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Protein

Hypoxia-inducible factor 3-alpha

Gene

Hif3a

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Acts as a transcriptional regulator in adaptive response to low oxygen tension. 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. Plays a role in the development of the cardiorespiratory system. May also be involved in apoptosis. May act as a tumor suppressor.By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Repressor

Keywords - Biological processi

Angiogenesis, Apoptosis, Stress response, Transcription, Transcription regulation

Names & Taxonomyi

Protein namesi
Recommended name:
Hypoxia-inducible factor 3-alpha1 PublicationImported
Short name:
HIF-3-alpha
Short name:
HIF3-alpha
Alternative name(s):
HIF3-alpha-1
Gene namesi
Name:Hif3a1 PublicationImported
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi70332. Hif3a.

Subcellular locationi

  • Nucleus PROSITE-ProRule annotation1 Publication
  • Cytoplasm 1 Publication
  • Nucleus speckle By similarity
  • Mitochondrion By similarity

  • Note: In the nuclei of all periportal and perivenous hepatocytes. In the distal perivenous zone, detected in the cytoplasm of the hepatocytes (PubMed:11237857). Localized in the cytoplasm and nuclei under normoxia, but increased in the nucleus under hypoxic conditions. Colocalized with HIF1A in kidney tumors. Colocalizes with BAD in the cytoplasm. Colocalizes with EPAS1 and HIF1A in the nucleus and speckles. Shuttles between the nucleus and the cytoplasm in a CRM1-dependent manner.By similarity

GO - Cellular componenti

  • cytoplasm Source: RGD
  • mitochondrion Source: UniProtKB-SubCell
  • nuclear speck Source: UniProtKB-SubCell
  • nucleus Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Mitochondrion, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 662662Hypoxia-inducible factor 3-alphaPRO_0000284416Add
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
Ubiquitinated; ubiquitination occurs in a VHL- and oxygen-dependent pathway and subsequently targeted for proteasomal degradation.By similarity

Keywords - PTMi

Hydroxylation, Isopeptide bond, Ubl conjugation

Proteomic databases

PaxDbiQ9JHS2.
PRIDEiQ9JHS2.

PTM databases

iPTMnetiQ9JHS2.
PhosphoSiteiQ9JHS2.

Expressioni

Tissue specificityi

Expressed in the perivenous zone of the liver (PubMed:11237857). Expressed in all tissues examined during normoxia (PubMed:12824304). Expressed in brain and lung. Expressed in periportal and perivenous hepatocytes and in endothelial cells of the central vein (at protein level) (PubMed:11237857). Expressed in the perivenous zone of the liver (PubMed:11237857). Highest expression seen in the cerebral cortex, hippocampus, and lung. Low expression in myocardial tissue and liver (PubMed:12824304).2 Publications

Inductioni

Up-regulated by hypoxia.1 Publication

Interactioni

Subunit structurei

Interacts with ARNT, BAD, BCL2L2, EPAS1, HIF1A, MCL1 and VHL.By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000023490.

Structurei

3D structure databases

ProteinModelPortaliQ9JHS2.
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
Regioni75 – 9824Nuclear localization signalBy similarityAdd
BLAST
Regioni228 – 27245Nuclear export signalBy similarityAdd
BLAST
Regioni448 – 581134ODDAdd
BLAST
Regioni450 – 50152NTADAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi410 – 4134LRRLL
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

eggNOGiKOG3558. Eukaryota.
ENOG410YK57. LUCA.
HOGENOMiHOG000234306.
HOVERGENiHBG060456.
InParanoidiQ9JHS2.
KOiK09096.

Family and domain databases

InterProiIPR011598. bHLH_dom.
IPR021537. HIF_alpha_subunit.
IPR000014. PAS.
IPR013767. PAS_fold.
IPR013655. PAS_fold_3.
[Graphical view]
PfamiPF11413. HIF-1. 1 hit.
PF00989. PAS. 1 hit.
PF08447. PAS_3. 1 hit.
[Graphical view]
SMARTiSM00353. HLH. 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]

Sequencei

Sequence statusi: Complete.

Q9JHS2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDWDQDRSST ELRKEKSRDA ARSRRSQETE VLYQLAHTLP FARGVSAHLD
60 70 80 90 100
KASIMRLTIS YLRMHRLCAA GEWNQVRKEG EPLDACYLKA LEGFVMVLTA
110 120 130 140 150
EGDMAYLSEN VSKHLGLSQL ELIGHSIFDF IHPCDQEELQ DALTPRPSLS
160 170 180 190 200
KKKSEAATGR HFSLRMKSTL TSRGRALNLK 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 RVEENGVVLS
360 370 380 390 400
LEQTEQHTRR PPQLGTSSKK GIPGNSLDPP APRILAFLHP PALSEASLAA
410 420 430 440 450
DPRRFCSPDL RRLMAPILDG PPTAATPSTP QAARRPQSPL PADLPDQLAV
460 470 480 490 500
GLENAHRLST ARKNKTMETD LDIAQDPDTP DLEMLAPYIS MDDDFQLNSS
510 520 530 540 550
EQLPKVHRRP PRTARRPRAR SFHGLSPPIP EATLLPRWGS DPRLNCSSPS
560 570 580 590 600
KGDPPTAPLT PRTRKRALAQ SSEDKGLELL ETKPPKRSPR LEPGSVLLPP
610 620 630 640 650
LSLSFLLQGR QLPGNQPDPR APLVDSHEPL GLAPSLLSLY QHEETIQSRN
660
HFLPAAGLAQ TH
Length:662
Mass (Da):72,888
Last modified:October 1, 2000 - v1
Checksum:iAC9672E340544010
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ277827 mRNA. Translation: CAB96611.1.
RefSeqiNP_071973.1. NM_022528.2.
UniGeneiRn.161814.

Genome annotation databases

GeneIDi64345.
KEGGirno:64345.
UCSCiRGD:70332. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ277827 mRNA. Translation: CAB96611.1.
RefSeqiNP_071973.1. NM_022528.2.
UniGeneiRn.161814.

3D structure databases

ProteinModelPortaliQ9JHS2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000023490.

PTM databases

iPTMnetiQ9JHS2.
PhosphoSiteiQ9JHS2.

Proteomic databases

PaxDbiQ9JHS2.
PRIDEiQ9JHS2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi64345.
KEGGirno:64345.
UCSCiRGD:70332. rat.

Organism-specific databases

CTDi64344.
RGDi70332. Hif3a.

Phylogenomic databases

eggNOGiKOG3558. Eukaryota.
ENOG410YK57. LUCA.
HOGENOMiHOG000234306.
HOVERGENiHBG060456.
InParanoidiQ9JHS2.
KOiK09096.

Miscellaneous databases

PROiQ9JHS2.

Family and domain databases

InterProiIPR011598. bHLH_dom.
IPR021537. HIF_alpha_subunit.
IPR000014. PAS.
IPR013767. PAS_fold.
IPR013655. PAS_fold_3.
[Graphical view]
PfamiPF11413. HIF-1. 1 hit.
PF00989. PAS. 1 hit.
PF08447. PAS_3. 1 hit.
[Graphical view]
SMARTiSM00353. HLH. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiHIF3A_RAT
AccessioniPrimary (citable) accession number: Q9JHS2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 17, 2007
Last sequence update: October 1, 2000
Last modified: July 6, 2016
This is version 109 of the entry and version 1 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. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.