Q0VBL6 · HIF3A_MOUSE

  • Protein
    Hypoxia-inducible factor 3-alpha
  • Gene
    Hif3a
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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).

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).

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).

GO annotations

AspectTerm
Cellular Componentchromatin
Cellular Componentcytoplasm
Cellular Componentcytosol
Cellular Componentmitochondrion
Cellular Componentnuclear speck
Cellular Componentnucleus
Cellular Componentplasma membrane
Molecular FunctionDNA binding
Molecular FunctionDNA-binding transcription factor activity
Molecular FunctionDNA-binding transcription factor activity, RNA polymerase II-specific
Molecular Functionprotein dimerization activity
Molecular FunctionRNA polymerase II cis-regulatory region sequence-specific DNA binding
Molecular FunctionRNA polymerase II transcription regulatory region sequence-specific DNA binding
Biological Processangiogenesis
Biological Processapoptotic process
Biological Processcellular response to hypoxia
Biological Processpositive regulation of transcription by RNA polymerase II
Biological Processregulation of transcription by RNA polymerase II
Biological Processresponse to hypoxia
Biological Processtranscription by RNA polymerase II

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Hypoxia-inducible factor 3-alpha
  • Short names
    HIF-3-alpha; HIF3-alpha
  • Alternative names
    • Basic-helix-loop-helix-PAS protein MOP7
    • HIF3-alpha-1
    • Inhibitory PAS domain protein
      (IPAS
      )
    • Member of PAS protein 7
    • Neonatal and embryonic PAS protein

Gene names

    • Name
      Hif3a
    • Synonyms
      Mop7
      , Nepas

Organism names

  • Taxonomic identifier
  • Strain
    • C57BL/6J
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q0VBL6
  • Secondary accessions
    • A1IM61
    • E9QLB1
    • Q3UN40
    • Q8VHR1
    • Q9QX54
    • Q9Z2I5

Proteomes

Organism-specific databases

Subcellular Location

Nucleus
Cytoplasm
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

Nucleus
Cytoplasm
Nucleus speckle
Mitochondrion
Note: Colocalizes with BAD in the cytoplasm (PubMed:21546903).
Colocalizes with EPAS1 and HIF1A in the nucleus and speckles (PubMed:21546903).
Shuttles between the nucleus and the cytoplasm in a CRM1-dependent manner (PubMed:24092767).

Keywords

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.

Go to variant viewer

Keywords

PTM/Processing

Features

Showing features for chain, cross-link, modified residue.

TypeIDPosition(s)Description
ChainPRO_00002844151-662Hypoxia-inducible factor 3-alpha
Cross-link463Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Modified residue4874-hydroxyproline
Cross-link565Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)

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

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).

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).

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).

Protein-protein interaction databases

Miscellaneous

Family & Domains

Features

Showing features for region, domain, compositional bias, motif.

TypeIDPosition(s)Description
Region1-25Disordered
Domain12-65bHLH
Region75-98Nuclear localization signal (isoform 2)
Domain80-150PAS 1
Domain225-295PAS 2
Region228-272Nuclear export signal (isoform 2)
Compositional bias352-375Polar residues
Region352-377Disordered
Motif414-418LRRLL
Region416-446Disordered
Region448-581ODD
Region450-501NTAD
Motif485-492LAPYISMD
Region500-595Disordered
Compositional bias568-588Basic and acidic residues

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

Phylogenomic databases

Family and domain databases

Sequence & Isoforms

Align isoforms (3)
  • Sequence status
    Complete

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.

  • Length
    662
  • Mass (Da)
    73,044
  • Last updated
    2011-07-27 v2
  • Checksum
    D05E2B9CB2B63E4E
MDWDQDRSNTELRKEKSRDAARSRRSQETEVLYQLAHTLPFARGVSAHLDKASIMRLTISYLRMHRLCAAGEWNQVEKGGEPLDACYLKALEGFVMVLTAEGDMAYLSENVSKHLGLSQLELIGHSIFDFIHPCDQEELQDALTPRPNLSKKKLEAPTERHFSLRMKSTLTSRGRTLNLKAATWKVLHCSGHMRAYKPPAQTSPAGSPRSEPPLQCLVLICEAIPHPASLEPPLGRGAFLSRHSLDMKFTYCDERIAEVAGYSPDDLIGCSAYEYIHALDSDAVSRSIHTLLSKGQAVTGQYRFLARTGGYLWTQTQATVVSGGRGPQSESIICVHFLISRVEETGVVLSLEQTEQHTRRPPRLSASSQKGIPGNSVDSPAPRILAFLHPPALSEASLAADPRRFCSPDLRRLMAPILDGPPPAATPSTPQATRRPQSPLPADLPDKLTVGLENAHRLSTAQKNKTVETDLDIAQDPDTLDLEMLAPYISMDDDFQLNSSEQLPKVHRRPPRVARRPRARSFHGLSPPIPEPSLLPRWGSDPRLNCSSPSRGDRPTASLMPGTRKRALAQSSEDKGLELLETKPPKRSPRLEPGSFLLPPLSLSFLLQGRQLPGNQQDPRAPLVHSHEPLGLAPSLLSLCQHEETVQPRNRFPPAAGLGQTH

Q0VBL6-2

  • Name
    2
  • Note
    Mutagenesis 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.
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 1-6: MDWDQD → MALGLQRV
    • 72-119: EWNQVEKGGEPLDACYLKALEGFVMVLTAEGDMAYLSENVSKHLGLSQ → GKRGRATGRLLPEGPGGFRHGTHRRGRHGLPVGKCQQAPGPQSVDLCSSSLIHNPTPGTNFS
    • 226-291: HPASLEPPLGRGAFLSRHSLDMKFTYCDERIAEVAGYSPDDLIGCSAYEYIHALDSDAVSRSIHTL → QLPFHDGATLGLPQEKTPISTLFTPLWKALLCLVKRWPVQVLQGKGTESSLPSWVLWALNRKNCPG
    • 292-662: Missing

Q0VBL6-3

  • Name
    3
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 1-6: MDWDQD → MALGLQRV

Computationally mapped potential isoform sequences

There are 2 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
A0A0U1RQ59A0A0U1RQ59_MOUSEHif3a76
D3Z377D3Z377_MOUSEHif3a152

Features

Showing features for alternative sequence, sequence conflict, compositional bias.

TypeIDPosition(s)Description
Alternative sequenceVSP_0245281-6in isoform 2 and isoform 3
Alternative sequenceVSP_02452972-119in isoform 2
Alternative sequenceVSP_024530226-291in isoform 2
Alternative sequenceVSP_024531292-662in isoform 2
Sequence conflict345in Ref. 6; BAE25907
Compositional bias352-375Polar residues
Sequence conflict449in Ref. 1; AAC72734/AAF21782, 5; AAI20588 and 3; BAF44519
Sequence conflict477in Ref. 1; AAC72734/AAF21782, 5; AAI20588 and 3; BAF44519
Sequence conflict484in Ref. 6; BAE25907
Compositional bias568-588Basic and acidic residues
Sequence conflict582in Ref. 1; AAC72734/AAF21782
Sequence conflict613in Ref. 1; AAC72734/AAF21782, 5; AAI20588 and 3; BAF44519
Sequence conflict651in Ref. 1; AAC72734 and 3; BAF44519

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

Disclaimer

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