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    SCAP SREBF chaperone [ Homo sapiens (human) ]

    Gene ID: 22937, updated on 14-Nov-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_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (47413681..47477127, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (47430101..47496247, complement)
    RS_2024_09 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 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. Deficiency of SCAP inhibits HBV pathogenesis via activation of the interferon signaling pathway. Makokha GN, et al. Virology, 2023 Aug. PMID 37437369
    3. Genomic structure and chromosomal mapping of the human sterol regulatory element binding protein (SREBP) cleavage-activating protein (SCAP) gene. Nakajima T, et al. J Hum Genet, 1999. PMID 10570913
    4. A common Ile796Val polymorphism of the human SREBP cleavage-activating protein (SCAP) gene. Iwaki K, et al. J Hum Genet, 1999. PMID 10570919
    5. 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

    See all (92) 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)

    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 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_2024_08

    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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