Q0VBL6 · HIF3A_MOUSE
- ProteinHypoxia-inducible factor 3-alpha
- GeneHif3a
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids662 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Acts as a transcriptional regulator in adaptive response to low oxygen tension. Acts as a regulator of hypoxia-inducible gene expression (PubMed:11734856, PubMed:21546903, PubMed:9840812).
Plays a role in the development of the cardiorespiratory system (PubMed:18070924).
Plays a role in the development of the cardiorespiratory system (PubMed:18070924).
Isoform 1
Acts as a positive regulator of hypoxia-inducible gene expression. Associates to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters in a ARNT-dependent manner, and hence also participates in the transcriptional activation of reporter genes driven by HRE (PubMed:9840812).
Isoform 2
Attenuates the ability of transcription factor HIF1A, EPAS1 and the HIF1A-ARNT complex to bind to hypoxia-responsive elements (HRE) located within the enhancer/promoter of hypoxia-inducible target genes and hence inhibits HRE-driven transcriptional activation. Functions as an inhibitor of angiogenesis in hypoxic cells of the cornea. May act as a tumor suppressor (PubMed:11734856).
May also be involved in apoptosis (PubMed:21546903).
May also be involved in apoptosis (PubMed:21546903).
Isoform 3
Attenuates the ability of transcription factor HIF1A, EPAS1 and the HIF1A-ARNT complex to bind to hypoxia-responsive elements (HRE) located within the enhancer/promoter of hypoxia-inducible target genes and hence inhibits HRE-driven transcriptional activation (PubMed:18070924).
Also plays a role in the development of the lung and heart during embryonic and neonatal stages (PubMed:18070924).
Also plays a role in the development of the lung and heart during embryonic and neonatal stages (PubMed:18070924).
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | chromatin | |
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | mitochondrion | |
Cellular Component | nuclear speck | |
Cellular Component | nucleus | |
Cellular Component | plasma membrane | |
Molecular Function | DNA binding | |
Molecular Function | DNA-binding transcription factor activity | |
Molecular Function | DNA-binding transcription factor activity, RNA polymerase II-specific | |
Molecular Function | protein dimerization activity | |
Molecular Function | RNA polymerase II cis-regulatory region sequence-specific DNA binding | |
Molecular Function | RNA polymerase II transcription regulatory region sequence-specific DNA binding | |
Biological Process | angiogenesis | |
Biological Process | apoptotic process | |
Biological Process | cellular response to hypoxia | |
Biological Process | positive regulation of transcription by RNA polymerase II | |
Biological Process | regulation of transcription by RNA polymerase II | |
Biological Process | response to hypoxia | |
Biological Process | transcription by RNA polymerase II |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameHypoxia-inducible factor 3-alpha
- Short namesHIF-3-alpha; HIF3-alpha
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ0VBL6
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: In the nuclei of all periportal and perivenous hepatocytes. In the distal perivenous zone, detected in the cytoplasm of the hepatocytes. Localized in the cytoplasm and nuclei under normoxia, but increased in the nucleus under hypoxic conditions. Colocalized with HIF1A in kidney tumors.
Isoform 2
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Mice appeared outwardly normal and are viable and fertile. Show hypertrophy of the right atrium and ventricle, disarrangement of striated muscle fibers in the heart, and pulmonary hyperplasia (PubMed:18070924).
