SRBP1_PIG
ID SRBP1_PIG Reviewed; 1151 AA.
AC O97676; Q1W0S6; Q6RIB9; Q7YS02;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 05-FEB-2008, sequence version 2.
DT 25-MAY-2022, entry version 120.
DE RecName: Full=Sterol regulatory element-binding protein 1 {ECO:0000303|Ref.2};
DE Short=SREBP-1 {ECO:0000303|Ref.2};
DE AltName: Full=Adipocyte determination and differentiation-dependent factor 1 {ECO:0000303|Ref.1};
DE AltName: Full=Sterol regulatory element-binding transcription factor 1 {ECO:0000303|Ref.2};
DE Contains:
DE RecName: Full=Processed sterol regulatory element-binding protein 1 {ECO:0000305};
DE AltName: Full=Transcription factor SREBF1 {ECO:0000305};
GN Name=SREBF1; Synonyms=ADD1 {ECO:0000303|Ref.1}, SREBP1;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RA Li C., Meng H., Zhao W., Pan Y.;
RT "Pig ADD1 gene cloning and expression.";
RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 159-1151.
RC TISSUE=Uterus;
RA Palin M.F., Beaudry D., Murphy B.D.;
RT "SREBP-1c mRNA levels in the pig uterus.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 229-372.
RX PubMed=10481259; DOI=10.1016/s0305-0491(99)00077-2;
RA Ding S.T., McNeel R.L., Mersmann H.J.;
RT "Expression of porcine adipocyte transcripts: tissue distribution and
RT differentiation in vitro and in vivo.";
RL Comp. Biochem. Physiol. 123B:307-318(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 230-363.
RA Chen J.F., Jiang S.W.;
RL Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: [Sterol regulatory element-binding protein 1]: Precursor of
CC the transcription factor form (Processed sterol regulatory element-
CC binding protein 1), which is embedded in the endoplasmic reticulum
CC membrane (By similarity). Low sterol concentrations promote processing
CC of this form, releasing the transcription factor form that translocates
CC into the nucleus and activates transcription of genes involved in
CC cholesterol biosynthesis and lipid homeostasis (By similarity).
CC {ECO:0000250|UniProtKB:P36956, ECO:0000250|UniProtKB:Q9WTN3}.
CC -!- FUNCTION: [Processed sterol regulatory element-binding protein 1]: Key
CC transcription factor that regulates expression of genes involved in
CC cholesterol biosynthesis and lipid homeostasis. Binds to the sterol
CC regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3'). Has dual sequence
CC specificity binding to both an E-box motif (5'-ATCACGTGA-3') and to
CC SRE-1 (5'-ATCACCCCAC-3'). Regulates the promoters of genes involved in
CC cholesterol biosynthesis and the LDL receptor (LDLR) pathway of sterol
CC regulation. {ECO:0000250|UniProtKB:P36956}.
CC -!- SUBUNIT: [Sterol regulatory element-binding protein 1]: Forms a tight
CC complex with SCAP, the SCAP-SREBP complex, in the endoplasmic reticulum
CC membrane. {ECO:0000250|UniProtKB:P36956}.
CC -!- SUBUNIT: [Processed sterol regulatory element-binding protein 1]:
CC Efficient DNA binding of the soluble transcription factor fragment
CC requires dimerization with another bHLH protein (By similarity).
CC Interacts with CEBPA, the interaction produces a transcriptional
CC synergy. Interacts with LMNA (By similarity).
CC {ECO:0000250|UniProtKB:P36956, ECO:0000250|UniProtKB:Q9WTN3}.
CC -!- SUBCELLULAR LOCATION: [Sterol regulatory element-binding protein 1]:
CC Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P36956}; Multi-
CC pass membrane protein {ECO:0000255}. Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:Q9WTN3}; Multi-pass membrane protein
CC {ECO:0000255}. Cytoplasmic vesicle, COPII-coated vesicle membrane
CC {ECO:0000250|UniProtKB:Q9WTN3}; 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:Q9WTN3}.
CC -!- SUBCELLULAR LOCATION: [Processed sterol regulatory element-binding
CC protein 1]: Nucleus {ECO:0000250|UniProtKB:P36956}.
CC -!- DOMAIN: The 9aaTAD motif is a transactivation domain present in a large
CC number of yeast and animal transcription factors.
CC {ECO:0000250|UniProtKB:P36956}.
CC -!- PTM: [Sterol regulatory element-binding protein 1]: 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:P36956}.
CC -!- PTM: Phosphorylated by AMPK, leading to suppress protein processing and
CC nuclear translocation, and repress target gene expression.
CC Phosphorylation at Ser-403 by SIK1 represses activity possibly by
CC inhibiting DNA-binding. {ECO:0000250|UniProtKB:Q9WTN3}.
CC -!- PTM: [Processed sterol regulatory element-binding protein 1]:
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:P36956}.
CC -!- SIMILARITY: Belongs to the SREBP family. {ECO:0000305}.
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DR EMBL; AY496867; AAS18238.1; -; mRNA.
DR EMBL; AY307771; AAP74567.1; -; mRNA.
DR EMBL; AF102873; AAC78685.1; -; mRNA.
DR EMBL; DQ464433; ABE02287.1; -; Genomic_DNA.
DR RefSeq; NP_999322.1; NM_214157.1.
DR AlphaFoldDB; O97676; -.
DR SMR; O97676; -.
DR PRIDE; O97676; -.
DR GeneID; 397308; -.
DR KEGG; ssc:397308; -.
DR CTD; 6720; -.
DR InParanoid; O97676; -.
DR OrthoDB; 330300at2759; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
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; 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:0008610; P:lipid biosynthetic process; ISS:UniProtKB.
DR GO; GO:0045542; P:positive regulation of cholesterol biosynthetic process; ISS:UniProtKB.
DR GO; GO:0010867; P:positive regulation of triglyceride biosynthetic process; 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; 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; Phosphoprotein; Reference proteome; Steroid metabolism;
KW Sterol metabolism; Transcription; Transcription regulation; Transmembrane;
KW Transmembrane helix; Ubl conjugation.
FT CHAIN 1..1151
FT /note="Sterol regulatory element-binding protein 1"
FT /id="PRO_0000127449"
FT CHAIN 1..490
FT /note="Processed sterol regulatory element-binding protein
FT 1"
FT /evidence="ECO:0000250|UniProtKB:Q12772"
FT /id="PRO_0000317058"
FT TOPO_DOM 1..487
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 488..508
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 509..547
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 548..568
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 569..1151
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 324..374
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 1..59
FT /note="Transcriptional activation (acidic)"
FT /evidence="ECO:0000250|UniProtKB:P36956"
FT REGION 39..125
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 164..184
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 234..497
FT /note="Interaction with LMNA"
FT /evidence="ECO:0000250|UniProtKB:Q9WTN3"
FT REGION 374..396
FT /note="Leucine-zipper"
FT REGION 399..479
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 987..1006
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 27..35
FT /note="9aaTAD"
FT /evidence="ECO:0000250|UniProtKB:P36956"
FT COMPBIAS 88..113
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 429..462
FT /note="Polar 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 490..491
FT /note="Cleavage; by MBTPS2"
FT /evidence="ECO:0000250|UniProtKB:Q12772"
FT SITE 530..531
FT /note="Cleavage; by MBTPS1"
FT /evidence="ECO:0000250|UniProtKB:P36956"
FT MOD_RES 98
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P56720"
FT MOD_RES 117
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P36956"
FT MOD_RES 338
FT /note="Phosphoserine; by SIK1"
FT /evidence="ECO:0000250|UniProtKB:Q9WTN3"
FT MOD_RES 339
FT /note="Phosphoserine; by SIK1"
FT /evidence="ECO:0000250|UniProtKB:Q9WTN3"
FT MOD_RES 397
FT /note="Phosphoserine; by AMPK"
FT /evidence="ECO:0000250|UniProtKB:Q9WTN3"
FT MOD_RES 403
FT /note="Phosphoserine; by SIK1"
FT /evidence="ECO:0000250|UniProtKB:Q9WTN3"
FT MOD_RES 457
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9WTN3"
FT MOD_RES 1060
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P36956"
FT CONFLICT 197
FT /note="L -> P (in Ref. 2; AAP74567)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1151 AA; 121502 MW; F9AEA7FCAF831F2D CRC64;
MDEPPFTEAA LEQALAEPCE LDAALLTDIE DMLQLINNQD SDFPGLFDAP YAGVAGGTDP
TSPDASSPGS PTPPPSTMSS PLEGFLGGAR TPPPPPVSPT QPAPTPLKMY PSVPAFSPGP
GIKEEPVPLT ILQPPTPQPL SGALLPQSLP ALAPPQLSPA PVLGYPSPPG SFSSATPPGS
TSQTLPGLPL ASLPGVLPVS VHTQVQSAAP QQLLTATATP VVSPGTTTVT SQIQQVPVLL
QPHFIKADSL LLTTMKTDMG TPVKAAGIGS LAPGTAVQAA PLQTLVSGGT ILATVPLVVD
TDKLPINRLA AGGKALSSGQ SRGEKRTAHN AIEKRYRSSI NDKIIELKDL VVGTEAKLNK
SAVLRKAIDY IRFLQQSNQK LKQENLSLRT AAHKSKSLKD LVSCSSGGRT DVPMEGVKPE
VVDTLSPPPS DAGSPSQSSP LSLGSRGSSS GGSGSDSEPD SPVFEDSQMK PEQLPAPHGR
GMLDRSRLAL CVLVFLCLSC NPLASLMGSW ALPGPSDATS AYHGPWRSVL GAEGRDGPGW
VLWLLPPLVW LTNGLLVLLF LALLFVYGEP VTRPHSDPAV RFWRHRKQAD LDLARGDFAQ
AAQQLWLALR ALGRPLPTSH LDLACSLLWN LIRHLLQRLW VGRWLAGRAG GLRRDSALEA
DTRTSACDAA LVYHKLHQLH TMGKYPGGHL DAANLALSAL NLAECAGDAL SVAVLAEVYV
AAALRVKTSL PRALHFLTRF FLSSARQACL AQSGSVPVAM QWLCHPVGHR FFVDGDWAVC
GAPRDSLYSV AGNPVDPLAQ VTQLFREHLL EQALHCVAQP SPGPGSADGD REFSEALGFL
QLLNSCCDTA GAPACSFSIA SSTAATAGTD PVAKWWASLT AVVTHWLGRD EEAAERLYPL
VEHLPRALQE SERPLPRAAL HSFKAARALL GRGKAESGSA SLAMCEKASG YLQDSLAATP
AGSSIDKAMQ LLLCDLLLVA RTSLWQRQKP PPPSQASQGS SSGAQASALE LRGFQRDLSG
LRRLAQSFRP AMRRVFLHEA TARLMAGASP ARTHQLLDRS LRRRAGPCGR GGAAAAAAAE
LEPRPTRREQ AEALLLASCY LPPGFLSAPG QRVGMLAEAA RTLEKLGDRR LLHDCQQMLM
RLGGGTTVTS S
