SRBP2_RAT
ID SRBP2_RAT Reviewed; 1133 AA.
AC Q3T1I5;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 112.
DE RecName: Full=Sterol regulatory element-binding protein 2 {ECO:0000250|UniProtKB:Q12772};
DE Short=SREBP-2 {ECO:0000250|UniProtKB:Q12772};
DE AltName: Full=Sterol regulatory element-binding transcription factor 2 {ECO:0000250|UniProtKB:Q12772};
DE Contains:
DE RecName: Full=Processed sterol regulatory element-binding protein 2 {ECO:0000305};
DE AltName: Full=Transcription factor SREBF2 {ECO:0000305};
GN Name=Srebf2 {ECO:0000312|RGD:1307751};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: [Sterol regulatory element-binding protein 2]: Precursor of
CC the transcription factor form (Processed sterol regulatory element-
CC binding protein 2), which is embedded in the endoplasmic reticulum
CC membrane. Low sterol concentrations promote processing of this form,
CC releasing the transcription factor form that translocates into the
CC nucleus and activates transcription of genes involved in cholesterol
CC biosynthesis. {ECO:0000250|UniProtKB:Q12772}.
CC -!- FUNCTION: [Processed sterol regulatory element-binding protein 2]: Key
CC transcription factor that regulates expression of genes involved in
CC cholesterol biosynthesis. Binds to the sterol regulatory element 1
CC (SRE-1) (5'-ATCACCCCAC-3'). Has dual sequence specificity binding to
CC both an E-box motif (5'-ATCACGTGA-3') and to SRE-1 (5'-ATCACCCCAC-3').
CC Regulates transcription of genes related to cholesterol synthesis
CC pathway. {ECO:0000250|UniProtKB:Q12772}.
CC -!- SUBUNIT: [Sterol regulatory element-binding protein 2]: Forms a tight
CC complex with SCAP, the SCAP-SREBP complex, in the endoplasmic reticulum
CC membrane. Interacts (via C-terminal domain) with RNF139.
CC {ECO:0000250|UniProtKB:Q12772}.
CC -!- SUBUNIT: [Processed sterol regulatory element-binding protein 2]:
CC Homodimer; efficient DNA binding of the soluble transcription factor
CC fragment requires dimerization with another bHLH protein. Interacts
CC with LMNA. {ECO:0000250|UniProtKB:Q3U1N2}.
CC -!- SUBCELLULAR LOCATION: [Sterol regulatory element-binding protein 2]:
CC Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q12772}; Multi-
CC pass membrane protein {ECO:0000255}. Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:Q12772}; Multi-pass membrane protein
CC {ECO:0000255}. Cytoplasmic vesicle, COPII-coated vesicle membrane
CC {ECO:0000250|UniProtKB:Q12772}; 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:Q12772}.
CC -!- SUBCELLULAR LOCATION: [Processed sterol regulatory element-binding
CC protein 2]: Nucleus {ECO:0000250|UniProtKB:Q12772}. Note=Transported
CC into the nucleus with the help of importin-beta. Dimerization of the
CC bHLH domain is a prerequisite for importin beta-dependent nuclear
CC import. {ECO:0000250|UniProtKB:Q3U1N2}.
CC -!- PTM: [Sterol regulatory element-binding protein 2]: 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. Apoptosis triggers cleavage by the cysteine proteases
CC caspase-3 and caspase-7. Cleavage and activation is induced by mediated
CC cholesterol efflux. {ECO:0000250|UniProtKB:Q12772}.
CC -!- PTM: Phosphorylated by AMPK, leading to suppress protein processing and
CC nuclear translocation, and repress target gene expression.
CC {ECO:0000250|UniProtKB:Q3U1N2}.
CC -!- PTM: [Processed sterol regulatory element-binding protein 2]:
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:Q12772}.
CC -!- SIMILARITY: Belongs to the SREBP family. {ECO:0000305}.
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DR EMBL; BC101902; AAI01903.1; -; mRNA.
DR RefSeq; NP_001028866.1; NM_001033694.1.
DR AlphaFoldDB; Q3T1I5; -.
DR SMR; Q3T1I5; -.
DR STRING; 10116.ENSRNOP00000052893; -.
DR PhosphoSitePlus; Q3T1I5; -.
DR PaxDb; Q3T1I5; -.
DR PRIDE; Q3T1I5; -.
DR GeneID; 300095; -.
DR KEGG; rno:300095; -.
DR UCSC; RGD:1307751; rat.
DR CTD; 6721; -.
DR RGD; 1307751; Srebf2.
DR eggNOG; KOG2588; Eukaryota.
DR InParanoid; Q3T1I5; -.
DR OrthoDB; 330300at2759; -.
DR PhylomeDB; Q3T1I5; -.
DR Reactome; R-RNO-1655829; Regulation of cholesterol biosynthesis by SREBP (SREBF).
DR Reactome; R-RNO-191273; Cholesterol biosynthesis.
DR PRO; PR:Q3T1I5; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
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:0043231; C:intracellular membrane-bounded organelle; IDA:RGD.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0032937; C:SREBP-SCAP-Insig complex; ISO:RGD.
DR GO; GO:0003682; F:chromatin binding; IDA:RGD.
DR GO; GO:0003677; F:DNA binding; ISO:RGD.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0070888; F:E-box binding; ISO:RGD.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:RGD.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:RGD.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0071404; P:cellular response to low-density lipoprotein particle stimulus; ISO:RGD.
DR GO; GO:0009267; P:cellular response to starvation; ISO:RGD.
DR GO; GO:0042632; P:cholesterol homeostasis; ISO:RGD.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0008610; P:lipid biosynthetic process; TAS:RGD.
DR GO; GO:0090370; P:negative regulation of cholesterol efflux; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045542; P:positive regulation of cholesterol biosynthetic process; ISS:UniProtKB.
DR GO; GO:0010886; P:positive regulation of cholesterol storage; ISO:RGD.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:RGD.
DR GO; GO:0008593; P:regulation of Notch signaling pathway; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0009725; P:response to hormone; IMP:RGD.
DR GO; GO:0010288; P:response to lead ion; IEP:RGD.
DR GO; GO:0033993; P:response to lipid; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0007283; P:spermatogenesis; IEP:RGD.
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 InterPro; IPR003006; Ig/MHC_CS.
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; Isopeptide bond; Lipid metabolism;
KW Membrane; Nucleus; Phosphoprotein; Reference proteome; Steroid metabolism;
KW Sterol metabolism; Transcription; Transcription regulation; Transmembrane;
KW Transmembrane helix; Ubl conjugation.
FT CHAIN 1..1133
FT /note="Sterol regulatory element-binding protein 2"
FT /id="PRO_0000317061"
FT CHAIN 1..476
FT /note="Processed sterol regulatory element-binding protein
FT 2"
FT /evidence="ECO:0000250|UniProtKB:Q12772"
FT /id="PRO_0000317062"
FT TOPO_DOM 1..473
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 474..494
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 495..525
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 526..546
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 547..1133
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 322..372
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 1..50
FT /note="Transcriptional activation (acidic)"
FT /evidence="ECO:0000250|UniProtKB:P36956"
FT REGION 56..136
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 229..483
FT /note="Interaction with LMNA"
FT /evidence="ECO:0000250|UniProtKB:Q3U1N2"
FT REGION 372..393
FT /note="Leucine-zipper"
FT COMPBIAS 56..76
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 87..109
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 118..134
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 460..461
FT /note="Cleavage; by caspase-3 and caspase-7"
FT /evidence="ECO:0000250|UniProtKB:Q12772"
FT SITE 476..477
FT /note="Cleavage; by MBTPS2"
FT /evidence="ECO:0000250|UniProtKB:Q12772"
FT SITE 514..515
FT /note="Cleavage; by MBTPS1"
FT /evidence="ECO:0000250|UniProtKB:Q12772"
FT MOD_RES 1090
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12772"
FT CROSSLNK 456
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q12772"
SQ SEQUENCE 1133 AA; 122976 MW; 148A5DA3165A0236 CRC64;
MDENSELGGL ETMETLTELG DELTLGDIDE MLQFVSNQVG EFSDLFSEQL CSSFPGGGGG
SGSGGTSNNS SGRGTSGGAA DPAVQRSFSQ VPLSTFSPSS TSPQAPALQV KVSPTPPRAT
PVLQPRPQPQ PQPPAQLQQQ TVMITPTFST APQTRIIQQP LIYQNAATSF QVLQPQVQSL
VTSSQVQPVT IQQQVQTVQA QRVLTQTANG TLQTLAPATV QTVATPQVQQ VPVLVQPQII
KTDSLVLTTL KTDGSPVMAA VQNPALTALT APIQTAALQV PTLVGSNGAI LTTMPVMMGQ
EKVPIKQVPG GVKQLEPPKE GERRTTHNII EKRYRSSIND KIIELKDLVM GTDAKMHKSG
VLRKAIDYIK YLQQVNHKLR QENMVLKLAN QKNKLLKGID LGSLVDSDVD LKIDDFNQNV
LLMSPPASDS GSQAGFSPYS IDSEPGSPLL DDAKVKDEPD SPPVALGMVD RSRILLCVLT
FLGLSFNPLT SLLQWGGAHN PDQHPYSGSG RNVLSLESGS GGWFDWMMPT LLLWLLNGVI
VLSVFVKLLV HGEPVIRPHS RSSVTFWRHR KQADLDLAKG DFAAAAANLQ TCLSVLGRAL
PTSRLDLACS LSWNVIRYSL QKLRLVRWLL KKVFQRWRAT PATAAGFEDE AKSSARDAAL
AYHRLHQLHI TGKLPAGSAC SDVHMALCAV NLAECAEEKI PPSTLVEIHL TAAMGLKTRC
GGKLGFLASY FLNRAQSLCG PEHSAVPDSL RWLCHPLGQK FFMERSWSIK SAAKDSLYCA
QRNPADPIAQ VHQAFCKHLL ERAVEALVKP QAKKKAGDRE EESCEFSSAL EFLKLLHSFV
DSVGFVASPF SSSSVLRSAL GPDVVCRWWT SAITVAISWL QGDDAAVRSH FTEVERVPKA
LEVTESPLVK AVFYACRAMH ASLSGKADGQ QNSFCHCERA SGHLWSSLNV SGTTSDPSLN
HVVQLLTCDL LLSLRTTLWQ KQASASQLLG ETYHASGTEL AGFQRDLGSL RRLAHSFRPA
YRKVFLHEAT VRLMAGASPT RTHQLLEHSL RRRTTQNTKH GEVDTWPGQR ERATAILLAC
RHLPLSFLSS PGQRAVLLAE AARTLEKVGD RRSCSDCQQM IVKLGGGTAI AAS
