[1]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SREBP-1A), NUCLEOTIDE SEQUENCE [MRNA] OF 1-29 (ISOFORM SREBP-1C), NUCLEOTIDE SEQUENCE [MRNA] OF 1035-1147 (ISOFORMS SREBP-1B AND SREBP-1C), PARTIAL PROTEIN SEQUENCE, AND VARIANT ALA-1000. TISSUE=Cervix carcinoma; DOI=10.1016/0092-8674(93)90690-R; PubMed=8402897 [NCBI, ExPASy, EBI, Israel, Japan] Yokoyama C., Wang X., Briggs M.R., Admon A., Wu J., Hua X., Goldstein J.L., Brown M.S.; "SREBP-1, a basic-helix-loop-helix-leucine zipper protein that controls transcription of the low density lipoprotein receptor gene."; Cell 75:187-197(1993).
[2]	NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-1000. TISSUE=Fetal brain; DOI=10.1016/0888-7543(95)80009-B; PubMed=7759101 [NCBI, ExPASy, EBI, Israel, Japan] Hua X., Wu J., Goldstein J.L., Brown M.S., Hobbs H.H.; "Structure of the human gene encoding sterol regulatory element binding protein-1 (SREBF1) and localization of SREBF1 and SREBF2 to chromosomes 17p11.2 and 22q13."; Genomics 25:667-673(1995).
[3]	NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ISOFORM SREBP-1A). Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.; Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
[4]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS SREBP-1A AND 4), AND VARIANTS SER-306 AND LEU-834. TISSUE=Brain, Placenta, and Uterus; DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[5]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 31-1147 (ISOFORM SREBP-1A/4). TISSUE=Spleen; Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F.; Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
[6]	CHARACTERIZATION, AND MUTAGENESIS. DOI=10.1074/jbc.271.17.10379; PubMed=8626610 [NCBI, ExPASy, EBI, Israel, Japan] Hua X., Sakai J., Brown M.S., Goldstein J.L.; "Regulated cleavage of sterol regulatory element binding proteins requires sequences on both sides of the endoplasmic reticulum membrane."; J. Biol. Chem. 271:10379-10384(1996).
[7]	PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1019 AND SER-1020, AND MASS SPECTROMETRY. TISSUE=Epithelium; DOI=10.1016/j.cell.2006.09.026; PubMed=17081983 [NCBI, ExPASy, EBI, Israel, Japan] Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."; Cell 127:635-648(2006).
[8]	X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 319-394. DOI=10.1016/S0969-2126(98)00067-7; PubMed=9634703 [NCBI, ExPASy, EBI, Israel, Japan] Parraga A., Bellsolell L., Ferre-D'Amare A.R., Burley S.K.; "Co-crystal structure of sterol regulatory element binding protein 1a at 2.3-A resolution."; Structure 6:661-672(1998).

Comments

FUNCTION: Transcriptional activator required for lipid homeostasis. Regulates transcription of the LDL receptor gene as well as the fatty acid and to a lesser degree the cholesterol synthesis pathway (By similarity). Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3'). Has dual sequence specificity binding to both an E-box motif (5'-ATCACGTGA-3') and to SRE-1 (5'-ATCACCCCAC-3').
SUBUNIT: Forms a tight complex with SCAP in the ER membrane. Efficient DNA binding of the soluble transcription factor fragment requires dimerization with another bHLH protein. Interacts with LMNA.
INTERACTION:
P45481:Crebbp (xeno); NbExp=1; IntAct=EBI-948328, EBI-296306;
Q96RN5:MED15; NbExp=4; IntAct=EBI-948328, EBI-394506;
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein. Golgi apparatus membrane; Multi-pass membrane protein. Cytoplasmic vesicle, COPII-coated vesicle membrane; Multi-pass membrane protein. Note=Moves from the endoplasmic reticulum to the Golgi in the absence of sterols.
SUBCELLULAR LOCATION: Processed sterol regulatory element-binding protein 1: Nucleus.

ALTERNATIVE PRODUCTS: 4 named isoforms [FASTA] produced by alternative splicing. Additional isoforms seem to exist.

Name	SREBP-1A
Isoform ID	P36956-1
This is the isoform sequence displayed in this entry.

Name	SREBP-1B
Isoform ID	P36956-2
Features which should be applied to build the isoform sequence: VSP_002150.

Name	SREBP-1C
Isoform ID	P36956-3
Features which should be applied to build the isoform sequence: VSP_002149, VSP_002150.

Name	4
Isoform ID	P36956-4
Note: No experimental confirmation available.
Features which should be applied to build the isoform sequence: VSP_030859.

TISSUE SPECIFICITY: Expressed in a wide variety of tissues, most abundant in liver and adrenal gland. In fetal tissues lung and liver shows highest expression. Isoform SREBP-1C predominates in liver, adrenal gland and ovary, whereas isoform SREBP-1A predominates in hepatoma cell lines. Isoform SREBP-1A and isoform SREBP-1C are found in kidney, brain, white fat, and muscle.
PTM: At low cholesterol the SCAP/SREBP complex is recruited into COPII vesicles for export from the ER. In the Golgi complex SREBPs are cleaved sequentially by site-1 and site-2 protease. The first cleavage by site-1 protease occurs within the luminal loop, the second cleavage by site-2 protease occurs within the first transmembrane domain and releases the transcription factor from the Golgi membrane. Apoptosis triggers cleavage by the cysteine proteases caspase-3 and caspase-7.
SIMILARITY: Belongs to the SREBP family.
SIMILARITY: Contains 1 basic helix-loop-helix (bHLH) domain.
SEQUENCE CAUTION:
- Sequence=BAD92846.1; Type=Miscellaneous discrepancy; Note=Intron retention
WEB RESOURCE: Name=Wikipedia; Note=Sterol regulatory element-binding protein entry; URL="http://en.wikipedia.org/wiki/Sterol_regulatory_element_binding_protein";.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

U00968; AAC50051.2; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
S66167; AAB28522.2; ALT_INIT; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
S66168; AAB28523.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
CH471196; EAW55689.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC023621; AAH23621.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC026962; AAH26962.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC057388; AAH57388.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC063281; AAH63281.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AB209609; BAD92846.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

PIR

A48845; A48845.

RefSeq

NP_001005291.1; -.
NP_004167.3; -.

UniGene

Hs.592123

3D structure databases

PDB

1AM9; X-ray; 2.30 A; A/B/C/D=319-400.

[ExPASy / RCSB / EBI]

PDBsum

1AM9; -.

ModBase

P36956.

Protein-protein interaction databases

IntAct

P36956; -.

PTM databases

PhosphoSite

P36956; -.

Organism-specific databases

HGNC

HGNC:11289; SREBF1.

GeneLynx

SREBF1; Homo sapiens.

CAB005406; -.

184756; gene. [NCBI / EBI]

PharmGKB

PA335; -.

GeneCards

P36956.

Gene expression databases

CleanEx

HS_SREBF1; -.

GermOnline

ENSG00000072310; Homo sapiens.

Ontologies

GO:0005789;	Cellular component: endoplasmic reticulum membrane (traceable author statement from ProtInc).
GO:0005635;	Cellular component: nuclear envelope (traceable author statement from ProtInc).
GO:0005515;	Molecular function: protein binding (inferred from physical interaction from IntAct).
GO:0003702;	Molecular function: RNA polymerase II transcription factor activity (traceable author statement from ProtInc).
GO:0032810;	Molecular function: sterol response element binding (inferred from direct assay from HGNC).
GO:0003700;	Molecular function: transcription factor activity (inferred from direct assay from HGNC).
GO:0009267;	Biological process: cellular response to starvation (inferred from sequence or structural similarity from HGNC).
GO:0006629;	Biological process: lipid metabolic process (traceable author statement from ProtInc).
GO:0006357;	Biological process: regulation of transcription from RNA polymerase II promoter (traceable author statement from ProtInc).
QuickGo view.

Family and domain databases

InterPro

IPR001092; HLH_basic.
IPR011598; HLH_DNA_bd.
Graphical view of domain structure.

Gene3D

G3DSA:4.10.280.10; HLH_DNA_bd; 1.

Pfam

PF00010; HLH; 1.
Pfam graphical view of domain structure.

SMART

SM00353; HLH; 1.
SMART graphical view of domain structure.

PROSITE

PS50888; HLH; 1.
PROSITE graphical view of domain structure (profiles).

BLOCKS

P36956.

Genome annotation databases

Ensembl

ENSG00000072310; Homo sapiens. [Contig view]

GeneID

6720; -.

KEGG

hsa:6720; -.

Phylogenomic databases

HOVERGEN

P36956; -.

Other

LinkHub

P36956; -.

SOURCE

SREBF1; Homo sapiens.

ProtoNet

P36956.

UniRef

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

3D-structure; Activator; Alternative splicing; Cholesterol metabolism; Cytoplasmic vesicle; Direct protein sequencing; DNA-binding; Endoplasmic reticulum; Golgi apparatus; Lipid metabolism; Membrane; Nucleus; Phosphoprotein; Polymorphism; Steroid metabolism; Transcription; Transcription regulation; Transmembrane.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 1147`	`1147`	`Sterol regulatory element-binding protein 1.`	`PRO_0000127447`
`CHAIN`	`1 490`	`490`	`Processed sterol regulatory element-binding protein 1.`	`PRO_0000314029`
`TOPO_DOM`	`1 487`	`487`	`Cytoplasmic (Potential).`
`TRANSMEM`	`488 508`	`21`	`Potential.`
`TOPO_DOM`	`509 547`	`39`	`Lumenal (Potential).`
`TRANSMEM`	`548 568`	`21`	`Potential.`
`TOPO_DOM`	`569 1147`	`579`	`Cytoplasmic (Potential).`
`DOMAIN`	`337 374`	`38`	`Helix-loop-helix motif.`
`DOMAIN`	`373 394`	`22`	`Leucine-zipper (Potential).`
`DNA_BIND`	`323 336`	`14`	`Basic motif.`
`REGION`	`1 60`	`60`	`Transcriptional activation (acidic).`
`REGION`	`234 497`	`264`	`Interaction with LMNA (By similarity).`
`COMPBIAS`	`61 178`	`118`	`Pro/Ser-rich.`
`COMPBIAS`	`427 462`	`36`	`Gly/Pro/Ser-rich.`
`SITE`	`460 461`	`2`	`Cleavage; by caspase-3 and caspase-7 (By similarity).`
`SITE`	`490 491`	`2`	`Cleavage; by S2P (By similarity).`
`SITE`	`530 531`	`2`	`Cleavage; by S1P (Probable).`
`MOD_RES`	`110 110`		`Phosphotyrosine (By similarity).`
`MOD_RES`	`1019 1019`		`Phosphoserine.`
`MOD_RES`	`1020 1020`		`Phosphoserine.`
`VAR_SEQ`	`1 29`		`MDEPPFSEAALEQALGEPCDLDAALLTDI -> MDCTF (in isoform SREBP-1C).`	`VSP_002149`
`VAR_SEQ`	`30 30`		`E -> EGEVGAGRGRANGLDAPRAGADRGAMDCTFE (in isoform 4).`	`VSP_030859`
`VAR_SEQ`	`1035 1147`		`VFLHEATARLMAGASPTRTHQLLDRSLRRRAGPGGKGGAV` `AELEPRPTRREHAEALLLASCYLPPGFLSAPGQRVGMLAE` `AARTLEKLGDRRLLHDCQQMLMRLGGGTTVTSS -> LMDVLTSESAWALPQHLGKGFPSPSGHKVPGWHGRMD (in isoform SREBP-1B and isoform SREBP-1C).`	`VSP_002150`
`VARIANT`	`306 306`	`1`	`N -> S (in dbSNP:rs17855793 [NCBI]).`	`VAR_038468`
`VARIANT`	`309 309`	`1`	`A -> T (in dbSNP:rs35188700 [NCBI]).`	`VAR_038469`
`VARIANT`	`417 417`	`1`	`V -> M (in dbSNP:rs2229590 [NCBI]).`	`VAR_038470`
`VARIANT`	`580 580`	`1`	`V -> M (in dbSNP:rs36215896 [NCBI]).`	`VAR_038471`
`VARIANT`	`746 746`	`1`	`R -> H (in dbSNP:rs2228461 [NCBI]).`	`VAR_038472`
`VARIANT`	`834 834`	`1`	`S -> L (in dbSNP:rs17855792 [NCBI]).`	`VAR_038473`
`VARIANT`	`1000 1000`	`1`	`T -> A (in dbSNP:rs1042017 [NCBI]).`	`VAR_038474`
`VARIANT`	`1008 1008`	`1`	`A -> P (in dbSNP:rs35014224 [NCBI]).`	`VAR_038475`
`MUTAGEN`	`455 455`		`S->A: No effect on proteolytic processing.`
`MUTAGEN`	`456 456`		`D->A: No effect on proteolytic processing.`
`MUTAGEN`	`457 457`		`S->A: No effect on proteolytic processing.`
`MUTAGEN`	`460 460`		`D->A: No effect on proteolytic processing.`
`MUTAGEN`	`466 466`		`D->A: No effect on proteolytic processing.`
`MUTAGEN`	`481 481`		`G->A: No effect on proteolytic processing.`
`MUTAGEN`	`482 482`		`M->A: No effect on proteolytic processing.`
`MUTAGEN`	`483 483`		`L->A: No effect on proteolytic processing.`
`MUTAGEN`	`484 487`		`DRSR->AS: Strong reduction of proteolytic processing in response to low sterol.`
`MUTAGEN`	`484 484`		`D->A: Loss of proteolytic processing in response to low sterol.`
`MUTAGEN`	`485 485`		`R->A: No effect on proteolytic processing.`
`MUTAGEN`	`527 527`		`R->A: Loss of proteolytic processing in response to low sterol.`
`HELIX`	`321 350`	`30`
`HELIX`	`359 396`	`38`

Sequence information

Length: 1147 AA [This is the length of the unprocessed precursor]

Molecular weight: 121675 Da [This is the MW of the unprocessed precursor]

CRC64: 58F28870739FF259 [This is a checksum on the sequence]

        10         20         30         40         50         60 
MDEPPFSEAA LEQALGEPCD LDAALLTDIE DMLQLINNQD SDFPGLFDPP YAGSGAGGTD 

        70         80         90        100        110        120 
PASPDTSSPG SLSPPPATLS SSLEAFLSGP QAAPSPLSPP QPAPTPLKMY PSMPAFSPGP 

       130        140        150        160        170        180 
GIKEESVPLS ILQTPTPQPL PGALLPQSFP APAPPQFSST PVLGYPSPPG GFSTGSPPGN 

       190        200        210        220        230        240 
TQQPLPGLPL ASPPGVPPVS LHTQVQSVVP QQLLTVTAAP TAAPVTTTVT SQIQQVPVLL 

       250        260        270        280        290        300 
QPHFIKADSL LLTAMKTDGA TVKAAGLSPL VSGTTVQTGP LPTLVSGGTI LATVPLVVDA 

       310        320        330        340        350        360 
EKLPINRLAA GSKAPASAQS RGEKRTAHNA IEKRYRSSIN DKIIELKDLV VGTEAKLNKS 

       370        380        390        400        410        420 
AVLRKAIDYI RFLQHSNQKL KQENLSLRTA VHKSKSLKDL VSACGSGGNT DVLMEGVKTE 

       430        440        450        460        470        480 
VEDTLTPPPS DAGSPFQSSP LSLGSRGSGS GGSGSDSEPD SPVFEDSKAK PEQRPSLHSR 

       490        500        510        520        530        540 
GMLDRSRLAL CTLVFLCLSC NPLASLLGAR GLPSPSDTTS VYHSPGRNVL GTESRDGPGW 

       550        560        570        580        590        600 
AQWLLPPVVW LLNGLLVLVS LVLLFVYGEP VTRPHSGPAV YFWRHRKQAD LDLARGDFAQ 

       610        620        630        640        650        660 
AAQQLWLALR ALGRPLPTSH LDLACSLLWN LIRHLLQRLW VGRWLAGRAG GLQQDCALRV 

       670        680        690        700        710        720 
DASASARDAA LVYHKLHQLH TMGKHTGGHL TATNLALSAL NLAECAGDAV SVATLAEIYV 

       730        740        750        760        770        780 
AAALRVKTSL PRALHFLTRF FLSSARQACL AQSGSVPPAM QWLCHPVGHR FFVDGDWSVL 

       790        800        810        820        830        840 
STPWESLYSL AGNPVDPLAQ VTQLFREHLL ERALNCVTQP NPSPGSADGD KEFSDALGYL 

       850        860        870        880        890        900 
QLLNSCSDAA GAPAYSFSIS SSMATTTGVD PVAKWWASLT AVVIHWLRRD EEAAERLCPL 

       910        920        930        940        950        960 
VEHLPRVLQE SERPLPRAAL HSFKAARALL GCAKAESGPA SLTICEKASG YLQDSLATTP 

       970        980        990       1000       1010       1020 
ASSSIDKAVQ LFLCDLLLVV RTSLWRQQQP PAPAPAAQGT SSRPQASALE LRGFQRDLSS 

      1030       1040       1050       1060       1070       1080 
LRRLAQSFRP AMRRVFLHEA TARLMAGASP TRTHQLLDRS LRRRAGPGGK GGAVAELEPR 

      1090       1100       1110       1120       1130       1140 
PTRREHAEAL LLASCYLPPG FLSAPGQRVG MLAEAARTLE KLGDRRLLHD CQQMLMRLGG 


GTTVTSS

P36956 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools