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Protein

Sterol regulatory element-binding protein 2

Gene

SREBF2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Transcriptional activator required for lipid homeostasis. Regulates transcription of the LDL receptor gene as well as the cholesterol and to a lesser degree the fatty acid synthesis pathway (By similarity). Binds the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') found in the flanking region of the LDRL and HMG-CoA synthase genes.By similarity

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator, DNA-binding
Biological processCholesterol metabolism, Lipid metabolism, Steroid metabolism, Sterol metabolism, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-1655829 Regulation of cholesterol biosynthesis by SREBP (SREBF)
R-HSA-1989781 PPARA activates gene expression
R-HSA-2426168 Activation of gene expression by SREBF (SREBP)
R-HSA-381340 Transcriptional regulation of white adipocyte differentiation
SIGNORiQ12772

Names & Taxonomyi

Protein namesi
Recommended name:
Sterol regulatory element-binding protein 2
Short name:
SREBP-2
Alternative name(s):
Class D basic helix-loop-helix protein 2
Short name:
bHLHd2
Sterol regulatory element-binding transcription factor 2
Cleaved into the following chain:
Gene namesi
Name:SREBF2
Synonyms:BHLHD2, SREBP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

EuPathDBiHostDB:ENSG00000198911.11
HGNCiHGNC:11290 SREBF2
MIMi600481 gene
neXtProtiNX_Q12772

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 479CytoplasmicSequence analysisAdd BLAST479
Transmembranei480 – 500HelicalSequence analysisAdd BLAST21
Topological domaini501 – 533LumenalSequence analysisAdd BLAST33
Transmembranei534 – 554HelicalSequence analysisAdd BLAST21
Topological domaini555 – 1139CytoplasmicSequence analysisAdd BLAST585

Keywords - Cellular componenti

Cytoplasmic vesicle, Endoplasmic reticulum, Golgi apparatus, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi478 – 481DRSR → AAAA: Loss of cleavage by S2P. 2 Publications4
Mutagenesisi478 – 481DRSR → AS: Loss of cleavage by S2P. 2 Publications4
Mutagenesisi478D → A: No effect on proteolytic processing in response to low sterol. 1 Publication1
Mutagenesisi479 – 481RSR → AAA: Loss of cleavage by S2P. 1 Publication3
Mutagenesisi479R → A: No effect on cleavage by S2P. 1 Publication1
Mutagenesisi481R → A: No effect on cleavage by S2P. 1 Publication1
Mutagenesisi484 – 485LC → FF: No effect on cleavage by S2P. 1 Publication2
Mutagenesisi484L → A: No effect on cleavage by S2P. 1 Publication1
Mutagenesisi485C → A: No effect on cleavage by S2P. 1 Publication1
Mutagenesisi490 – 491LC → NP: Restores cleavage by S2P; when associated with F-495 and L-496. No effect on site of cleavage by S2P. 1 Publication2
Mutagenesisi495 – 496NP → FL: Loss of cleavage by S2P. 1 Publication2
Mutagenesisi495N → F: Reduced cleavage by S2P. 1 Publication1
Mutagenesisi496P → L: Reduced cleavage by S2P. 1 Publication1
Mutagenesisi519R → A: Loss of proteolytic processing in response to low sterol. 1 Publication1
Mutagenesisi519R → K: No effect on proteolytic processing in response to low sterol. 1 Publication1

Organism-specific databases

DisGeNETi6721
OpenTargetsiENSG00000198911
PharmGKBiPA336

Chemistry databases

ChEMBLiCHEMBL1795166

Polymorphism and mutation databases

BioMutaiSREBF2
DMDMi116242800

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001274521 – 1141Sterol regulatory element-binding protein 2Add BLAST1141
ChainiPRO_00003140331 – 484Processed sterol regulatory element-binding protein 2Add BLAST484

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki464Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei855PhosphoserineCombined sources1
Modified residuei1098PhosphoserineCombined sources1

Post-translational modificationi

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-7.3 Publications
Phosphorylated by AMPK, leading to suppress protein processing and nuclear translocation, and repress target gene expression.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei468 – 469Cleavage; by caspase-3 and caspase-71 Publication2
Sitei484 – 485Cleavage; by S2P2 Publications2
Sitei522 – 523Cleavage; by S1P1 Publication2

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ12772
MaxQBiQ12772
PaxDbiQ12772
PeptideAtlasiQ12772
PRIDEiQ12772
ProteomicsDBi58919

PTM databases

CarbonylDBiQ12772
iPTMnetiQ12772
PhosphoSitePlusiQ12772

Miscellaneous databases

PMAP-CutDBiQ12772

Expressioni

Tissue specificityi

Ubiquitously expressed in adult and fetal tissues.

Gene expression databases

BgeeiENSG00000198911 Expressed in 233 organ(s), highest expression level in right hemisphere of cerebellum
CleanExiHS_SREBF2
ExpressionAtlasiQ12772 baseline and differential
GenevisibleiQ12772 HS

Organism-specific databases

HPAiHPA031962
HPA031963

Interactioni

Subunit structurei

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. Component of SCAP/SREBP complex composed of SREBF2, SCAP and RNF139; the complex hampers the interaction between SCAP and SEC24B, thereby reducing SREBF2 proteolytic processing. Interacts (via C-terminal domain) with RNF139.1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112599, 73 interactors
DIPiDIP-263N
ELMiQ12772
IntActiQ12772, 48 interactors
MINTiQ12772
STRINGi9606.ENSP00000354476

Chemistry databases

BindingDBiQ12772

Structurei

Secondary structure

11141
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ12772
SMRiQ12772
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ12772

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini330 – 380bHLHPROSITE-ProRule annotationAdd BLAST51

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 50Transcriptional activation (acidic)Add BLAST50
Regioni237 – 491Interaction with LMNABy similarityAdd BLAST255
Regioni380 – 401Leucine-zipperAdd BLAST22

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi52 – 124Gly/Pro/Ser-richAdd BLAST73
Compositional biasi125 – 244Gln-richAdd BLAST120

Sequence similaritiesi

Belongs to the SREBP family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2588 Eukaryota
ENOG410XSVP LUCA
GeneTreeiENSGT00390000017651
HOGENOMiHOG000007091
HOVERGENiHBG082276
InParanoidiQ12772
KOiK09107
OMAiGEVDAWP
OrthoDBiEOG091G01RE
PhylomeDBiQ12772
TreeFamiTF313894

Family and domain databases

CDDicd00083 HLH, 1 hit
Gene3Di4.10.280.10, 1 hit
InterProiView protein in InterPro
IPR011598 bHLH_dom
IPR036638 HLH_DNA-bd_sf
PfamiView protein in Pfam
PF00010 HLH, 1 hit
SMARTiView protein in SMART
SM00353 HLH, 1 hit
SUPFAMiSSF47459 SSF47459, 1 hit
PROSITEiView protein in PROSITE
PS50888 BHLH, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q12772-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MDDSGELGGL ETMETLTELG DELTLGDIDE MLQFVSNQVG EFPDLFSEQL
60 70 80 90 100
CSSFPGSGGS GSSSGSSGSS SSSSNGRGSS SGAVDPSVQR SFTQVTLPSF
110 120 130 140 150
SPSAASPQAP TLQVKVSPTS VPTTPRATPI LQPRPQPQPQ PQTQLQQQTV
160 170 180 190 200
MITPTFSTTP QTRIIQQPLI YQNAATSFQV LQPQVQSLVT SSQVQPVTIQ
210 220 230 240 250
QQVQTVQAQR VLTQTANGTL QTLAPATVQT VAAPQVQQVP VLVQPQIIKT
260 270 280 290 300
DSLVLTTLKT DGSPVMAAVQ NPALTALTTP IQTAALQVPT LVGSSGTILT
310 320 330 340 350
TMPVMMGQEK VPIKQVPGGV KQLEPPKEGE RRTTHNIIEK RYRSSINDKI
360 370 380 390 400
IELKDLVMGT DAKMHKSGVL RKAIDYIKYL QQVNHKLRQE NMVLKLANQK
410 420 430 440 450
NKLLKGIDLG SLVDNEVDLK IEDFNQNVLL MSPPASDSGS QAGFSPYSID
460 470 480 490 500
SEPGSPLLDD AKVKDEPDSP PVALGMVDRS RILLCVLTFL CLSFNPLTSL
510 520 530 540 550
LQWGGAHDSD QHPHSGSGRS VLSFESGSGG WFDWMMPTLL LWLVNGVIVL
560 570 580 590 600
SVFVKLLVHG EPVIRPHSRS SVTFWRHRKQ ADLDLARGDF AAAAGNLQTC
610 620 630 640 650
LAVLGRALPT SRLDLACSLS WNVIRYSLQK LRLVRWLLKK VFQCRRATPA
660 670 680 690 700
TEAGFEDEAK TSARDAALAY HRLHQLHITG KLPAGSACSD VHMALCAVNL
710 720 730 740 750
AECAEEKIPP STLVEIHLTA AMGLKTRCGG KLGFLASYFL SRAQSLCGPE
760 770 780 790 800
HSAVPDSLRW LCHPLGQKFF MERSWSVKSA AKESLYCAQR NPADPIAQVH
810 820 830 840 850
QAFCKNLLER AIESLVKPQA KKKAGDQEEE SCEFSSALEY LKLLHSFVDS
860 870 880 890 900
VGVMSPPLSR SSVLKSALGP DIICRWWTSA ITVAISWLQG DDAAVRSHFT
910 920 930 940 950
KVERIPKALE VTESPLVKAI FHACRAMHAS LPGKADGQQS SFCHCERASG
960 970 980 990 1000
HLWSSLNVSG ATSDPALNHV VQLLTCDLLL SLRTALWQKQ ASASQAVGET
1010 1020 1030 1040 1050
YHASGAELAG FQRDLGSLRR LAHSFRPAYR KVFLHEATVR LMAGASPTRT
1060 1070 1080 1090 1100
HQLLEHSLRR RTTQSTKHGE VDAWPGQRER ATAILLACRH LPLSFLSSPG
1110 1120 1130 1140
QRAVLLAEAA RTLEKVGDRR SCNDCQQMIV KLGGGTAIAA S
Length:1,141
Mass (Da):123,688
Last modified:October 17, 2006 - v2
Checksum:i481B1D8E2A2306D2
GO
Isoform 2 (identifier: Q12772-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     273-275: Missing.
     589-684: DFAAAAGNLQ...QLHITGKLPA → VYGKKSGATH...LPVPAGHASH
     685-1141: Missing.

Note: No experimental confirmation available.
Show »
Length:681
Mass (Da):73,153
Checksum:i7006587698A23FF8
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A087X1T2A0A087X1T2_HUMAN
Sterol regulatory element-binding p...
SREBF2
654Annotation score:
G3V0I8G3V0I8_HUMAN
Sterol regulatory element binding t...
SREBF2 hCG_41541
684Annotation score:
H0Y7E5H0Y7E5_HUMAN
Sterol regulatory element-binding p...
SREBF2
257Annotation score:

Sequence cautioni

The sequence AAH51799 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti961A → G in AAA50746 (PubMed:7903453).Curated1
Sequence conflicti1045A → G in AAA50746 (PubMed:7903453).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_036394273A → S in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_036395347N → K in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_049550536M → L. Corresponds to variant dbSNP:rs17002714Ensembl.1
Natural variantiVAR_028440595G → A1 PublicationCorresponds to variant dbSNP:rs2228314Ensembl.1
Natural variantiVAR_028441623V → M. Corresponds to variant dbSNP:rs2229440Ensembl.1
Natural variantiVAR_049551860R → S. Corresponds to variant dbSNP:rs2228313Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_054283273 – 275Missing in isoform 2. 1 Publication3
Alternative sequenceiVSP_054284589 – 684DFAAA…GKLPA → VYGKKSGATHSIEEELNIHI SRGTRTRTLLSSRRFCSCCR QPTNLPGSFGPGTAHLPPGP GLQPLLERDPLQPAEATPGA LAAQESLPVPAGHASH in isoform 2. 1 PublicationAdd BLAST96
Alternative sequenceiVSP_054285685 – 1141Missing in isoform 2. 1 PublicationAdd BLAST457

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U02031 mRNA Translation: AAA50746.1
CT841522 mRNA Translation: CAJ86452.1
AL021453 Genomic DNA No translation available.
Z99716 Genomic DNA No translation available.
BC051385 mRNA Translation: AAH51385.1
BC051799 mRNA Translation: AAH51799.1 Different initiation.
BC056158 mRNA Translation: AAH56158.1
CCDSiCCDS14023.1 [Q12772-1]
PIRiA49397 A54962
RefSeqiNP_004590.2, NM_004599.3 [Q12772-1]
UniGeneiHs.443258

Genome annotation databases

EnsembliENST00000361204; ENSP00000354476; ENSG00000198911 [Q12772-1]
GeneIDi6721
KEGGihsa:6721
UCSCiuc003bbi.5 human [Q12772-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U02031 mRNA Translation: AAA50746.1
CT841522 mRNA Translation: CAJ86452.1
AL021453 Genomic DNA No translation available.
Z99716 Genomic DNA No translation available.
BC051385 mRNA Translation: AAH51385.1
BC051799 mRNA Translation: AAH51799.1 Different initiation.
BC056158 mRNA Translation: AAH56158.1
CCDSiCCDS14023.1 [Q12772-1]
PIRiA49397 A54962
RefSeqiNP_004590.2, NM_004599.3 [Q12772-1]
UniGeneiHs.443258

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1UKLX-ray3.00C/D/E/F343-403[»]
ProteinModelPortaliQ12772
SMRiQ12772
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112599, 73 interactors
DIPiDIP-263N
ELMiQ12772
IntActiQ12772, 48 interactors
MINTiQ12772
STRINGi9606.ENSP00000354476

Chemistry databases

BindingDBiQ12772
ChEMBLiCHEMBL1795166

PTM databases

CarbonylDBiQ12772
iPTMnetiQ12772
PhosphoSitePlusiQ12772

Polymorphism and mutation databases

BioMutaiSREBF2
DMDMi116242800

Proteomic databases

EPDiQ12772
MaxQBiQ12772
PaxDbiQ12772
PeptideAtlasiQ12772
PRIDEiQ12772
ProteomicsDBi58919

Protocols and materials databases

DNASUi6721
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000361204; ENSP00000354476; ENSG00000198911 [Q12772-1]
GeneIDi6721
KEGGihsa:6721
UCSCiuc003bbi.5 human [Q12772-1]

Organism-specific databases

CTDi6721
DisGeNETi6721
EuPathDBiHostDB:ENSG00000198911.11
GeneCardsiSREBF2
HGNCiHGNC:11290 SREBF2
HPAiHPA031962
HPA031963
MIMi600481 gene
neXtProtiNX_Q12772
OpenTargetsiENSG00000198911
PharmGKBiPA336
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2588 Eukaryota
ENOG410XSVP LUCA
GeneTreeiENSGT00390000017651
HOGENOMiHOG000007091
HOVERGENiHBG082276
InParanoidiQ12772
KOiK09107
OMAiGEVDAWP
OrthoDBiEOG091G01RE
PhylomeDBiQ12772
TreeFamiTF313894

Enzyme and pathway databases

ReactomeiR-HSA-1655829 Regulation of cholesterol biosynthesis by SREBP (SREBF)
R-HSA-1989781 PPARA activates gene expression
R-HSA-2426168 Activation of gene expression by SREBF (SREBP)
R-HSA-381340 Transcriptional regulation of white adipocyte differentiation
SIGNORiQ12772

Miscellaneous databases

ChiTaRSiSREBF2 human
EvolutionaryTraceiQ12772
GeneWikiiSREBF2
GenomeRNAii6721
PMAP-CutDBiQ12772
PROiPR:Q12772
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000198911 Expressed in 233 organ(s), highest expression level in right hemisphere of cerebellum
CleanExiHS_SREBF2
ExpressionAtlasiQ12772 baseline and differential
GenevisibleiQ12772 HS

Family and domain databases

CDDicd00083 HLH, 1 hit
Gene3Di4.10.280.10, 1 hit
InterProiView protein in InterPro
IPR011598 bHLH_dom
IPR036638 HLH_DNA-bd_sf
PfamiView protein in Pfam
PF00010 HLH, 1 hit
SMARTiView protein in SMART
SM00353 HLH, 1 hit
SUPFAMiSSF47459 SSF47459, 1 hit
PROSITEiView protein in PROSITE
PS50888 BHLH, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiSRBP2_HUMAN
AccessioniPrimary (citable) accession number: Q12772
Secondary accession number(s): Q05BD5
, Q6GTH7, Q86V36, Q9UH04
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: October 17, 2006
Last modified: October 10, 2018
This is version 192 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. SIMILARITY comments
    Index of protein domains and families
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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