SRBP2_CRIGR
ID SRBP2_CRIGR Reviewed; 1139 AA.
AC Q60429; Q60418; Q60427; Q60428;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 25-MAY-2022, entry version 128.
DE RecName: Full=Sterol regulatory element-binding protein 2 {ECO:0000303|PubMed:7958866};
DE Short=SREBP-2 {ECO:0000303|PubMed:7958866};
DE AltName: Full=Sterol regulatory element-binding transcription factor 2 {ECO:0000303|PubMed:7958866};
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; Synonyms=SREBP2 {ECO:0000303|PubMed:7958866};
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], FUNCTION, AND CHROMOSOMAL TRANSLOCATION SRD-1.
RX PubMed=7958866; DOI=10.1101/gad.8.16.1910;
RA Yang J., Sato R., Goldstein J.L., Brown M.S.;
RT "Sterol-resistant transcription in CHO cells caused by gene rearrangement
RT that truncates SREBP-2.";
RL Genes Dev. 8:1910-1919(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND CHROMOSOMAL TRANSLOCATIONS SRD-1; SRD-2 AND
RP SRD-3.
RX PubMed=7744865; DOI=10.1074/jbc.270.20.12152;
RA Yang J., Brown M.S., Ho Y.K., Goldstein J.L.;
RT "Three different rearrangements in a single intron truncate sterol
RT regulatory element binding protein-2 and produce sterol-resistant phenotype
RT in three cell lines. Role of introns in protein evolution.";
RL J. Biol. Chem. 270:12152-12161(1995).
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 (PubMed:7958866). Binds to the sterol
CC regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') (By similarity). Has
CC dual sequence specificity binding to both an E-box motif (5'-ATCACGTGA-
CC 3') and to SRE-1 (5'-ATCACCCCAC-3'). Regulates transcription of genes
CC related to cholesterol synthesis pathway (By similarity).
CC {ECO:0000250|UniProtKB:Q12772, ECO:0000269|PubMed:7958866}.
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 -!- DISEASE: Note=Sterol-resistant defective (srd) phenotypes express
CC truncated forms of SREBP-2 protein, often found fused to other
CC proteins, as is the case in SRD-1, where SREBP-2 is fused to an out-of-
CC frame KU p70 protein or, in SRD-2 where the fusion protein is a LIM
CC domain-containing protein. Srd phenotypes are resistant to sterol
CC biosynthesis repression by sterols. {ECO:0000269|PubMed:7744865,
CC ECO:0000269|PubMed:7958866}.
CC -!- SIMILARITY: Belongs to the SREBP family. {ECO:0000305}.
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DR EMBL; U12330; AAA74141.1; -; mRNA.
DR EMBL; U12329; AAA74140.1; ALT_TERM; mRNA.
DR EMBL; U22819; AAA85719.1; ALT_TERM; mRNA.
DR EMBL; U22818; AAA85718.1; ALT_TERM; mRNA.
DR PIR; B54962; B54962.
DR RefSeq; NP_001230933.1; NM_001244004.1.
DR AlphaFoldDB; Q60429; -.
DR SMR; Q60429; -.
DR CORUM; Q60429; -.
DR STRING; 10029.NP_001230933.1; -.
DR GeneID; 100689017; -.
DR KEGG; cge:100689017; -.
DR CTD; 6721; -.
DR eggNOG; KOG2588; Eukaryota.
DR OrthoDB; 330300at2759; -.
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:0032936; C:SREBP-SCAP complex; IDA: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 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; Chromosomal rearrangement;
KW Cytoplasmic vesicle; DNA-binding; Endoplasmic reticulum; Golgi apparatus;
KW Isopeptide bond; Lipid metabolism; Membrane; Nucleus; Phosphoprotein;
KW Steroid metabolism; Sterol metabolism; Transcription;
KW Transcription regulation; Transmembrane; Transmembrane helix;
KW Ubl conjugation.
FT CHAIN 1..1139
FT /note="Sterol regulatory element-binding protein 2"
FT /id="PRO_0000127451"
FT CHAIN 1..482
FT /note="Processed sterol regulatory element-binding protein
FT 2"
FT /evidence="ECO:0000250|UniProtKB:Q12772"
FT /id="PRO_0000314032"
FT TOPO_DOM 1..479
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 480..500
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 501..531
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 532..552
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 553..1139
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 328..378
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 48..104
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 119..143
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 235..489
FT /note="Interaction with LMNA"
FT /evidence="ECO:0000250|UniProtKB:Q3U1N2"
FT REGION 378..399
FT /note="Leucine-zipper"
FT COMPBIAS 52..104
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 122..138
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 460..461
FT /note="Breakpoint for translocation to form SREBP-2 fusion
FT proteins in srd phenotypes"
FT SITE 466..467
FT /note="Cleavage; by caspase-3 and caspase-7"
FT /evidence="ECO:0000250|UniProtKB:Q12772"
FT SITE 482..483
FT /note="Cleavage; by MBTPS2"
FT /evidence="ECO:0000250|UniProtKB:Q12772"
FT SITE 520..521
FT /note="Cleavage; by MBTPS1"
FT /evidence="ECO:0000250|UniProtKB:Q12772"
FT MOD_RES 1096
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12772"
FT CROSSLNK 462
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q12772"
FT VARIANT 493
FT /note="S -> N (in 50% of the molecules)"
SQ SEQUENCE 1139 AA; 123655 MW; E81C2778EBF02653 CRC64;
MDESSELGGL ETMDTLTELG DELTLGDIDE MLQFVSNQVG EFPDLFSEQL CSSFPGGGSS
GSSSSSNSSS SSGSNSRGNG GAATDPGVQR SFSQVPLPTF SPSTASPQAL ALQVKVSPTP
PRATPVLQPR PQPQPQPQPS AQLQQQTVMI TPTFSTAPQT RIIQQPLIYQ NAATSFQVLQ
AQVQSLVTSS QVQPVTIQQQ VQTVQAQRVL TQTANGTLQT LAPATVQTVA APQVQQVPVL
VQPQIIKTDS LVLTTLKTDG SPVMAAVQNP ALTALTTPLQ TGALQVPTLV GSNGTILTTM
PVMMGQEKVP IKQVPGGVKQ LEPPKEGERR TTHNIIEKRY RSSINDKIIE LKDLVMGTDA
KMHKSGVLRK AIDYIKYLQQ VNHKLRQENM VLKLANQKNK LLKGIDLGSL VDSDVDLKIE
DFNQNVLLMS PPASDSGSQA GFSPYSIDSE PGSPLLDDAK VKDEPDSPPV ALGMVDRSRI
LLCVLTFLGL SFSPLTSLLQ WGGAHDTDQH PYSGSGRSVL SLESGSGGWF DWMMPTLLLW
LVNGVIVLSV FVKLLVHGEP VIRPHTRSSV TFWRHRKQAD LDLARGDFAA AAANLQTCLS
VLGRALPTSR LDLACSLSWN VIRYSLQKLR LVRWILKKVF QRWRATPATA AGFEDEAKSS
ARDAALAYHR LHQLHITGKL PAGSTCSDVH MALCAVNLAE CAEEKIPPST LIEIHLTAAM
GLKTGCGGKL GFLASYFLNR AQSLCGPEHS TVPDSLRWLC HPLGQKFFME RSWSIKSAAK
ESLYCAQRNP ADPIAQVHQA FCKNLLERAV ESLVKPQSKK KSGDQEDESC EFSSALEYLR
LLHSFVDSVG FVTPPFSSSS VLKSALGPDI ICRWWTSAVT MAISWLQGDD AAVRSHFTEV
ERIPKALEVT ESPLVKAVFY ACRAMHASLS GKGDGQQNSF CHCERASGHL WNSLNVSGAT
SDPSLNHVVQ LLTCDLLLSL RTALWQKQAG ASQGLGETYH ASGTELAGFQ RDLGSLRRLA
HSFRPAYRKV FLHEPTVRLM AGANPTRTHQ LLEHSLRRRT SQNTKHGEID TWPGQRERAT
AILLACRHLP LSFLSSPGQR AVLLAEAART LEKVGDRRSC NDCQQMIVKL GGGTAIAAS
