Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Hypoxia-inducible factor 3-alpha

Gene

HIF3A

Organism
Homo sapiens (Human)
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. Acts as a regulator of hypoxia-inducible gene expression (PubMed:11573933, PubMed:16126907, PubMed:19694616, PubMed:20416395, PubMed:21069422). 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 (By similarity).By similarity5 Publications
Isoform 2: Attenuates the ability of transcription factor HIF1A to bind to hypoxia-responsive elements (HRE) located within the enhancer/promoter of hypoxia-inducible target genes and hence inhibits HRE-driven transcriptional activation. Also inhibits hypoxia-inducible ARNT-mediated gene expression.1 Publication
Isoform 3: Attenuates the ability of transcription factor HIF1A to bind to hypoxia-responsive elements (HRE) located within the enhancer/promoter of hypoxia-inducible target genes and hence inhibits HRE-driven transcriptional activation.3 Publications
isoform 4: Attenuates the ability of transcription factor HIF1A and EPAS1/HIF2A 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:16126907, PubMed:17998805, PubMed:19694616, PubMed:20416395). May act as a tumor suppressor and inhibits malignant cell transformation (PubMed:17998805).4 Publications
Isoform 5: Attenuates the ability of transcription factor HIF1A to bind to hypoxia-responsive elements (HRE) located within the enhancer/promoter of hypoxia-inducible target genes and hence inhibits HRE-driven transcriptional activation.1 Publication

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

Enzyme and pathway databases

ReactomeiREACT_120916. Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
REACT_121092. Regulation of gene expression by Hypoxia-inducible Factor.
REACT_263856. Transcriptional regulation of pluripotent stem cells.

Names & Taxonomyi

Protein namesi
Recommended name:
Hypoxia-inducible factor 3-alpha1 Publication
Short name:
HIF-3-alpha1 Publication
Short name:
HIF3-alpha
Alternative name(s):
Basic-helix-loop-helix-PAS protein MOP7
Class E basic helix-loop-helix protein 17
Short name:
bHLHe17
HIF3-alpha-1
Inhibitory PAS domain protein
Short name:
IPAS
Member of PAS protein 7
PAS domain-containing protein 7
Gene namesi
Name:HIF3AImported
Synonyms:BHLHE17, MOP7, PASD7
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:15825. HIF3A.

Subcellular locationi

  • Nucleus 2 Publications
  • 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. Shuttles between the nucleus and the cytoplasm in a CRM1-dependent manner. Colocalizes with BAD in the cytoplasm. Colocalizes with EPAS1 and HIF1A in the nucleus and speckles (By similarity). Localized in the cytoplasm and nuclei under normoxia, but increased in the nucleus under hypoxic conditions (PubMed:19694616). Colocalized with HIF1A in kidney tumors (PubMed:19694616).By similarity1 Publication

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Mitochondrion, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi467 – 4671K → R: No loss of ubiquitination. Reduced ubiquitination; when associated with R-570. 1 Publication
Mutagenesisi492 – 4921P → A: Reduced hydroxylation activity. Reduced ubiquitination. 1 Publication
Mutagenesisi570 – 5701K → R: No loss of ubiquitination. Reduced ubiquitination; when associated with R-467. 1 Publication

Keywords - Diseasei

Tumor suppressor

Organism-specific databases

PharmGKBiPA29285.

Polymorphism and mutation databases

BioMutaiHIF3A.
DMDMi145558932.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 669669Hypoxia-inducible factor 3-alphaPRO_0000284414Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki467 – 467Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei492 – 49214-hydroxyproline1 Publication
Cross-linki570 – 570Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication

Post-translational modificationi

In normoxia, hydroxylated on Pro-492 in the oxygen-dependent degradation domain (ODD) by prolyl hydroxylase(s) (PHD). The hydroxylated proline promotes interaction with VHL, initiating rapid ubiquitination and subsequent proteasomal degradation.1 Publication
Ubiquitinated; ubiquitination occurs in a VHL- and oxygen-dependent pathway and subsequently targeted for proteasomal degradation.1 Publication

Keywords - PTMi

Hydroxylation, Isopeptide bond, Ubl conjugation

Proteomic databases

PaxDbiQ9Y2N7.
PRIDEiQ9Y2N7.

