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Reviewed, UniProtKB/Swiss-Prot P36956 (SRBP1_HUMAN)

Last modified November 24, 2009. Version 109. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Sterol regulatory element-binding protein 1
      Short name=SREBP-1
Alternative name(s):
    Sterol regulatory element-binding transcription factor 1
Cleaved into the following chain:
    1- Recommended name:
            Processed sterol regulatory element-binding protein 1
Gene names
Name: SREBF1
Synonyms: SREBP1
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1147 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (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 structure

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.

Subcellular location

Endoplasmic reticulum membrane; Multi-pass membrane protein. Golgi apparatus membrane; Multi-pass membrane protein. Cytoplasmic vesicleCOPII-coated vesicle membrane; Multi-pass membrane protein. Note: Moves from the endoplasmic reticulum to the Golgi in the absence of sterols.

Processed sterol regulatory element-binding protein 1: Nucleus.

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.

Post-translational modification

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.

Sequence similarities

Belongs to the SREBP family.

Contains 1 basic helix-loop-helix (bHLH) domain.

Sequence caution

The sequence BAD92846.1 differs from that shown. Reason: Miscellaneous discrepancy. Intron retention.

Ontologies

Keywords
   Biological processCholesterol metabolism
Lipid metabolism
Steroid metabolism
Transcription
Transcription regulation
   Cellular componentCytoplasmic vesicle
Endoplasmic reticulum
Golgi apparatus
Membrane
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainTransmembrane
   LigandDNA-binding
   Molecular functionActivator
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Gene Ontology (GO)
   Biological processcellular response to starvation

Inferred from sequence or structural similarity. Source: HGNC

cholesterol metabolic process

Inferred from electronic annotation. Source: UniProtKB-KW

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay. Source: UniProtKB

regulation of transcription from RNA polymerase II promoter

Traceable author statement. Source: ProtInc

transcription

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular componentGolgi apparatus

Inferred from electronic annotation. Source: UniProtKB-KW

cytoplasmic vesicle

Inferred from electronic annotation. Source: UniProtKB-KW

endoplasmic reticulum

Inferred from direct assay. Source: UniProtKB

endoplasmic reticulum membrane

Traceable author statement. Source: ProtInc

integral to membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

nuclear envelope

Traceable author statement. Source: ProtInc

nucleus

Inferred from direct assay. Source: UniProtKB

   Molecular functionRNA polymerase II transcription factor activity

Traceable author statement. Source: ProtInc

protein binding

Inferred from physical interaction. Source: UniProtKB

sterol response element binding

Inferred from direct assay. Source: HGNC

transcription factor activity

Inferred from direct assay. Source: HGNC

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CrebbpP454811EBI-948328,EBI-296306From a different organism.
MED15Q96RN54EBI-948328,EBI-394506

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform SREBP-1A (identifier: P36956-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform SREBP-1B (identifier: P36956-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1035-1147: VFLHEATARL...LGGGTTVTSS → LMDVLTSESA...KVPGWHGRMD
Isoform SREBP-1C (identifier: P36956-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-29: MDEPPFSEAALEQALGEPCDLDAALLTDI → MDCTF
     1035-1147: VFLHEATARL...LGGGTTVTSS → LMDVLTSESA...KVPGWHGRMD
Isoform 4 (identifier: P36956-4)

The sequence of this isoform differs from the canonical sequence as follows:
     30-30: E → EGEVGAGRGRANGLDAPRAGADRGAMDCTFE
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11471147Sterol regulatory element-binding protein 1
PRO_0000127447
Chain1 – 490490Processed sterol regulatory element-binding protein 1
PRO_0000314029

Regions

Topological domain1 – 487487Cytoplasmic Potential
Transmembrane488 – 50821 Potential
Topological domain509 – 54739Lumenal Potential
Transmembrane548 – 56821 Potential
Topological domain569 – 1147579Cytoplasmic Potential
Domain337 – 37438Helix-loop-helix motif
Domain373 – 39422Leucine-zipper Potential
DNA binding323 – 33614Basic motif
Region1 – 6060Transcriptional activation (acidic)
Region234 – 497264Interaction with LMNA By similarity
Compositional bias61 – 178118Pro/Ser-rich
Compositional bias427 – 46236Gly/Pro/Ser-rich

Sites

Site460 – 4612Cleavage; by caspase-3 and caspase-7 By similarity
Site490 – 4912Cleavage; by S2P By similarity
Site530 – 5312Cleavage; by S1P Probable

Amino acid modifications

Modified residue1101Phosphotyrosine By similarity
Modified residue1171Phosphoserine Ref.8
Modified residue10191Phosphoserine Ref.7
Modified residue10201Phosphoserine Ref.7

Natural variations

Alternative sequence1 – 2929MDEPP…LLTDI → MDCTF in isoform SREBP-1C.
VSP_002149
Alternative sequence301E → EGEVGAGRGRANGLDAPRAG ADRGAMDCTFE in isoform 4.
VSP_030859
Alternative sequence1035 – 1147113VFLHE…TVTSS → LMDVLTSESAWALPQHLGKG FPSPSGHKVPGWHGRMD in isoform SREBP-1B and isoform SREBP-1C.
VSP_002150
Natural variant3061N → S: dbSNP rs17855793. Ref.4
VAR_038468
Natural variant3091A → T: dbSNP rs35188700.
VAR_038469
Natural variant4171V → M: dbSNP rs2229590.
VAR_038470
Natural variant5801V → M: dbSNP rs36215896.
VAR_038471
Natural variant7461R → H: dbSNP rs2228461.
VAR_038472
Natural variant8341S → L: dbSNP rs17855792. Ref.4
VAR_038473
Natural variant10001T → A: dbSNP rs1042017. Ref.1 Ref.2
VAR_038474
Natural variant10081A → P: dbSNP rs35014224.
VAR_038475

Experimental info

Mutagenesis4551S → A: No effect on proteolytic processing.
Mutagenesis4561D → A: No effect on proteolytic processing.
Mutagenesis4571S → A: No effect on proteolytic processing.
Mutagenesis4601D → A: No effect on proteolytic processing.
Mutagenesis4661D → A: No effect on proteolytic processing.
Mutagenesis4811G → A: No effect on proteolytic processing.
Mutagenesis4821M → A: No effect on proteolytic processing.
Mutagenesis4831L → A: No effect on proteolytic processing.
Mutagenesis484 – 4874DRSR → AS: Strong reduction of proteolytic processing in response to low sterol.
Mutagenesis4841D → A: Loss of proteolytic processing in response to low sterol.
Mutagenesis4851R → A: No effect on proteolytic processing.
Mutagenesis5271R → A: Loss of proteolytic processing in response to low sterol.

Secondary structure

..... 1147
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform SREBP-1A [UniParc].

Last modified February 5, 2008. Version 2.
Checksum: 58F28870739FF259

FASTA1,147121,675
        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 

« Hide

Isoform SREBP-1B.

Checksum: B71B6010CDB8D1ED
Show »

FASTA1,071113,562
Isoform SREBP-1C.

Checksum: 05CF039C7707AFB9
Show »

FASTA1,047111,102
Isoform 4.

Checksum: 1C9257FFC7FC7FEB
Show »

FASTA1,177124,635

References

« Hide 'large scale' references
[1]"SREBP-1, a basic-helix-loop-helix-leucine zipper protein that controls transcription of the low density lipoprotein receptor gene."
Yokoyama C., Wang X., Briggs M.R., Admon A., Wu J., Hua X., Goldstein J.L., Brown M.S.
Cell 75:187-197(1993) [PubMed: 8402897] [Abstract]
Cited for: 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, VARIANT ALA-1000.
Tissue: Cervix carcinoma.
[2]"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."
Hua X., Wu J., Goldstein J.L., Brown M.S., Hobbs H.H.
Genomics 25:667-673(1995) [PubMed: 7759101] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ALA-1000.
Tissue: Fetal brain.
[3]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. expand/collapse author list , 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
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ISOFORM SREBP-1A).
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS SREBP-1A AND 4), VARIANTS SER-306 AND LEU-834.
Tissue: Brain, Placenta and Uterus.
[5]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
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 31-1147 (ISOFORM SREBP-1A/4).
Tissue: Spleen.
[6]"Regulated cleavage of sterol regulatory element binding proteins requires sequences on both sides of the endoplasmic reticulum membrane."
Hua X., Sakai J., Brown M.S., Goldstein J.L.
J. Biol. Chem. 271:10379-10384(1996) [PubMed: 8626610] [Abstract]
Cited for: CHARACTERIZATION, MUTAGENESIS.
[7]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed: 17081983] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1019 AND SER-1020, MASS SPECTROMETRY.
Tissue: Epithelium.
[8]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-117, MASS SPECTROMETRY.
[9]"Co-crystal structure of sterol regulatory element binding protein 1a at 2.3-A resolution."
Parraga A., Bellsolell L., Ferre-D'Amare A.R., Burley S.K.
Structure 6:661-672(1998) [PubMed: 9634703] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 319-394.
+Additional computationally mapped references.

Web resources

Wikipedia

Sterol regulatory element-binding protein entry

Cross-references

Sequence databases

U00968 mRNA. Translation: AAC50051.2.
S66167 mRNA. Translation: AAB28522.2. Different initiation.
S66168 mRNA. Translation: AAB28523.1.
CH471196 Genomic DNA. Translation: EAW55689.1.
BC023621 mRNA. Translation: AAH23621.1.
BC026962 mRNA. Translation: AAH26962.1.
BC057388 mRNA. Translation: AAH57388.1.
BC063281 mRNA. Translation: AAH63281.1.
AB209609 mRNA. Translation: BAD92846.1.
IPIIPI00220878.
IPI00418428.
IPI00419318.
IPI00795043.
PIRA48845.
RefSeqNP_001005291.1.
NP_004167.3.
UniGeneHs.592123
Hs.655395

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1AM9X-ray2.30A/B/C/D319-400[»]
ModBaseSearch...

Protein-protein interaction databases

IntActP36956. 14 interactions.
STRINGP36956.

PTM databases

PhosphoSiteP36956.

Proteomic databases

PRIDEP36956.

Genome annotation databases

EnsemblENST00000261646; ENSP00000261646; ENSG00000072310; Homo sapiens. [Genome view]
GeneID6720.
KEGGhsa:6720.
UCSCuc002grs.1. human.
uc002gru.1. human.

Organism-specific databases

CTD6720.
GeneCardsGC17M017655.
HGNCHGNC:11289. SREBF1.
HPACAB005406.
MIM184756. gene.
PharmGKBPA335.
GenAtlasSearch...

Phylogenomic databases

HOVERGENP36956.
OMASDFPGLF
OrthoDBEOG9QJV6D

Enzyme and pathway databases

BioCycCATTLE:ENSBTAG00000007884-MON.
Pathway_Interaction_DBcaspase_pathway. Caspase cascade in apoptosis.
rxr_vdr_pathway. RXR and RAR hetrodimerization with other nuclear receptor.
ReactomeREACT_602. Metabolism of lipids and lipoproteins.

Gene expression databases

ArrayExpressP36956.
BgeeP36956.
CleanExHS_SREBF1.
GenevestigatorP36956.
GermOnlineENSG00000072310. Homo sapiens.

Family and domain databases

InterProIPR001092. HLH_basic.
IPR011598. HLH_DNA_bd.
[Graphical view]
Gene3DG3DSA:4.10.280.10. HLH_DNA_bd. 1 hit.
PfamPF00010. HLH. 1 hit.
[Graphical view]
SMARTSM00353. HLH. 1 hit.
[Graphical view]
PROSITEPS50888. HLH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio26212.
PMAP-CutDBP36956.
SOURCESearch...

Entry information

Entry nameSRBP1_HUMAN
AccessionPrimary (citable) accession number: P36956
Secondary accession number(s): Q16062 expand/collapse secondary AC list , Q59F52, Q6P4R7, Q6PFW7, Q6PJ36, Q8TAK9
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: February 5, 2008
Last modified: November 24, 2009
This is version 109 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

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Human chromosome 17: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents