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SCAP SREBF chaperone [ Homo sapiens (human) ]

Gene ID: 22937, updated on 7-Apr-2024

Summary

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Official Symbol
SCAPprovided by HGNC
Official Full Name
SREBF chaperoneprovided by HGNC
Primary source
HGNC:HGNC:30634
See related
Ensembl:ENSG00000114650 MIM:601510; AllianceGenome:HGNC:30634
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Summary
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]
Expression
Ubiquitous expression in adrenal (RPKM 22.6), testis (RPKM 19.9) and 25 other tissues See more
Orthologs
mouse all
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Genomic context

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See SCAP in Genome Data Viewer
Location:
3p21.31
Exon count:
29
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (47413681..47477127, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (47430101..47496247, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (47455171..47517431, complement)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr3:47323613-47324812 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19812 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14308 Neighboring gene kelch like family member 18 Neighboring gene Sharpr-MPRA regulatory region 13740 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr3:47403837-47405036 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:47421897-47422574 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:47422575-47423250 Neighboring gene PTPN23 divergent transcript Neighboring gene ReSE screen-validated silencer GRCh37_chr3:47440022-47440203 Neighboring gene protein tyrosine phosphatase non-receptor type 23 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:47446437-47446936 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:47447130-47447995 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:47457771-47458270 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:47457269-47457770 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19815 Neighboring gene small nucleolar RNA U13 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:47508426-47508527 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14309 Neighboring gene uncharacterized LOC105377073 Neighboring gene SPMIP3 pseudogene 1 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:47529703-47530204 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:47530205-47530704 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:47546017-47546910 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19816 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19817 Neighboring gene bolA family member 2 pseudogene 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19818 Neighboring gene elongator acetyltransferase complex subunit 6 Neighboring gene uncharacterized LOC105377074

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Interaction between lifestyle behaviors and genetic polymorphism in SCAP gene on blood pressure among Chinese children. Yang YD, et al. Pediatr Res, 2019 Sep. PMID 31003232
  2. Genetic variations in sterol regulatory element binding protein cleavage-activating protein (SCAP) are associated with blood pressure in overweight/obese Chinese children. Yang YD, et al. PLoS One, 2017. PMID 28542467, Free PMC Article
  3. Cholesterol-induced conformational changes in the sterol-sensing domain of the Scap protein suggest feedback mechanism to control cholesterol synthesis. Gao Y, et al. J Biol Chem, 2017 May 26. PMID 28377508, Free PMC Article
  4. Endoplasmic Reticulum Protein SCAP Inhibits Dengue Virus NS2B3 Protease by Suppressing Its K27-Linked Polyubiquitylation. Liu H, et al. J Virol, 2017 May 1. PMID 28228593, Free PMC Article
  5. SCAP gene polymorphisms decrease the risk of nonalcoholic fatty liver disease in females with metabolic syndrome. Sun S, et al. J Genet, 2013 Dec. PMID 24371177

