Reactome | VHL [cytosol]

VHL [cytosol]

Stable Identifier

R-HSA-391423

Type

Protein [EntityWithAccessionedSequence]

Species

Homo sapiens

Compartment

cytosol

Locations in the PathwayBrowser

Expand all

Disease (Homo sapiens)

- Infectious disease (Homo sapiens)
  - Viral Infection Pathways (Homo sapiens)
    - SARS-CoV Infections (Homo sapiens)
      - SARS-CoV-1 Infection (Homo sapiens)
        
        SARS-CoV-1 Genome Replication and Transcription (Homo sapiens)
        
        Replication of the SARS-CoV-1 genome (Homo sapiens)
        
        nsp16 binds VHL (Homo sapiens)
        
        VHL [cytosol] (Homo sapiens)
        
        nsp16:VHL [cytosol] (Homo sapiens)
        
        VHL [cytosol] (Homo sapiens)
      - SARS-CoV-2 Infection (Homo sapiens)
        
        Early SARS-CoV-2 Infection Events (Homo sapiens)
        
        SARS-CoV-2 Genome Replication and Transcription (Homo sapiens)
        
        Replication of the SARS-CoV-2 genome (Homo sapiens)
        
        nsp16 binds VHL (Homo sapiens)
        
        VHL [cytosol] (Homo sapiens)
        
        nsp16:VHL [cytosol] (Homo sapiens)
        
        VHL [cytosol] (Homo sapiens)

Immune System (Homo sapiens)

- Adaptive Immune System (Homo sapiens)
  - Class I MHC mediated antigen processing & presentation (Homo sapiens)
    - Antigen processing: Ubiquitination & Proteasome degradation (Homo sapiens)
      - Interaction of E3 with substrate and E2-Ub complex (Homo sapiens)
        
        Ag-substrate:E3:E2:Ub [cytosol] (Homo sapiens)
        
        E3 ligases in proteasomal degradation [cytosol] (Homo sapiens)
        
        RBX1-CUL2-EloB,C-VHL [cytosol] (Homo sapiens)
        
        VBC complex [cytosol] (Homo sapiens)
        
        VHL [cytosol] (Homo sapiens)
        
        E3 ligases in proteasomal degradation [cytosol] (Homo sapiens)
        
        RBX1-CUL2-EloB,C-VHL [cytosol] (Homo sapiens)
        
        VBC complex [cytosol] (Homo sapiens)
        
        VHL [cytosol] (Homo sapiens)
      - Polyubiquitination of substrate (Homo sapiens)
        
        E3 ligases in proteasomal degradation [cytosol] (Homo sapiens)
        
        RBX1-CUL2-EloB,C-VHL [cytosol] (Homo sapiens)
        
        VBC complex [cytosol] (Homo sapiens)
        
        VHL [cytosol] (Homo sapiens)
        
        E3:K48-polyubiquitinated substrate [cytosol] (Homo sapiens)
        
        E3 ligases in proteasomal degradation [cytosol] (Homo sapiens)
        
        RBX1-CUL2-EloB,C-VHL [cytosol] (Homo sapiens)
        
        VBC complex [cytosol] (Homo sapiens)
        
        VHL [cytosol] (Homo sapiens)
        
        E3:Ub:substrate [cytosol] (Homo sapiens)
        
        E3 ligases in proteasomal degradation [cytosol] (Homo sapiens)
        
        RBX1-CUL2-EloB,C-VHL [cytosol] (Homo sapiens)
        
        VBC complex [cytosol] (Homo sapiens)
        
        VHL [cytosol] (Homo sapiens)
      - Release of E3 from polyubiquitinated substrate (Homo sapiens)
        
        E3 ligases in proteasomal degradation [cytosol] (Homo sapiens)
        
        RBX1-CUL2-EloB,C-VHL [cytosol] (Homo sapiens)
        
        VBC complex [cytosol] (Homo sapiens)
        
        VHL [cytosol] (Homo sapiens)
        
        E3:K48-polyubiquitinated substrate [cytosol] (Homo sapiens)
        
        E3 ligases in proteasomal degradation [cytosol] (Homo sapiens)
        
        RBX1-CUL2-EloB,C-VHL [cytosol] (Homo sapiens)
        
        VBC complex [cytosol] (Homo sapiens)
        
        VHL [cytosol] (Homo sapiens)
      - Transfer of Ub from E2 to substrate and release of E2 (Homo sapiens)
        
        Ag-substrate:E3:E2:Ub [cytosol] (Homo sapiens)
        
        E3 ligases in proteasomal degradation [cytosol] (Homo sapiens)
        
        RBX1-CUL2-EloB,C-VHL [cytosol] (Homo sapiens)
        
        VBC complex [cytosol] (Homo sapiens)
        
        VHL [cytosol] (Homo sapiens)
        
        E3 ligases in proteasomal degradation [cytosol] (Homo sapiens)
        
        RBX1-CUL2-EloB,C-VHL [cytosol] (Homo sapiens)
        
        VBC complex [cytosol] (Homo sapiens)
        
        VHL [cytosol] (Homo sapiens)
        
        E3:Ub:substrate [cytosol] (Homo sapiens)
        
        E3 ligases in proteasomal degradation [cytosol] (Homo sapiens)
        
        RBX1-CUL2-EloB,C-VHL [cytosol] (Homo sapiens)
        
        VBC complex [cytosol] (Homo sapiens)
        
        VHL [cytosol] (Homo sapiens)

Metabolism of proteins (Homo sapiens)

- Post-translational protein modification (Homo sapiens)
  - Neddylation (Homo sapiens)
    - 26S proteasome degrades HIFalpha (Homo sapiens)
      - RBX1:NEDD8-CUL2:EloB,C:VHL:COMMDs:CCDC22:DCUN1D1,2,4,5 [cytosol] (Homo sapiens)
        
        VBC complex [cytosol] (Homo sapiens)
        
        VHL [cytosol] (Homo sapiens)
      - ub-hydroxyPro-HIF-alpha:VHL:EloB:EloC:NEDD8-CUL2:RBX1:COMMDs:CCDC22:DCUN1D1,2,4,5 [cytosol] (Homo sapiens)
        
        RBX1:NEDD8-CUL2:EloB,C:VHL:COMMDs:CCDC22:DCUN1D1,2,4,5 [cytosol] (Homo sapiens)
        
        VBC complex [cytosol] (Homo sapiens)
        
        VHL [cytosol] (Homo sapiens)
    - AcM-UBE2M transfers NEDD8 to CRL2 E3 ubiquitin ligase complex (Homo sapiens)
      - NEDD8-AcM-UBE2M:CRL2 E3 ubiquitin ligase:COMMDs:CCDC22:DCUN1D1,2,4,5 [cytosol] (Homo sapiens)
        
        CRL2 E3 ubiquitin ligase:COMMDs:CCDC22 [cytosol] (Homo sapiens)
        
        CRL2 E3 ubiquitin ligase [cytosol] (Homo sapiens)
        
        CUL2-box protein [cytosol] (Homo sapiens)
        
        VHL [cytosol] (Homo sapiens)
      - NEDD8-CRL2 E3 ubiquitin ligase:COMMDs:CCDC22:DCUN1D1,2,4,5 [cytosol] (Homo sapiens)
        
        NEDD8-CRL2 E3 ligase complex [cytosol] (Homo sapiens)
        
        CUL2-box protein [cytosol] (Homo sapiens)
        
        VHL [cytosol] (Homo sapiens)
    - CAND1 binds cytosolic CRL E3 ubiquitin ligases (Homo sapiens)
      - CRL E3 ubiquitin ligase:CAND1 [cytosol] (Homo sapiens)
        
        CRL E3 ubiquitin ligases [cytosol] (Homo sapiens)
        
        CRL2 E3 ubiquitin ligase [cytosol] (Homo sapiens)
        
        CUL2-box protein [cytosol] (Homo sapiens)
        
        VHL [cytosol] (Homo sapiens)
      - CRL E3 ubiquitin ligases [cytosol] (Homo sapiens)
        
        CRL2 E3 ubiquitin ligase [cytosol] (Homo sapiens)
        
        CUL2-box protein [cytosol] (Homo sapiens)
        
