SCD (stearoyl-CoA desaturase (delta-9-desaturase))

Note	SCD1 gene encodes an enzyme that serves as a fatty acid synthesizing enzyme and mostly produces oleic acid from stearic acid. Transcripts with alternative polyadenlyation and sizes 3.9 and 5.2 kb has been detected for this gene.
	Schematic representation of the genomic organization of exons of the SCD1 gene (17817 bp).
Description	SCD1 gene is located on chromosome 10q24.31, spans approximately 24 kb and has 6 exons and is mostly expressed in white adipose tissue and the liver (Arregui et al., 2012). The exon 1 is only 324bp while the exon 6 encodes for around 2 kb 3'-untranslated region (Mauvoisin & Mounier, 2011).
Transcription	The critical region for promoter activity is located between nucleotides 496-609 upstream of the translation start site. CCAAT box is identified as an important cis-element binding site in this region (Zhang, Ge, Tran, Stenn, & Prouty, 2001). Different transcription factors such as SREBP-1c, LXR, PPAR-a, C/EBP-a, NF-1, NF-Y, AP-1, Sp1, TR and PGC1-a bind to SCD1 promoter controlling the expression level of SCD1 (Mauvoisin & Mounier, 2011).
Pseudogene	Pseudogene of this gene is located on chromosome 17 at 17p11.2. The SCD1 pseudogene has two premature in-frame stop codons and is transcriptionally inactive (Zhang, Ge, Parimoo, Stenn, & Prouty, 1999).

Note	SCD1 is an iron containing enzyme which catalyses the oxidation of palmitoyl-CoA and stearoyl-CoA in ?9 position to produce corresponding derivatives palmitoleoyl-CoA and oleoyl-CoA, respectively. Formation of cis double bond is mediated by electeron-transfer proteins sequentially NADH-cytochrome b5 reductase, cytochrome b5 and SCD. Electrons flow from NADPH source to cytochrome b5 reductase and to the cytochrome b5 as the direct electron donor to SCD1 and finally to O2 which is reduced to H2O. The rate-limiting step in this reaction is desaturase (Zhang et al., 1999).
	A schematic representation of the domain structure of SCD1 protein (359 amino acids total), which consists of cytoplasmic, transmembrane, and lumenal domains.
Description	SCD1 contains four transmembrane domain which two NH2 and COOH terminals are located in cytoplasmic side. The single cytoplasmic loop and COOH terminus collectively contain eight Histidine residues forming His box and bind to iron at the center of catalytic site of desaturase. Two ER luminal loops are relatively smaller than cytosolic loop which contain two of the three conserved His motifs. Purified SCD1 remains in 37kDa band on SDS-PAGE and His segments located in 119, 156 and 296 provide ligands for nonheme iron within the catalytic site of the SCD1 (Paton & Ntambi, 2009).
Expression	SCD1 promoter contains several transcription factor binding sites that are involved in positive or negative regulation of SCD1 gene. Sterol regulatory element-binding proteins (SREBP) are a group of transcriptional factors belonging to helix-loop-helix leucine zipper family and are responsible for regulating cholesterol, fatty acids and triglyceride synthesis enzymes (Miyazaki et al., 2004). SREBP-1a is the dominant isoform of SREBP in human cultured cells and induces SCD1 gene expression (Shimomura, Shimano, Horton, Goldstein, & Brown, 1997). Furthermore, Liver X Receptors (LXR) including LXR-? and LXR-? serve as positive inducers of SCD1 gene (Peter et al., 2008). Therefore, PPAR? in combination with LXR causes elevation in the levels of SCD1 gene expression (Hebbachi, Knight, Wiggins, Patel, & Gibbons, 2008). The involvement of PPAR? in transcriptional regulation of SCD1 has also been reported in human pancreatic cells. Specifically, MEK/ERK1/2- and EGFR-dependent pathways exerted inhibitory effect on the expression and activity of SCD1 in these cells, possibly via PPAR? activation (Byagowi et al. 2015).
Localisation	SCD1 is anchored to reticulum endoplasmic membrane (Liu, Strable, & Ntambi, 2011).
Function	SCD1 is a rate-limiting enzyme which converts SFA to MUFA mainly oleate and palmitate causing high contents of MUFA in membrane phospholipids, triclycerides and cholesterol esters (Matsui et al., 2012).
Homology	Two SCD isoforms, SCD1 and SCD5 have been identified in human. SCD1 has a high degree of homology with SCD5 in human genome. Four SCD isoforms, SCD1 to SCD4 have also been identified in mouse. SCD1 shares about 85% amino acid identity with all 4 mouse SCD isoforms, as well as with rat SCD1 and SCD2. In contrast, SCD5 shares limited homology with the rodent SCDs and appears to be unique to primates (Wang et al., 2005). [supplied by OMIM, Mar 2008]. (Leung & Kim, 2013).

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