See all (84) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. The Role of SCAP/SREBP as Central Regulators of Lipid Metabolism in Hepatic Steatosis.
    Title: The Role of SCAP/SREBP as Central Regulators of Lipid Metabolism in Hepatic Steatosis.
  2. SARS-CoV-2 nucleocapsid protein promotes TMAO-induced NLRP3 inflammasome activation by SCAP-SREBP signaling pathway.
    Title: SARS-CoV-2 nucleocapsid protein promotes TMAO-induced NLRP3 inflammasome activation by SCAP-SREBP signaling pathway.
  3. Deficiency of SCAP inhibits HBV pathogenesis via activation of the interferon signaling pathway.
    Title: Deficiency of SCAP inhibits HBV pathogenesis via activation of the interferon signaling pathway.
  4. Structural basis for sterol sensing by Scap and Insig.
    Title: Structural basis for sterol sensing by Scap and Insig.
  5. Discovery of a potent SCAP degrader that ameliorates HFD-induced obesity, hyperlipidemia and insulin resistance via an autophagy-independent lysosomal pathway.
    Title: Discovery of a potent SCAP degrader that ameliorates HFD-induced obesity, hyperlipidemia and insulin resistance via an autophagy-independent lysosomal pathway.
  6. PKM2-TMEM33 axis regulates lipid homeostasis in cancer cells by controlling SCAP stability.
    Title: PKM2-TMEM33 axis regulates lipid homeostasis in cancer cells by controlling SCAP stability.
  7. The ER cholesterol sensor SCAP promotes CARTS biogenesis at ER-Golgi membrane contact sites.
    Title: The ER cholesterol sensor SCAP promotes CARTS biogenesis at ER-Golgi membrane contact sites.
  8. A structure of human Scap bound to Insig-2 suggests how their interaction is regulated by sterols.
    Title: A structure of human Scap bound to Insig-2 suggests how their interaction is regulated by sterols.
  9. Ring finger protein 5 activates sterol regulatory element-binding protein 2 (SREBP2) to promote cholesterol biosynthesis via inducing polyubiquitination of SREBP chaperone SCAP.
    Title: Ring finger protein 5 activates sterol regulatory element-binding protein 2 (SREBP2) to promote cholesterol biosynthesis via inducing polyubiquitination of SREBP chaperone SCAP.
  10. Interaction between lifestyle behaviors and genetic polymorphism in SCAP gene on blood pressure among Chinese children.
    Title: Interaction between lifestyle behaviors and genetic polymorphism in SCAP gene on blood pressure among Chinese children.
Submit: New GeneRIF Correction See all GeneRIFs (36)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • KIAA0199

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein-containing complex binding IEA
Inferred from Electronic Annotation
more info
  
enables sterol binding ISS
Inferred from Sequence or Structural Similarity
more info
  
enables unfolded protein binding NAS
Non-traceable Author Statement
more info
 PubMed 
Process Evidence Code Pubs
involved_in COPII-coated vesicle cargo loading ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in SREBP signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in SREBP signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in cellular lipid metabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in cholesterol metabolic process ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in immune response IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of cholesterol biosynthetic process NAS
Non-traceable Author Statement
more info
  
involved_in positive regulation of cholesterol biosynthetic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of cholesterol biosynthetic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in regulation of fatty acid biosynthetic process IEA
Inferred from Electronic Annotation
more info
  
involved_in response to hypoxia IEA
Inferred from Electronic Annotation
more info
  
involved_in response to insulin IEA
Inferred from Electronic Annotation
more info
  
involved_in response to vitamin B3 IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in ER to Golgi transport vesicle membrane IEA
Inferred from Electronic Annotation
more info
  
located_in Golgi apparatus NAS
Non-traceable Author Statement
more info
 PubMed 
located_in Golgi membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in Golgi membrane TAS
Traceable Author Statement
more info
  
part_of SREBP-SCAP complex IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in endoplasmic reticulum NAS
Non-traceable Author Statement
more info
 PubMed 
is_active_in endoplasmic reticulum membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in endoplasmic reticulum membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in membrane NAS
Non-traceable Author Statement
more info
 PubMed 

General protein information

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Preferred Names
sterol regulatory element-binding protein cleavage-activating protein
Names
SREBP cleavage-activating protein

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001320044.2 → NP_001306973.1  sterol regulatory element-binding protein cleavage-activating protein isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) has multiple differences compared to variant 1. These differences result in a distinct 5' UTR and cause translation initiation at a downstream start codon, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.
    Source sequence(s)
    AC099778, AK300311, BG179218, CN313163
    UniProtKB/TrEMBL
    B7Z6H0
    Conserved Domains (4) summary
    COG2319
    Location:683 → 979
    WD40; WD40 repeat [General function prediction only]
    pfam12349
    Location:53 → 202
    Sterol-sensing; Sterol-sensing domain of SREBP cleavage-activation
    sd00039
    Location:703 → 749
    7WD40; WD40 repeat [structural motif]
    cl02567
    Location:822 → 979
    WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

  2. NM_012235.4 → NP_036367.2  sterol regulatory element-binding protein cleavage-activating protein isoform 1

    See identical proteins and their annotated locations for NP_036367.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AC099778, BG179218, D83782
    Consensus CDS
    CCDS2755.2
    UniProtKB/Swiss-Prot
    Q12770, Q8N2E0, Q8WUA1
    Related
    ENSP00000265565.5, ENST00000265565.10
    Conserved Domains (4) summary
    COG2319
    Location:939 → 1235
    WD40; WD40 repeat [General function prediction only]
    pfam12349
    Location:308 → 457
    Sterol-sensing; Sterol-sensing domain of SREBP cleavage-activation
    sd00039
    Location:959 → 1005
    7WD40; WD40 repeat [structural motif]
    cl02567
    Location:1078 → 1235
    WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000003.12 Reference GRCh38.p14 Primary Assembly

    Range
    47413681..47477127 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011533501.2 → XP_011531803.1  sterol regulatory element-binding protein cleavage-activating protein isoform X1

    See identical proteins and their annotated locations for XP_011531803.1

    UniProtKB/Swiss-Prot
    Q12770, Q8N2E0, Q8WUA1
    Conserved Domains (4) summary
    COG2319
    Location:939 → 1235
    WD40; WD40 repeat [General function prediction only]
    pfam12349
    Location:308 → 457
    Sterol-sensing; Sterol-sensing domain of SREBP cleavage-activation
    sd00039
    Location:959 → 1005
    7WD40; WD40 repeat [structural motif]
    cl02567
    Location:1078 → 1235
    WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

  2. XM_005264967.3 → XP_005265024.1  sterol regulatory element-binding protein cleavage-activating protein isoform X2

    UniProtKB/TrEMBL
    B7Z6H0
    Conserved Domains (4) summary
    COG2319
    Location:938 → 1234
    WD40; WD40 repeat [General function prediction only]
    pfam12349
    Location:308 → 457
    Sterol-sensing; Sterol-sensing domain of SREBP cleavage-activation
    sd00039
    Location:958 → 1004
    7WD40; WD40 repeat [structural motif]
    cl02567
    Location:1077 → 1234
    WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

  3. XM_047447740.1 → XP_047303696.1  sterol regulatory element-binding protein cleavage-activating protein isoform X2

  4. XM_017005918.2 → XP_016861407.1  sterol regulatory element-binding protein cleavage-activating protein isoform X1

    UniProtKB/Swiss-Prot
    Q12770, Q8N2E0, Q8WUA1
    Conserved Domains (4) summary
    COG2319
    Location:939 → 1235
    WD40; WD40 repeat [General function prediction only]
    pfam12349
    Location:308 → 457
    Sterol-sensing; Sterol-sensing domain of SREBP cleavage-activation
    sd00039
    Location:959 → 1005
    7WD40; WD40 repeat [structural motif]
    cl02567
    Location:1078 → 1235
    WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

  5. XM_047447739.1 → XP_047303695.1  sterol regulatory element-binding protein cleavage-activating protein isoform X2

  6. XM_047447737.1 → XP_047303693.1  sterol regulatory element-binding protein cleavage-activating protein isoform X2

  7. XM_047447732.1 → XP_047303688.1  sterol regulatory element-binding protein cleavage-activating protein isoform X1

    UniProtKB/Swiss-Prot
    Q12770, Q8N2E0, Q8WUA1

  8. XM_047447738.1 → XP_047303694.1  sterol regulatory element-binding protein cleavage-activating protein isoform X2

  9. XM_047447734.1 → XP_047303690.1  sterol regulatory element-binding protein cleavage-activating protein isoform X1

    UniProtKB/Swiss-Prot
    Q12770, Q8N2E0, Q8WUA1

  10. XM_047447736.1 → XP_047303692.1  sterol regulatory element-binding protein cleavage-activating protein isoform X1

    UniProtKB/Swiss-Prot
    Q12770, Q8N2E0, Q8WUA1

  11. XM_047447733.1 → XP_047303689.1  sterol regulatory element-binding protein cleavage-activating protein isoform X1

    UniProtKB/Swiss-Prot
    Q12770, Q8N2E0, Q8WUA1

  12. XM_047447735.1 → XP_047303691.1  sterol regulatory element-binding protein cleavage-activating protein isoform X1

    UniProtKB/Swiss-Prot
    Q12770, Q8N2E0, Q8WUA1
    Related
    ENSP00000497087.1, ENST00000648151.1

  13. XM_047447744.1 → XP_047303700.1  sterol regulatory element-binding protein cleavage-activating protein isoform X7

  14. XM_047447742.1 → XP_047303698.1  sterol regulatory element-binding protein cleavage-activating protein isoform X4

  15. XM_047447741.1 → XP_047303697.1  sterol regulatory element-binding protein cleavage-activating protein isoform X3

  16. XM_047447743.1 → XP_047303699.1  sterol regulatory element-binding protein cleavage-activating protein isoform X6

  17. XM_011533502.4 → XP_011531804.1  sterol regulatory element-binding protein cleavage-activating protein isoform X5

    UniProtKB/TrEMBL
    A8K619
    Conserved Domains (4) summary
    COG2319
    Location:558 → 854
    WD40; WD40 repeat [General function prediction only]
    sd00039
    Location:578 → 624
    7WD40; WD40 repeat [structural motif]
    cl02567
    Location:697 → 854
    WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...
    cl21543
    Location:3 → 76
    MMPL; MMPL family

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060927.1 Alternate T2T-CHM13v2.0

    Range
    47430101..47496247 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054345725.1 → XP_054201700.1  sterol regulatory element-binding protein cleavage-activating protein isoform X1

  2. XM_054345727.1 → XP_054201702.1  sterol regulatory element-binding protein cleavage-activating protein isoform X2

  3. XM_054345731.1 → XP_054201706.1  sterol regulatory element-binding protein cleavage-activating protein isoform X2

  4. XM_054345722.1 → XP_054201697.1  sterol regulatory element-binding protein cleavage-activating protein isoform X1

  5. XM_054345730.1 → XP_054201705.1  sterol regulatory element-binding protein cleavage-activating protein isoform X2

  6. XM_054345728.1 → XP_054201703.1  sterol regulatory element-binding protein cleavage-activating protein isoform X2

  7. XM_054345721.1 → XP_054201696.1  sterol regulatory element-binding protein cleavage-activating protein isoform X1

  8. XM_054345729.1 → XP_054201704.1  sterol regulatory element-binding protein cleavage-activating protein isoform X2

  9. XM_054345724.1 → XP_054201699.1  sterol regulatory element-binding protein cleavage-activating protein isoform X1

  10. XM_054345726.1 → XP_054201701.1  sterol regulatory element-binding protein cleavage-activating protein isoform X1

  11. XM_054345723.1 → XP_054201698.1  sterol regulatory element-binding protein cleavage-activating protein isoform X1

  12. XM_054345733.1 → XP_054201708.1  sterol regulatory element-binding protein cleavage-activating protein isoform X4

  13. XM_054345736.1 → XP_054201711.1  sterol regulatory element-binding protein cleavage-activating protein isoform X7

  14. XM_054345732.1 → XP_054201707.1  sterol regulatory element-binding protein cleavage-activating protein isoform X3

  15. XM_054345735.1 → XP_054201710.1  sterol regulatory element-binding protein cleavage-activating protein isoform X6

  16. XM_054345734.1 → XP_054201709.1  sterol regulatory element-binding protein cleavage-activating protein isoform X5

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q12770.4 GenPept UniProtKB/Swiss-Prot:Q12770

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