Human Gene SCAP (uc003crh.1) Description and Page Index
  Description: Homo sapiens SREBF chaperone (SCAP), mRNA.
RefSeq Summary (NM_012235): This gene encodes a protein with a sterol sensing domain (SSD) and seven WD domains. In the presence of cholesterol, this protein binds to sterol regulatory element binding proteins (SREBPs) and mediates their transport from the ER to the Golgi. The SREBPs are then proteolytically cleaved and regulate sterol biosynthesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016].
Transcript (Including UTRs)
   Position: hg19 chr3:47,455,184-47,517,445 Size: 62,262 Total Exon Count: 23 Strand: -
Coding Region
   Position: hg19 chr3:47,455,344-47,484,483 Size: 29,140 Coding Exon Count: 22 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsCTDGene Alleles
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr3:47,455,184-47,517,445)mRNA (may differ from genome)Protein (1279 aa)
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UniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: SCAP_HUMAN
DESCRIPTION: RecName: Full=Sterol regulatory element-binding protein cleavage-activating protein; Short=SCAP; Short=SREBP cleavage-activating protein;
FUNCTION: Escort protein required for cholesterol as well as lipid homeostasis. Regulates export of the SCAP/SREBF complex from the ER upon low cholesterol. Formation of a ternary complex with INSIG at high sterol concentrations leads to masking of an ER-export signal in SCAP and retention of the complex in the ER. Low sterol concentrations trigger release of INSIG, a conformational change in the SSC domain of SCAP, unmasking of the ER export signal, recruitment into COPII-coated vesicles, transport to the Golgi complex, proteolytic cleavage of SREBF in the Golgi, release of the transcription factor fragment of SREBF from the membrane, its import into the nucleus and up-regulation of LDLR, INSIG1 and the mevalonate pathway (By similarity).
SUBUNIT: Membrane region forms a homotetramer. Forms a stable complex with SREBF1/SREBP1 or SREBF2/SREBP2 through its C-terminal cytoplasmic domain. Forms a ternary complex with INSIG1 or INSIG2 through its transmembrane domains at high sterol concentrations. Interacts with the SEC23/SEC24 complex in a SAR1-GTP-dependent manner through an ER export signal in its third cytoplasmic loop. Binds cholesterol through its SSC domain (By similarity). Component of SCAP/SREBP complex composed of SREBF2, SCAP and RNF139; the complex hampers the interaction between SCAP and SEC24B, thereby reducing SREBF2 proteolytic processing. Interacts with RNF139; the interaction inhibits the interaction of SCAP with SEC24B and hampering the ER to Golgi transport of the SCAP/SREBP complex.
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity). Golgi apparatus membrane; Multi- pass membrane protein (By similarity). Cytoplasmic vesicle, COPII- coated vesicle membrane; Multi-pass membrane protein (By similarity). Note=Moves from the endoplasmic reticulum to the Golgi in the absence of sterols (By similarity).
INDUCTION: By androgen-bound AR and glucocorticoid-bound NR3C1 in a prostate cancer cell line (LNCaP).
DOMAIN: Cholesterol bound to SSC domain of SCAP or oxysterol bound to INSIG1/2 leads to masking of an ER export signal on SCAP possibly by moving the signal further away from the ER membrane (By similarity).
SIMILARITY: Belongs to the WD repeat SCAP family.
SIMILARITY: Contains 1 SSD (sterol-sensing) domain.
SIMILARITY: Contains 7 WD repeats.
SEQUENCE CAUTION: Sequence=BAA12111.2; Type=Erroneous initiation; Sequence=BAC11673.1; Type=Erroneous initiation;

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): SCAP
CDC HuGE Published Literature: SCAP

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 42.58 RPKM in Adrenal Gland
Total median expression: 901.06 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -114.00255-0.447 Picture PostScript Text
3' UTR -48.95160-0.306 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR026964 - SCAP
IPR000731 - SSD
IPR015943 - WD40/YVTN_repeat-like_dom
IPR001680 - WD40_repeat
IPR019775 - WD40_repeat_CS
IPR017986 - WD40_repeat_dom

Pfam Domains:
PF00400 - WD domain, G-beta repeat
PF02460 - Patched family
PF12349 - Sterol-sensing domain of SREBP cleavage-activation

SCOP Domains:
50952 - Soluble quinoprotein glucose dehydrogenase
50960 - TolB, C-terminal domain
63829 - Calcium-dependent phosphotriesterase
69304 - Tricorn protease N-terminal domain
101898 - NHL repeat
50965 - Galactose oxidase, central domain
75011 - 3-carboxy-cis,cis-mucoante lactonizing enzyme
101908 - Putative isomerase YbhE
50969 - YVTN repeat-like/Quinoprotein amine dehydrogenase
50974 - Nitrous oxide reductase, N-terminal domain
50978 - WD40 repeat-like
50993 - Prolyl oligopeptidase, N-terminal domain
69322 - Tricorn protease domain 2
50998 - Quinoprotein alcohol dehydrogenase-like
51004 - C-terminal (heme d1) domain of cytochrome cd1-nitrite reductase
82866 - Multidrug efflux transporter AcrB transmembrane domain

ModBase Predicted Comparative 3D Structure on Q12770
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserGenome BrowserGenome BrowserNo ortholog
   Gene DetailsGene Details 
   Gene SorterGene Sorter 
  EnsemblFlyBaseWormBase 
  Protein SequenceProtein SequenceProtein Sequence 
  AlignmentAlignmentAlignment 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005515 protein binding
GO:0015485 cholesterol binding
GO:0044877 macromolecular complex binding
GO:0051082 unfolded protein binding

Biological Process:
GO:0001666 response to hypoxia
GO:0006629 lipid metabolic process
GO:0007568 aging
GO:0008202 steroid metabolic process
GO:0008203 cholesterol metabolic process
GO:0019217 regulation of fatty acid metabolic process
GO:0032868 response to insulin
GO:0032933 SREBP signaling pathway
GO:0042304 regulation of fatty acid biosynthetic process
GO:0045540 regulation of cholesterol biosynthetic process
GO:0045541 negative regulation of cholesterol biosynthetic process
GO:0045716 positive regulation of low-density lipoprotein particle receptor biosynthetic process

Cellular Component:
GO:0000139 Golgi membrane
GO:0005783 endoplasmic reticulum
GO:0005789 endoplasmic reticulum membrane
GO:0005794 Golgi apparatus
GO:0012507 ER to Golgi transport vesicle membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0031410 cytoplasmic vesicle
GO:0032991 macromolecular complex
GO:0043231 intracellular membrane-bounded organelle


-  Descriptions from all associated GenBank mRNAs
  KJ902260 - Synthetic construct Homo sapiens clone ccsbBroadEn_11654 SCAP gene, encodes complete protein.
AK291484 - Homo sapiens cDNA FLJ77751 complete cds, highly similar to Homo sapiens SREBP cleavage-activating protein (SCAP), mRNA.
BC027207 - Homo sapiens SREBF chaperone, mRNA (cDNA clone IMAGE:4178439), complete cds.
BC020987 - Homo sapiens SREBF chaperone, mRNA (cDNA clone MGC:9728 IMAGE:3852258), complete cds.
AK091005 - Homo sapiens cDNA FLJ33686 fis, clone BRAWH2002679, moderately similar to SREBP cleavage activating protein.
AK075528 - Homo sapiens cDNA PSEC0227 fis, clone HEMBA1006019, highly similar to Sterol regulatory element binding protein cleavage-activating protein.
AK027402 - Homo sapiens cDNA FLJ14496 fis, clone NT2RM1000035.
AK300311 - Homo sapiens cDNA FLJ55669 complete cds, highly similar to Sterol regulatory element-binding protein cleavage-activating protein.
D83782 - Homo sapiens mRNA for KIAA0199 gene.
JD434739 - Sequence 415763 from Patent EP1572962.
JD458152 - Sequence 439176 from Patent EP1572962.
JD363343 - Sequence 344367 from Patent EP1572962.
JD074882 - Sequence 55906 from Patent EP1572962.
JD388559 - Sequence 369583 from Patent EP1572962.
JD431605 - Sequence 412629 from Patent EP1572962.
JD399089 - Sequence 380113 from Patent EP1572962.
AB383794 - Synthetic construct DNA, clone: pF1KSDA0199, Homo sapiens SCAP gene for sterol regulatory element-binding protein cleavage-activating protein, complete cds, without stop codon, in Flexi system.
DL492120 - Novel nucleic acids.
DL490656 - Novel nucleic acids.
CU676804 - Synthetic construct Homo sapiens gateway clone IMAGE:100017506 5' read SCAP mRNA.
DQ582850 - Homo sapiens piRNA piR-32962, complete sequence.
JD493499 - Sequence 474523 from Patent EP1572962.
JD530440 - Sequence 511464 from Patent EP1572962.
JD162742 - Sequence 143766 from Patent EP1572962.
JD421362 - Sequence 402386 from Patent EP1572962.
JD271291 - Sequence 252315 from Patent EP1572962.
JD458510 - Sequence 439534 from Patent EP1572962.
JD458511 - Sequence 439535 from Patent EP1572962.
JD406055 - Sequence 387079 from Patent EP1572962.
JD458514 - Sequence 439538 from Patent EP1572962.
JD056228 - Sequence 37252 from Patent EP1572962.
JD057274 - Sequence 38298 from Patent EP1572962.
JD406801 - Sequence 387825 from Patent EP1572962.
JD458513 - Sequence 439537 from Patent EP1572962.
JD461601 - Sequence 442625 from Patent EP1572962.
JD354702 - Sequence 335726 from Patent EP1572962.
JD390189 - Sequence 371213 from Patent EP1572962.
JD406891 - Sequence 387915 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q12770 (Reactome details) participates in the following event(s):

R-HSA-1655842 S1P hydrolyzes SREBP1A,1C,2
R-HSA-1655829 Regulation of cholesterol biosynthesis by SREBP (SREBF)
R-HSA-8957322 Metabolism of steroids
R-HSA-556833 Metabolism of lipids
R-HSA-1430728 Metabolism

-  Other Names for This Gene
  Alternate Gene Symbols: KIAA0199, NM_012235, NP_036367, PSEC0227, Q12770, Q8N2E0, Q8WUA1, SCAP_HUMAN
UCSC ID: uc003crh.1
RefSeq Accession: NM_012235
Protein: Q12770 (aka SCAP_HUMAN)
CCDS: CCDS2755.2

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_012235.2
exon count: 23CDS single in 3' UTR: no RNA size: 4255
ORF size: 3840CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 7644.00frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.