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 30 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
PTM/Processing
Features
Showing features for chain, cross-link, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000284415 | 1-662 | Hypoxia-inducible factor 3-alpha | |||
Sequence: MDWDQDRSNTELRKEKSRDAARSRRSQETEVLYQLAHTLPFARGVSAHLDKASIMRLTISYLRMHRLCAAGEWNQVEKGGEPLDACYLKALEGFVMVLTAEGDMAYLSENVSKHLGLSQLELIGHSIFDFIHPCDQEELQDALTPRPNLSKKKLEAPTERHFSLRMKSTLTSRGRTLNLKAATWKVLHCSGHMRAYKPPAQTSPAGSPRSEPPLQCLVLICEAIPHPASLEPPLGRGAFLSRHSLDMKFTYCDERIAEVAGYSPDDLIGCSAYEYIHALDSDAVSRSIHTLLSKGQAVTGQYRFLARTGGYLWTQTQATVVSGGRGPQSESIICVHFLISRVEETGVVLSLEQTEQHTRRPPRLSASSQKGIPGNSVDSPAPRILAFLHPPALSEASLAADPRRFCSPDLRRLMAPILDGPPPAATPSTPQATRRPQSPLPADLPDKLTVGLENAHRLSTAQKNKTVETDLDIAQDPDTLDLEMLAPYISMDDDFQLNSSEQLPKVHRRPPRVARRPRARSFHGLSPPIPEPSLLPRWGSDPRLNCSSPSRGDRPTASLMPGTRKRALAQSSEDKGLELLETKPPKRSPRLEPGSFLLPPLSLSFLLQGRQLPGNQQDPRAPLVHSHEPLGLAPSLLSLCQHEETVQPRNRFPPAAGLGQTH | ||||||
Cross-link | 463 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | ||||||
Modified residue | 487 | 4-hydroxyproline | ||||
Sequence: P | ||||||
Cross-link | 565 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K |
Post-translational modification
In normoxia, hydroxylated on Pro-487 in the oxygen-dependent degradation domain (ODD) by PHD. The hydroxylated proline promotes interaction with VHL, initiating rapid ubiquitination and subsequent proteasomal degradation (By similarity).
Ubiquitinated; ubiquitination occurs in a VHL- and oxygen-dependent pathway and subsequently targeted for proteasomal degradation.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Isoform 3 is expressed in endothelial cells of vessels and capillaries in alveoli of the neonatal lung (at protein level) (PubMed:18070924).
Expressed in lung, brain, heart and kidney (PubMed:9840812).
Isoform 2 is expressed in heart and lung (PubMed:12119283).
Isoform 2 is highly expressed in the epithelial cell layer of the cornea with lower expression in the layers of ganglion cells, inner nuclear cells, and rods and cones of the retina (PubMed:11734856).
Isoform 2 is expressed in the cerebellum only in the Purkinje cell layer (PubMed:11734856).
Expressed in lung, brain, heart and kidney (PubMed:9840812).
Isoform 2 is expressed in heart and lung (PubMed:12119283).
Isoform 2 is highly expressed in the epithelial cell layer of the cornea with lower expression in the layers of ganglion cells, inner nuclear cells, and rods and cones of the retina (PubMed:11734856).
Isoform 2 is expressed in the cerebellum only in the Purkinje cell layer (PubMed:11734856).
Induction
Isoform 2 is up-regulated in corneal epithelium cells under hypoxia (at protein level) (PubMed:11734856).
Isoform 2 is up-regulated by hypoxia in a HIF1A-dependent manner (PubMed:12119283, PubMed:17355974).
Isoform 3 is up-regulated by hypoxia (PubMed:18070924).
Isoform 2 is up-regulated by hypoxia in a HIF1A-dependent manner (PubMed:12119283, PubMed:17355974).
Isoform 3 is up-regulated by hypoxia (PubMed:18070924).
Developmental stage
Isoform 3 is expressed in brain, heart, lung, liver and kidney at 15.5 dpc. Isoform 3 is expressed in heart, lung, liver and kidney at 18.5 dpc.
Gene expression databases
Interaction
Subunit
Isoform 1 interacts with ARNT (PubMed:9840812).
Isoform 2 interacts with HIF1A (PubMed:11734856, PubMed:21546903).
Isoform 2 interacts EPAS1 (PubMed:21546903).
Isoform 2 interacts (via C-terminus domain) with BAD; the interaction reduces the binding between BAD and BAX (PubMed:21546903).
Isoform 2 (via C-terminus domain) interacts with BCL2L2 and MCL1 (PubMed:21546903).
Interacts with VHL (By similarity).
Isoform 2 interacts with HIF1A (PubMed:11734856, PubMed:21546903).
Isoform 2 interacts EPAS1 (PubMed:21546903).
Isoform 2 interacts (via C-terminus domain) with BAD; the interaction reduces the binding between BAD and BAX (PubMed:21546903).
Isoform 2 (via C-terminus domain) interacts with BCL2L2 and MCL1 (PubMed:21546903).
Interacts with VHL (By similarity).
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, domain, compositional bias, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-25 | Disordered | ||||
Sequence: MDWDQDRSNTELRKEKSRDAARSRR | ||||||
Domain | 12-65 | bHLH | ||||
Sequence: LRKEKSRDAARSRRSQETEVLYQLAHTLPFARGVSAHLDKASIMRLTISYLRMH | ||||||
Region | 75-98 | Nuclear localization signal (isoform 2) | ||||
Sequence: QVEKGGEPLDACYLKALEGFVMVL | ||||||
Domain | 80-150 | PAS 1 | ||||
Sequence: GEPLDACYLKALEGFVMVLTAEGDMAYLSENVSKHLGLSQLELIGHSIFDFIHPCDQEELQDALTPRPNLS | ||||||
Domain | 225-295 | PAS 2 | ||||
Sequence: PHPASLEPPLGRGAFLSRHSLDMKFTYCDERIAEVAGYSPDDLIGCSAYEYIHALDSDAVSRSIHTLLSKG | ||||||
Region | 228-272 | Nuclear export signal (isoform 2) | ||||
Sequence: ASLEPPLGRGAFLSRHSLDMKFTYCDERIAEVAGYSPDDLIGCSA | ||||||
Compositional bias | 352-375 | Polar residues | ||||
Sequence: EQTEQHTRRPPRLSASSQKGIPGN | ||||||
Region | 352-377 | Disordered | ||||
Sequence: EQTEQHTRRPPRLSASSQKGIPGNSV | ||||||
Motif | 414-418 | LRRLL | ||||
Sequence: MAPIL | ||||||
Region | 416-446 | Disordered | ||||
Sequence: PILDGPPPAATPSTPQATRRPQSPLPADLPD | ||||||
Region | 448-581 | ODD | ||||
Sequence: LTVGLENAHRLSTAQKNKTVETDLDIAQDPDTLDLEMLAPYISMDDDFQLNSSEQLPKVHRRPPRVARRPRARSFHGLSPPIPEPSLLPRWGSDPRLNCSSPSRGDRPTASLMPGTRKRALAQSSEDKGLELLE | ||||||
Region | 450-501 | NTAD | ||||
Sequence: VGLENAHRLSTAQKNKTVETDLDIAQDPDTLDLEMLAPYISMDDDFQLNSSE | ||||||
Motif | 485-492 | LAPYISMD | ||||
Sequence: LAPYISMD | ||||||
Region | 500-595 | Disordered | ||||
Sequence: SEQLPKVHRRPPRVARRPRARSFHGLSPPIPEPSLLPRWGSDPRLNCSSPSRGDRPTASLMPGTRKRALAQSSEDKGLELLETKPPKRSPRLEPGS | ||||||
Compositional bias | 568-588 | Basic and acidic residues | ||||
Sequence: LAQSSEDKGLELLETKPPKRS |
Domain
Isoform 2
Contains a nuclear localization signal between amino acid positions 75 and 98. Contains a nuclear export signal between amino acid positions 228 and 272.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 3 isoforms produced by Alternative splicing.
Q0VBL6-1
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.
- Name1
- Length662
- Mass (Da)73,044
- Last updated2011-07-27 v2
- ChecksumD05E2B9CB2B63E4E
Q0VBL6-2
- Name2
- NoteMutagenesis of Lys-75, Arg-76, Arg-97 and Arg-98 increase strongly cytoplasmic localization. Mutagenesis of Pro-228, Pro-229, Leu-271 and Leu-272 increase strongly nuclear localization.
