SPTLC2

SPTLC2
Identifiers
Aliases	SPTLC2, HSN1C, LCB2, LCB2A, NSAN1C, SPT2, hLCB2a, serine palmitoyltransferase long chain base subunit 2
External IDs	OMIM: 605713; MGI: 108074; HomoloGene: 21610; GeneCards: SPTLC2; OMA:SPTLC2 - orthologs
Gene location (Human) Chr. Chromosome 14 (human) Band 14q24.3 Start 77,505,997 bp End 77,616,637 bp
Gene location (Mouse) Chr. Chromosome 12 (mouse) Band 12|12 D2 Start 87,351,832 bp End 87,435,129 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in corpus callosum inferior ganglion of vagus nerve internal globus pallidus monocyte subthalamic nucleus C1 segment stromal cell of endometrium buccal mucosa cell pars reticulata blood Top expressed in decidua gastrula genital tubercle granulocyte duodenum tail of embryo ileum gastric mucosa mucous cell of stomach epithelium of stomach More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity catalytic activity serine C-palmitoyltransferase activity pyridoxal phosphate binding acyltransferase activity Cellular component integral component of membrane serine C-palmitoyltransferase complex endoplasmic reticulum membrane membrane endoplasmic reticulum mitochondrion Biological process lipid metabolism sphinganine biosynthetic process sphingosine biosynthetic process sphingolipid biosynthetic process biosynthesis sphingomyelin biosynthetic process positive regulation of lipophagy metabolism ceramide biosynthetic process sphingolipid metabolic process adipose tissue development Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 9517 20773 Ensembl ENSG00000100596 ENSMUSG00000021036 UniProt O15270 P97363 RefSeq (mRNA) NM_004863 NM_011479 RefSeq (protein) NP_004854 NP_004854.1 NP_035609 Location (UCSC) Chr 14: 77.51 – 77.62 Mb Chr 12: 87.35 – 87.44 Mb PubMed search
Wikidata
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Serine palmitoyltransferase, long chain base subunit 2, also known as SPTLC2, is a protein which in humans is encoded by the SPTLC2 gene. 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.

Tissue distribution

SPTLC2 is widely expressed in all tissues.

Clinical significance

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

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.

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

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.

Further reading

• Takeda J, Yano H, Eng S, Zeng Y, Bell GI (November 1993). "A molecular inventory of human pancreatic islets: sequence analysis of 1000 cDNA clones". Human Molecular Genetics. 2 (11): 1793–1798. doi:10.1093/hmg/2.11.1793. PMID 7506601.
• Hillier LD, Lennon G, Becker M, Bonaldo MF, Chiapelli B, Chissoe S, et al. (September 1996). "Generation and analysis of 280,000 human expressed sequence tags". Genome Research. 6 (9): 807–828. doi:10.1101/gr.6.9.807. PMID 8889549.
• 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.
• 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.
• Nagase T, Ishikawa K, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (February 1998). "Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro". DNA Research. 5 (1): 31–39. CiteSeerX 10.1.1.610.1181. doi:10.1093/dnares/5.1.31. PMID 9628581.
• Hanada K, Hara T, Nishijima M (March 2000). "Purification of the serine palmitoyltransferase complex responsible for sphingoid base synthesis by using affinity peptide chromatography techniques". The Journal of Biological Chemistry. 275 (12): 8409–8415. doi:10.1074/jbc.275.12.8409. PMID 10722674.
• Dias Neto E, Correa RG, Verjovski-Almeida S, Briones MR, Nagai MA, da Silva W, et al. (March 2000). "Shotgun sequencing of the human transcriptome with ORF expressed sequence tags". Proceedings of the National Academy of Sciences of the United States of America. 97 (7): 3491–3496. Bibcode:2000PNAS...97.3491D. doi:10.1073/pnas.97.7.3491. PMC 16267. PMID 10737800.
• Dawkins JL, Brahmbhatt S, Auer-Grumbach M, Wagner K, Hartung HP, Verhoeven K, et al. (October 2002). "Exclusion of serine palmitoyltransferase long chain base subunit 2 (SPTLC2) as a common cause for hereditary sensory neuropathy". Neuromuscular Disorders. 12 (7–8): 656–658. doi:10.1016/S0960-8966(02)00015-9. PMID 12207934. S2CID 1248860.
• Stachowitz S, Alessandrini F, Abeck D, Ring J, Behrendt H (November 2002). "Permeability barrier disruption increases the level of serine palmitoyltransferase in human epidermis". The Journal of Investigative Dermatology. 119 (5): 1048–1052. doi:10.1046/j.1523-1747.2002.19524.x. PMID 12445191.
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, et al. (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–1178. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (November 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–648. doi:10.1016/j.cell.2006.09.026. PMID 17081983.
• Chen M, Han G, Dietrich CR, Dunn TM, Cahoon EB (December 2006). "The essential nature of sphingolipids in plants as revealed by the functional identification and characterization of the Arabidopsis LCB1 subunit of serine palmitoyltransferase". The Plant Cell. 18 (12): 3576–3593. doi:10.1105/tpc.105.040774. PMC 1785403. PMID 17194770.
• Hornemann T, Wei Y, von Eckardstein A (July 2007). "Is the mammalian serine palmitoyltransferase a high-molecular-mass complex?". The Biochemical Journal. 405 (1): 157–164. doi:10.1042/BJ20070025. PMC 1925250. PMID 17331073.