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Q0VBL6 (HIF3A_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 71. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Hif3a
Synonyms:Mop7
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length662 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1

Subunit structure

Heterodimerizes with ARNT. Interacts via the oxygen-dependent degradation domain (ODD) with the beta domain of VHL. Ref.1 Ref.2

Subcellular location

Nucleus By similarity. Cytoplasm By similarity.

Tissue specificity

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. Ref.1 Ref.2

Induction

Strongly induced by hypoxia By similarity.

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.

Sequence similarities

Contains 1 bHLH (basic helix-loop-helix) domain.

Contains 2 PAS (PER-ARNT-SIM) domains.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: 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.
Isoform 2 (identifier: Q0VBL6-2)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 662662Hypoxia-inducible factor 3-alpha
PRO_0000284415

Regions

Domain12 – 6554bHLH
Domain80 – 15071PAS 1
Domain225 – 29571PAS 2
Region448 – 581134ODD
Region450 – 50152NTAD
Motif414 – 4185LRRLL
Motif485 – 4928LAPYISMD

Amino acid modifications

Modified residue48714-hydroxyproline By similarity
Cross-link463Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link565Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Natural variations

Alternative sequence1 – 66MDWDQD → MALGLQRV in isoform 2.
VSP_024528
Alternative sequence72 – 11948EWNQV…LGLSQ → GKRGRATGRLLPEGPGGFRH GTHRRGRHGLPVGKCQQAPG PQSVDLCSSSLIHNPTPGTN FS in isoform 2.
VSP_024529
Alternative sequence226 – 29166HPASL…SIHTL → QLPFHDGATLGLPQEKTPIS TLFTPLWKALLCLVKRWPVQ VLQGKGTESSLPSWVLWALN RKNCPG in isoform 2.
VSP_024530
Alternative sequence292 – 662371Missing in isoform 2.
VSP_024531

Experimental info

Sequence conflict3451T → N in BAE25907. Ref.5
Sequence conflict4491T → A in AAC72734. Ref.1
Sequence conflict4491T → A in AAF21782. Ref.1
Sequence conflict4491T → A in AAI20588. Ref.4
Sequence conflict4771P → S in AAC72734. Ref.1
Sequence conflict4771P → S in AAF21782. Ref.1
Sequence conflict4771P → S in AAI20588. Ref.4
Sequence conflict4841M → I in BAE25907. Ref.5
Sequence conflict5821T → I in AAC72734. Ref.1
Sequence conflict5821T → I in AAF21782. Ref.1
Sequence conflict6131P → L in AAC72734. Ref.1
Sequence conflict6131P → L in AAF21782. Ref.1
Sequence conflict6131P → L in AAI20588. Ref.4
Sequence conflict6511R → H in AAC72734. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: D05E2B9CB2B63E4E

FASTA66273,044
        10         20         30         40         50         60 
MDWDQDRSNT ELRKEKSRDA ARSRRSQETE VLYQLAHTLP FARGVSAHLD KASIMRLTIS 

        70         80         90        100        110        120 
YLRMHRLCAA GEWNQVEKGG EPLDACYLKA LEGFVMVLTA EGDMAYLSEN VSKHLGLSQL 

       130        140        150        160        170        180 
ELIGHSIFDF IHPCDQEELQ DALTPRPNLS KKKLEAPTER HFSLRMKSTL TSRGRTLNLK 

       190        200        210        220        230        240 
AATWKVLHCS GHMRAYKPPA QTSPAGSPRS EPPLQCLVLI CEAIPHPASL EPPLGRGAFL 

       250        260        270        280        290        300 
SRHSLDMKFT YCDERIAEVA GYSPDDLIGC SAYEYIHALD SDAVSRSIHT LLSKGQAVTG 

       310        320        330        340        350        360 
QYRFLARTGG YLWTQTQATV VSGGRGPQSE SIICVHFLIS RVEETGVVLS LEQTEQHTRR 

       370        380        390        400        410        420 
PPRLSASSQK GIPGNSVDSP APRILAFLHP PALSEASLAA DPRRFCSPDL RRLMAPILDG 

       430        440        450        460        470        480 
PPPAATPSTP QATRRPQSPL PADLPDKLTV GLENAHRLST AQKNKTVETD LDIAQDPDTL 

       490        500        510        520        530        540 
DLEMLAPYIS MDDDFQLNSS EQLPKVHRRP PRVARRPRAR SFHGLSPPIP EPSLLPRWGS 

       550        560        570        580        590        600 
DPRLNCSSPS RGDRPTASLM PGTRKRALAQ SSEDKGLELL ETKPPKRSPR LEPGSFLLPP 

       610        620        630        640        650        660 
LSLSFLLQGR QLPGNQQDPR APLVHSHEPL GLAPSLLSLC QHEETVQPRN RFPPAAGLGQ 


TH 

« Hide

Isoform 2 [UniParc].

Checksum: D89D3B225C9C3967
Show »

FASTA30733,990

References

« Hide 'large scale' references
[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]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
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. expand/collapse author list , 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS20860.1. [Q0VBL6-1]
RefSeqNP_058564.2. NM_016868.3. [Q0VBL6-1]
UniGeneMm.135110.

3D structure databases

ProteinModelPortalQ0VBL6.
SMRQ0VBL6. Positions 10-340.
ModBaseSearch...
MobiDBSearch...

PTM databases

PhosphoSiteQ0VBL6.

Proteomic databases

PRIDEQ0VBL6.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000037762; ENSMUSP00000048248; ENSMUSG00000004328. [Q0VBL6-1]
GeneID53417.
KEGGmmu:53417.
UCSCuc009fir.2. mouse. [Q0VBL6-1]

Organism-specific databases

CTD64344.
MGIMGI:1859778. Hif3a.

Phylogenomic databases

eggNOGNOG288942.
GeneTreeENSGT00730000110711.
HOGENOMHOG000234306.
HOVERGENHBG060456.
KOK09096.

Gene expression databases

ArrayExpressQ0VBL6.
BgeeQ0VBL6.
CleanExMM_HIF3A.
GenevestigatorQ0VBL6.

Family and domain databases

InterProIPR011598. bHLH_dom.
IPR021537. HIF_alpha_subunit.
IPR001610. PAC.
IPR000014. PAS.
IPR013767. PAS_fold.
[Graphical view]
PfamPF11413. HIF-1. 1 hit.
PF00989. PAS. 1 hit.
[Graphical view]
SMARTSM00353. HLH. 1 hit.
SM00086. PAC. 1 hit.
SM00091. PAS. 2 hits.
[Graphical view]
SUPFAMSSF47459. SSF47459. 1 hit.
SSF55785. SSF55785. 2 hits.
TIGRFAMsTIGR00229. sensory_box. 1 hit.
PROSITEPS50888. BHLH. 1 hit.
PS50112. PAS. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

NextBio310241.
PROQ0VBL6.
SOURCESearch...

Entry information

Entry nameHIF3A_MOUSE
AccessionPrimary (citable) accession number: Q0VBL6
Secondary accession number(s): E9QLB1 expand/collapse secondary AC list , Q3UN40, Q8VHR1, Q9QX54, Q9Z2I5
Entry history
Integrated into UniProtKB/Swiss-Prot: April 17, 2007
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 71 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot