UniProtKB - Q0VBL6 (HIF3A_MOUSE)
Hypoxia-inducible factor 3-alpha
Hif3a
Functioni
Acts as a transcriptional regulator in adaptive response to low oxygen tension. Acts as a regulator of hypoxia-inducible gene expression (PubMed:9840812, PubMed:11734856, PubMed:21546903).
Plays a role in the development of the cardiorespiratory system (PubMed:18070924).
4 PublicationsActs as 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).
1 PublicationAttenuates 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).
2 PublicationsAttenuates 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).
Plays also a role in the development of the lung and heart during embryonic and neonatal stages (PubMed:18070924).
1 PublicationGO - Molecular functioni
- DNA binding Source: MGI
- DNA-binding transcription factor activity Source: MGI
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: UniProtKB
- protein dimerization activity Source: InterPro
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: MGI
- RNA polymerase II transcription regulatory region sequence-specific DNA binding Source: GO_Central
GO - Biological processi
- angiogenesis Source: UniProtKB-KW
- apoptotic process Source: UniProtKB-KW
- cellular response to hypoxia Source: GO_Central
- positive regulation of transcription by RNA polymerase II Source: MGI
- regulation of transcription by RNA polymerase II Source: MGI
- response to hypoxia Source: MGI
- transcription by RNA polymerase II Source: MGI
Keywordsi
Molecular function | Developmental protein, Repressor |
Biological process | Angiogenesis, Apoptosis, Stress response, Transcription, Transcription regulation |
Enzyme and pathway databases
Reactomei | R-MMU-1234158, Regulation of gene expression by Hypoxia-inducible Factor R-MMU-1234176, Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha R-MMU-8951664, Neddylation |
Names & Taxonomyi
Protein namesi | Recommended name: Hypoxia-inducible factor 3-alpha1 PublicationShort name: HIF-3-alpha Short name: HIF3-alpha Alternative name(s): Basic-helix-loop-helix-PAS protein MOP7 HIF3-alpha-1 Inhibitory PAS domain protein1 Publication Short name: IPAS1 Publication Member of PAS protein 7 Neonatal and embryonic PAS protein1 Publication |
Gene namesi | |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1859778, Hif3a |
VEuPathDBi | HostDB:ENSMUSG00000004328 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm By similarity
Nucleus
- Nucleus By similarity
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.By similarity
Mitochondrion
- Mitochondrion 1 Publication
Cytoplasm and Cytosol
- Cytoplasm 2 Publications
Nucleus
- Nucleus 2 Publications
- Nucleus speckle 1 Publication
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).2 Publications
Cytosol
- cytosol Source: MGI
Mitochondrion
- mitochondrion Source: UniProtKB
Nucleus
- nuclear speck Source: UniProtKB
- nucleoplasm Source: MGI
- nucleus Source: UniProtKB
Plasma Membrane
- plasma membrane Source: MGI
Other locations
Keywords - Cellular componenti
Cytoplasm, Mitochondrion, NucleusPathology & Biotechi
Disruption phenotypei
Keywords - Diseasei
Tumor suppressorPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000284415 | 1 – 662 | Hypoxia-inducible factor 3-alphaAdd BLAST | 662 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Cross-linki | 463 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity | ||
Modified residuei | 487 | 4-hydroxyprolineBy similarity | 1 | |
Cross-linki | 565 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity |
Post-translational modificationi
Keywords - PTMi
Hydroxylation, Isopeptide bond, Ubl conjugationProteomic databases
EPDi | Q0VBL6 |
PaxDbi | Q0VBL6 |
PRIDEi | Q0VBL6 |
ProteomicsDBi | 269749 [Q0VBL6-1] 269751 [Q0VBL6-3] |
PTM databases
iPTMneti | Q0VBL6 |
PhosphoSitePlusi | Q0VBL6 |
Expressioni
Tissue specificityi
Developmental stagei
Inductioni
Gene expression databases
Bgeei | ENSMUSG00000004328, Expressed in fetal liver hematopoietic progenitor cell and 225 other tissues |
Genevisiblei | Q0VBL6, MM |
Interactioni
Subunit structurei
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).
