Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

HIF1AN (Q9NWT6) - Overview - Molecular Target Synopsis

Protein


HIF1AN, Hypoxia-inducible factor 1-alpha inhibitor
Enzyme Classification 1.14.11.30
UniProt Q9NWT6

Also Known as HIF1N_HUMAN, HIF1AN, FIH1

Hydroxylates HIF-1 alpha at 'Asn-803' in the C-terminal transactivation domain (CAD). Functions as an oxygen sensor and, under normoxic conditions, the hydroxylation prevents interaction of HIF-1 with transcriptional coactivators including Cbp/p300-interacting transactivator. Involved in transcriptional repression through interaction with HIF1A, VHL and histone deacetylases. Hydroxylates specific Asn residues within ankyrin repeat domains (ARD) of NFKB1, NFKBIA, NOTCH1, ASB4, PPP1R12A and several other ARD-containing proteins. Also hydroxylates Asp and His residues within ARDs of ANK1 and TNKS2, respectively. Negatively regulates NOTCH1 activity, accelerating myogenic differentiation. Positively regulates ASB4 activity, promoting vascular differentiation. Homodimer; homodimerization is essential for catalytic activity. Interacts with VHL and HIF1A. Part of a complex with VHL, HIF1A and HDAC1 or HDAC2 or HDAC3. Interacts with NFKB1 and NFKBIA. Interacts with NOTCH1, NOTCH2 and NOTCH3 but not with NOTCH4. Interacts with APBA3; binding inhibits HIF1AN binding to HIF1A. Interacts with TNKS2. Interacts with PPP1R12A. Interacts with ASB4 (By similarity). Interacts with UBE3A. Interacts with ANKS3 (By similarity). Interacts with NECAB3; the interaction is indirect and seems to be mediated by APBA3.

5OPC
FACTOR INHIBITING HIF (FIH) IN COMPLEX WITH ZINC AND VADADUSTAT
RCSB/PDB
Inspect Structure
See all 3D Structures for HIF1AN

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: HIF1AN is active in the following subcellular-locations: cytoplasm, nucleus, perinuclear region.
GO terms: HIF1AN is active in the following subcellular-locations: cytoplasm, cytosol, nucleoplasm, nucleus, perinuclear region of cytoplasm.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project HIF1AN has gain in 0 cell-lines, loss in 1 cell-lines and no signal in 1004 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: T47D, 786_0, OVCAR_3

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: LN-18, NIH:OVCAR-3, SNU-398

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, HSMM, NHLF

(see details)

3D Structures


For HIF1AN there are:
38 structures (38 chains) solved
36 are solved in complex with at least one small molecule ligand
3 are solved with an approved drug

HIF1AN is solved in complex with the approved drug(s):

TAR/TARTARIC ACID (1MZE_A),
FUM/FUMARIC ACID (2CGO_A),
CQL/CLIOQUINOL (3KCX_A).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


HIF1AN has been screened with 38 compounds (39 bioactivities). (see details)