PTM databases

PhosphoSiteiQ9Y2N7.

Expressioni

Tissue specificityi

Expressed in vascular cells (at protein level) (PubMed:21069422). Expressed in kidney (PubMed:11573933, PubMed:19694616). Expressed in lung epithelial cells (PubMed:16775626). Expressed in endothelial cells (venous and arterial cells from umbilical cord and aortic endothelial cells) and in vascular smooth muscle cells (aorta) (PubMed:21069422). Strongly expressed in the heart, placenta, and skeletal muscle, whereas a weak expression profile was found in the lung, liver, and kidney (PubMed:12538644). Expressed weakly in cell renal cell carcinoma (CC-RCC) compared to normal renal cells (PubMed:16126907). Expression is down-regulated in numerous kidney tumor cells compared to non tumor kidney tissues (PubMed:16126907). Isoform 2 is expressed in heart, placenta, lung, liver, skeletal muscle and pancreas and in numerous cancer cell lines (PubMed:20416395). Isoform 3 and isoform 4 are weakly expressed in heart, placenta, lung, liver, skeletal muscle and pancreas (PubMed:20416395). Isoform 4 is expressed in fetal tissues, such as heart, brain, thymus, lung, liver, skeletal kidney and spleen (PubMed:20416395). Isoform 3 is weakly expressed in fetal tissues, such as liver and kidney (PubMed:20416395).7 Publications

Inductioni

Up-regulated by hypoxia (at protein level) (PubMed:16775626). Induced by hypoxia (PubMed:16775626). Isoform 2, isoform 3, isoform 4 and isoform 5 are up-regulated by hypoxia in a HIF1A- and EPAS1/HIF2A-dependent manner (PubMed:19694616, PubMed:20416395, PubMed:21069422). Isoform 4 is down-regulated by hypoxia and up-regulated upon restoring normoxia in embryonic kidney cells (PubMed:16126907).5 Publications

Gene expression databases

BgeeiQ9Y2N7.
CleanExiHS_HIF3A.
ExpressionAtlasiQ9Y2N7. baseline and differential.
GenevisibleiQ9Y2N7. HS.

Organism-specific databases

HPAiHPA041141.

Interactioni

Subunit structurei

Isoform 2 interacts (via ODD domain) with VHL (via beta domain) (PubMed:12538644). Isoform 4 interacts with HIF1A; the interaction inhibits the binding of HIF1A to hypoxia-responsive element (HRE) and HIF1A/ARNT-dependent transcriptional activation (PubMed:16126907). Isoform 4 interacts with ARNT; the interaction occurs in a HIF1A- and DNA-binding-independent manner and does not induce HIF1A/ARNT-dependent transcriptional activation (PubMed:16126907). Isoform 4 interacts with EPAS1 (PubMed:17998805). Interacts with BAD, BCL2L2 and MCL1 (By similarity).By similarity3 Publications

Protein-protein interaction databases

BioGridi122143. 4 interactions.
STRINGi9606.ENSP00000366898.

Structurei

3D structure databases

ProteinModelPortaliQ9Y2N7.
SMRiQ9Y2N7. Positions 16-342.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini14 – 6754bHLHPROSITE-ProRule annotationAdd
BLAST
Domaini82 – 15473PAS 1PROSITE-ProRule annotationAdd
BLAST
Domaini227 – 29771PAS 2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni77 – 10024Nuclear localization signalBy similarityAdd
BLAST
Regioni230 – 27445Nuclear export signalBy similarityAdd
BLAST
Regioni452 – 581130ODDAdd
BLAST
Regioni454 – 50653NTADAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi414 – 4185LRRLL
Motifi490 – 4978LAPYISMD

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.
GeneTreeiENSGT00760000118788.
HOGENOMiHOG000234306.
HOVERGENiHBG060456.
InParanoidiQ9Y2N7.
KOiK09096.
OMAiAVGQSIH.
OrthoDBiEOG7JDQX8.
PhylomeDBiQ9Y2N7.
TreeFamiTF317772.

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 (7)i

Sequence statusi: Complete.

This entry describes 7 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.2 Publications

Isoform 1 (identifier: Q9Y2N7-1) [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

        10         20         30         40         50
MALGLQRARS TTELRKEKSR DAARSRRSQE TEVLYQLAHT LPFARGVSAH
60 70 80 90 100
LDKASIMRLT ISYLRMHRLC AAGEWNQVGA GGEPLDACYL KALEGFVMVL
110 120 130 140 150
TAEGDMAYLS ENVSKHLGLS QLELIGHSIF DFIHPCDQEE LQDALTPQQT
160 170 180 190 200
LSRRKVEAPT ERCFSLRMKS TLTSRGRTLN LKAATWKVLN CSGHMRAYKP
210 220 230 240 250
PAQTSPAGSP DSEPPLQCLV LICEAIPHPG SLEPPLGRGA FLSRHSLDMK
260 270 280 290 300
FTYCDDRIAE VAGYSPDDLI GCSAYEYIHA LDSDAVSKSI HTLLSKGQAV
310 320 330 340 350
TGQYRFLARS GGYLWTQTQA TVVSGGRGPQ SESIVCVHFL ISQVEETGVV
360 370 380 390 400
LSLEQTEQHS RRPIQRGAPS QKDTPNPGDS LDTPGPRILA FLHPPSLSEA
410 420 430 440 450
ALAADPRRFC SPDLRRLLGP ILDGASVAAT PSTPLATRHP QSPLSADLPD
460 470 480 490 500
ELPVGTENVH RLFTSGKDTE AVETDLDIAQ DADALDLEML APYISMDDDF
510 520 530 540 550
QLNASEQLPR AYHRPLGAVP RPRARSFHGL SPPALEPSLL PRWGSDPRLS
560 570 580 590 600
CSSPSRGDPS ASSPMAGARK RTLAQSSEDE DEGVELLGVR PPKRSPSPEH
610 620 630 640 650
ENFLLFPLSL SFLLTGGPAP GSLQDPSTPL LNLNEPLGLG PSLLSPYSDE
660
DTTQPGGPFQ PRAGSAQAD
Length:669
Mass (Da):72,433
Last modified:April 17, 2007 - v2
Checksum:i81C4C84517000DE2
GO
Isoform 2 (identifier: Q9Y2N7-2) [UniParc]FASTAAdd to basket

Also known as: HIF-3alpha11 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     1-8: MALGLQRA → MDWQDH

Show »
Length:667
Mass (Da):72,405
Checksum:i67B8794FF9DCCF4B
GO
Isoform 3 (identifier: Q9Y2N7-3) [UniParc]FASTAAdd to basket

Also known as: HIF-3alpha21 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     611-669: SFLLTGGPAP...QPRAGSAQAD → VCWGINGILWPSLPSWLKPTVL

Show »
Length:632
Mass (Da):68,964
Checksum:i9665B0AF3998F8EF
GO
Isoform 4 (identifier: Q9Y2N7-4) [UniParc]FASTAAdd to basket

Also known as: HIF-3alpha41 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     293-363: LLSKGQAVTG...EQTEQHSRRP → CMYPISPGAK...FSPHLPPWWP
     364-669: Missing.

Show »
Length:363
Mass (Da):39,962
Checksum:i66CE5B85A2C50A15
GO
Isoform 5 (identifier: Q9Y2N7-5) [UniParc]FASTAAdd to basket

Also known as: HIF-3alpha31 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     1-56: Missing.

Note: Incomplete sequence. No experimental confirmation available.
Show »
Length:613
Mass (Da):66,142
Checksum:i4F2122D0D17C55A6
GO
Isoform 6 (identifier: Q9Y2N7-6) [UniParc]FASTAAdd to basket

Also known as: HIF-3alpha61 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     1-86: Missing.
     87-137: ACYLKALEGF...SIFDFIHPCD → MRPAAGAARR...ATCACTASAP

Note: Incomplete sequence. No experimental confirmation available.
Show »
Length:583
Mass (Da):62,393
Checksum:i04D6B8408073EEB4
GO
Isoform 7 (identifier: Q9Y2N7-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-120: MALGLQRARS...ENVSKHLGLS → MRPAAGAARR...ATCACTASAP

Note: No experimental confirmation available.
Show »
Length:600
Mass (Da):64,359
Checksum:i822B55E0513AF129
GO

Sequence cautioni

The sequence AAL69947.1 differs from that shown.Intron retention.Curated
The sequence BAB13865.1 differs from that shown.Aberrant splicing site.Curated
The sequence BAB14824.1 differs from that shown.Unlikely isoform. Aberrant splice sites.Curated
The sequence BAB55324.1 differs from that shown.Intron retention.Curated
The sequence BAD93355.1 differs from that shown.Intron retention.Curated
The sequence BAG07185.1 differs from that shown.Intron retention.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti202 – 2021A → V in BAB55324 (PubMed:14702039).Curated
Sequence conflicti497 – 4971D → G in BAB55324 (PubMed:14702039).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti343 – 3431Q → R.1 Publication
Corresponds to variant rs3764609 [ dbSNP | Ensembl ].
VAR_031731
Natural varianti463 – 4631F → L.
Corresponds to variant rs7253301 [ dbSNP | Ensembl ].
VAR_031732

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 120120MALGL…HLGLS → MRPAAGAARRPRCCTSWLTR CPSPAASAPTWTRPLSCASP SATCACTASAP in isoform 7. 1 PublicationVSP_043429Add
BLAST
Alternative sequencei1 – 8686Missing in isoform 6. CuratedVSP_024518Add
BLAST
Alternative sequencei1 – 5656Missing in isoform 5. 1 PublicationVSP_024519Add
BLAST
Alternative sequencei1 – 88MALGLQRA → MDWQDH in isoform 2. 1 PublicationVSP_024520
Alternative sequencei87 – 13751ACYLK…IHPCD → MRPAAGAARRPRCCTSWLTR CPSPAASAPTWTRPLSCASP SATCACTASAP in isoform 6. CuratedVSP_024521Add
BLAST
Alternative sequencei293 – 36371LLSKG…HSRRP → CMYPISPGAKPAATWPPADT RTPQLPIPQDALPPHLNTSS LLPKPQGTVSFLAPSYPVPR SFSPHLPPWWP in isoform 4. 1 PublicationVSP_024523Add
BLAST
Alternative sequencei364 – 669306Missing in isoform 4. 1 PublicationVSP_024525Add
BLAST
Alternative sequencei611 – 66959SFLLT…SAQAD → VCWGINGILWPSLPSWLKPT VL in isoform 3. 3 PublicationsVSP_024526Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB054067 mRNA. Translation: BAB69689.1.
AF463492 mRNA. Translation: AAL69947.1. Sequence problems.
AB118749 mRNA. Translation: BAD93355.1. Sequence problems.
AB295039 mRNA. Translation: BAG07185.1. Sequence problems.
AK021653 mRNA. Translation: BAB13865.1. Sequence problems.
AK024095 mRNA. Translation: BAB14824.1. Sequence problems.
AK027725 mRNA. Translation: BAB55324.1. Sequence problems.
AK297828 mRNA. Translation: BAG60164.1.
AC007193 Genomic DNA. Translation: AAD22668.1.
CH471126 Genomic DNA. Translation: EAW57410.1.
BC026308 mRNA. Translation: AAH26308.1.
BC080551 mRNA. Translation: AAH80551.1.
CCDSiCCDS12681.2. [Q9Y2N7-1]
CCDS12682.1. [Q9Y2N7-2]
CCDS42580.2. [Q9Y2N7-7]
PIRiJC7771.
RefSeqiNP_071907.4. NM_022462.4. [Q9Y2N7-7]
NP_690007.1. NM_152794.3. [Q9Y2N7-2]
NP_690008.2. NM_152795.3. [Q9Y2N7-1]
XP_005259211.1. XM_005259154.3. [Q9Y2N7-7]
XP_006723388.1. XM_006723325.1. [Q9Y2N7-7]
UniGeneiHs.420830.

Genome annotation databases

EnsembliENST00000244303; ENSP00000244303; ENSG00000124440. [Q9Y2N7-7]
ENST00000300862; ENSP00000300862; ENSG00000124440. [Q9Y2N7-2]
ENST00000377670; ENSP00000366898; ENSG00000124440. [Q9Y2N7-1]
GeneIDi64344.
KEGGihsa:64344.
UCSCiuc002peg.4. human. [Q9Y2N7-3]
uc002peh.3. human. [Q9Y2N7-1]
uc002pel.3. human. [Q9Y2N7-2]
uc010xxy.2. human. [Q9Y2N7-7]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

Hypoxia inducible factor entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB054067 mRNA. Translation: BAB69689.1.
AF463492 mRNA. Translation: AAL69947.1. Sequence problems.
AB118749 mRNA. Translation: BAD93355.1. Sequence problems.
AB295039 mRNA. Translation: BAG07185.1. Sequence problems.
AK021653 mRNA. Translation: BAB13865.1. Sequence problems.
AK024095 mRNA. Translation: BAB14824.1. Sequence problems.
AK027725 mRNA. Translation: BAB55324.1. Sequence problems.
AK297828 mRNA. Translation: BAG60164.1.
AC007193 Genomic DNA. Translation: AAD22668.1.
CH471126 Genomic DNA. Translation: EAW57410.1.
BC026308 mRNA. Translation: AAH26308.1.
BC080551 mRNA. Translation: AAH80551.1.
CCDSiCCDS12681.2. [Q9Y2N7-1]
CCDS12682.1. [Q9Y2N7-2]
CCDS42580.2. [Q9Y2N7-7]
PIRiJC7771.
RefSeqiNP_071907.4. NM_022462.4. [Q9Y2N7-7]
NP_690007.1. NM_152794.3. [Q9Y2N7-2]
NP_690008.2. NM_152795.3. [Q9Y2N7-1]
XP_005259211.1. XM_005259154.3. [Q9Y2N7-7]
XP_006723388.1. XM_006723325.1. [Q9Y2N7-7]
UniGeneiHs.420830.

3D structure databases

ProteinModelPortaliQ9Y2N7.
SMRiQ9Y2N7. Positions 16-342.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122143. 4 interactions.
STRINGi9606.ENSP00000366898.

PTM databases

PhosphoSiteiQ9Y2N7.

Polymorphism and mutation databases

BioMutaiHIF3A.
DMDMi145558932.

Proteomic databases

PaxDbiQ9Y2N7.
PRIDEiQ9Y2N7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000244303; ENSP00000244303; ENSG00000124440. [Q9Y2N7-7]
ENST00000300862; ENSP00000300862; ENSG00000124440. [Q9Y2N7-2]
ENST00000377670; ENSP00000366898; ENSG00000124440. [Q9Y2N7-1]
GeneIDi64344.
KEGGihsa:64344.
UCSCiuc002peg.4. human. [Q9Y2N7-3]
uc002peh.3. human. [Q9Y2N7-1]
uc002pel.3. human. [Q9Y2N7-2]
uc010xxy.2. human. [Q9Y2N7-7]

Organism-specific databases

CTDi64344.
GeneCardsiGC19P046800.
HGNCiHGNC:15825. HIF3A.
HPAiHPA041141.
MIMi609976. gene.
neXtProtiNX_Q9Y2N7.
PharmGKBiPA29285.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG288942.
GeneTreeiENSGT00760000118788.
HOGENOMiHOG000234306.
HOVERGENiHBG060456.
InParanoidiQ9Y2N7.
KOiK09096.
OMAiAVGQSIH.
OrthoDBiEOG7JDQX8.
PhylomeDBiQ9Y2N7.
TreeFamiTF317772.

Enzyme and pathway databases

ReactomeiREACT_120916. Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
REACT_121092. Regulation of gene expression by Hypoxia-inducible Factor.
REACT_263856. Transcriptional regulation of pluripotent stem cells.

Miscellaneous databases

GenomeRNAii64344.
NextBioi35533871.
PROiQ9Y2N7.
SOURCEiSearch...

Gene expression databases

BgeeiQ9Y2N7.
CleanExiHS_HIF3A.
ExpressionAtlasiQ9Y2N7. baseline and differential.
GenevisibleiQ9Y2N7. HS.

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Expression and characterization of hypoxia-inducible factor (HIF)-3alpha in human kidney: suppression of HIF-mediated gene expression by HIF-3alpha."
    Hara S., Hamada J., Kobayashi C., Kondo Y., Imura N.
    Biochem. Biophys. Res. Commun. 287:808-813(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION (ISOFORM 2), TISSUE SPECIFICITY.
    Tissue: Kidney.
  2. "Cloning and characterization of human inhibitory PAS domain protein."
    Cheng J.Q.
    Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
  3. "Human HIF-3alpha4 is a dominant-negative regulator of HIF-1 and is down-regulated in renal cell carcinoma."
    Maynard M.A., Evans A.J., Hosomi T., Hara S., Jewett M.A., Ohh M.
    FASEB J. 19:1396-1406(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), FUNCTION (ISOFORM 4), INTERACTION WITH HIF1A AND ARNT (ISOFORM 4), INDUCTION (ISOFORM 4), TISSUE SPECIFICITY.
    Tissue: Cerebellum.
  4. "HIF-3alpha2, one of splicing variants of human hypoxia-inducible factor-3alpha, functions as an inhibitor of hypoxia-induced gene expression and tumor growth."
    Hara S., Hosomi T., Mita M., Sakaue M., Kondo Y.
    Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
    Tissue: Kidney.
  5. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 7), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-626 (ISOFORM 5), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-233 (ISOFORM 6), VARIANT ARG-343.
    Tissue: Embryo, Heart and Ovary.
  6. "The DNA sequence and biology of human chromosome 19."
    Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V.
    , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
    Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  8. "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] (ISOFORMS 1 AND 4), VARIANT ARG-343.
    Tissue: Brain and Pancreas.
  9. "Multiple splice variants of the human HIF-3 alpha locus are targets of the von Hippel-Lindau E3 ubiquitin ligase complex."
    Maynard M.A., Qi H., Chung J., Lee E.H., Kondo Y., Hara S., Conaway R.C., Conaway J.W., Ohh M.
    J. Biol. Chem. 278:11032-11040(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH VHL (ISOFORM 2), ALTERNATIVE SPLICING, UBIQUITINATION AT LYS-467 AND LYS-570, HYDROXYLATION AT PRO-492, TISSUE SPECIFICITY, MUTAGENESIS OF LYS-467; PRO-492 AND LYS-570.
  10. "Hypoxia upregulates hypoxia inducible factor (HIF)-3alpha expression in lung epithelial cells: characterization and comparison with HIF-1alpha."
    Li Q.F., Wang X.R., Yang Y.W., Lin H.
    Cell Res. 16:548-558(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION.
  11. "Dominant-negative HIF-3 alpha 4 suppresses VHL-null renal cell carcinoma progression."
    Maynard M.A., Evans A.J., Shi W., Kim W.Y., Liu F.F., Ohh M.
    Cell Cycle 6:2810-2816(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION (ISOFORM 4), INTERACTION WITH EPAS1 (ISOFORM 4).
  12. "The human HIF (hypoxia-inducible factor)-3alpha gene is a HIF-1 target gene and may modulate hypoxic gene induction."
    Tanaka T., Wiesener M., Bernhardt W., Eckardt K.U., Warnecke C.
    Biochem. J. 424:143-151(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION (ISOFORMS 3 AND 4), SUBCELLULAR LOCATION, INDUCTION, TISSUE SPECIFICITY.
  13. "Hypoxia-inducible factor (HIF)-3alpha is subject to extensive alternative splicing in human tissues and cancer cells and is regulated by HIF-1 but not HIF-2."
    Pasanen A., Heikkila M., Rautavuoma K., Hirsila M., Kivirikko K.I., Myllyharju J.
    Int. J. Biochem. Cell Biol. 42:1189-1200(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION (ISOFORMS 3 AND 4), ALTERNATIVE SPLICING, TISSUE SPECIFICITY (ISOFORMS 2; 3 AND 4), INDUCTION.
  14. "Cell-specific and hypoxia-dependent regulation of human HIF-3alpha: inhibition of the expression of HIF target genes in vascular cells."
    Augstein A., Poitz D.M., Braun-Dullaeus R.C., Strasser R.H., Schmeisser A.
    Cell. Mol. Life Sci. 68:2627-2642(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION (ISOFORMS 3 AND 5), TISSUE SPECIFICITY, INDUCTION (ISOFORMS 2; 3 AND 5).

Entry informationi

Entry nameiHIF3A_HUMAN
AccessioniPrimary (citable) accession number: Q9Y2N7
Secondary accession number(s): B0M185
, B4DNA2, I6L988, Q58A43, Q66K72, Q8WXA1, Q96K34, Q9H7Z9, Q9HAI2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 17, 2007
Last sequence update: April 17, 2007
Last modified: June 24, 2015
This is version 123 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.