120] RefSeq:NP_004854.1 [DatabaseIdentifier:12810003] ZINC - Predictions - Purchasable:SPTC2_HUMAN
databaseName	UniProt
dbId	58443
description	recommendedName: fullName evidence="17"Serine palmitoyltransferase 2 ecNumber evidence="5"2.3.1.50 alternativeName: Long chain base biosynthesis protein 2 shortName: LCB 2 alternativeName: Long chain base biosynthesis protein 2a shortName evidence="16"LCB2a alternativeName: Serine-palmitoyl-CoA transferase 2 shortName: SPT 2
displayName	UniProt:O15270 SPTLC2
geneName	SPTLC2 KIAA0526 LCB2
identifier	O15270
isSequenceChanged	false
keyword	3D-structure Acyltransferase Disease variant Endoplasmic reticulum Lipid metabolism Membrane Neurodegeneration Neuropathy Proteomics identification Pyridoxal phosphate Reference proteome Sphingolipid metabolism Transferase Transmembrane Transmembrane helix
modified	[InstanceEdit:9939033] Weiser, Joel, 2025-02-21
moleculeType	Protein
name	SPTLC2
otherIdentifier	11720645_at 11720646_at 11758838_at 16795192 203127_PM_s_at 203127_s_at 203128_PM_at 203128_at 216202_PM_s_at 216202_s_at 216203_PM_at 216203_at 225095_PM_at 225095_at 3573153 3573154 3573155 3573156 3573157 3573158 3573160 3573161 3573162 3573166 3573177 3573178 3573179 3573180 3573181 3573182 3573183 3573191 3573192 3573193 3573194 3573197 3573198 3573199 3573200 3573205 3573212 3573213 3573214 36518_at 63368_at 7980438 9517 A_23_P3146 A_24_P150486 GE53256 GE88612 GO:0004758 GO:0005515 GO:0005783 GO:0005789 GO:0006629 GO:0006665 GO:0006686 GO:0009058 GO:0016020 GO:0016740 GO:0016746 GO:0017059 GO:0030148 GO:0030170 GO:0046511 GO:0046512 GO:0046513 GO:0048856 GO:0060612 GO:1904504 HMNXSV003012274 Hs.315482.0.A1_3p_at Hs.59403.1.S1_3p_at ILMN_1704290 PH_hs_0003815 TC14001348.hg TC14002098.hg U15555_at g13477298_3p_a_at g4758667_3p_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-428146] PXLP-K379-SPTLC2 [endoplasmic reticulum membrane] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000100596] ENSEMBL:ENSG00000100596 SPTLC2 [ReferenceDNASequence:11339154] BioGPS Gene:9517 SPTLC2 [ReferenceDNASequence:11399711] COSMIC - genes:SPTLC2 SPTLC2 [ReferenceDNASequence:11415110] CTD Gene:9517 SPTLC2 [ReferenceDNASequence:11436733] dbSNP Gene:9517 SPTLC2 [ReferenceDNASequence:11820383] HGNC:11278 SPTLC2 [ReferenceDNASequence:11880026] KEGG:hsa:9517 SPTLC2 [ReferenceDNASequence:11968943] Monarch:9517 SPTLC2 [ReferenceDNASequence:12053036] NCBI Gene:9517 SPTLC2 [ReferenceDNASequence:12111389] OMIM:605713 SPTLC2 [ReferenceDNASequence:12739145] UCSC:O15270 SPTLC2
referenceTranscript	[ReferenceRNASequence:12553905] RefSeq:NM_004863.4 SPTLC2
schemaClass	ReferenceGeneProduct
secondaryIdentifier	SPTC2_HUMAN Q16685
sequenceLength	562
species	[Species:48887] Homo sapiens
stId	uniprot:O15270
url	http://purl.uniprot.org/uniprot/O15270

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-428146] PXLP-K379-SPTLC2 [endoplasmic reticulum membrane]
(referenceSequence)	[ModifiedResidue:554223] N6-pyridoxal phosphate-L-lysine at 379
(interactor)	[UndirectedInteraction:11148857] UniProt:P13569 <-> UniProt:O15270 (IntAct) [UndirectedInteraction:11185235] UniProt:Q9H1C4 <-> UniProt:O15270 (IntAct)

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