SPTLC2

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SPTLC2
Identifiers
AliasesSPTLC2, HSN1C, LCB2, LCB2A, NSAN1C, SPT2, hLCB2a, serine palmitoyltransferase long chain base subunit 2
External IDsOMIM: 605713 MGI: 108074 HomoloGene: 21610 GeneCards: SPTLC2
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_004863

NM_011479

RefSeq (protein)

NP_004854
NP_004854.1

NP_035609

Location (UCSC)Chr 14: 77.51 – 77.62 MbChr 12: 87.35 – 87.44 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Serine palmitoyltransferase, long chain base subunit 2, also known as SPTLC2, is a protein which in humans is encoded by the SPTLC2 gene.[5][6][7] SPTLC2 belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family.

Function

SPTLC2 encodes a long chain base subunit of serine palmitoyltransferase (SPT). The heterodimer formed with LCB1/SPTLC1 constitutes the catalytic core. It catalyzes the pyridoxal 5'-phosphate dependent condensation of L-serine with an acyl-CoA thioester to yield an amino alcohol. The composition of the SPT complex determines the substrate preference. The SPTLC1-SPTLC2-SPTSSA complex shows a strong preference for C16-CoA substrate, while the SPTLC1-SPTLC2-SPTSSB complex displays a preference for C18-CoA substrate.

The SPT complex synthesizes molecules used in various biological processes. For example, sphingosine, an 18-carbon amino alcohol with an unsaturated hydrocarbon chain, can be phosphorylated via sphingosine kinase. The resulting sphingosine-1-phosphate is a potent signaling lipid. Sphingosine is also a substrate for the synthesis of various other molecules including, ceramides, sphingomyelin, cerebrosides and globosides.

Epidermal ceramides are critical for normal skin barrier function and SPTLC2 is differentially expressed across body sites to regulate epidermal ceramide composition. In particular, SPTLC2 is upregulated in acral granular layer keratinocytes.[8]

Tissue distribution

SPTLC2 is widely expressed in all tissues.

Clinical significance

Mutations in SPTLC2 were identified in patients with hereditary sensory neuropathy type I.[9]

In response to IL-17A and TNF, SPTLC2 is highly upregulated in psoriasis and is likely responsible for some of the epidermal ceramide alterations seen in psoriasis plaques.[8]

Alternatively spliced variants encoding different isoforms of SPTLC2 have been identified.[5]

SPTLC2 expression is highly increased at the protein level in brains of patients with Alzheimer's disease. No changes are observed at the mRNA level.[10]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000100596 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021036 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b "Entrez Gene: SPTLC2 serine palmitoyltransferase, long chain base subunit 2".
  6. ^ Nagiec MM, Lester RL, Dickson RC (October 1996). "Sphingolipid synthesis: identification and characterization of mammalian cDNAs encoding the Lcb2 subunit of serine palmitoyltransferase". Gene. 177 (1–2): 237–241. doi:10.1016/0378-1119(96)00309-5. PMID 8921873.
  7. ^ Weiss B, Stoffel W (October 1997). "Human and murine serine-palmitoyl-CoA transferase--cloning, expression and characterization of the key enzyme in sphingolipid synthesis". European Journal of Biochemistry. 249 (1): 239–247. doi:10.1111/j.1432-1033.1997.00239.x. PMID 9363775.
  8. ^ a b Merleev AA, Le ST, Alexanian C, Toussi A, Xie Y, Marusina AI, et al. (August 2022). "Biogeographic and disease-specific alterations in epidermal lipid composition and single-cell analysis of acral keratinocytes". JCI Insight. 7 (16): e159762. doi:10.1172/jci.insight.159762. PMC 9462509. PMID 35900871.
  9. ^ Murphy SM, Ernst D, Wei Y, Laurà M, Liu YT, Polke J, et al. (June 2013). "Hereditary sensory and autonomic neuropathy type 1 (HSANI) caused by a novel mutation in SPTLC2". Neurology. 80 (23): 2106–2111. doi:10.1212/WNL.0b013e318295d789. PMC 3716354. PMID 23658386.
  10. ^ Geekiyanage H, Chan C (October 2011). "MicroRNA-137/181c regulates serine palmitoyltransferase and in turn amyloid β, novel targets in sporadic Alzheimer's disease". The Journal of Neuroscience. 31 (41): 14820–14830. doi:10.1523/JNEUROSCI.3883-11.2011. PMC 3200297. PMID 21994399.

Further reading