SRBP2_XENLA
ID SRBP2_XENLA Reviewed; 1088 AA.
AC Q6GQ26;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 88.
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:0000250|UniProtKB:Q12772};
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver {ECO:0000312|EMBL:AAH72922.1};
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
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. {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.
CC {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}.
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. {ECO:0000250|UniProtKB:Q12772}.
CC -!- SIMILARITY: Belongs to the SREBP family. {ECO:0000305}.
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DR EMBL; BC072922; AAH72922.1; -; mRNA.
DR RefSeq; NP_001085554.2; NM_001092085.1.
DR AlphaFoldDB; Q6GQ26; -.
DR SMR; Q6GQ26; -.
DR GeneID; 443980; -.
DR CTD; 443980; -.
DR Xenbase; XB-GENE-1011364; srebf2.L.
DR OrthoDB; 171695at2759; -.
DR Proteomes; UP000186698; Genome assembly.
DR Bgee; 443980; Expressed in blastula and 19 other tissues.
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:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0045542; P:positive regulation of cholesterol biosynthetic process; ISS:UniProtKB.
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: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; Reference proteome; Steroid metabolism; Sterol metabolism;
KW Transcription; Transcription regulation; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..1088
FT /note="Sterol regulatory element-binding protein 2"
FT /id="PRO_0000317065"
FT CHAIN 1..443
FT /note="Processed sterol regulatory element-binding protein
FT 2"
FT /evidence="ECO:0000250|UniProtKB:Q12772"
FT /id="PRO_0000317066"
FT TOPO_DOM 1..440
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 441..461
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 462..494
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 495..515
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 516..1088
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 290..340
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 1..38
FT /note="Transcriptional activation (acidic)"
FT /evidence="ECO:0000250|UniProtKB:P36956"
FT REGION 59..87
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 340..361
FT /note="Leucine-zipper"
FT REGION 392..431
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 443..444
FT /note="Cleavage; by MBTPS2"
FT /evidence="ECO:0000250|UniProtKB:Q12772"
FT SITE 481..482
FT /note="Cleavage; by MBTPS1"
FT /evidence="ECO:0000250|UniProtKB:Q12772"
SQ SEQUENCE 1088 AA; 119824 MW; CBBC13D6400F48C9 CRC64;
METLTELGDE LTLGDIDEML QFVSNQVGEF PDLFEEQLCQ SYQGNNAMDT TLPKAYNQAA
QQPYTTSAPQ PQLLPVKAPP QATPQRTAPL LQPRPVVQTS PQPQLQQQTV MLTPNFSTAP
QTRIIQQPLI YQNAATTSFQ VLQPPVQSLM TTQQMQPVTI QQQVQTVQAQ RVLTQAANGT
IQTLTPATVQ TVTPHVQQVP VLVQPQIIKT ESLVLTAVKA DGSPVMTAVQ NPAITTLAGT
LQTTALQVPT LMGSNGTILT TMPVMMGQEK MPIKQVPGSL KLAEVPKEGE RRTTHNIIEK
RYRSSINDKI MELKDLVMGT DAKMHKSGVL KKAIDYIKYL QQVNQKLRQE NMALKLANQK
NKYLKGIDLS SLVDTSIGMK IDEFNQNALM MSPPASDSGS PAVFSPYSVD SEPGSPLLDD
EKVKDEPDSP TGLGMMDRSR MLLCTMTFLC LSFNPLTSLL HPESGQYSER AVQHGTGRTM
LGVEMSGFYG SWFDWLIPTI ILWLVNGVIV LSVFMKLLIH GEPVTRLHSR SSVKFWRHRK
QADLDLAKGD FGAAALNLQT CLCVLGRSLP ATRLDLACSL SWNIIRCSLQ KISLVRWLLK
HSPGYCKKAE FQDEATTSAR DAALVYHKLH QLHLTGKLPS NWNCSGLNLA LCAVNLAECA
GNKISPTLLA EIHLTTAIQM KTSFPSRFRF LTAYFLGYAQ NASSEETLPD PMRWLAHPLG
KYFFINSNWA LKSAAKDSLY TSTRNPANPV TQIHRAFCES LLEKAMYTMA KPETSKAASE
EESCEFSRAQ EYLKLLSGFA DSVGNVASLP LGGSSPMSSA DPICRWWYSV SSMAIGWLQG
DDSVVKSHFA EVERIPKLLD SDNPLVKAVI HMCRAMQAAV LGKCDGQQNS FYHCEKASAF
LWNSLNISST GNTNLNKVVQ LLICDLLLSL RTSLWQKQSS SPAAGDSIHA PTPALTGFQR
DLSSLRRLSL TFKPAHCKLF LHEATVRLMA DASPTRTHQL LQHSLQKCTA LANKQGDLDS
LPGQRERATA ILLACRHLPL SFLSSPGQRA IMLAEAARTL EKVGDRRSYH DCQQMMVKLS
GGTAMAAS
