SRBP2_DANRE
ID SRBP2_DANRE Reviewed; 1099 AA.
AC A3KNA7;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2007, sequence version 1.
DT 03-AUG-2022, entry version 84.
DE RecName: Full=Sterol regulatory element-binding protein 2 {ECO:0000303|PubMed:30705153};
DE Short=SREBP-2 {ECO:0000303|PubMed:30705153};
DE AltName: Full=Sterol regulatory element-binding transcription factor 2 {ECO:0000303|PubMed:30705153};
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};
GN Synonyms=SREBP2 {ECO:0000303|PubMed:30705153}; ORFNames=zgc:158371;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1] {ECO:0000312|EMBL:AAI33738.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo {ECO:0000312|EMBL:AAI33738.1};
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=30705153; DOI=10.1126/science.aav1749;
RA Gu Q., Yang X., Lv J., Zhang J., Xia B., Kim J.D., Wang R., Xiong F.,
RA Meng S., Clements T.P., Tandon B., Wagner D.S., Diaz M.F., Wenzel P.L.,
RA Miller Y.I., Traver D., Cooke J.P., Li W., Zon L.I., Chen K., Bai Y.,
RA Fang L.;
RT "AIBP-mediated cholesterol efflux instructs hematopoietic stem and
RT progenitor cell fate.";
RL Science 363:1085-1088(2019).
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 (By similarity). Activated by mediated cholesterol efflux,
CC transactivates NOTCH and promotes hematopoietic stem and progenitor
CC cell emergence (PubMed:30705153). {ECO:0000250|UniProtKB:Q12772,
CC ECO:0000269|PubMed:30705153}.
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
CC (PubMed:30705153). At low cholesterol the SCAP-SREBP complex is
CC recruited into COPII vesicles for export from the endoplasmic reticulum
CC (By similarity). In the Golgi, complex SREBPs are cleaved sequentially
CC by site-1 (mbtps1, S1P) and site-2 (mbtps2, S2P) protease. The first
CC cleavage by site-1 protease occurs within the luminal loop, the second
CC cleavage by site-2 protease occurs within the first transmembrane
CC domain, releasing the transcription factor from the Golgi membrane (By
CC similarity). {ECO:0000250|UniProtKB:Q12772,
CC ECO:0000269|PubMed:30705153}.
CC -!- SIMILARITY: Belongs to the SREBP family. {ECO:0000305}.
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DR EMBL; BC133737; AAI33738.1; -; mRNA.
DR RefSeq; NP_001082935.1; NM_001089466.1.
DR AlphaFoldDB; A3KNA7; -.
DR SMR; A3KNA7; -.
DR STRING; 7955.ENSDARP00000087122; -.
DR PaxDb; A3KNA7; -.
DR GeneID; 100037309; -.
DR KEGG; dre:100037309; -.
DR CTD; 6721; -.
DR ZFIN; ZDB-GENE-070410-8; srebf2.
DR eggNOG; KOG2588; Eukaryota.
DR InParanoid; A3KNA7; -.
DR OrthoDB; 330300at2759; -.
DR PhylomeDB; A3KNA7; -.
DR Reactome; R-DRE-1655829; Regulation of cholesterol biosynthesis by SREBP (SREBF).
DR Reactome; R-DRE-191273; Cholesterol biosynthesis.
DR PRO; PR:A3KNA7; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
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: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:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0001889; P:liver development; IGI:ZFIN.
DR GO; GO:0045542; P:positive regulation of cholesterol biosynthetic process; ISS:UniProtKB.
DR GO; GO:0010886; P:positive regulation of cholesterol storage; IBA:GO_Central.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0008593; P:regulation of Notch signaling pathway; IMP: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 1: Evidence at protein 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..1099
FT /note="Sterol regulatory element-binding protein 2"
FT /id="PRO_0000317063"
FT CHAIN 1..464
FT /note="Processed sterol regulatory element-binding protein
FT 2"
FT /evidence="ECO:0000250|UniProtKB:Q12772"
FT /id="PRO_0000317064"
FT TOPO_DOM 1..461
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 462..482
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 483..513
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 514..534
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 535..1099
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 320..370
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 1..47
FT /note="Transcriptional activation (acidic)"
FT /evidence="ECO:0000250|UniProtKB:P36956"
FT REGION 65..107
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 370..391
FT /note="Leucine-zipper"
FT COMPBIAS 67..102
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 464..465
FT /note="Cleavage; by MBTPS2"
FT /evidence="ECO:0000250|UniProtKB:Q12772"
FT SITE 502..503
FT /note="Cleavage; by MBTPS1"
FT /evidence="ECO:0000250|UniProtKB:Q12772"
SQ SEQUENCE 1099 AA; 120321 MW; B4F421D3947BC012 CRC64;
MDASEFMDTM DPSLSELGDE FTLGDIDEML QFVSNQVDFP DIFEDQMGGG ATARTLPQAV
PSAILTPPHT PVQTSSQTHT QTLTQAHTQT HTQTHTQTRT PPVLQPRPQP ITQVQTQTFP
MQTLAVQTQA QPQTVMITPT ATPSRFIQNQ VICQQNNATS FQVLQPQMQS IMTSPQVQPM
TIQHQRVLTP AGQTIQTLST APTTVHTMSQ QVPVLVHQPQ ILKTDSLLLT TKPDGTQVLS
TVQSPTGITT LTTPIQTTAL QMPTLMSSNI LTTVPVVMGG GDKLPIKQLS SGPAHNIGGA
RVGVEQSPVV GPGGVVKEGE RRTTHNIIEK RYRSSINDKI LELRDLVLGN DAKMHKSGVL
RKAIDYIKYL QQVNHKLRQE NLTLKMANQK NKSACVSDVD LELKAEVSLI SPPPSDSGSS
SPAQLSPYCI DSEPGSPLLE HEQLKSEPDS PSCVGVMDRS RLLLCALSFL CLSLNPLPSL
LGAEAPAGSP EVAGHGPTRT LFSLPAQTQS FGAWLWCVLP FLLVWVVSGV GVVWGCVRVL
YLWEPVTPLH SPTSVRFWRH RKQADLQLYR GDYAGAVLSL QTCLSVLSRV LPVTTLDIMC
SLSWNLIRYC LRRPAPLGWL VRLVGGRHEG EESQTSSRDA ALVYHKLSQL QLTGQMERRP
LWGVCVSLSA VNLCESAEGK LTATQQVQVY VTAAISVRAA LGKHLTCLPA YLLSCAEALT
CQSDSKPLPD CLRWIFTPLG RQFFLSCDWS VRSESDGQIF TSARDKADPI AQLHRCFCQK
LLERATHTLI EPQSREDAGE FTGVLEFLQL LNSCTEDSAP STAPFPALAN QSSTSVRDPV
CRWWASVLTA AVHWLQGDDA SVRSLLAEAE RMPRALHTLD HPLPKAVLAL CKAVQMSVCP
QKGEGVVSCL SHCQRASAQL HISVCQSHNN TWLHKGVELL VCDLLLTLRT SLWQRGGGSN
GEPGPAPGSQ LSGFQRDLSS LRRLGQAHRQ AQHKLFLHET TVRLMAGASP TRTHQLLRHR
THNYTTTDGE CVLGERERAH AILLACRHLP LPLLTPPGHR ARLLAEAKRT LERVGDRRSL
QDCQHILLRL SGGTTIAAS
