Reviewed, UniProtKB/Swiss-Prot Q16665 (HIF1A_HUMAN)

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
    Member of PAS protein 1
    Basic-helix-loop-helix-PAS protein MOP1

Gene names

Name:	HIF1A
Synonyms:	MOP1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	826 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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, 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.
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 CREBBP and EP300 (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.
Subcellular location	Cytoplasm. Nucleus. Note= Cytoplasmic in normoxia, nuclear translocation in response to hypoxia. Colocalizes with SUMO1 in the nucleus, under hypoxia.
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 FGF-2 FGF-2 IGF-2, TGF-1 beta, HGF, TNF alpha, IL-1 beta, angiotensin-2 and thrombin. However, this induction is less intense than that stimulated by hypoxia.
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).
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. 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. Sumoylated; by SUMO1 under hypoxia. Sumoylation is enhanced through interaction with RWDD3. Desumoylation by SENP1 leads to increased HIF1A stability and transriptional activity By similarity. 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.
Sequence similarities	Contains 1 basic helix-loop-helix (bHLH) 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 Phosphoprotein S-nitrosylation Ubl conjugation
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	collagen metabolic process Inferred from sequence or structural similarity. Source: UniProtKB connective tissue replacement during inflammatory response Inferred from sequence or structural similarity. Source: UniProtKB elastin metabolic process Inferred from sequence or structural similarity. Source: UniProtKB epithelial to mesenchymal transition Inferred from sequence or structural similarity. Source: UniProtKB mRNA transcription from RNA polymerase II promoter Ref.1 Inferred by curator. Source: UniProtKB oxygen homeostasis Inferred from direct assay. Source: HGNC positive regulation of angiogenesis Inferred by curator. Source: UniProtKB positive regulation of chemokine production Traceable author statement. Source: UniProtKB positive regulation of endothelial cell proliferation Inferred by curator. Source: UniProtKB positive regulation of epithelial cell migration Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of erythrocyte differentiation Inferred by curator. Source: UniProtKB positive regulation of gene-specific transcription Inferred from direct assay. Source: UniProtKB positive regulation of glycolysis Inferred by curator. Source: UniProtKB positive regulation of hormone biosynthetic process Inferred from direct assay. Source: UniProtKB positive regulation of nitric-oxide synthase activity Traceable author statement. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from genetic interaction. Source: MGI positive regulation of vascular endothelial growth factor receptor signaling pathway Inferred by curator. Source: UniProtKB positive regulation vascular endothelial growth factor production Inferred from direct assay. Source: UniProtKB regulation of transcription from RNA polymerase II promoter in response to oxidative stress Inferred from direct assay. Source: UniProtKB regulation of transforming growth factor-beta2 production Inferred from mutant phenotype. Source: UniProtKB response to hypoxia Inferred from direct assay. Source: UniProtKB
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW nucleolus Inferred from direct assay. Source: HPA transcription factor complex Inferred from physical interaction. Source: MGI
Molecular function	Hsp90 protein binding Ref.2 Inferred from direct assay. Source: UniProtKB RNA polymerase II transcription factor activity, enhancer binding Ref.1 Ref.2 Inferred from direct assay. Source: UniProtKB histone acetyltransferase binding Inferred from physical interaction. Source: UniProtKB protein heterodimerization activity Ref.2 Inferred from physical interaction. Source: UniProtKB signal transducer activity Inferred from electronic annotation. Source: InterPro transcription factor binding Ref.1 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
AR	P10275	1	EBI-447269,EBI-608057
EP300	Q09472	2	EBI-447269,EBI-447295
FAF2	Q96CS3	1	EBI-447269,EBI-1055805
HIF1AN	Q9NWT6	1	EBI-447269,EBI-745632
MAX	P61244	1	EBI-447269,EBI-878388
OS9	Q13438	2	EBI-447269,EBI-1174342
OS9	Q13438-1	1	EBI-447269,EBI-1174351
OS9	Q13438-2	1	EBI-447269,EBI-1174355
PCAF	Q92831	2	EBI-447269,EBI-477430
RWDD3	Q9Y3V2	1	EBI-447269,EBI-1549885
SEPT9	Q9UHD8-1	3	EBI-447269,EBI-851558
UBXN7	O94888	2	EBI-447269,EBI-1993627
VHL	P40337	1	EBI-447269,EBI-301246

Alternative products

This entry describes 2 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.

Notes: No experimental confirmation available.

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

31 – 71

41

Helix-loop-helix motif

Domain

85 – 158

74

PAS 1

Domain

228 – 298

71

PAS 2

Domain

302 – 345

44

PAC

DNA binding

17 – 30

14

Basic motif

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

402

1

4-hydroxyproline

Modified residue

564

1

4-hydroxyproline

Modified residue

800

1

S-nitrosocysteine Probable

Modified residue

803

1

3-hydroxyasparagine

Cross-link

391

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

Cross-link

477

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

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

736 – 826

91

Missing in isoform 2.

VSP_007738

Natural variant

796

1

T → A: dbSNP rs1802821.

VAR_015854

Experimental info

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

Mutagenesis

389

1

K → R: No change in sumoylation

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

Mutagenesis

392

1

K → R: No change in sumoylation

Mutagenesis

394

1

P → A: No change in VHLE3-dependent ubiquitination

Mutagenesis

397

1

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

Mutagenesis

400

1

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

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

Mutagenesis

442

1

K → R: No change in sumoylation

Mutagenesis

460

1

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

Mutagenesis

477

1

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

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

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

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

Mutagenesis

551

1

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

Mutagenesis

552

1

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

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

Mutagenesis

719

1

K → T: Dramatic reduction of accumulation in the nucleus in response to hypoxia

Mutagenesis

800

1

C → A: Blocks increase in transcriptional activation caused by nitrosylation

Mutagenesis

800

1

C → S: Abolishes hypoxia-inducible transcriptional activation of ctaD

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

Sequence conflict

572

1

F → L in AAC68568. Ref.3

Sequence conflict

735

1

G → I in BAB70608. Ref.6

Secondary structure

1

.

.

.

.

.

826

Helix Strand Turn

Details...

Turn

779 – 783

5

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		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

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: 7539918] [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: 9079689] [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: 9782081] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[4]	"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].
[5]	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.
[6]	"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.
[7]	"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].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Choriocarcinoma and Placenta.
[9]	"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: 8917528] [Abstract] Cited for: IDENTIFICATION IN COMPLEX WITH EP300 AND CREBBP, INTERACTION WITH EP300.
[10]	"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: 9235919] [Abstract] Cited for: TRANSACTIVATION DOMAINS NTAD AND CTAD.
[11]	"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: 9822602] [Abstract] Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-719.
[12]	"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: 9653127] [Abstract] Cited for: OXYGEN-DEPENDENT DEGRADATION DOMAIN.
[13]	"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: 10202154] [Abstract] Cited for: TRANSACTIVATION DOMAINS NTAD AND CTAD, INTERACTION WITH APEX, MUTAGENESIS OF CYS-800.
[14]	"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: 11006129] [Abstract] Cited for: INTERACTION WITH VHL.
[15]	"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) [