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FLASH GENE
Symbol SCAP contributors: mct - updated : 30-12-2015
HGNC name SREBF chaperone
HGNC id 30634
Location 3p21.31      Physical location : 47.455.183 - 47.517.445
Synonym name
  • SREBP cleavage-activating protein
  • sterol regulatory element-binding protein cleavage-activating protein
  • Synonym symbol(s) KIAA0199
    DNA
    TYPE functioning gene
    STRUCTURE 62.26 kb     23 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    LTF 3p21.31 lactotransferrin TMEM7 3p21.3 transmembrane protein 7 LRRC2 3p21.3 leucine-rich repeat-containing 2 TDGF1 3p21.31 teratocarcinoma-derived growth factor 1 FLJ36525 3p21.31 hypothetical protein LOC259173 TMIE 3p21 hypothetical protein LOC259173 TSP50 3p14-p12 testes-specific protease 50 TESSP5 3p21.31 testis serine protease 5 LOC391534 3 hypothetical gene supported by AK128390 TESSP2 3p21.31 testis serine protease 2 MYL3 3p21.3 myosin, light polypeptide 3, alkali; ventricular, skeletal, slow PTHR1 3p21.3 parathyroid hormone receptor 1 MGC23918 3p21.31 hypothetical protein MGC23918 KIAA0540 3p21.31 KIAA0540 protein LOC391535 3 similar to p75-like apoptosis-inducing death domain protein PLAIDD HYPB 3p21.2-q22.2 similar to p75-like apoptosis-inducing death domain protein PLAIDD MRP63P3 3p21.31 mitochondrial ribosomal protein 63 pseudogene 3 KIF9 3p21.31 kinesin family member 9 KIAA0795 3p21.31 kinesin family member 9 PTPN23 3p21.3 protein tyrosine phosphatase, non-receptor type 23 SCAP 3p24.3-p22.1 protein tyrosine phosphatase, non-receptor type 23 FLJ20211 3p21.31 hypothetical protein FLJ20211 CSPG5 3p21.3 chondroitin sulfate proteoglycan 5 (neuroglycan C) SMARCC1 3p23-p21 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily c, member 1 DHX30 3p31.31 DEAH (Asp-Glu-Ala-His) box polypeptide 30 MAP4 3p21.3 microtubule-associated protein 4 LOC391536 3 similar to 60S ribosomal protein L17 (L23) CDC25A 3p21.3 cell division cycle 25A CAMP 3p21.3 cathelicidin antimicrobial peptide SZF1 3p21 KRAB-zinc finger protein SZF1-1 MRPS18AP1 3p21.31 mitochondrial ribosomal protein S18A pseudogene 1 NME6 3p21.3 non-metastatic cells 6, protein expressed in (nucleoside-diphosphate kinase) LOC391537 3 similar to hypothetical protein PLXNB1 3p21.31 plexin B1 FLJ12436 3p21.31 hypothetical protein FLJ12436 HSPC016 3p21.31 hypothetical protein HSPC016 TREX1 3p21.3-p21.2 three prime repair exonuclease 1 SCOTIN 3p21.31 scotin PFKFB4 3p22-p21 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    23 - 4255 - 1279 - 2006 16705418
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • eight transmembrane helices (TM) joined by four small hydrophilic loops and three large loops
  • a sterol sensing domain (SSD)
  • WD40 repeats
  • HOMOLOGY
    interspecies homolog to murine Scap
    intraspecies homolog to NPC1L1
    Homologene
    FAMILY
  • hydroxymethylglutaryl CoA reductase family
  • WD repeat SCAP family
  • CATEGORY chaperone/stress
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic,vesicle
    intracellular,cytoplasm,cytosolic,microsome
    basic FUNCTION
  • in sterol-depleted cells, escorting SREBPs protein from the ER to the Golgi
  • regulating the sterol-dependent transcription of cholesterol biosynthetic genes carrying cis-acting sterol response elements (SREs)
  • subject to endoplasmic reticulum retention upon INSIG1 binding
  • key regulator of activation of SREBPs, which stimulate most enzymes in cholesterol and lipid synthesis
  • crucial role of SCAP-mediated control of cholesterol and lipid metabolism necessary for production of a proper myelin membrane by Schwann cells
  • cellular cholesterol homeostasis is maintained by SCAP, an endoplasmic reticulum (ER) protein with eight transmembrane helices
  • polytopic protein of the endoplasmic reticulum (ER) that controls cholesterol homeostasis by transporting sterol regulatory element-binding proteins (SREBPs) from the ER to the Golgi complex
  • enhanced SCAP glycosylation by inflammation induces macrophage foam cell formation
  • cellular cholesterol levels are controlled by endoplasmic reticulum (ER) sterol sensing proteins, which include SCAP and INSIG1
  • unlike the liver, the intestine requires SCAP to sustain tissue integrity by maintaining the high levels of lipid synthesis necessary for proliferation of intestinal crypts
  • SCAP is required for sterol synthesis and crypt growth in intestinal mucosa
  • SCAP is retrieved from the Golgi and moves to the ER after processing of SREBF under sterol-deficient conditions
  • acts as key glucose-responsive protein linking oncogenic signaling and fuel availability to SREBF-dependent lipogenesis
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism lipid/lipoprotein
    signaling
  • cholesterol, steroid
  • SCAP-SREBP pathway governing the massive lipid synthesis by Schwann cells that is required for myelin membrane expansion
  • a component part of SREBF-SCAP-INSIG complex
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • activating the serine proteases MBTBS1 and MBTBS2 the enzymes that process SREB (SREBF1, SREBF2)
  • with INSIG2
  • RNF139 hinders SREBPF2 processing through interaction with SREBPF2 and SCAP, regulating its own turnover rate by means of its E3 ubiquitin ligase activity
  • sterol sensor SCAP is a key regulator of SREBF2, the major transcription factor controlling cholesterol synthesis
  • ERLIN1, ERLIN2 promote stability of the SREBF-SCAP-INSIG complex and may contribute to the highly cooperative control of this system
  • SREBF1, SREBF2 actively prevents premature recycling of SCAP-SREBF until initiation of SREBF cleavage
  • PAQR3 interacts with SCAP and SREBF and tethers them to the Golgi
  • cell & other
    REGULATION
    Other regulated by 25-hydroxycholesterol
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   deletion    
    seriously affected the dynamics of myelin membrane synthesis and caused congenital hypomyelinating neuropathy
    constitutional     --low  
    and the consequent suppression of cholesterol synthesis in the brain may play an important role in the increased rates of cognitive decline and Alzheimer disease observed in diabetic states
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    diabetemetabolic syndrom 
    targeting SCAP N-glycosylation may provide a promising means of treating metabolic diseases
    cancer  
    targeting SCAP N-glycosylation may provide a promising means of treating malignancies
    ANIMAL & CELL MODELS
  • in mice with conditional SCAP deficiency in liver, decreased fatty acid synthesis in the liver is balanced by an equal increase in non hepatic tissues, primarily in adipose tissue
  • mice with haploinsufficiency of Scap in the brain show a ~30p100 reduction protein in brain cholesterol synthesis, similar to what is observed in diabetic mice
  • this compensatory response is mediated by an insulin-dependent increase in adipocyte SREBP1c and disappeared upon fasting
  • adipocytes showed insulin hypersensitivity and plasma VLDL triglycerides were dramatically reduced