By similarity3 PublicationsGO - Molecular functioni
- protein dimerization activity Source: InterPro
Protein-protein interaction databases
BioGRIDi | 207311, 6 interactors |
STRINGi | 10090.ENSMUSP00000104132 |
Miscellaneous databases
RNActi | Q0VBL6, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 12 – 65 | bHLHPROSITE-ProRule annotationAdd BLAST | 54 | |
Domaini | 80 – 150 | PAS 1PROSITE-ProRule annotationAdd BLAST | 71 | |
Domaini | 225 – 295 | PAS 2PROSITE-ProRule annotationAdd BLAST | 71 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 25 | DisorderedSequence analysisAdd BLAST | 25 | |
Regioni | 75 – 98 | Nuclear localization signal (isoform 2)1 PublicationAdd BLAST | 24 | |
Regioni | 228 – 272 | Nuclear export signal (isoform 2)1 PublicationAdd BLAST | 45 | |
Regioni | 352 – 377 | DisorderedSequence analysisAdd BLAST | 26 | |
Regioni | 416 – 446 | DisorderedSequence analysisAdd BLAST | 31 | |
Regioni | 448 – 581 | ODDAdd BLAST | 134 | |
Regioni | 450 – 501 | NTADAdd BLAST | 52 | |
Regioni | 500 – 595 | DisorderedSequence analysisAdd BLAST | 96 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 414 – 418 | LRRLL | 5 | |
Motifi | 485 – 492 | LAPYISMD | 8 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 352 – 375 | Polar residuesSequence analysisAdd BLAST | 24 | |
Compositional biasi | 568 – 588 | Basic and acidic residuesSequence analysisAdd BLAST | 21 |
Domaini
Keywords - Domaini
RepeatPhylogenomic databases
eggNOGi | KOG3558, Eukaryota |
GeneTreei | ENSGT00940000161745 |
HOGENOMi | CLU_010044_5_0_1 |
InParanoidi | Q0VBL6 |
OMAi | DKSAIMR |
OrthoDBi | 547545at2759 |
Family and domain databases
CDDi | cd00130, PAS, 2 hits |
Gene3Di | 4.10.280.10, 1 hit |
InterProi | View protein in InterPro IPR011598, bHLH_dom IPR021537, HIF_alpha_subunit IPR036638, HLH_DNA-bd_sf IPR000014, PAS IPR035965, PAS-like_dom_sf IPR013767, PAS_fold IPR013655, PAS_fold_3 |
Pfami | View protein in Pfam PF11413, HIF-1, 1 hit PF00989, PAS, 1 hit PF08447, PAS_3, 1 hit |
SMARTi | View protein in SMART SM00353, HLH, 1 hit SM00091, PAS, 2 hits |
SUPFAMi | SSF47459, SSF47459, 1 hit SSF55785, SSF55785, 2 hits |
TIGRFAMsi | TIGR00229, sensory_box, 1 hit |
PROSITEi | View protein in PROSITE PS50888, BHLH, 1 hit PS50112, PAS, 2 hits |
s (3+)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MDWDQDRSNT ELRKEKSRDA ARSRRSQETE VLYQLAHTLP FARGVSAHLD
60 70 80 90 100
KASIMRLTIS YLRMHRLCAA GEWNQVEKGG EPLDACYLKA LEGFVMVLTA
110 120 130 140 150
EGDMAYLSEN VSKHLGLSQL ELIGHSIFDF IHPCDQEELQ DALTPRPNLS
160 170 180 190 200
KKKLEAPTER HFSLRMKSTL TSRGRTLNLK AATWKVLHCS GHMRAYKPPA
210 220 230 240 250
QTSPAGSPRS EPPLQCLVLI CEAIPHPASL EPPLGRGAFL SRHSLDMKFT
260 270 280 290 300
YCDERIAEVA GYSPDDLIGC SAYEYIHALD SDAVSRSIHT LLSKGQAVTG
310 320 330 340 350
QYRFLARTGG YLWTQTQATV VSGGRGPQSE SIICVHFLIS RVEETGVVLS
360 370 380 390 400
LEQTEQHTRR PPRLSASSQK GIPGNSVDSP APRILAFLHP PALSEASLAA
410 420 430 440 450
DPRRFCSPDL RRLMAPILDG PPPAATPSTP QATRRPQSPL PADLPDKLTV
460 470 480 490 500
GLENAHRLST AQKNKTVETD LDIAQDPDTL DLEMLAPYIS MDDDFQLNSS
510 520 530 540 550
EQLPKVHRRP PRVARRPRAR SFHGLSPPIP EPSLLPRWGS DPRLNCSSPS
560 570 580 590 600
RGDRPTASLM PGTRKRALAQ SSEDKGLELL ETKPPKRSPR LEPGSFLLPP
610 620 630 640 650
LSLSFLLQGR QLPGNQQDPR APLVHSHEPL GLAPSLLSLC QHEETVQPRN
660
RFPPAAGLGQ TH
The sequence of this isoform differs from the canonical sequence as follows:
1-6: MDWDQD → MALGLQRV
72-119: EWNQVEKGGE...NVSKHLGLSQ → GKRGRATGRL...HNPTPGTNFS
226-291: HPASLEPPLG...DAVSRSIHTL → QLPFHDGATL...WALNRKNCPG
292-662: Missing.
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketD3Z377 | D3Z377_MOUSE | Hypoxia-inducible factor 3-alpha | Hif3a | 152 | Annotation score: | ||
A0A0U1RQ59 | A0A0U1RQ59_MOUSE | Hypoxia-inducible factor 3-alpha | Hif3a | 76 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 345 | T → N in BAE25907 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 449 | T → A in AAC72734 (PubMed:9840812).Curated | 1 | |
Sequence conflicti | 449 | T → A in AAF21782 (PubMed:9840812).Curated | 1 | |
Sequence conflicti | 449 | T → A in AAI20588 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 449 | T → A in BAF44519 (PubMed:18070924).Curated | 1 | |
Sequence conflicti | 477 | P → S in AAC72734 (PubMed:9840812).Curated | 1 | |
Sequence conflicti | 477 | P → S in AAF21782 (PubMed:9840812).Curated | 1 | |
Sequence conflicti | 477 | P → S in AAI20588 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 477 | P → S in BAF44519 (PubMed:18070924).Curated | 1 | |
Sequence conflicti | 484 | M → I in BAE25907 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 582 | T → I in AAC72734 (PubMed:9840812).Curated | 1 | |
Sequence conflicti | 582 | T → I in AAF21782 (PubMed:9840812).Curated | 1 | |
Sequence conflicti | 613 | P → L in AAC72734 (PubMed:9840812).Curated | 1 | |
Sequence conflicti | 613 | P → L in AAF21782 (PubMed:9840812).Curated | 1 | |
Sequence conflicti | 613 | P → L in AAI20588 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 613 | P → L in BAF44519 (PubMed:18070924).Curated | 1 | |
Sequence conflicti | 651 | R → H in AAC72734 (PubMed:9840812).Curated | 1 | |
Sequence conflicti | 651 | R → H in BAF44519 (PubMed:18070924).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_024528 | 1 – 6 | MDWDQD → MALGLQRV in isoform 2 and isoform 3. 2 Publications | 6 | |
Alternative sequenceiVSP_024529 | 72 – 119 | EWNQV…LGLSQ → GKRGRATGRLLPEGPGGFRH GTHRRGRHGLPVGKCQQAPG PQSVDLCSSSLIHNPTPGTN FS in isoform 2. 1 PublicationAdd BLAST | 48 | |
Alternative sequenceiVSP_024530 | 226 – 291 | HPASL…SIHTL → QLPFHDGATLGLPQEKTPIS TLFTPLWKALLCLVKRWPVQ VLQGKGTESSLPSWVLWALN RKNCPG in isoform 2. 1 PublicationAdd BLAST | 66 | |
Alternative sequenceiVSP_024531 | 292 – 662 | Missing in isoform 2. 1 PublicationAdd BLAST | 371 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF060194 mRNA Translation: AAC72734.1 AH008971 Genomic DNA Translation: AAF21782.1 AF416641 mRNA Translation: AAL39015.1 AB289606 mRNA Translation: BAF44519.1 AC148976 Genomic DNA No translation available. BC120587 mRNA Translation: AAI20588.1 AK144472 mRNA Translation: BAE25907.1 |
CCDSi | CCDS20860.1 [Q0VBL6-1] CCDS52045.1 [Q0VBL6-3] |
RefSeqi | NP_001156422.1, NM_001162950.1 [Q0VBL6-3] NP_058564.2, NM_016868.3 [Q0VBL6-1] |
Genome annotation databases
Ensembli | ENSMUST00000037762; ENSMUSP00000048248; ENSMUSG00000004328 [Q0VBL6-1] ENSMUST00000108492; ENSMUSP00000104132; ENSMUSG00000004328 [Q0VBL6-3] |
GeneIDi | 53417 |
KEGGi | mmu:53417 |
UCSCi | uc009fir.2, mouse [Q0VBL6-1] uc009fit.2, mouse [Q0VBL6-2] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF060194 mRNA Translation: AAC72734.1 AH008971 Genomic DNA Translation: AAF21782.1 AF416641 mRNA Translation: AAL39015.1 AB289606 mRNA Translation: BAF44519.1 AC148976 Genomic DNA No translation available. BC120587 mRNA Translation: AAI20588.1 AK144472 mRNA Translation: BAE25907.1 |
CCDSi | CCDS20860.1 [Q0VBL6-1] CCDS52045.1 [Q0VBL6-3] |
RefSeqi | NP_001156422.1, NM_001162950.1 [Q0VBL6-3] NP_058564.2, NM_016868.3 [Q0VBL6-1] |
3D structure databases
SMRi | Q0VBL6 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 207311, 6 interactors |
STRINGi | 10090.ENSMUSP00000104132 |
PTM databases
iPTMneti | Q0VBL6 |
PhosphoSitePlusi | Q0VBL6 |
Proteomic databases
EPDi | Q0VBL6 |
PaxDbi | Q0VBL6 |
PRIDEi | Q0VBL6 |
ProteomicsDBi | 269749 [Q0VBL6-1] 269751 [Q0VBL6-3] |
Protocols and materials databases
Antibodypediai | 18071, 373 antibodies from 31 providers |
DNASUi | 53417 |
Genome annotation databases
Ensembli | ENSMUST00000037762; ENSMUSP00000048248; ENSMUSG00000004328 [Q0VBL6-1] ENSMUST00000108492; ENSMUSP00000104132; ENSMUSG00000004328 [Q0VBL6-3] |
GeneIDi | 53417 |
KEGGi | mmu:53417 |
UCSCi | uc009fir.2, mouse [Q0VBL6-1] uc009fit.2, mouse [Q0VBL6-2] |
Organism-specific databases
CTDi | 64344 |
MGIi | MGI:1859778, Hif3a |
VEuPathDBi | HostDB:ENSMUSG00000004328 |
Phylogenomic databases
eggNOGi | KOG3558, Eukaryota |
GeneTreei | ENSGT00940000161745 |
HOGENOMi | CLU_010044_5_0_1 |
InParanoidi | Q0VBL6 |
OMAi | DKSAIMR |
OrthoDBi | 547545at2759 |
Enzyme and pathway databases
Reactomei | R-MMU-1234158, Regulation of gene expression by Hypoxia-inducible Factor R-MMU-1234176, Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha R-MMU-8951664, Neddylation |
Miscellaneous databases
BioGRID-ORCSi | 53417, 0 hits in 65 CRISPR screens |
ChiTaRSi | Hif3a, mouse |
PROi | PR:Q0VBL6 |
RNActi | Q0VBL6, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000004328, Expressed in fetal liver hematopoietic progenitor cell and 225 other tissues |
Genevisiblei | Q0VBL6, MM |
Family and domain databases
CDDi | cd00130, PAS, 2 hits |
Gene3Di | 4.10.280.10, 1 hit |
InterProi | View protein in InterPro IPR011598, bHLH_dom IPR021537, HIF_alpha_subunit IPR036638, HLH_DNA-bd_sf IPR000014, PAS IPR035965, PAS-like_dom_sf IPR013767, PAS_fold IPR013655, PAS_fold_3 |
Pfami | View protein in Pfam PF11413, HIF-1, 1 hit PF00989, PAS, 1 hit PF08447, PAS_3, 1 hit |
SMARTi | View protein in SMART SM00353, HLH, 1 hit SM00091, PAS, 2 hits |
SUPFAMi | SSF47459, SSF47459, 1 hit SSF55785, SSF55785, 2 hits |
TIGRFAMsi | TIGR00229, sensory_box, 1 hit |
PROSITEi | View protein in PROSITE PS50888, BHLH, 1 hit PS50112, PAS, 2 hits |
MobiDBi | Search... |
Entry informationi
Entry namei | HIF3A_MOUSE | |
Accessioni | Q0VBL6Primary (citable) accession number: Q0VBL6 Secondary accession number(s): A1IM61 Q9Z2I5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 17, 2007 |
Last sequence update: | July 27, 2011 | |
Last modified: | February 23, 2022 | |
This is version 121 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot