Gene/Proteome Database (LMPD)
LMPD ID
LMP001471
Gene ID
Species
Homo sapiens (Human)
Gene Name
SREBF chaperone
Gene Symbol
Synonyms
-
Alternate Names
sterol regulatory element-binding protein cleavage-activating protein; SREBP cleavage-activating protein; sterol regulatory element binding protein cleavage-activating protein
Chromosome
3
Map Location
3p21.31
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. [provided by RefSeq, Jul 2008]
Orthologs
Proteins
| sterol regulatory element-binding protein cleavage-activating protein | |
|---|---|
| Refseq ID | NP_036367 |
| Protein GI | 66932902 |
| UniProt ID | Q12770 |
| mRNA ID | NM_012235 |
| Length | 1279 |
| RefSeq Status | REVIEWED |
| MTLTERLREKISRAFYNHGLLCASYPIPIILFTGFCILACCYPLLKLPLPGTGPVEFTTPVKDYSPPPVDSDRKQGEPTEQPEWYVGAPVAYVQQIFVKSSVFPWHKNLLAVDVFRSPLSRAFQLVEEIRNHVLRDSSGIRSLEELCLQVTDLLPGLRKLRNLLPEHGCLLLSPGNFWQNDWERFHADPDIIGTIHQHEPKTLQTSATLKDLLFGVPGKYSGVSLYTRKRMVSYTITLVFQHYHAKFLGSLRARLMLLHPSPNCSLRAESLVHVHFKEEIGVAELIPLVTTYIILFAYIYFSTRKIDMVKSKWGLALAAVVTVLSSLLMSVGLCTLFGLTPTLNGGEIFPYLVVVIGLENVLVLTKSVVSTPVDLEVKLRIAQGLSSESWSIMKNMATELGIILIGYFTLVPAIQEFCLFAVVGLVSDFFLQMLFFTTVLSIDIRRMELADLNKRLPPEACLPSAKPVGQPTRYERQLAVRPSTPHTITLQPSSFRNLRLPKRLRVVYFLARTRLAQRLIMAGTVVWIGILVYTDPAGLRNYLAAQVTEQSPLGEGALAPMPVPSGMLPPSHPDPAFSIFPPDAPKLPENQTSPGESPERGGPAEVVHDSPVPEVTWGPEDEELWRKLSFRHWPTLFSYYNITLAKRYISLLPVIPVTLRLNPREALEGRHPQDGRSAWPPPGPIPAGHWEAGPKGPGGVQAHGDVTLYKVAALGLATGIVLVLLLLCLYRVLCPRNYGQLGGGPGRRRRGELPCDDYGYAPPETEIVPLVLRGHLMDIECLASDGMLLVSCCLAGHVCVWDAQTGDCLTRIPRPGRQRRDSGVGSGLEAQESWERLSDGGKAGPEEPGDSPPLRHRPRGPPPPSLFGDQPDLTCLIDTNFSAQPRSSQPTQPEPRHRAVCGRSRDSPGYDFSCLVQRVYQEEGLAAVCTPALRPPSPGPVLSQAPEDEGGSPEKGSPSLAWAPSAEGSIWSLELQGNLIVVGRSSGRLEVWDAIEGVLCCSSEEVSSGITALVFLDKRIVAARLNGSLDFFSLETHTALSPLQFRGTPGRGSSPASPVYSSSDTVACHLTHTVPCAHQKPITALKAAAGRLVTGSQDHTLRVFRLEDSCCLFTLQGHSGAITTVYIDQTMVLASGGQDGAICLWDVLTGSRVSHVFAHRGDVTSLTCTTSCVISSGLDDLISIWDRSTGIKFYSIQQDLGCGASLGVISDNLLVTGGQGCVSFWDLNYGDLLQTVYLGKNSEAQPARQILVLDNAAIVCNFGSELSLVYVPSVLEKLD | |
Gene Information
Gene Ontology (GO Annotations)
| GO ID | Source | Type | Description |
|---|---|---|---|
| GO:0005794 | NAS:UniProtKB | C | Golgi apparatus |
| GO:0000139 | TAS:Reactome | C | Golgi membrane |
| GO:0031410 | IEA:UniProtKB-KW | C | cytoplasmic vesicle |
| GO:0005783 | NAS:UniProtKB | C | endoplasmic reticulum |
| GO:0005789 | IEA:Ensembl | C | endoplasmic reticulum membrane |
| GO:0016021 | NAS:UniProtKB | C | integral component of membrane |
| GO:0043234 | IEA:Ensembl | C | protein complex |
| GO:0051082 | NAS:UniProtKB | F | unfolded protein binding |
| GO:0032933 | IMP:UniProtKB | P | SREBP signaling pathway |
| GO:0007568 | IEA:Ensembl | P | aging |
| GO:0008203 | IEA:UniProtKB-KW | P | cholesterol metabolic process |
| GO:0045541 | NAS:UniProtKB | P | negative regulation of cholesterol biosynthetic process |
| GO:0045716 | NAS:UniProtKB | P | positive regulation of low-density lipoprotein particle receptor biosynthetic process |
| GO:0042304 | IEA:Ensembl | P | regulation of fatty acid biosynthetic process |
| GO:0001666 | IEA:Ensembl | P | response to hypoxia |
| GO:0032868 | IEA:Ensembl | P | response to insulin |
| GO:0044281 | TAS:Reactome | P | small molecule metabolic process |
REACTOME Pathway Links
| REACTOME Pathway ID | Description |
|---|---|
| REACT_111217 | Metabolism |
| REACT_22258 | Metabolism of lipids and lipoproteins |
| REACT_147797 | Regulation of cholesterol biosynthesis by SREBP (SREBF) |
Domain Information
UniProt Annotations
Entry Information
Comments
| Comment Type | Description |
|---|---|
| Alternative Products | Event=Alternative splicing; Named isoforms=4; Name=1; IsoId=Q12770-1; Sequence=Displayed; Name=2; IsoId=Q12770-2; Sequence=VSP_007451, VSP_021106; Note=No experimental confirmation available.; Name=3; IsoId=Q12770-3; Sequence=VSP_007452; Note=No experimental confirmation available.; Name=4; IsoId=Q12770-4; Sequence=VSP_021105, VSP_021106; Note=No experimental confirmation available.; |
| 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. |
| 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). |
| Induction | By androgen-bound AR and glucocorticoid-bound NR3C1 in a prostate cancer cell line (LNCaP). |
| Sequence Caution | Sequence=BAA12111.2; Type=Erroneous initiation; Evidence= ; Sequence=BAC11673.1; Type=Erroneous initiation; Evidence= ; |
| Similarity | Belongs to the WD repeat SCAP family. |
| Similarity | Contains 1 SSD (sterol-sensing) domain. |
| Similarity | Contains 7 WD repeats. {ECO |
| Subcellular Location | Endoplasmic reticulum membrane {ECO |
| 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. |
Identical and Related Proteins
Unique RefSeq proteins for LMP001471 (as displayed in Record Overview)
| Protein GI | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| 66932902 | RefSeq | NP_036367 | 1279 | sterol regulatory element-binding protein cleavage-activating protein |
Identical Sequences to LMP001471 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:66932902 | DBBJ | BAG09650.1 | 1279 | sterol regulatory element-binding protein cleavage-activating protein, partial [synthetic construct] |
| GI:66932902 | RefSeq | XP_006713097.1 | 1279 | PREDICTED: sterol regulatory element-binding protein cleavage-activating protein isoform X8 [Homo sapiens] |
| GI:66932902 | SwissProt | Q12770.4 | 1279 | RecName: Full=Sterol regulatory element-binding protein cleavage-activating protein; Short=SCAP; Short=SREBP cleavage-activating protein [Homo sapiens] |
Related Sequences to LMP001471 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:66932902 | DBBJ | BAA12111.2 | 1283 | KIAA0199, partial [Homo sapiens] |
| GI:66932902 | GenBank | EAW64826.1 | 1279 | SREBP cleavage-activating protein, isoform CRA_b [Homo sapiens] |
| GI:66932902 | GenBank | JAA04187.1 | 1279 | SREBF chaperone [Pan troglodytes] |
| GI:66932902 | GenBank | JAA15154.1 | 1279 | SREBF chaperone [Pan troglodytes] |
| GI:66932902 | GenBank | JAA30174.1 | 1279 | SREBF chaperone [Pan troglodytes] |
| GI:66932902 | RefSeq | XP_005265024.1 | 1278 | PREDICTED: sterol regulatory element-binding protein cleavage-activating protein isoform X2 [Homo sapiens] |