P97363 · SPTC2_MOUSE
- ProteinSerine palmitoyltransferase 2
- GeneSptlc2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids560 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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 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. The composition of the serine palmitoyltransferase (SPT) complex determines the substrate preference. 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. 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 (By similarity).
Crucial for adipogenesis (PubMed:28698261).
Crucial for adipogenesis (PubMed:28698261).
Catalytic activity
- H+ + hexadecanoyl-CoA + L-serine = 3-oxosphinganine + CO2 + CoAThis reaction proceeds in the forward direction.
- H+ + L-serine + octadecanoyl-CoA = 3-oxoeicosasphinganine + CO2 + CoA
Cofactor
Activity regulation
SPT complex catalytic activity is negatively regulated by ORMDL proteins, including ORMDL3, in the presence of ceramides. 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.
Pathway
Lipid metabolism; sphingolipid metabolism.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | endoplasmic reticulum membrane | |
Cellular Component | mitochondrion | |
Cellular Component | serine palmitoyltransferase complex | |
Molecular Function | pyridoxal phosphate binding | |
Molecular Function | serine C-palmitoyltransferase activity | |
Biological Process | adipose tissue development | |
Biological Process | ceramide biosynthetic process | |
Biological Process | lipophagy | |
Biological Process | positive regulation of lipophagy | |
Biological Process | sphinganine biosynthetic process | |
Biological Process | sphingolipid biosynthetic process | |
Biological Process | sphingomyelin biosynthetic process | |
Biological Process | sphingosine biosynthetic process |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameSerine palmitoyltransferase 2
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionP97363
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Endoplasmic reticulum membrane ; Single-pass membrane protein
Features
Showing features for transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transmembrane | 65-85 | Helical | ||||
Sequence: PMLVAVLTYVGYGVLTLFGYL |
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Adipocyte-specific knockout mice have reduced adipose tissue mass and develop hepatosteatosis with insulin resistance and hyperglycemia.
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 29 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000163859 | 1-560 | Serine palmitoyltransferase 2 | |||
Sequence: MRPEPGGCCCRRPMRANGCVKNGEVRNGYLRSSTATVAAAGQIHHVTENGGLYKRPFNEAFEETPMLVAVLTYVGYGVLTLFGYLRDFLRHWRIEKCHHATEREEQKDFVSLYQDFENFYTRNLYMRIRDNWNRPICSVPGAKVDIMERKSHDYNWSFKYTGNIIKGVINMGSYNYLGFARNTGSCQEAAAEVLKEYGAGVCSTRQEIGNLDKHEELEKLVARFLGVEAAMTYGMGFATNSMNIPALVGKGCLILSDELNHASLVLGARLSGATIRIFKHNNMQSLEKLLKDAIVYGQPRTRRPWKKILILVEGIYSMEGSIVRLPEVIALKKKYKAYLYLDEAHSIGALGPSGRGVVDYFGLDPEDVDVMMGTFTKSFGASGGYIGGKKELIDYLRTHSHSAVYATSMSPPVMEQIITSMKCIMGQDGTSLGKECIQQLAENTRYFRRRLKEMGFIIYGNEDSPVVPLMLYMPAKIGAFGREMLKRNIGVVVVGFPATPIIESRARFCLSAAHTKEILDTALKEIDEVGDLLQLKYSRHRLVPLLDRPFDETTYEETED | ||||||
Modified residue | 377 | N6-(pyridoxal phosphate)lysine | ||||
Sequence: K |
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in a variety of tissues. Expressed in brains cortices (at protein level) (PubMed:21994399).
Expressed in brown and white adipose tissues (PubMed:27818258, PubMed:28698261).
Expressed in liver (PubMed:27818258).
Expressed in brown and white adipose tissues (PubMed:27818258, PubMed:28698261).
Expressed in liver (PubMed:27818258).
Induction
Expression levels increase upon high-fat diet (at protein level).
Developmental stage
In brains, expressed at low levels after birth, expression highly increases at 2 weeks after birth to decrease and be maintained at 4 weeks after birth until, at least, 18 months (PubMed:21994399).
Expression increases in differentiated adipocytes (PubMed:28698261).
Expression increases in differentiated adipocytes (PubMed:28698261).
Gene expression databases
Interaction
Subunit
Component of the serine palmitoyltransferase (SPT) complex, which is composed of SPTLC1, SPTLC2 or SPTLC3 and SPTSSA or SPTSSB. The heterodimer consisting of SPTLC1 and SPTLC2/SPTLC3 forms the catalytic core of the enzyme, while SPTSSA or SPTSSB subunits determine substrate specificity. SPT also interacts with ORMDL proteins, especially ORMDL3, which negatively regulate SPT activity in the presence of ceramides. Forms dimers of heterodimers with SPTLC1.
Protein-protein interaction databases
Miscellaneous
Structure
Sequence
- Sequence statusComplete
- Length560
- Mass (Da)62,982
- Last updated1998-01-01 v2
- Checksum6429566979B18D1C
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U27455 EMBL· GenBank· DDBJ | AAC53310.1 EMBL· GenBank· DDBJ | mRNA | ||
X95642 EMBL· GenBank· DDBJ | CAA64898.1 EMBL· GenBank· DDBJ | mRNA | ||
BC003227 EMBL· GenBank· DDBJ | AAH03227.1 EMBL· GenBank· DDBJ | mRNA |