SRBP1_CRIGR
ID SRBP1_CRIGR Reviewed; 1133 AA.
AC Q60416;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Sterol regulatory element-binding protein 1 {ECO:0000303|PubMed:8006035};
DE Short=SREBP-1 {ECO:0000303|PubMed:8006035};
DE AltName: Full=Sterol regulatory element-binding transcription factor 1 {ECO:0000303|PubMed:8006035};
DE Contains:
DE RecName: Full=Processed sterol regulatory element-binding protein 1 {ECO:0000305};
DE AltName: Full=Transcription factor SREBF1 {ECO:0000305};
GN Name=SREBF1 {ECO:0000250|UniProtKB:P36956};
GN Synonyms=SREBP1 {ECO:0000303|PubMed:8006035};
OS Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10029;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8006035; DOI=10.1016/s0021-9258(17)32550-4;
RA Sato R., Yang J., Wang X., Evans M.J., Ho Y.K., Goldstein J.L., Brown M.S.;
RT "Assignment of the membrane attachment, DNA binding, and transcriptional
RT activation domains of sterol regulatory element-binding protein-1 (SREBP-
RT 1).";
RL J. Biol. Chem. 269:17267-17273(1994).
CC -!- FUNCTION: [Sterol regulatory element-binding protein 1]: Precursor of
CC the transcription factor form (Processed sterol regulatory element-
CC binding protein 1), which is embedded in the endoplasmic reticulum
CC membrane (By similarity). Low sterol concentrations promote processing
CC of this form, releasing the transcription factor form that translocates
CC into the nucleus and activates transcription of genes involved in
CC cholesterol biosynthesis and lipid homeostasis (By similarity).
CC {ECO:0000250|UniProtKB:P36956, ECO:0000250|UniProtKB:Q9WTN3}.
CC -!- FUNCTION: [Processed sterol regulatory element-binding protein 1]: Key
CC transcription factor that regulates expression of genes involved in
CC cholesterol biosynthesis and lipid homeostasis. Binds to the sterol
CC regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3'). Has dual sequence
CC specificity binding to both an E-box motif (5'-ATCACGTGA-3') and to
CC SRE-1 (5'-ATCACCCCAC-3'). Regulates the promoters of genes involved in
CC cholesterol biosynthesis and the LDL receptor (LDLR) pathway of sterol
CC regulation. {ECO:0000250|UniProtKB:P36956}.
CC -!- SUBUNIT: [Sterol regulatory element-binding protein 1]: Forms a tight
CC complex with SCAP, the SCAP-SREBP complex, in the endoplasmic reticulum
CC membrane. {ECO:0000250|UniProtKB:P36956}.
CC -!- SUBUNIT: [Processed sterol regulatory element-binding protein 1]:
CC Efficient DNA binding of the soluble transcription factor fragment
CC requires dimerization with another bHLH protein (By similarity).
CC Interacts with CEBPA, the interaction produces a transcriptional
CC synergy. Interacts with LMNA (By similarity).
CC {ECO:0000250|UniProtKB:P36956, ECO:0000250|UniProtKB:Q9WTN3}.
CC -!- SUBCELLULAR LOCATION: [Sterol regulatory element-binding protein 1]:
CC Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P36956}; Multi-
CC pass membrane protein {ECO:0000255}. Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:Q9WTN3}; Multi-pass membrane protein
CC {ECO:0000255}. Cytoplasmic vesicle, COPII-coated vesicle membrane
CC {ECO:0000250|UniProtKB:Q9WTN3}; Multi-pass membrane protein
CC {ECO:0000255}. Note=At high sterol concentrations, the SCAP-SREBP is
CC retained in the endoplasmic reticulum. Low sterol concentrations
CC promote recruitment into COPII-coated vesicles and transport of the
CC SCAP-SREBP to the Golgi, where it is processed.
CC {ECO:0000250|UniProtKB:Q9WTN3}.
CC -!- SUBCELLULAR LOCATION: [Processed sterol regulatory element-binding
CC protein 1]: Nucleus {ECO:0000250|UniProtKB:P36956}.
CC -!- DOMAIN: The 9aaTAD motif is a transactivation domain present in a large
CC number of yeast and animal transcription factors.
CC {ECO:0000250|UniProtKB:P36956}.
CC -!- PTM: [Sterol regulatory element-binding protein 1]: Processed in the
CC Golgi apparatus, releasing the protein from the membrane. At low
CC cholesterol the SCAP-SREBP complex is recruited into COPII vesicles for
CC export from the endoplasmic reticulum. In the Golgi, complex SREBPs are
CC cleaved sequentially by site-1 (MBTPS1, S1P) and site-2 (MBTPS2, S2P)
CC proteases. The first cleavage by site-1 protease occurs within the
CC luminal loop, the second cleavage by site-2 protease occurs within the
CC first transmembrane domain, releasing the transcription factor from the
CC Golgi membrane. {ECO:0000250|UniProtKB:P36956}.
CC -!- PTM: Phosphorylated by AMPK, leading to suppress protein processing and
CC nuclear translocation, and repress target gene expression.
CC Phosphorylation at Ser-396 by SIK1 represses activity possibly by
CC inhibiting DNA-binding. {ECO:0000250|UniProtKB:Q9WTN3}.
CC -!- PTM: [Processed sterol regulatory element-binding protein 1]:
CC Ubiquitinated; the nuclear form has a rapid turnover and is rapidly
CC ubiquitinated and degraded by the proteasome in the nucleus.
CC {ECO:0000250|UniProtKB:P36956}.
CC -!- SIMILARITY: Belongs to the SREBP family. {ECO:0000305}.
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DR EMBL; U09103; AAA20085.1; -; mRNA.
DR PIR; A54164; A54164.
DR RefSeq; NP_001230932.1; NM_001244003.1.
DR AlphaFoldDB; Q60416; -.
DR SMR; Q60416; -.
DR CORUM; Q60416; -.
DR STRING; 10029.NP_001230932.1; -.
DR Ensembl; ENSCGRT00001013004; ENSCGRP00001008853; ENSCGRG00001011040.
DR GeneID; 100689018; -.
DR KEGG; cge:100689018; -.
DR CTD; 6720; -.
DR eggNOG; KOG2588; Eukaryota.
DR GeneTree; ENSGT00940000159156; -.
DR OrthoDB; 330300at2759; -.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0012507; C:ER to Golgi transport vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0004879; F:nuclear receptor activity; IEA:Ensembl.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0032810; F:sterol response element binding; IEA:Ensembl.
DR GO; GO:0001221; F:transcription coregulator binding; IEA:Ensembl.
DR GO; GO:0009267; P:cellular response to starvation; IEA:Ensembl.
DR GO; GO:0006695; P:cholesterol biosynthetic process; IEA:Ensembl.
DR GO; GO:0007623; P:circadian rhythm; IEA:Ensembl.
DR GO; GO:0045444; P:fat cell differentiation; IEA:Ensembl.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0030073; P:insulin secretion; IEA:Ensembl.
DR GO; GO:0008610; P:lipid biosynthetic process; ISS:UniProtKB.
DR GO; GO:0042789; P:mRNA transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0046676; P:negative regulation of insulin secretion; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0045542; P:positive regulation of cholesterol biosynthetic process; ISS:UniProtKB.
DR GO; GO:0031065; P:positive regulation of histone deacetylation; IEA:Ensembl.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; IEA:Ensembl.
DR GO; GO:0010867; P:positive regulation of triglyceride biosynthetic process; ISS:UniProtKB.
DR GO; GO:1903146; P:regulation of autophagy of mitochondrion; IEA:Ensembl.
DR GO; GO:0019217; P:regulation of fatty acid metabolic process; IEA:Ensembl.
DR GO; GO:0003062; P:regulation of heart rate by chemical signal; IEA:Ensembl.
DR GO; GO:0031647; P:regulation of protein stability; IEA:Ensembl.
DR GO; GO:1903214; P:regulation of protein targeting to mitochondrion; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0009749; P:response to glucose; IEA:Ensembl.
DR GO; GO:0032933; P:SREBP signaling pathway; ISS:UniProtKB.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR Pfam; PF00010; HLH; 1.
DR SMART; SM00353; HLH; 1.
DR SUPFAM; SSF47459; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
PE 2: Evidence at transcript level;
KW Activator; Cholesterol metabolism; Cytoplasmic vesicle; DNA-binding;
KW Endoplasmic reticulum; Golgi apparatus; Lipid metabolism; Membrane;
KW Nucleus; Phosphoprotein; Steroid metabolism; Sterol metabolism;
KW Transcription; Transcription regulation; Transmembrane;
KW Transmembrane helix; Ubl conjugation.
FT CHAIN 1..1133
FT /note="Sterol regulatory element-binding protein 1"
FT /id="PRO_0000127446"
FT CHAIN 1..479
FT /note="Processed sterol regulatory element-binding protein
FT 1"
FT /evidence="ECO:0000250|UniProtKB:Q12772"
FT /id="PRO_0000314028"
FT TOPO_DOM 1..476
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 477..497
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 498..535
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 536..556
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 557..1133
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 317..367
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 1..60
FT /note="Transcriptional activation (acidic)"
FT /evidence="ECO:0000250|UniProtKB:P36956"
FT REGION 46..78
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 131..219
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 227..486
FT /note="Interaction with LMNA"
FT /evidence="ECO:0000250|UniProtKB:Q9WTN3"
FT REGION 367..388
FT /note="Leucine-zipper"
FT REGION 415..456
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 27..35
FT /note="9aaTAD"
FT /evidence="ECO:0000250|UniProtKB:P36956"
FT COMPBIAS 61..78
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 131..157
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 166..219
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 423..454
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 452..453
FT /note="Cleavage; by caspase-3 and caspase-7"
FT /evidence="ECO:0000250|UniProtKB:Q12772"
FT SITE 479..480
FT /note="Cleavage; by MBTPS2"
FT /evidence="ECO:0000250|UniProtKB:Q12772"
FT SITE 518..519
FT /note="Cleavage; by MBTPS1"
FT /evidence="ECO:0000250|UniProtKB:P36956"
FT MOD_RES 97
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P56720"
FT MOD_RES 116
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P36956"
FT MOD_RES 331
FT /note="Phosphoserine; by SIK1"
FT /evidence="ECO:0000250|UniProtKB:Q9WTN3"
FT MOD_RES 332
FT /note="Phosphoserine; by SIK1"
FT /evidence="ECO:0000250|UniProtKB:Q9WTN3"
FT MOD_RES 390
FT /note="Phosphoserine; by AMPK"
FT /evidence="ECO:0000250|UniProtKB:Q9WTN3"
FT MOD_RES 396
FT /note="Phosphoserine; by SIK1"
FT /evidence="ECO:0000250|UniProtKB:Q9WTN3"
FT MOD_RES 449
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9WTN3"
FT MOD_RES 1046
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P36956"
SQ SEQUENCE 1133 AA; 120466 MW; 01A77B09DEDCDA84 CRC64;
MDELPFGEAA VEQALDELGE LDAALLTDIQ DMLQLINNQD SDFPGLFDSP YAGGGAGDTE
PTSPGANSPE SLSSPASLGS SLEAFLGEPK ATPASLSPVP SASTALKMYP SVPPFSPGPG
IKEEPVPLTI LQPPAAQPSP GTLLPPSFPP PPLQLSPAPV LGYSSLPSGF SGTLPGNTQQ
PPSSLSLASA PGVSPISLHT QVQSSASQQP LPASTAPRTT TVTSQIQRVP VVLQPHFIKA
DSLLLTTVKT DTGATMKTAG ISTLAPGTAV QAGPLQTLVS GGTILATVPL VVDTDKLPIH
RLAAGSKALG SAQSRGEKRT AHNAIEKRYR SSINDKIVEL KDLVVGTEAK LNKSAVLRKA
IDYIRFLQHS NQKLKQENLA LRNAAHKSKS LKDLVSACGS AGGTDVAMEG VKPEVVDTLT
PPPSDAGSPS QSSPLSLGSR GSSSGGSDSE PDSPVFEDSQ VKAQRLHSHG MLDRSRLALC
ALVFLCLTCN PLASLFGWGI PGPSSASGAH HSSGRSMLEA ESRDGSNWTQ WLLPPLVWLA
NGLLVLACLA LLFVYGEPVT RPHTSPAVHF WRHRKQADLD LARGDFAQAA QQLWLALQAL
GRPLPTSNLD LACSLLWNLI RHLLQRLWVG RWLAGRAGGL RRDCGLRMDA RASARDAALV
YHKLHQLHAM GKYTGGHLIA SNLALSALNL AECAGDAVSM ATLAEIYVAA ALRVKTSLPR
ALHFLTRFFL SSARQACLAQ SGSVPLAMQW LCHPVGHRFF VDGDWAVHGA PQESLYSVAG
NPVDPLAQVT RLFCEHLLER ALNCIAQPSP GTADGDREFS DALGYLQLLN RCSDAVGTPA
CSFSVSSSMA STTGTDPVAK WWASLTAVVI HWLRRDEEAA ERLYPLVERM PHVLQETERP
LPKAALYSFK AARALLDHRK VESGPASLAI CEKASGYLRD SLAAPPTGSS IDKAMQLLLC
DLLLVARTSM WQRQQSPASA QVAHSASNGS QASALELRGF QQDLSSLRRL AQNFRPAMRR
VFLHEATARL MAGASPARTH QLLDRSLRRR AGSSGKGGTV AELEPRPTWR EHTEALLLAS
CYLPPAFLSA PGQQMSMLAE AARTVEKLGD HRLLLDCQQM LLRLGGGTTV TSS