        VHL [cytosol] (Homo sapiens)
    - COMMDs displace CAND1 from cytosolic CRL E3 ubiquitin ligase complexes (Homo sapiens)
      - CRL E3 ubiquitin ligase:CAND1 [cytosol] (Homo sapiens)
        
        CRL E3 ubiquitin ligases [cytosol] (Homo sapiens)
        
        CRL2 E3 ubiquitin ligase [cytosol] (Homo sapiens)
        
        CUL2-box protein [cytosol] (Homo sapiens)
        
        VHL [cytosol] (Homo sapiens)
      - CRL E3 ubiquitin ligase:COMMDs:CCDC22 [cytosol] (Homo sapiens)
        
        CRL2 E3 ubiquitin ligase:COMMDs:CCDC22 [cytosol] (Homo sapiens)
        
        CRL2 E3 ubiquitin ligase [cytosol] (Homo sapiens)
        
        CUL2-box protein [cytosol] (Homo sapiens)
        
        VHL [cytosol] (Homo sapiens)
    - COP9 signalosome deneddylates cytosolic CRL E3 ubiquitin ligase complexes (Homo sapiens)
      - CRL E3 ubiquitin ligase complex:COMMDs:CCDC22:DCUN1Ds [cytosol] (Homo sapiens)
        
        CRL2 E3 ubiquitin ligase:COMMDs:CCDC22:DCUN1D1,2,4,5 [cytosol] (Homo sapiens)
        
        CRL2 E3 ubiquitin ligase [cytosol] (Homo sapiens)
        
        CUL2-box protein [cytosol] (Homo sapiens)
        
        VHL [cytosol] (Homo sapiens)
      - NEDD8 CRL E3 ubiquitin ligases:COMMDs:CCDC22:DCUN1Ds [cytosol] (Homo sapiens)
        
        NEDD8-CRL2 E3 ubiquitin ligase:COMMDs:CCDC22:DCUN1D1,2,4,5 [cytosol] (Homo sapiens)
        
        NEDD8-CRL2 E3 ligase complex [cytosol] (Homo sapiens)
        
        CUL2-box protein [cytosol] (Homo sapiens)
        
        VHL [cytosol] (Homo sapiens)
    - NEDD8:AcM-UBE2M binds CRL2 E3 ubiquitin ligase complex (Homo sapiens)
      - CRL2 E3 ubiquitin ligase:COMMDs:CCDC22 [cytosol] (Homo sapiens)
        
        CRL2 E3 ubiquitin ligase [cytosol] (Homo sapiens)
        
        CUL2-box protein [cytosol] (Homo sapiens)
        
        VHL [cytosol] (Homo sapiens)
      - NEDD8-AcM-UBE2M:CRL2 E3 ubiquitin ligase:COMMDs:CCDC22:DCUN1D1,2,4,5 [cytosol] (Homo sapiens)
        
        CRL2 E3 ubiquitin ligase:COMMDs:CCDC22 [cytosol] (Homo sapiens)
        
        CRL2 E3 ubiquitin ligase [cytosol] (Homo sapiens)
        
        CUL2-box protein [cytosol] (Homo sapiens)
        
        VHL [cytosol] (Homo sapiens)
    - VHL:EloB,C:NEDD8-CUL2:RBX1 complex binds UBXN7 (Homo sapiens)
      - RBX1:NEDD8-CUL2:EloB,C:VHL:COMMDs:CCDC22:DCUN1D1,2,4,5 [cytosol] (Homo sapiens)
        
        VBC complex [cytosol] (Homo sapiens)
        
        VHL [cytosol] (Homo sapiens)
      - RBX1:NEDD8-CUL2:EloB,C:VHL:COMMDs:CCDC22:DCUN1D1,2,4,5:UBXN7 [cytosol] (Homo sapiens)
        
        RBX1:NEDD8-CUL2:EloB,C:VHL:COMMDs:CCDC22:DCUN1D1,2,4,5 [cytosol] (Homo sapiens)
        
        VBC complex [cytosol] (Homo sapiens)
        
        VHL [cytosol] (Homo sapiens)
    - VHL:EloB,C:NEDD8-CUL2:RBX1 complex binds hydroxyprolyl-HIF-alpha (Homo sapiens)
      - RBX1:NEDD8-CUL2:EloB,C:VHL:COMMDs:CCDC22:DCUN1D1,2,4,5 [cytosol] (Homo sapiens)
        
        VBC complex [cytosol] (Homo sapiens)
        
        VHL [cytosol] (Homo sapiens)
      - RBX1:NEDD8-CUL2:EloB,C:VHL:COMMDs:CCDC22:DCUN1D1,2,4,5:hydroxyPro-HIF-alpha [cytosol] (Homo sapiens)
        
        RBX1:NEDD8-CUL2:EloB,C:VHL:COMMDs:CCDC22:DCUN1D1,2,4,5 [cytosol] (Homo sapiens)
        
        VBC complex [cytosol] (Homo sapiens)
        
        VHL [cytosol] (Homo sapiens)
    - VHL:EloB,C:NEDD8-CUL2:RBX1 complex ubiquitinylates HIF-alpha (Homo sapiens)
      - RBX1:NEDD8-CUL2:EloB,C:VHL:COMMDs:CCDC22:DCUN1D1,2,4,5:UBXN7 [cytosol] (Homo sapiens)
        
        RBX1:NEDD8-CUL2:EloB,C:VHL:COMMDs:CCDC22:DCUN1D1,2,4,5 [cytosol] (Homo sapiens)
        
        VBC complex [cytosol] (Homo sapiens)
        
        VHL [cytosol] (Homo sapiens)
      - RBX1:NEDD8-CUL2:EloB,C:VHL:COMMDs:CCDC22:DCUN1D1,2,4,5:hydroxyPro-HIF-alpha [cytosol] (Homo sapiens)
        
        RBX1:NEDD8-CUL2:EloB,C:VHL:COMMDs:CCDC22:DCUN1D1,2,4,5 [cytosol] (Homo sapiens)
        
        VBC complex [cytosol] (Homo sapiens)
        
        VHL [cytosol] (Homo sapiens)
      - ub-hydroxyPro-HIF-alpha:VHL:EloB:EloC:NEDD8-CUL2:RBX1:COMMDs:CCDC22:DCUN1D1,2,4,5 [cytosol] (Homo sapiens)
        
        RBX1:NEDD8-CUL2:EloB,C:VHL:COMMDs:CCDC22:DCUN1D1,2,4,5 [cytosol] (Homo sapiens)
        
        VBC complex [cytosol] (Homo sapiens)
        
        VHL [cytosol] (Homo sapiens)

External Reference Information

External Reference

UniProt:P40337 VHL

Gene Names

VHL

Chain

chain:1-213

Reference Genes

BioGPS Gene:7428 VHL

COSMIC (genes):VHL VHL

CTD Gene:7428 VHL

dbSNP Gene:7428 VHL

ENSEMBL:ENSG00000134086 VHL

ENSEMBL:ENSG00000134086.9 VHL

HGNC:12687 VHL

KEGG Gene (Homo sapiens):7428 VHL

Monarch:7428 VHL

NCBI Gene:7428 VHL

OMIM:608537 VHL

UCSC:P40337 VHL

Reference Transcript

Other Identifiers

11748633_a_at

11752180_x_at

1559227_PM_s_at

1559227_s_at

1668_s_at

16937571

203844_PM_at

203844_at

2610338

2610339

2610340

2610342

2610344

2610345

2610346

2610347

2610348

2610349

2610350

2610351

2610352

2610353

2610354

40871_at

7428

8077781

A_23_P132606

A_24_P134942

A_33_P3419938

GE54104

GO:0000122

GO:0000902

GO:0001525

GO:0001666

GO:0003309

GO:0003310

GO:0003711

GO:0003714

GO:0003824

GO:0004842

GO:0005515

GO:0005634

GO:0005654

GO:0005730

GO:0005737

GO:0005739

GO:0005783

GO:0005829

GO:0005929

GO:0006351

GO:0006355

GO:0006508

GO:0006582

GO:0006914

GO:0008285

GO:0009968

GO:0010468

GO:0010498

GO:0010507

GO:0010629

GO:0012501

GO:0014069

GO:0015031

GO:0016020

GO:0016567

GO:0016740

GO:0019899

GO:0023052

GO:0030154

GO:0030163

GO:0030182

GO:0030198

GO:0030891

GO:0031462

GO:0032880

GO:0034244

GO:0034330

GO:0036211

GO:0042069

GO:0043066

GO:0043226

GO:0043232

GO:0043534

GO:0044877

GO:0045446

GO:0045471

GO:0045597

GO:0045602

GO:0045893

GO:0046426

GO:0048069

GO:0048593

GO:0048856

GO:0048870

GO:0048877

GO:0050679

GO:0050821

GO:0060090

GO:0061072

GO:0061073

GO:0061428

GO:0061912

GO:0070243

GO:0070244

GO:0071456

GO:0097411

GO:0098978

GO:0099175

GO:0140096

GO:0140110

GO:0140252

GO:0140297

GO:1900037

GO:1902072

GO:1990000

GO:1990756

GO:2001233

HMNXSV003025175

Hs2.421597.1.A1_3p_s_at

ILMN_1738579

ILMN_1801984

ILMN_2376625

L15409_at

PH_hs_0033268

TC03000055.hg

TC03002213.hg

g4507890_3p_at

Participates

as a member of

as an input of

as a component of

Other forms of this molecule

monoSUMO1-K159,171,196-VHL [nucleoplasm]

VHL [nucleoplasm]

Inferred To

Vhl [cytosol] (Drosophila melanogaster)

Vhl [cytosol] (Mus musculus)

Vhl [cytosol] (Rattus norvegicus)

vhl-1 [cytosol] (Caenorhabditis elegans)

Ghost homologue of VHL [cytosol] (Xenopus tropicalis)

VHL [cytosol] (Bos taurus)

VHL [cytosol] (Canis familiaris)

VHL [cytosol] (Danio rerio)

VHL [cytosol] (Gallus gallus)

VHL [cytosol] (Sus scrofa)

Cross References

RefSeq

NP_000542.1, NP_937799.1

Guide to Pharmacology - Targets

3204

OpenTargets

ENSG00000134086

ZINC - Substances

VHL_HUMAN

ZINC target

P40337

PRO

P40337

PDB

4W9I, 6FMK, 6HR2, 8BDI, 7Q2J, 4AWJ, 8BDT, 6FMI, 6BVB, 3ZTD, 1LQB, 4W9C, 6GFY, 8BB2, 8BDJ, 4W9D, 5NVW, 6HAX, 8BDL, 6GMN, 5NVX, 5NW0, 8BDX, 4W9E, 6I7Q, 7Z76, 8BEB, 5NVZ, 5N4W, 7PI4, 6GMQ, 6ZHC, 4BKS, 3ZRC, 4B9K, 4W9G, 6GMR, 6I7R, 4BKT, 8BDN, 6SIS, 6R7F, 5LLI, 3ZTC, 3ZRF, 7S4E, 4W9J, 6FMJ, 4WQO, 6GMX, 4W9K, 7JTP, 6GFZ, 8BDS, 7JTO, 4W9L, 7Z6L, 6R6H, 5NVV, 7KHH, 1LM8, 4B95, 6HAY, 5NVY, 8BB4, 8BDM, 5T35, 4W9F, 1VCB, 5NW1, 7ZNT, 8BB3, 5NW2, 7CJB, 8BDO, 4W9H, 3ZUN, 7Z77, 6GFX, 8BB5, 4AJY, 8C13

GeneCards

P40337

HPA

ENSG00000134086-VHL

Ensembl

ENST00000345392, ENST00000256474, ENSG00000134086, ENSP00000344757, ENSP00000256474

Pharos - Targets

P40337

Orphanet

15708

ZINC - Predictions - Purchasable

VHL_HUMAN

Interactors (15)

Accession	#Entities	Entities	Confidence Score	Evidence (IntAct)
UniProt:Q16665 HIF1A	7	HN-HIF1A [cytosol] (R-HSA-1234110) 2xHP-HIF1A [nucleoplasm] (R-HSA-1234105) 2xHP-HIF1A [cytosol] (R-HSA-1234131) p-Y565,S797-HIF1A [cytosol] (R-HSA-9634700) p-Y565-HIF1A [cytosol] (R-HSA-8857584) HIF1A [cytosol] (R-HSA-1234102) HIF1A [nucleoplasm] (R-HSA-1234135)	0.957	20
UniProt:Q15370 ELOB	2	TCEB2 [nucleoplasm] (R-HSA-112423) ELOB [cytosol] (R-HSA-180551)	0.928	11
UniProt:Q13617 CUL2	3	G76-NEDD8-K689-CUL2 [cytosol] (R-HSA-8952511) CUL2 [nucleoplasm] (R-HSA-1234126) CUL2 [cytosol] (R-HSA-416982)	0.886	17
UniProt:Q15369 ELOC	2	TCEB1 [nucleoplasm] (R-HSA-112422) ELOC [cytosol] (R-HSA-180535)	0.784	7
UniProt:Q99750 MDFI			0.666	4
UniProt:Q99814 EPAS1	5	HN-EPAS1 [cytosol] (R-HSA-1234112) 2xHP-EPAS1 [cytosol] (R-HSA-1234149) 2xHP-EPAS1 [nucleoplasm] (R-HSA-1234151) EPAS1 [nucleoplasm] (R-HSA-452560) EPAS1 [cytosol] (R-HSA-1234119)	0.659	3
UniProt:P62877 RBX1	2	RBX1 [nucleoplasm] (R-HSA-1234142) RBX1 [cytosol] (R-HSA-180582)	0.623	4
UniProt:P63244 RACK1	1	GNB2L1 [cytosol] (R-HSA-5626956)	0.611	9
UniProt:P0C6X7-PRO_0000037322 REP			0.602	7
UniProt:P21980 TGM2			0.602	10
UniProt:Q99873 PRMT1	2	PRMT1 [cytosol] (R-HSA-9632173) PRMT1 [nucleoplasm] (R-HSA-3215140)	0.508	2
UniProt:P02751 FN1	10	FN1(32-2386) [platelet alpha granule lumen] (R-HSA-114620) FN1(32-271) [extracellular region] (R-HSA-3787935) FN1(272-2386) [extracellular region] (R-HSA-3788024) FN1(32-?) [extracellular region] (R-HSA-2533850) FN1(?-2386) [extracellular region] (R-HSA-2533841) FN1(32-1201)-p-7Y-ALK(1022-1620) fusion [plasma membrane] (R-HSA-9713462) FN1(32-1201)-ALK(1022-1620) fusion [plasma membrane] (R-HSA-9713459) p-FN1 [endoplasmic reticulum lumen] (R-HSA-8956937) FN1 [endoplasmic reticulum lumen] (R-HSA-8956708) FN1(32-2386) [extracellular region] (R-HSA-54851)	0.499	2
UniProt:Q61221	7	Hif1a [cytosol] (R-MMU-1234110) Hif1a [nucleoplasm] (R-MMU-1234105) Hif1a [cytosol] (R-MMU-1234131) phospho-Hif1a [cytosol] (R-MMU-9634700) phospho-Hif1a [cytosol] (R-MMU-8857584) Hif1a [cytosol] (R-MMU-1234102) Hif1a [nucleoplasm] (R-MMU-1234135)	0.499	3
UniProt:Q05513 PRKCZ	5	pS, p-T410-PRKCZ [cytosol] (R-HSA-9632824) p-T410,T563-PRKCZ [cytosol] (R-HSA-5218698) PRKCZ [cell junction] (R-HSA-2134483) PRKCZ [cytosol] (R-HSA-58218) p-T410-PRKCZ [cytosol] (R-HSA-437181)	0.463	3
UniProt:P08151 GLI1	9	ub-pS-GLI1 [ciliary base] (R-HSA-5610514) pS-GLI1 [ciliary base] (R-HSA-5610497) ub-GLI1 [cytosol] (R-HSA-5635833) GLI1 [cytosol] (R-HSA-445457) p-GLI1 [ciliary tip] (R-HSA-5635040) 2p-GLI1 [nucleoplasm] (R-HSA-5635057) p-GLI1 [nucleoplasm] (R-HSA-5635042) GLI1 [ciliary tip] (R-HSA-5610360) GLI1 [ciliary base] (R-HSA-5610357)	0.463	2

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