Q16665 (HIF1A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Hypoxia-inducible factor 1-alpha
Short name=HIF-1-alpha
Short name=HIF1-alpha

Alternative name(s):
ARNT-interacting protein
Basic-helix-loop-helix-PAS protein MOP1
Class E basic helix-loop-helix protein 78
Short name=bHLHe78
Member of PAS protein 1
PAS domain-containing protein 8

Gene names

Name:	HIF1A
Synonyms:	BHLHE78, MOP1, PASD8

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	826 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Binds to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) of target gene promoters. Activation requires recruitment of transcriptional coactivators such as CREBPB and EP300. Activity is enhanced by interaction with both, NCOA1 or NCOA2. Interaction with redox regulatory protein APEX seems to activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia. Ref.16 Ref.21 Ref.23 Ref.30 Ref.34 Ref.35 Ref.36 Ref.43 Ref.44
Subunit structure	Interacts with the HIF1A beta/ARNT subunit; heterodimerization is required for DNA binding. Interacts with COPS5; the interaction increases the transcriptional activity of HIF1A through increased stability By similarity. Interacts with EP300 (via TAZ-type 1 domains); the interaction is stimulated in response to hypoxia and inhibited by CITED2. Interacts with CREBBP (via TAZ-type 1 domains). Interacts with NCOA1, NCOA2, APEX and HSP90. Interacts (hydroxylated within the ODD domain) with VHLL (via beta domain); the interaction, leads to polyubiquitination and subsequent HIF1A proteasomal degradation. During hypoxia, sumoylated HIF1A also binds VHL; the interaction promotes the ubiquitination of HIF1A. Interacts with SENP1; the interaction desumoylates HIF1A resulting in stabilization and activation of transcription. Interacts (Via the ODD domain) with ARD1A; the interaction appears not to acetylate HIF1A nor have any affect on protein stability, during hypoxia. Interacts with RWDD3; the interaction enhances HIF1A sumoylation. Interacts with TSGA10 By similarity. Interacts with RORA (via the DNA binding domain); the interaction enhances HIF1A transcription under hypoxia through increasing protein stability. Interaction with PSMA7 inhibits the transactivation activity of HIF1A under both normoxic and hypoxia-mimicking conditions. Interacts with USP20. Interacts with GNB2L1/RACK1; promotes HIF1A ubiquitination and proteasome-mediated degradation. Interacts (via N-terminus) with USP19. Ref.11 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.21 Ref.22 Ref.24 Ref.29 Ref.31 Ref.32 Ref.33 Ref.34 Ref.35 Ref.37 Ref.38 Ref.39 Ref.40 Ref.46 Ref.47
Subcellular location	Cytoplasm. Nucleus. Note: Cytoplasmic in normoxia, nuclear translocation in response to hypoxia. Colocalizes with SUMO1 in the nucleus, under hypoxia. Ref.13
Tissue specificity	Expressed in most tissues with highest levels in kidney and heart. Overexpressed in the majority of common human cancers and their metastases, due to the presence of intratumoral hypoxia and as a result of mutations in genes encoding oncoproteins and tumor suppressors.
Induction	Under reduced oxygen tension. Induced also by various receptor-mediated factors such as growth factors, cytokines, and circulatory factors such as PDGF, EGF, FGF2, IGF2, TGFB1, HGF, TNF, IL1B/interleukin-1 beta, angiotensin-2 and thrombin. However, this induction is less intense than that stimulated by hypoxia. Repressed by HIPK2 and LIMD1. Ref.42 Ref.48
Domain	Contains two independent C-terminal transactivation domains, NTAD and CTAD, which function synergistically. Their transcriptional activity is repressed by an intervening inhibitory domain (ID). Ref.12 Ref.14 Ref.15
Post-translational modification	In normoxia, is hydroxylated on Pro-402 and Pro-564 in the oxygen-dependent degradation domain (ODD) by EGLN1/PHD1 and EGLN2/PHD2. EGLN3/PHD3 has also been shown to hydroxylate Pro-564. The hydroxylated prolines promote interaction with VHL, initiating rapid ubiquitination and subsequent proteasomal degradation. Deubiquitinated by USP20. Under hypoxia, proline hydroxylation is impaired and ubiquitination is attenuated, resulting in stabilization. In normoxia, is hydroxylated on Asn-803 by HIF1AN, thus abrogating interaction with CREBBP and EP300 and preventing transcriptional activation. This hydroxylation is inhibited by the Cu/Zn-chelator, Clioquinol. S-nitrosylation of Cys-800 may be responsible for increased recruitment of p300 coactivator necessary for transcriptional activity of HIF-1 complex. Requires phosphorylation for DNA-binding. Phosphorylation at Ser-247 by CSNK1D/CK1 represses kinase activity and impairs ARNT binding. Phosphorylation by GSK3-beta and PLK3 promote degradation by the proteasome. Sumoylated; with SUMO1 under hypoxia. Sumoylation is enhanced through interaction with RWDD3. Desumoylation by SENP1 leads to increased HIF1A stability and transriptional activity By similarity. Ref.30 Ref.36 Ref.37 Ubiquitinated; in normoxia, following hydroxylation and interaction with VHL. Lys-532 appears to be the principal site of ubiquitination. Clioquinol, the Cu/Zn-chelator, inhibits ubiquitination through preventing hydroxylation at Asn-803. Ref.14 Ref.20 Ref.21 Ref.23 Ref.32 Ref.35 Ref.39 The iron and 2-oxoglutarate dependent 3-hydroxylation of asparagine is (S) stereospecific within HIF CTAD domains.
Sequence similarities	Contains 1 bHLH (basic helix-loop-helix) domain. Contains 1 PAC (PAS-associated C-terminal) domain. Contains 2 PAS (PER-ARNT-SIM) domains.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat
Ligand	DNA-binding
Molecular function	Activator
PTM	Hydroxylation Isopeptide bond Phosphoprotein S-nitrosylation Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	B-1 B cell homeostasis Inferred from electronic annotation. Source: Compara Notch signaling pathway Traceable author statement. Source: Reactome angiogenesis Inferred from electronic annotation. Source: Compara axon transport of mitochondrion Inferred from mutant phenotype Ref.43. Source: UniProtKB cardiac ventricle morphogenesis Inferred from electronic annotation. Source: Compara cartilage development Inferred from electronic annotation. Source: Compara cellular iron ion homeostasis Inferred from electronic annotation. Source: Compara cellular response to interleukin-1 Inferred from expression pattern PubMed 12958148. Source: BHF-UCL cerebral cortex development Inferred from electronic annotation. Source: Compara collagen metabolic process Inferred from sequence or structural similarity PubMed 18037992. Source: BHF-UCL connective tissue replacement involved in inflammatory response wound healing Inferred from sequence or structural similarity PubMed 18037992. Source: BHF-UCL digestive tract morphogenesis Inferred from electronic annotation. Source: Compara dopaminergic neuron differentiation Inferred from electronic annotation. Source: Compara elastin metabolic process Inferred from sequence or structural similarity PubMed 18037992. Source: BHF-UCL embryonic hemopoiesis Inferred from electronic annotation. Source: Compara embryonic placenta development Inferred from electronic annotation. Source: Compara epithelial cell differentiation involved in mammary gland alveolus development Inferred from electronic annotation. Source: Compara epithelial to mesenchymal transition Inferred from sequence or structural similarity PubMed 18037992. Source: BHF-UCL glucose homeostasis Inferred from electronic annotation. Source: Compara heart looping Inferred from electronic annotation. Source: Compara hemoglobin biosynthetic process Inferred from electronic annotation. Source: Compara intestinal epithelial cell maturation Inferred from electronic annotation. Source: Compara lactate metabolic process Inferred from electronic annotation. Source: Compara lactation Inferred from electronic annotation. Source: Compara mRNA transcription from RNA polymerase II promoter Inferred by curator Ref.1. Source: BHF-UCL muscle cell homeostasis Inferred from electronic annotation. Source: Compara negative regulation of TOR signaling cascade Inferred from electronic annotation. Source: Compara negative regulation of bone mineralization Inferred from electronic annotation. Source: Compara negative regulation of growth Inferred from electronic annotation. Source: Compara negative regulation of mesenchymal cell apoptotic process Inferred from electronic annotation. Source: Compara negative regulation of neuron apoptotic process Inferred from electronic annotation. Source: Compara neural crest cell migration Inferred from electronic annotation. Source: Compara neural fold elevation formation Inferred from electronic annotation. Source: Compara outflow tract morphogenesis Inferred from electronic annotation. Source: Compara oxygen homeostasis Inferred from direct assay PubMed 16956324. Source: HGNC positive regulation of angiogenesis Inferred by curator PubMed 8756616. Source: BHF-UCL positive regulation of chemokine production Traceable author statement PubMed 18370914. Source: BHF-UCL positive regulation of chemokine-mediated signaling pathway Inferred by curator PubMed 17178876. Source: BHF-UCL positive regulation of endothelial cell proliferation Inferred by curator PubMed 8756616. Source: BHF-UCL positive regulation of epithelial cell migration Inferred from sequence or structural similarity PubMed 18037992. Source: BHF-UCL positive regulation of erythrocyte differentiation Inferred by curator PubMed 1448077. Source: BHF-UCL positive regulation of glycolysis Inferred by curator PubMed 8089148. Source: BHF-UCL positive regulation of hormone biosynthetic process Inferred from direct assay PubMed 1448077. Source: BHF-UCL positive regulation of insulin secretion involved in cellular response to glucose stimulus Inferred from electronic annotation. Source: Compara positive regulation of neuroblast proliferation Inferred from electronic annotation. Source: Compara positive regulation of nitric-oxide synthase activity Traceable author statement PubMed 18254728. Source: BHF-UCL positive regulation of receptor biosynthetic process Inferred from mutant phenotype PubMed 17178876. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter in response to hypoxia Inferred from direct assay PubMed 22735262. Source: BHF-UCL positive regulation of vascular endothelial growth factor receptor signaling pathway Inferred by curator PubMed 12958148PubMed 8756616. Source: BHF-UCL positive regulation vascular endothelial growth factor production Inferred from direct assay PubMed 8756616. Source: BHF-UCL regulation of transcription from RNA polymerase II promoter in response to oxidative stress Inferred from direct assay PubMed 8089148PubMed 8387214. Source: BHF-UCL regulation of transforming growth factor beta2 production Inferred from mutant phenotype PubMed 12411310. Source: BHF-UCL response to muscle activity Inferred from electronic annotation. Source: Compara retina vasculature development in camera-type eye Inferred from electronic annotation. Source: Compara vascular endothelial growth factor production Inferred from direct assay PubMed 12958148. Source: BHF-UCL visual learning Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleolus Inferred from direct assay. Source: HPA transcription factor complex Inferred from physical interaction PubMed 9576906. Source: MGI
Molecular_function	Hsp90 protein binding Inferred from direct assay Ref.2. Source: BHF-UCL RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Inferred from electronic annotation. Source: Compara RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Inferred from direct assay PubMed 8387214Ref.2. Source: BHF-UCL protein binding transcription factor activity Inferred from direct assay PubMed 22735262. Source: BHF-UCL protein heterodimerization activity Traceable author statement PubMed 15261140. Source: UniProtKB sequence-specific DNA binding Inferred from electronic annotation. Source: Compara signal transducer activity Inferred from electronic annotation. Source: InterPro transcription regulatory region DNA binding Inferred from direct assay PubMed 99104162. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
AR	P10275	2	EBI-447269,EBI-608057
ARNT	P27540	7	EBI-447269,EBI-80809
ARRB1	P49407	3	EBI-447269,EBI-743313
EP300	Q09472	5	EBI-447269,EBI-447295
HIF1AN	Q9NWT6	3	EBI-447269,EBI-745632
KAT2B	Q92831	2	EBI-447269,EBI-477430
OS9	Q13438	9	EBI-447269,EBI-1174342
PIAS4	Q8N2W9	3	EBI-447269,EBI-473160
PKM	P14618-1	7	EBI-447269,EBI-4304679
Rbfox3	Q8BIF2	2	EBI-447269,EBI-4567146	From a different organism.
Rorc	P51450-2	2	EBI-447269,EBI-4422078	From a different organism.
SEPT9	Q9UHD8-1	4	EBI-447269,EBI-851558
SUMO1	P63165	2	EBI-447269,EBI-80140
UBXN7	O94888	3	EBI-447269,EBI-1993627
VHL	P40337	6	EBI-447269,EBI-301246

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q16665-1)

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: Q16665-2)

The sequence of this isoform differs from the canonical sequence as follows:
     736-826: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: Q16665-3)

Also known as: I.3;

The sequence of this isoform differs from the canonical sequence as follows:
     1-12: MEGAGGANDKKK → MSSQCRSLENKFVFLKEGLGNSKPEELEEIRIENGR

Note: Up-regulated in peripheral T lymphocytes after T-cell receptor stimulation. Highest expression in peripheral blood leukocytes and thymus.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 826

826

Hypoxia-inducible factor 1-alpha

PRO_0000127220

Regions

Domain

17 – 70

54

bHLH

Domain

85 – 158

74

PAS 1

Domain

228 – 298

71

PAS 2

Domain

302 – 345

44

PAC

Region

1 – 401

401

Interaction with TSGA10 By similarity

Region

380 – 417

38

N-terminal VHL recognition site

Region

401 – 603

203

ODD

Region

531 – 575

45

NTAD

Region

556 – 572

17

C-terminal VHL recognition site

Region

576 – 785

210

ID

Region

786 – 826

41

CTAD

Motif

718 – 721

4

Nuclear localization signal Potential

Compositional bias

615 – 621

7

Poly-Thr

Amino acid modifications

Modified residue

247

1

Phosphoserine; by CK1 Ref.46

Modified residue

402

1

4-hydroxyproline Ref.21

Modified residue

551

1

Phosphoserine; by GSK3-beta Ref.45

Modified residue

555

1

Phosphothreonine; by GSK3-beta Ref.45

Modified residue

564

1

4-hydroxyproline Ref.21 Ref.23 Ref.26

Modified residue

576

1

Phosphoserine; by PLK3 Ref.45

Modified residue

589

1

Phosphoserine; by GSK3-beta Ref.45

Modified residue

657

1

Phosphoserine; by PLK3 Ref.45

Modified residue

800

1

S-nitrosocysteine Probable

Modified residue

803

1

(3S)-3-hydroxyasparagine Ref.25

Cross-link

391

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.30 Ref.36

Cross-link

477

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.30 Ref.36

Cross-link

532

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Probable

Cross-link

538

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Probable

Cross-link

547

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Probable

Natural variations

Alternative sequence

1 – 12

12

MEGAG…NDKKK → MSSQCRSLENKFVFLKEGLG NSKPEELEEIRIENGR in isoform 3.

VSP_044942

Alternative sequence

736 – 826

91

Missing in isoform 2.

VSP_007738

Natural variant

582

1

P → S.
Corresponds to variant rs11549465 [ dbSNP | Ensembl ].

VAR_049541

Natural variant

588

1

A → T.
Corresponds to variant rs11549467 [ dbSNP | Ensembl ].

VAR_049542

Natural variant

796

1

T → A.
Corresponds to variant rs1802821 [ dbSNP | Ensembl ].

VAR_015854

Experimental info

Mutagenesis

247

1

S → A: Constitutive kinase activity. Ref.46

Mutagenesis

247

1

S → D: Impaired kinase activity. Ref.46

Mutagenesis

377

1

K → R: No change in HIF1A protein turnover rate but increased transcriptional activity; when associated with R-391; R-477 and R-532. Ref.30 Ref.36

Mutagenesis

389

1

K → R: No change in sumoylation. Ref.30

Mutagenesis

391

1

K → R: Abolishes 1 sumoylation. Abolishes 1 sumoylation; when associated with R-532. Abolishes 2 sumoylations; when associated with R-477. No change in HIF1A protein turnover rate but increased transcriptional activity; when associated with R-377; R-477 and R-532. Ref.30 Ref.36

Mutagenesis

392

1

K → R: No change in sumoylation. Ref.30

Mutagenesis

394

1

P → A: No change in VHLE3-dependent ubiquitination. Ref.21

Mutagenesis

397

1

L → A: Abolishes VHLE3-dependent ubiquitination; when associated with A-400. Ref.21

Mutagenesis

400

1

L → A: Abolishes VHLE3-dependent ubiquitination; when associated with A-397. Ref.21

Mutagenesis

402

1

P → A: Abolishes in VHLE3-dependent ubiquitination, abolishes oxygen-dependent regulation of VP16, partially reduced VHLE target site ubiquitination and no interaction with VHL. No VHLE target site ubiquitination; when associated with G-564. Ref.21 Ref.39

Mutagenesis

442

1

K → R: No change in sumoylation. Ref.30

Mutagenesis

460

1

K → R: No change in sumoylation nor in ARD1-mediated acetylation. Ref.30

Mutagenesis

477

1

K → R: Abolishes 1 sumoylation. Abolishes 2 sumoylations; when associated with R-391. No change in HIF1A protein turnover rate but increased transcriptional activity; when associated with R-377; R-391 and R-532. Ref.30 Ref.36

Mutagenesis

532

1

K → R: Reduced ubiquitination. No change in sumoylation nor on interaction with ARD1A. No change in HIF1A protein turnover rate but increased transcriptional activity; when associated with R-377; R-391 and R-477. Complete loss of ubiquitination, but no change in VHL binding; when associated with K-538 and K-547. Ref.18 Ref.30 Ref.33 Ref.36 Ref.39

Mutagenesis

538

1

K → R: No change in sumoylation, but reduced ubiquitination. Complete loss of ubiquitination, but no change in VHL binding; when associated with K-532 and K-547. Ref.18 Ref.30 Ref.39

Mutagenesis

547

1

K → R: No change in sumoylation, but reduced ubiquitination. Complete loss of ubiquitination, but no change in VHL binding; when associated with K-532 and K-538. Ref.18 Ref.30 Ref.39

Mutagenesis

551

1

S → G: Constitutive expression under nonhypoxic conditions by decreasing ubiquitination. Ref.20

Mutagenesis

552

1

T → A: Constitutive expression under nonhypoxic conditions by decreasing ubiquitination. Ref.20

Mutagenesis

564

1

P → G: No change in VHL-dependent ubiquitination. Partially reduced VHLE target site ubiquitination. No VHLE target site ubiquitination; when associated with A-402. Ref.21 Ref.39

Mutagenesis

576

1

S → A: Induces stabilization of the protein. Ref.45

Mutagenesis

657

1

S → A: Induces stabilization of the protein. Ref.45

Mutagenesis

719

1

K → T: Dramatic reduction of accumulation in the nucleus in response to hypoxia. Ref.13 Ref.18

Mutagenesis

795

1

L → A: Inhibits interaction with EP300 and transactivation activity. Ref.29

Mutagenesis

800

1

C → A: Blocks increase in transcriptional activation caused by nitrosylation. Ref.15 Ref.27

Mutagenesis

800

1

C → S: Abolishes hypoxia-inducible transcriptional activation of ctaD. Ref.15 Ref.27

Mutagenesis

803

1

N → A: Recruits CREBBP. No enhancement of CREBBP by Clioquinol in the presence of FIH1. No change in nuclear location nor on repression of transcriptional activity in the presence of histone deacetylase inhibitor. Ref.34 Ref.35

Sequence conflict

572

1

F → L in AAC68568. Ref.3

Sequence conflict

735

1

G → I in BAB70608. Ref.7

Secondary structure

1

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826

Helix Strand Turn

Details...

Beta strand

241 – 246

6

Beta strand

251 – 255

5

Helix

258 – 263

6

Helix

267 – 270

4

Helix

275 – 277

3

Turn

281 – 283

3

Helix

284 – 297

14

Beta strand

298 – 301

4

Beta strand

305 – 308

4

Beta strand

310 – 325

16

Turn

327 – 329

3

Beta strand

332 – 341

10

Helix

559 – 561

3

Turn

779 – 783

5

Helix

784 – 787

4

Beta strand

789 – 792

4

Helix

797 – 803

7

Beta strand

807 – 809

3

Helix

815 – 822

8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: ABD4F7DAA135BE2D	FASTA	826	92,670
	10 20 30 40 50 60 MEGAGGANDK KKISSERRKE KSRDAARSRR SKESEVFYEL AHQLPLPHNV SSHLDKASVM 70 80 90 100 110 120 RLTISYLRVR KLLDAGDLDI EDDMKAQMNC FYLKALDGFV MVLTDDGDMI YISDNVNKYM 130 140 150 160 170 180 GLTQFELTGH SVFDFTHPCD HEEMREMLTH RNGLVKKGKE QNTQRSFFLR MKCTLTSRGR 190 200 210 220 230 240 TMNIKSATWK VLHCTGHIHV YDTNSNQPQC GYKKPPMTCL VLICEPIPHP SNIEIPLDSK 250 260 270 280 290 300 TFLSRHSLDM KFSYCDERIT ELMGYEPEEL LGRSIYEYYH ALDSDHLTKT HHDMFTKGQV 310 320 330 340 350 360 TTGQYRMLAK RGGYVWVETQ ATVIYNTKNS QPQCIVCVNY VVSGIIQHDL IFSLQQTECV 370 380 390 400 410 420 LKPVESSDMK MTQLFTKVES EDTSSLFDKL KKEPDALTLL APAAGDTIIS LDFGSNDTET 430 440 450 460 470 480 DDQQLEEVPL YNDVMLPSPN EKLQNINLAM SPLPTAETPK PLRSSADPAL NQEVALKLEP 490 500 510 520 530 540 NPESLELSFT MPQIQDQTPS PSDGSTRQSS PEPNSPSEYC FYVDSDMVNE FKLELVEKLF 550 560 570 580 590 600 AEDTEAKNPF STQDTDLDLE MLAPYIPMDD DFQLRSFDQL SPLESSSASP ESASPQSTVT 610 620 630 640 650 660 VFQQTQIQEP TANATTTTAT TDELKTVTKD RMEDIKILIA SPSPTHIHKE TTSATSSPYR 670 680 690 700 710 720 DTQSRTASPN RAGKGVIEQT EKSHPRSPNV LSVALSQRTT VPEEELNPKI LALQNAQRKR 730 740 750 760 770 780 KMEHDGSLFQ AVGIGTLLQQ PDDHAATTSL SWKRVKGCKS SEQNGMEQKT IILIPSDLAC 790 800 810 820 RLLGQSMDES GLPQLTSYDC EVNAPIQGSR NLLQGEELLR ALDQVN
	Isoform 2 [UniParc]. Checksum: 3CFD604FB4E4418E	FASTA	735	82,690
	10 20 30 40 50 60 MEGAGGANDK KKISSERRKE KSRDAARSRR SKESEVFYEL AHQLPLPHNV SSHLDKASVM 70 80 90 100 110 120 RLTISYLRVR KLLDAGDLDI EDDMKAQMNC FYLKALDGFV MVLTDDGDMI YISDNVNKYM 130 140 150 160 170 180 GLTQFELTGH SVFDFTHPCD HEEMREMLTH RNGLVKKGKE QNTQRSFFLR MKCTLTSRGR 190 200 210 220 230 240 TMNIKSATWK VLHCTGHIHV YDTNSNQPQC GYKKPPMTCL VLICEPIPHP SNIEIPLDSK 250 260 270 280 290 300 TFLSRHSLDM KFSYCDERIT ELMGYEPEEL LGRSIYEYYH ALDSDHLTKT HHDMFTKGQV 310 320 330 340 350 360 TTGQYRMLAK RGGYVWVETQ ATVIYNTKNS QPQCIVCVNY VVSGIIQHDL IFSLQQTECV 370 380 390 400 410 420 LKPVESSDMK MTQLFTKVES EDTSSLFDKL KKEPDALTLL APAAGDTIIS LDFGSNDTET 430 440 450 460 470 480 DDQQLEEVPL YNDVMLPSPN EKLQNINLAM SPLPTAETPK PLRSSADPAL NQEVALKLEP 490 500 510 520 530 540 NPESLELSFT MPQIQDQTPS PSDGSTRQSS PEPNSPSEYC FYVDSDMVNE FKLELVEKLF 550 560 570 580 590 600 AEDTEAKNPF STQDTDLDLE MLAPYIPMDD DFQLRSFDQL SPLESSSASP ESASPQSTVT 610 620 630 640 650 660 VFQQTQIQEP TANATTTTAT TDELKTVTKD RMEDIKILIA SPSPTHIHKE TTSATSSPYR 670 680 690 700 710 720 DTQSRTASPN RAGKGVIEQT EKSHPRSPNV LSVALSQRTT VPEEELNPKI LALQNAQRKR 730 KMEHDGSLFQ AVGIG
	Isoform 3 (I.3) [UniParc]. Checksum: 272C9EFAFD7A1E48	FASTA	850	95,634
	10 20 30 40 50 60 MSSQCRSLEN KFVFLKEGLG NSKPEELEEI RIENGRISSE RRKEKSRDAA RSRRSKESEV 70 80 90 100 110 120 FYELAHQLPL PHNVSSHLDK ASVMRLTISY LRVRKLLDAG DLDIEDDMKA QMNCFYLKAL 130 140 150 160 170 180 DGFVMVLTDD GDMIYISDNV NKYMGLTQFE LTGHSVFDFT HPCDHEEMRE MLTHRNGLVK 190 200 210 220 230 240 KGKEQNTQRS FFLRMKCTLT SRGRTMNIKS ATWKVLHCTG HIHVYDTNSN QPQCGYKKPP 250 260 270 280 290 300 MTCLVLICEP IPHPSNIEIP LDSKTFLSRH SLDMKFSYCD ERITELMGYE PEELLGRSIY 310 320 330 340 350 360 EYYHALDSDH LTKTHHDMFT KGQVTTGQYR MLAKRGGYVW VETQATVIYN TKNSQPQCIV 370 380 390 400 410 420 CVNYVVSGII QHDLIFSLQQ TECVLKPVES SDMKMTQLFT KVESEDTSSL FDKLKKEPDA 430 440 450 460 470 480 LTLLAPAAGD TIISLDFGSN DTETDDQQLE EVPLYNDVML PSPNEKLQNI NLAMSPLPTA 490 500 510 520 530 540 ETPKPLRSSA DPALNQEVAL KLEPNPESLE LSFTMPQIQD QTPSPSDGST RQSSPEPNSP 550 560 570 580 590 600 SEYCFYVDSD MVNEFKLELV EKLFAEDTEA KNPFSTQDTD LDLEMLAPYI PMDDDFQLRS 610 620 630 640 650 660 FDQLSPLESS SASPESASPQ STVTVFQQTQ IQEPTANATT TTATTDELKT VTKDRMEDIK 670 680 690 700 710 720 ILIASPSPTH IHKETTSATS SPYRDTQSRT ASPNRAGKGV IEQTEKSHPR SPNVLSVALS 730 740 750 760 770 780 QRTTVPEEEL NPKILALQNA QRKRKMEHDG SLFQAVGIGT LLQQPDDHAA TTSLSWKRVK 790 800 810 820 830 840 GCKSSEQNGM EQKTIILIPS DLACRLLGQS MDESGLPQLT SYDCEVNAPI QGSRNLLQGE 850 ELLRALDQVN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension." Wang G.L., Jiang B.-H., Rue E.A., Semenza G.L. Proc. Natl. Acad. Sci. U.S.A. 92:5510-5514(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 166-170; 259-289 AND 771-781.
[2]	"Characterization of a subset of the basic-helix-loop-helix-PAS superfamily that interacts with components of the dioxin signaling pathway." Hogenesch J.B., Chan W.K., Jackiw V.H., Brown R.C., Gu Y.-Z., Pray-Grant M., Perdew G.H., Bradfield C.A. J. Biol. Chem. 272:8581-8593(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Hepatoma.
[3]	"The human hypoxia-inducible factor 1alpha gene: HIF1A structure and evolutionary conservation." Iyer N.V., Leung S.W., Semenza G.L. Genomics 52:159-165(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[4]	"Preferential expression of the novel alternative isoform I.3 of hypoxia-inducible factor 1alpha in activated human T lymphocytes." Lukashev D., Sitkovsky M. Hum. Immunol. 69:421-425(2008) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), ALTERNATIVE SPLICING.
[5]	"HIF1a sequence in the Quechua, a high altitude population." Rupert J.L., Hochachka P.W. Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[6]	Sun B., Zhao H.R., Yu R.T., Ni M.S.H. Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Glial tumor.
[7]	"Hypoxia-inducible factor-1 alpha variant isolated from human liver tissue." Tanaka S., Sugimachi K. Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Liver.
[8]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[9]	"The DNA sequence and analysis of human chromosome 14." Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J. Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	"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: Choriocarcinoma and Placenta.
[11]	"An essential role for p300/CBP in the cellular response to hypoxia." Arany Z., Huang L.E., Eckner R., Bhattacharya S., Jiang C., Goldberg M.A., Bunn H.F., Livingston D.M. Proc. Natl. Acad. Sci. U.S.A. 93:12969-12973(1996) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN COMPLEX WITH EP300 AND CREBBP, INTERACTION WITH EP300.
[12]	"Transactivation and inhibitory domains of hypoxia-inducible factor 1alpha. Modulation of transcriptional activity by oxygen tension." Jiang B.H., Zheng J.Z., Leung S.W., Roe R., Semenza G.L. J. Biol. Chem. 272:19253-19260(1997) [PubMed] [Europe PMC] [Abstract] Cited for: TRANSACTIVATION DOMAINS NTAD AND CTAD.
[13]	"Signal transduction in hypoxic cells: inducible nuclear translocation and recruitment of the CBP/p300 coactivator by the hypoxia-inducible factor-1alpha." Kallio P.J., Okamoto K., O'Brien S., Carrero P., Makino Y., Tanaka H., Poellinger L. EMBO J. 17:6573-6586(1998) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-719.
[14]	"Regulation of hypoxia-inducible factor 1alpha is mediated by an O2-dependent degradation domain via the ubiquitin-proteasome pathway." Huang L.E., Gu J., Schau M., Bunn H.F. Proc. Natl. Acad. Sci. U.S.A. 95:7987-7992(1998) [PubMed] [Europe PMC] [Abstract] Cited for: OXYGEN-DEPENDENT DEGRADATION DOMAIN.
[15]	"Molecular mechanisms of transcription activation by HLF and HIF1alpha in response to hypoxia: their stabilization and redox signal-induced interaction with CBP/p300." Ema M., Hirota K., Mimura J., Abe H., Yodoi J., Sogawa K., Poellinger L., Fujii-Kuriyama Y. EMBO J. 18:1905-1914(1999) [PubMed] [Europe PMC] [Abstract] Cited for: TRANSACTIVATION DOMAINS NTAD AND CTAD, INTERACTION WITH APEX, MUTAGENESIS OF CYS-800.
[16]	"Functional role of p35srj, a novel p300/CBP binding protein, during transactivation by HIF-1." Bhattacharya S., Michels C.M., Leung M.K., Arany Z.P., Kung A.L., Livingston D.M. Genes Dev. 13:64-75(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DNA-BINDING, INTERACTION WITH EP300.
[17]	"Drosophila von Hippel-Lindau tumor suppressor complex possesses E3 ubiquitin ligase activity." Aso T., Yamazaki K., Aigaki T., Kitajima S. Biochem. Biophys. Res. Commun. 276:355-361(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH VHL.
[18]	"Mechanism of regulation of the hypoxia-inducible factor-1 alpha by the von Hippel-Lindau tumor suppressor protein." Tanimoto K., Makino Y., Pereira T., Poellinger L. EMBO J. 19:4298-4309(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH VHL AND ARNT, MUTAGENESIS OF LYS-532; LYS-538; LYS-547 AND LYS-719.
[19]	"Redox-regulated recruitment of the transcriptional coactivators CREB-binding protein and SRC-1 to hypoxia-inducible factor 1alpha." Carrero P., Okamoto K., Coumailleau P., O'Brien S., Tanaka H., Poellinger L. Mol. Cell. Biol. 20:402-415(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NCOA1; NCOA2 AND APEX.
[20]	"Hypoxia-inducible factor 1alpha protein expression is controlled by oxygen-regulated ubiquitination that is disrupted by deletions and missense mutations." Sutter C.H., Laughner E., Semenza G.L. Proc. Natl. Acad. Sci. U.S.A. 97:4748-4753(2000) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF SER-551 AND THR-552, UBIQUITINATION.
[21]	"Independent function of two destruction domains in hypoxia-inducible factor-alpha chains activated by prolyl hydroxylation." Masson N., Willam C., Maxwell P.H., Pugh C.W., Ratcliffe P.J. EMBO J. 20:5197-5206(2001) [PubMed] [Europe PMC] [Abstract] Cited for: HYDROXYLATION AT PRO-402 AND PRO-564, UBIQUITINATION, INTERACTION WITH THE VHLE COMPLEX, FUNCTION, MUTAGENESIS OF PRO-394; LEU-397; LEU-400; PRO-402 AND PRO-564.
[22]	"Binding and regulation of HIF-1alpha by a subunit of the proteasome complex, PSMA7." Cho S., Choi Y.J., Kim J.M., Jeong S.T., Kim J.H., Kim S.H., Ryu S.E. FEBS Lett. 498:62-66(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PSMA7.
[23]	"Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation." Jaakkola P., Mole D.R., Tian Y.-M., Wilson M.I., Gielbert J., Gaskell S.J., von Kriegsheim A., Hebestreit H.F., Mukherji M., Schofield C.J., Maxwell P.H., Pugh C.W., Ratcliffe P.J. Science 292:468-472(2001) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION, FUNCTION, HYDROXYLATION AT PRO-564.