- Differences from canonical
- 1-6: MDWDQD → MALGLQRV
- 72-119: EWNQVEKGGEPLDACYLKALEGFVMVLTAEGDMAYLSENVSKHLGLSQ → GKRGRATGRLLPEGPGGFRHGTHRRGRHGLPVGKCQQAPGPQSVDLCSSSLIHNPTPGTNFS
- 226-291: HPASLEPPLGRGAFLSRHSLDMKFTYCDERIAEVAGYSPDDLIGCSAYEYIHALDSDAVSRSIHTL → QLPFHDGATLGLPQEKTPISTLFTPLWKALLCLVKRWPVQVLQGKGTESSLPSWVLWALNRKNCPG
- 292-662: Missing
Q0VBL6-3
- Name3
- Differences from canonical
- 1-6: MDWDQD → MALGLQRV
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A0U1RQ59 | A0A0U1RQ59_MOUSE | Hif3a | 76 | ||
D3Z377 | D3Z377_MOUSE | Hif3a | 152 |
Features
Showing features for alternative sequence, sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_024528 | 1-6 | in isoform 2 and isoform 3 | |||
Sequence: MDWDQD → MALGLQRV | ||||||
Alternative sequence | VSP_024529 | 72-119 | in isoform 2 | |||
Sequence: EWNQVEKGGEPLDACYLKALEGFVMVLTAEGDMAYLSENVSKHLGLSQ → GKRGRATGRLLPEGPGGFRHGTHRRGRHGLPVGKCQQAPGPQSVDLCSSSLIHNPTPGTNFS | ||||||
Alternative sequence | VSP_024530 | 226-291 | in isoform 2 | |||
Sequence: HPASLEPPLGRGAFLSRHSLDMKFTYCDERIAEVAGYSPDDLIGCSAYEYIHALDSDAVSRSIHTL → QLPFHDGATLGLPQEKTPISTLFTPLWKALLCLVKRWPVQVLQGKGTESSLPSWVLWALNRKNCPG | ||||||
Alternative sequence | VSP_024531 | 292-662 | in isoform 2 | |||
Sequence: Missing | ||||||
Sequence conflict | 345 | in Ref. 6; BAE25907 | ||||
Sequence: T → N | ||||||
Compositional bias | 352-375 | Polar residues | ||||
Sequence: EQTEQHTRRPPRLSASSQKGIPGN | ||||||
Sequence conflict | 449 | in Ref. 1; AAC72734/AAF21782, 5; AAI20588 and 3; BAF44519 | ||||
Sequence: T → A | ||||||
Sequence conflict | 477 | in Ref. 1; AAC72734/AAF21782, 5; AAI20588 and 3; BAF44519 | ||||
Sequence: P → S | ||||||
Sequence conflict | 484 | in Ref. 6; BAE25907 | ||||
Sequence: M → I | ||||||
Compositional bias | 568-588 | Basic and acidic residues | ||||
Sequence: LAQSSEDKGLELLETKPPKRS | ||||||
Sequence conflict | 582 | in Ref. 1; AAC72734/AAF21782 | ||||
Sequence: T → I | ||||||
Sequence conflict | 613 | in Ref. 1; AAC72734/AAF21782, 5; AAI20588 and 3; BAF44519 | ||||
Sequence: P → L | ||||||
Sequence conflict | 651 | in Ref. 1; AAC72734 and 3; BAF44519 | ||||
Sequence: R → H |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF060194 EMBL· GenBank· DDBJ | AAC72734.1 EMBL· GenBank· DDBJ | mRNA | ||
AH008971 EMBL· GenBank· DDBJ | AAF21782.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF416641 EMBL· GenBank· DDBJ | AAL39015.1 EMBL· GenBank· DDBJ | mRNA | ||
AB289606 EMBL· GenBank· DDBJ | BAF44519.1 EMBL· GenBank· DDBJ | mRNA | ||
AC148976 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC120587 EMBL· GenBank· DDBJ | AAI20588.1 EMBL· GenBank· DDBJ | mRNA | ||
AK144472 EMBL· GenBank· DDBJ | BAE25907.1 EMBL· GenBank· DDBJ | mRNA |