Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Q0VBL6

- HIF3A_MOUSE

UniProt

Q0VBL6 - HIF3A_MOUSE

Protein

Hypoxia-inducible factor 3-alpha

Gene

Hif3a

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 73 (01 Oct 2014)
      Sequence version 2 (27 Jul 2011)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    Functioni

    Involved in adaptive response to hypoxia. Suppresses hypoxia-inducible expression of HIF1A and EPAS1. Binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters. The complex HIF3A-ARNT activates the transcription of reporter genes driven by HRE. Isoform 2 has a dominant-negative function of inactivating HIF1-mediated transcription. Isoform 2 attenuates the binding of HIF1 to hypoxia-responsive elements (HRE), thus inhibiting HRE-driven transcription. Hypoxia induces down-regulation of isoform 2, leading to activation of HIF1A in hypoxia. Conversely, upon restoring normoxia, the expression of isoform 2 increases and thereby secures an inhibition of HIF1A activity By similarity. May be a negative regulator of hypoxia-inducible gene expression in the kidney. May be involved in renal tumorigenesis. Functions as an inhibitor of angiogenesis in the cornea.By similarity1 Publication

    GO - Molecular functioni

    1. DNA binding Source: MGI
    2. sequence-specific DNA binding transcription factor activity Source: MGI
    3. signal transducer activity Source: InterPro
    4. transcription coactivator activity Source: UniProtKB
    5. transcription corepressor activity Source: UniProtKB

    GO - Biological processi

    1. response to hypoxia Source: MGI
    2. transcription from RNA polymerase II promoter Source: MGI

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding

    Enzyme and pathway databases

    ReactomeiREACT_199107. Regulation of gene expression by Hypoxia-inducible Factor.
    REACT_199108. Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Hypoxia-inducible factor 3-alpha
    Short name:
    HIF-3-alpha
    Short name:
    HIF3-alpha
    Alternative name(s):
    Basic-helix-loop-helix-PAS protein MOP7
    HIF3-alpha-1
    Inhibitory PAS domain protein
    Short name:
    IPAS
    Member of PAS protein 7
    Gene namesi
    Name:Hif3a
    Synonyms:Mop7
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 7

    Organism-specific databases

    MGIiMGI:1859778. Hif3a.

    Subcellular locationi

    Nucleus PROSITE-ProRule annotation. Cytoplasm By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. nucleus Source: MGI

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 662662Hypoxia-inducible factor 3-alphaPRO_0000284415Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Cross-linki463 – 463Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
    Modified residuei487 – 48714-hydroxyprolineBy similarity
    Cross-linki565 – 565Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity

    Post-translational modificationi

    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.By similarity

    Keywords - PTMi

    Hydroxylation, Isopeptide bond, Ubl conjugation

    Proteomic databases

    PRIDEiQ0VBL6.

    PTM databases

    PhosphoSiteiQ0VBL6.

    Expressioni

    Tissue specificityi

    Expressed in lung, brain, heart and kidney. Isoform 2 is expressed predominantly in the eye and at lower levels in the cerebellum and the cerebrum. 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. In the cerebellum expressed only the Purkinje cell layer.2 Publications

    Inductioni

    Strongly induced by hypoxia.By similarity

    Gene expression databases

    ArrayExpressiQ0VBL6.
    BgeeiQ0VBL6.
    CleanExiMM_HIF3A.
    GenevestigatoriQ0VBL6.

    Interactioni

    Subunit structurei

    Heterodimerizes with ARNT. Interacts via the oxygen-dependent degradation domain (ODD) with the beta domain of VHL.2 Publications

    Structurei

    3D structure databases

    ProteinModelPortaliQ0VBL6.
    SMRiQ0VBL6. Positions 10-340.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini12 – 6554bHLHPROSITE-ProRule annotationAdd
    BLAST
    Domaini80 – 15071PAS 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini225 – 29571PAS 2PROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni448 – 581134ODDAdd
    BLAST
    Regioni450 – 50152NTADAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi414 – 4185LRRLL
    Motifi485 – 4928LAPYISMD

    Sequence similaritiesi

    Contains 1 bHLH (basic helix-loop-helix) domain.PROSITE-ProRule annotation
    Contains 2 PAS (PER-ARNT-SIM) domains.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiNOG288942.
    GeneTreeiENSGT00730000110711.
    HOGENOMiHOG000234306.
    HOVERGENiHBG060456.
    KOiK09096.

    Family and domain databases

    InterProiIPR011598. bHLH_dom.
    IPR021537. HIF_alpha_subunit.
    IPR001610. PAC.
    IPR000014. PAS.
    IPR013767. PAS_fold.
    [Graphical view]
    PfamiPF11413. HIF-1. 1 hit.
    PF00989. PAS. 1 hit.
    [Graphical view]
    SMARTiSM00353. HLH. 1 hit.
    SM00086. PAC. 1 hit.
    SM00091. PAS. 2 hits.
    [Graphical view]
    SUPFAMiSSF47459. SSF47459. 1 hit.
    SSF55785. SSF55785. 2 hits.
    TIGRFAMsiTIGR00229. sensory_box. 1 hit.
    PROSITEiPS50888. BHLH. 1 hit.
    PS50112. PAS. 2 hits.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q0VBL6-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MDWDQDRSNT ELRKEKSRDA ARSRRSQETE VLYQLAHTLP FARGVSAHLD    50
    KASIMRLTIS YLRMHRLCAA GEWNQVEKGG EPLDACYLKA LEGFVMVLTA 100
    EGDMAYLSEN VSKHLGLSQL ELIGHSIFDF IHPCDQEELQ DALTPRPNLS 150
    KKKLEAPTER HFSLRMKSTL TSRGRTLNLK AATWKVLHCS GHMRAYKPPA 200
    QTSPAGSPRS EPPLQCLVLI CEAIPHPASL EPPLGRGAFL SRHSLDMKFT 250
    YCDERIAEVA GYSPDDLIGC SAYEYIHALD SDAVSRSIHT LLSKGQAVTG 300
    QYRFLARTGG YLWTQTQATV VSGGRGPQSE SIICVHFLIS RVEETGVVLS 350
    LEQTEQHTRR PPRLSASSQK GIPGNSVDSP APRILAFLHP PALSEASLAA 400
    DPRRFCSPDL RRLMAPILDG PPPAATPSTP QATRRPQSPL PADLPDKLTV 450
    GLENAHRLST AQKNKTVETD LDIAQDPDTL DLEMLAPYIS MDDDFQLNSS 500
    EQLPKVHRRP PRVARRPRAR SFHGLSPPIP EPSLLPRWGS DPRLNCSSPS 550
    RGDRPTASLM PGTRKRALAQ SSEDKGLELL ETKPPKRSPR LEPGSFLLPP 600
    LSLSFLLQGR QLPGNQQDPR APLVHSHEPL GLAPSLLSLC QHEETVQPRN 650
    RFPPAAGLGQ TH 662
    Length:662
    Mass (Da):73,044
    Last modified:July 27, 2011 - v2
    Checksum:iD05E2B9CB2B63E4E
    GO
    Isoform 2 (identifier: Q0VBL6-2) [UniParc]FASTAAdd to Basket

    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.

    Show »
    Length:307
    Mass (Da):33,990
    Checksum:iD89D3B225C9C3967
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti345 – 3451T → N in BAE25907. (PubMed:16141072)Curated
    Sequence conflicti449 – 4491T → A in AAC72734. (PubMed:9840812)Curated
    Sequence conflicti449 – 4491T → A in AAF21782. (PubMed:9840812)Curated
    Sequence conflicti449 – 4491T → A in AAI20588. (PubMed:15489334)Curated
    Sequence conflicti477 – 4771P → S in AAC72734. (PubMed:9840812)Curated
    Sequence conflicti477 – 4771P → S in AAF21782. (PubMed:9840812)Curated
    Sequence conflicti477 – 4771P → S in AAI20588. (PubMed:15489334)Curated
    Sequence conflicti484 – 4841M → I in BAE25907. (PubMed:16141072)Curated
    Sequence conflicti582 – 5821T → I in AAC72734. (PubMed:9840812)Curated
    Sequence conflicti582 – 5821T → I in AAF21782. (PubMed:9840812)Curated
    Sequence conflicti613 – 6131P → L in AAC72734. (PubMed:9840812)Curated
    Sequence conflicti613 – 6131P → L in AAF21782. (PubMed:9840812)Curated
    Sequence conflicti613 – 6131P → L in AAI20588. (PubMed:15489334)Curated
    Sequence conflicti651 – 6511R → H in AAC72734. (PubMed:9840812)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 66MDWDQD → MALGLQRV in isoform 2. 1 PublicationVSP_024528
    Alternative sequencei72 – 11948EWNQV…LGLSQ → GKRGRATGRLLPEGPGGFRH GTHRRGRHGLPVGKCQQAPG PQSVDLCSSSLIHNPTPGTN FS in isoform 2. 1 PublicationVSP_024529Add
    BLAST
    Alternative sequencei226 – 29166HPASL…SIHTL → QLPFHDGATLGLPQEKTPIS TLFTPLWKALLCLVKRWPVQ VLQGKGTESSLPSWVLWALN RKNCPG in isoform 2. 1 PublicationVSP_024530Add
    BLAST
    Alternative sequencei292 – 662371Missing in isoform 2. 1 PublicationVSP_024531Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF060194 mRNA. Translation: AAC72734.1.
    AH008971 Genomic DNA. Translation: AAF21782.1.
    AF416641 mRNA. Translation: AAL39015.1.
    AC148976 Genomic DNA. No translation available.
    BC120587 mRNA. Translation: AAI20588.1.
    AK144472 mRNA. Translation: BAE25907.1.
    CCDSiCCDS20860.1. [Q0VBL6-1]
    RefSeqiNP_058564.2. NM_016868.3. [Q0VBL6-1]
    UniGeneiMm.135110.

    Genome annotation databases

    EnsembliENSMUST00000037762; ENSMUSP00000048248; ENSMUSG00000004328. [Q0VBL6-1]
    GeneIDi53417.
    KEGGimmu:53417.
    UCSCiuc009fir.2. mouse. [Q0VBL6-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF060194 mRNA. Translation: AAC72734.1 .
    AH008971 Genomic DNA. Translation: AAF21782.1 .
    AF416641 mRNA. Translation: AAL39015.1 .
    AC148976 Genomic DNA. No translation available.
    BC120587 mRNA. Translation: AAI20588.1 .
    AK144472 mRNA. Translation: BAE25907.1 .
    CCDSi CCDS20860.1. [Q0VBL6-1 ]
    RefSeqi NP_058564.2. NM_016868.3. [Q0VBL6-1 ]
    UniGenei Mm.135110.

    3D structure databases

    ProteinModelPortali Q0VBL6.
    SMRi Q0VBL6. Positions 10-340.
    ModBasei Search...
    MobiDBi Search...

    PTM databases

    PhosphoSitei Q0VBL6.

    Proteomic databases

    PRIDEi Q0VBL6.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000037762 ; ENSMUSP00000048248 ; ENSMUSG00000004328 . [Q0VBL6-1 ]
    GeneIDi 53417.
    KEGGi mmu:53417.
    UCSCi uc009fir.2. mouse. [Q0VBL6-1 ]

    Organism-specific databases

    CTDi 64344.
    MGIi MGI:1859778. Hif3a.

    Phylogenomic databases

    eggNOGi NOG288942.
    GeneTreei ENSGT00730000110711.
    HOGENOMi HOG000234306.
    HOVERGENi HBG060456.
    KOi K09096.

    Enzyme and pathway databases

    Reactomei REACT_199107. Regulation of gene expression by Hypoxia-inducible Factor.
    REACT_199108. Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.

    Miscellaneous databases

    NextBioi 310241.
    PROi Q0VBL6.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q0VBL6.
    Bgeei Q0VBL6.
    CleanExi MM_HIF3A.
    Genevestigatori Q0VBL6.

    Family and domain databases

    InterProi IPR011598. bHLH_dom.
    IPR021537. HIF_alpha_subunit.
    IPR001610. PAC.
    IPR000014. PAS.
    IPR013767. PAS_fold.
    [Graphical view ]
    Pfami PF11413. HIF-1. 1 hit.
    PF00989. PAS. 1 hit.
    [Graphical view ]
    SMARTi SM00353. HLH. 1 hit.
    SM00086. PAC. 1 hit.
    SM00091. PAS. 2 hits.
    [Graphical view ]
    SUPFAMi SSF47459. SSF47459. 1 hit.
    SSF55785. SSF55785. 2 hits.
    TIGRFAMsi TIGR00229. sensory_box. 1 hit.
    PROSITEi PS50888. BHLH. 1 hit.
    PS50112. PAS. 2 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Molecular characterization and chromosomal localization of a third alpha-class hypoxia inducible factor subunit, HIF3alpha."
      Gu Y.Z., Moran S.M., Hogenesch J.B., Wartman L., Bradfield C.A.
      Gene Expr. 7:205-213(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH ARNT.
    2. "Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression."
      Makino Y., Cao R., Svensson K., Bertilsson G., Asman M., Tanaka H., Cao Y., Berkenstam A., Poellinger L.
      Nature 414:550-554(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, INTERACTION WITH HIF1A.
      Strain: C57BL/6J.
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Brain.
    5. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 193-662 (ISOFORM 1).
      Strain: C57BL/6J.
      Tissue: Brain.

    Entry informationi

    Entry nameiHIF3A_MOUSE
    AccessioniPrimary (citable) accession number: Q0VBL6
    Secondary accession number(s): E9QLB1
    , Q3UN40, Q8VHR1, Q9QX54, Q9Z2I5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 17, 2007
    Last sequence update: July 27, 2011
    Last modified: October 1, 2014
    This is version 73 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3