Protein / target

Sterol regulatory element-binding protein 1

Encoded bySREBF1P36956Homo sapiensSwiss-Prot

UniProt: P36956 Ensembl: ENSG00000072310 HGNC: HGNC:11289 NCBI Gene: 6720

Small-molecule tractable

Druggability

High-Quality Ligand

Research papers

Protein at a glance

Biological role

Sequence-specific double-stranded DNA binding

Strongest disease association

Hirschsprung disease

Via encoding gene SREBF1 · Genetic evidence · score 0.61

Research activity

Emerging research

1 papers · latest 2000

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Precursor of the transcription factor form (Processed sterol regulatory element-binding protein 1), which is embedded in the endoplasmic reticulum membrane.

View complete UniProt function annotation

Precursor of the transcription factor form (Processed sterol regulatory element-binding protein 1), which is embedded in the endoplasmic reticulum membrane (PubMed:32322062). Low sterol concentrations promote processing of this form, releasing the transcription factor form that translocates into the nucleus and activates transcription of genes involved in cholesterol biosynthesis and lipid homeostasis (By similarity)

Subcellular location

Endoplasmic reticulum membraneGolgi apparatus membraneCytoplasmic vesicle, COPII-coated vesicle membraneNucleus

Domains and Gene Ontology detail (55)

Domains & features

bHLH

Gene Ontology

Cchromatin
Ccytoplasm
Ccytosol
Cendoplasmic reticulum
Cendoplasmic reticulum membrane
CER to Golgi transport vesicle membrane
CGolgi apparatus
CGolgi membrane
Cnuclear envelope
Cnucleoplasm
Cnucleus
Cprotein-containing complex

1147 aa · 122 kDa · 6 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Lipid & lipoprotein metabolismUniProt · GONuclear receptor signallingGOTranscriptional regulationUniProt · GO

View supporting evidence

Lipid & lipoprotein metabolism

·Precursor of the transcription factor form (Processed sterol regulatory element-binding…
·sterol response element binding
·cellular response to fatty acid
·cholesterol metabolic process

Nuclear receptor signalling

·nuclear receptor activity

Transcriptional regulation

·Precursor of the transcription factor form (Processed sterol regulatory element-binding…
·DNA-binding transcription activator activity, RNA polymerase II-specific
·DNA-binding transcription factor activity
·DNA-binding transcription factor activity, RNA polymerase II-specific

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene SREBF1

Gene-level evidence surfaced through the gene SREBF1that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Hirschsprung disease

0.61Moderately supported

Genetic evidence dominant · Open Targets 0.37

Diabetes Mellitus, Type 2

0.61Moderately supported

Genetic evidence dominant · Open Targets 0.36

Neurodegenerative Diseases

0.32Preliminary

Pathway evidence dominant · Open Targets 0.48 · no direct causal or clinical evidence

Alzheimer's Disease

0.28Preliminary

Pathway evidence dominant · Open Targets 0.38 · no direct causal or clinical evidence

Parkinson's Disease

0.27Preliminary

Pathway evidence dominant · Open Targets 0.38 · no direct causal or clinical evidence

View evidence synthesis (5)

Hirschsprung diseaseModerately supported

0.61

agreement 0.47–0.75

Genetic99%Literature1%

Open Targets aggregate 0.37 · 2 independent evidence families

Diabetes Mellitus, Type 2Moderately supported

0.61

agreement 0.48–0.73

Genetic87%Literature13%RNA expression1%

Open Targets aggregate 0.36 · 3 independent evidence families

Neurodegenerative DiseasesPreliminary

0.32

agreement 0.14–0.49

Pathway98%Literature2%

Open Targets aggregate 0.48 · 2 independent evidence families · no direct causal or clinical evidence

Alzheimer's DiseasePreliminary

0.28

agreement 0.10–0.45

Pathway84%Literature16%

Open Targets aggregate 0.38 · 2 independent evidence families · no direct causal or clinical evidence

Parkinson's DiseasePreliminary

0.27

agreement 0.10–0.45

Pathway87%Literature14%

Open Targets aggregate 0.38 · 2 independent evidence families · no direct causal or clinical evidence

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations

Neurodegenerative Diseases0.48

Alzheimer's Disease0.38

Parkinson's Disease0.38

Multiple Sclerosis0.37

Hirschsprung disease0.37

Lysosomal Storage Diseases0.37

Diabetes Mellitus, Type 20.36

Tractability

Small molecules — Emerging

Feasibility evidence (high-quality ligand) — no clinical-stage drug of this modality recorded.

Antibodies — Emerging

Feasibility evidence (uniprot sigp or tmhmm) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (uniprot ubiquitination and database ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (5)

SM · High-Quality LigandAB · UniProt SigP or TMHMMPR · UniProt UbiquitinationPR · Database UbiquitinationPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

Increased, Liver SteatosisAOP-WikiIncreased, Liver SteatosisAOP-Wikiincrease or decrease in total cholesterol levelsClinPGxregulation of transcription factor activityToxCastincrease in total cholesterol levelsClinPGxIncreased, Liver SteatosisAOP-WikiN/A, Liver SteatosisAOP-Wiki

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

Research activity

1 papers · to 2000

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Transcriptional regulation of adipogenesis.1,163 cites

Rosen ED · Genes & development · 2000

Recent

Transcriptional regulation of adipogenesis.

Rosen ED · Genes & development · 2000

Europe PMC papers linked directly to this protein.