[24]	"Regulation and destabilization of HIF-1alpha by ARD1-mediated acetylation." Jeong J.-W., Bae M.-K., Ahn M.-Y., Kim S.-H., Sohn T.-K., Bae M.-H., Yoo M.-A., Song E.-J., Lee K.-J., Kim K.-W. Cell 111:709-720(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ARD1A.
[25]	"FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor." Lando D., Peet D.J., Gorman J.J., Whelan D.A., Whitelaw M.L., Bruick R.K. Genes Dev. 16:1466-1471(2002) [PubMed] [Europe PMC] [Abstract] Cited for: HYDROXYLATION AT ASN-803, MASS SPECTROMETRY.
[26]	"Biochemical purification and pharmacological inhibition of a mammalian prolyl hydroxylase acting on hypoxia-inducible factor." Ivan M., Haberberger T., Gervasi D.C., Michelson K.S., Guenzler V., Kondo K., Yang H., Sorokina I., Conaway R.C., Conaway J.W., Kaelin W.G. Jr. Proc. Natl. Acad. Sci. U.S.A. 99:13459-13464(2002) [PubMed] [Europe PMC] [Abstract] Cited for: HYDROXYLATION AT PRO-564, MASS SPECTROMETRY.
[27]	"S-nitrosation of Cys-800 of HIF-1alpha protein activates its interaction with p300 and stimulates its transcriptional activity." Yasinska I.M., Sumbayev V.V. FEBS Lett. 549:105-109(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NITROSYLATION AT CYS-800, MUTAGENESIS OF CYS-800.
[28]	"HIF-1 alpha protein as a target for S-nitrosation." Sumbayev V.V., Budde A., Zhou J., Bruene B. FEBS Lett. 535:106-112(2003) [PubMed] [Europe PMC] [Abstract] Cited for: S-NITROSYLATION.
[29]	"Structural basis for negative regulation of hypoxia-inducible factor-1alpha by CITED2." Freedman S.J., Sun Z.Y., Kung A.L., France D.S., Wagner G., Eck M.J. Nat. Struct. Biol. 10:504-512(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH EP300, MUTAGENESIS OF LEU-795.
[30]	"Sumoylation increases HIF-1alpha stability and its transcriptional activity." Bae S.-H., Jeong J.-W., Park J.A., Kim S.-H., Bae M.-K., Choi S.-J., Kim K.-W. Biochem. Biophys. Res. Commun. 324:394-400(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SUMOYLATION AT LYS-391 AND LYS-477, FUNCTION, MUTAGENESIS OF LYS-389; LYS-391; LYS-392; LYS-442; LYS-460; LYS-477; LYS-532; LYS-538 AND LYS-547.
[31]	"Molecular cloning and characterization of the von Hippel-Lindau-like protein." Qi H., Gervais M.L., Li W., DeCaprio J.A., Challis J.R.G., Ohh M. Mol. Cancer Res. 2:43-52(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH VHLL.
[32]	"VHL protein-interacting deubiquitinating enzyme 2 deubiquitinates and stabilizes HIF-1alpha." Li Z., Wang D., Messing E.M., Wu G. EMBO Rep. 6:373-378(2005) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION, DEUBIQUITINATION BY USP20, INTERACTION WITH USP20.
[33]	"Interaction between HIF-1 alpha (ODD) and hARD1 does not induce acetylation and destabilization of HIF-1 alpha." Arnesen T., Kong X., Evjenth R., Gromyko D., Varhaug J.E., Lin Z., Sang N., Caro J., Lillehaug J.R. FEBS Lett. 579:6428-6432(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ARD1A, MUTAGENESIS OF LYS-532.
[34]	"Histone deacetylase inhibitors repress the transactivation potential of hypoxia-inducible factors independently of direct acetylation of HIF-alpha." Fath D.M., Kong X., Liang D., Lin Z., Chou A., Jiang Y., Fang J., Caro J., Sang N. J. Biol. Chem. 281:13612-13619(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH EP300 IN THE HIF1A/EP300/CREBBP COMPLEX, MUTAGENESIS OF ASN-803.
[35]	"Clioquinol, a Cu(II)/Zn(II) chelator, inhibits both ubiquitination and asparagine hydroxylation of hypoxia-inducible factor-1alpha, leading to expression of vascular endothelial growth factor and erythropoietin in normoxic cells." Choi S.M., Choi K.-O., Park Y.K., Cho H., Yang E.G., Park H. J. Biol. Chem. 281:34056-34063(2006) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION, HYDROXYLATION, FUNCTION, INTERACTION WITH CBPP, MASS SPECTROMETRY, MUTAGENESIS OF ASN-803.
[36]	"SUMOylation of hypoxia-inducible factor-1alpha reduces its transcriptional activity." Berta M.A., Mazure N., Hattab M., Pouyssegur J., Brahimi-Horn M.C. Biochem. Biophys. Res. Commun. 360:646-652(2007) [PubMed] [Europe PMC] [Abstract] Cited for: SUMOYLATION AT LYS-391 AND LYS-477, FUNCTION, MUTAGENESIS OF LYS-377; LYS-391; LYS-477 AND LYS-532.
[37]	"RSUME, a small RWD-containing protein, enhances SUMO conjugation and stabilizes HIF-1alpha during hypoxia." Carbia-Nagashima A., Gerez J., Perez-Castro C., Paez-Pereda M., Silberstein S., Stalla G.K., Holsboer F., Arzt E. Cell 131:309-323(2007) [PubMed] [Europe PMC] [Abstract] Cited for: SUMOYLATION, INTERACTION WITH RWDD3.
[38]	"RACK1 competes with HSP90 for binding to HIF-1alpha and is required for O(2)-independent and HSP90 inhibitor-induced degradation of HIF-1alpha." Liu Y.V., Baek J.H., Zhang H., Diez R., Cole R.N., Semenza G.L. Mol. Cell 25:207-217(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GNB2L1.
[39]	"HIF-1alpha and EPAS ubiquitination mediated by the VHL tumour suppressor involves flexibility in the ubiquitination mechanism, similar to other RING E3 ligases." Paltoglou S., Roberts B.J. Oncogene 26:604-609(2007) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION AT LYS-532; LYS-538 AND LYS-547, INTERACTION WITH VHL, MUTAGENESIS OF PRO-402; LYS-532; LYS-538; LYS-547 AND PRO-564.
[40]	"Transcriptional activation of HIF-1 by RORalpha and its role in hypoxia signaling." Kim E.J., Yoo Y.G., Yang W.K., Lim Y.S., Na T.Y., Lee I.K., Lee M.O. Arterioscler. Thromb. Vasc. Biol. 28:1796-1802(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RORA.
[41]	"Quantitative analysis of global ubiquitination in HeLa cells by mass spectrometry." Meierhofer D., Wang X., Huang L., Kaiser P. J. Proteome Res. 7:4566-4576(2008) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-538, MASS SPECTROMETRY.
[42]	"Transcriptional regulation of hypoxia-inducible factor 1alpha by HIPK2 suggests a novel mechanism to restrain tumor growth." Nardinocchi L., Puca R., Guidolin D., Belloni A.S., Bossi G., Michiels C., Sacchi A., Onisto M., D'Orazi G. Biochim. Biophys. Acta 1793:368-377(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION BY HIPK2.
[43]	"HUMMR, a hypoxia- and HIF-1alpha-inducible protein, alters mitochondrial distribution and transport." Li Y., Lim S., Hoffman D., Aspenstrom P., Federoff H.J., Rempe D.A. J. Cell Biol. 185:1065-1081(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN MITOCHONDRIAL TRANSPORT.
[44]	"Hypoxia-inducible protein 2 is a novel lipid droplet protein and a specific target gene of hypoxia-inducible factor-1." Gimm T., Wiese M., Teschemacher B., Deggerich A., Schodel J., Knaup K.X., Hackenbeck T., Hellerbrand C., Amann K., Wiesener M.S., Honing S., Eckardt K.U., Warnecke C. FASEB J. 24:4443-4458(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[45]	"Plk3 functions as an essential component of the hypoxia regulatory pathway by direct phosphorylation of HIF-1alpha." Xu D., Yao Y., Lu L., Costa M., Dai W. J. Biol. Chem. 285:38944-38950(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-551; THR-555; SER-576; SER-589 AND SER-657, MUTAGENESIS OF SER-576 AND SER-657.
[46]	"Casein kinase 1 regulates human hypoxia-inducible factor HIF-1." Kalousi A., Mylonis I., Politou A.S., Chachami G., Paraskeva E., Simos G. J. Cell Sci. 123:2976-2986(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-247 BY CSNK1D/CK1, MUTAGENESIS OF SER-247, INTERACTION WITH ARNT.
[47]	"Ubiquitin-specific protease 19 (USP19) regulates hypoxia-inducible factor 1alpha (HIF-1alpha) during hypoxia." Altun M., Zhao B., Velasco K., Liu H., Hassink G., Paschke J., Pereira T., Lindsten K. J. Biol. Chem. 287:1962-1969(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH USP19.
[48]	"The LIMD1 protein bridges an association between the prolyl hydroxylases and VHL to repress HIF-1 activity." Foxler D.E., Bridge K.S., James V., Webb T.M., Mee M., Wong S.C., Feng Y., Constantin-Teodosiu D., Petursdottir T.E., Bjornsson J., Ingvarsson S., Ratcliffe P.J., Longmore G.D., Sharp T.V. Nat. Cell Biol. 14:201-208(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
[49]	"A model for the complex between the hypoxia-inducible factor-1 (HIF-1) and its consensus DNA sequence." Michel G., Minet E., Ernest I., Roland I., Durant F., Remacle J., Michiels C. J. Biomol. Struct. Dyn. 18:169-179(2000) [PubMed] [Europe PMC] [Abstract] Cited for: 3D-STRUCTURE MODELING.
[50]	"Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals mechanism of oxidative modification of HIF-1 alpha." Elkins J.M., Hewitson K.S., McNeill L.A., Seibel J.F., Schlemminger I., Pugh C.W., Ratcliffe P.J., Schofield C.J. J. Biol. Chem. 278:1802-1806(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 775-826 IN COMPLEX WITH HIF1AN.
[51]	"Structural basis for recruitment of CBP/p300 by hypoxia-inducible factor-1 alpha." Freedman S.J., Sun Z.-Y.J., Poy F., Kung A.L., Livingston D.M., Wagner G., Eck M.J. Proc. Natl. Acad. Sci. U.S.A. 99:5367-5372(2002) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 786-826 IN COMPLEX WITH 302-418 OF EP300.
[52]	"Structural basis for Hif-1 alpha /CBP recognition in the cellular hypoxic response." Dames S.A., Martinez-Yamout M., De Guzman R.N., Dyson H.J., Wright P.E. Proc. Natl. Acad. Sci. U.S.A. 99:5271-5276(2002) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 776-826 IN COMPLEX WITH 345-439 OF CREBBP.
[53]	"Structure of an HIF-1alpha-pVHL complex: hydroxyproline recognition in signaling." Min J.-H., Yang H., Ivan M., Gertler F., Kaelin W.G. Jr., Pavletich N.P. Science 296:1886-1889(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 556-575 IN COMPLEX WITH TCEB1; TCEB2 AND 54-213 OF VHL.
[54]	"Structural basis for the recognition of hydroxyproline in HIF-1 alpha by pVHL." Hon W.-C., Wilson M.I., Harlos K., Claridge T.D.W., Schofield C.J., Pugh C.W., Maxwell P.H., Ratcliffe P.J., Stuart D.I., Jones E.Y. Nature 417:975-978(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 549-582 IN COMPLEX WITH 17-112 OF TCEB1; TCEB2 AND 52-213 OF VHL.
+	Additional computationally mapped references.

Web resources

Wikipedia

Hypoxia inducible factor entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U22431 mRNA. Translation: AAC50152.1.
U29165 mRNA. Translation: AAC51210.1.
AF050127 , AF050115, AF050116, AF050117, AF050118, AF050119, AF050120, AF050121, AF050122, AF050123, AF050124, AF050125, AF050126 Genomic DNA. Translation: AAC68568.1.
FJ790247 mRNA. Translation: ACN88547.1.
AF207601 mRNA. Translation: AAF20139.1.
AF207602 mRNA. Translation: AAF20140.1.
AF208487 Genomic DNA. Translation: AAF20149.1.
AF304431 mRNA. Translation: AAG43026.1.
AB073325 mRNA. Translation: BAB70608.1.
BT009776 mRNA. Translation: AAP88778.1.
AL137129 Genomic DNA. No translation available.
BC012527 mRNA. Translation: AAH12527.1.

IPI

IPI00003442.
IPI00332963.
IPI00788876.

PIR

I38972.

RefSeq

NP_001230013.1. NM_001243084.1.
NP_001521.1. NM_001530.3.
NP_851397.1. NM_181054.2.

UniGene

Hs.597216.
Hs.719495.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1D7G	model	-	D	15-73	[»]
1H2K	X-ray	2.15	S	786-826	[»]
1H2L	X-ray	2.25	S	786-826	[»]
1H2M	X-ray	2.50	S	775-826	[»]
1L3E	NMR	-	A	786-826	[»]
1L8C	NMR	-	B	776-826	[»]
1LM8	X-ray	1.85	H	556-575	[»]
1LQB	X-ray	2.00	D	549-582	[»]
2ILM	X-ray	2.30	S	786-826	[»]
3HQR	X-ray	2.00	S	558-574	[»]
3HQU	X-ray	2.30	S	558-574	[»]
4AJY	X-ray	1.73	H	562-577	[»]
4H6J	X-ray	1.52	A	238-348	[»]

DisProt

DP00262.

ProteinModelPortal

Q16665.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29722N.

IntAct

Q16665. 29 interactions.

MINT

MINT-133270.

STRING

9606.ENSP00000338018.

PTM databases

PhosphoSite

Q16665.

Polymorphism databases

DMDM

2498017.

Proteomic databases

PaxDb

Q16665.

PRIDE

Q16665.

Protocols and materials databases

DNASU

3091.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000323441; ENSP00000323326; ENSG00000100644.
ENST00000337138; ENSP00000338018; ENSG00000100644.
ENST00000539097; ENSP00000437955; ENSG00000100644.

GeneID

3091.

KEGG

hsa:3091.

UCSC

uc001xfq.2. human.

Organism-specific databases

CTD

3091.

GeneCards

GC14P062162.

HGNC

HGNC:4910. HIF1A.

HPA

CAB017442.
HPA001275.

MIM

603348. gene.

neXtProt

NX_Q16665.

PharmGKB

PA29283.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG289264.

HOGENOM

HOG000234306.

HOVERGEN

HBG060456.

KO

K08268.

OMA

QNAQRKR.

OrthoDB

EOG40CHGP.

PhylomeDB

Q16665.

Enzyme and pathway databases

Pathway_Interaction_DB

hif1_tfpathway. HIF-1-alpha transcription factor network.
hif1apathway. Hypoxic and oxygen homeostasis regulation of HIF-1-alpha.
pdgfrbpathway. PDGFR-beta signaling pathway.
vegfr1_2_pathway. Signaling events mediated by VEGFR1 and VEGFR2.
vegfr1_pathway. VEGFR1 specific signals.

Reactome

REACT_111102. Signal Transduction.
REACT_120956. Cellular responses to stress.

Gene expression databases

ArrayExpress

Q16665.

Bgee

Q16665.

CleanEx

HS_HIF1A.

Genevestigator

Q16665.

GermOnline

ENSG00000100644. Homo sapiens.

Family and domain databases

InterPro

IPR011598. bHLH_dom.
IPR001321. HIF-1_alpha.
IPR014887. HIF-1_TAD_C.
IPR021537. HIF_alpha_subunit.
IPR001610. PAC.
IPR000014. PAS.
IPR013767. PAS_fold.
IPR013655. PAS_fold_3.
[Graphical view]

Pfam

PF11413. HIF-1. 1 hit.
PF08778. HIF-1a_CTAD. 1 hit.
PF00989. PAS. 1 hit.
PF08447. PAS_3. 1 hit.
[Graphical view]

PRINTS

PR01080. HYPOXIAIF1A.

SMART

SM00353. HLH. 1 hit.
SM00086. PAC. 1 hit.
SM00091. PAS. 2 hits.
[Graphical view]

SUPFAM

SSF47459. HLH_basic. 1 hit.

TIGRFAMs

TIGR00229. sensory_box. 2 hits.

PROSITE

PS50888. BHLH. 1 hit.
PS50113. PAC. False negative.
PS50112. PAS. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q16665.

ChEMBL

CHEMBL4261.

ChiTaRS

HIF1A. human.

EvolutionaryTrace

Q16665.

GenomeRNAi

3091.

NextBio

12265.

SOURCE

Search...

Entry information

Entry name

HIF1A_HUMAN

Accession

Primary (citable) accession number: Q16665
Secondary accession number(s): C0LZJ3 , Q53XP6, Q96PT9, Q9UPB1

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 159 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.