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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
 
 
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