1LM8,1VCB,1LQB


Conserved Protein Domain Family
pVHL

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cd05468: pVHL 
Click on image for an interactive view with Cn3D
von Hippel-Landau (pVHL) tumor suppressor protein
von Hippel-Landau (pVHL) protein, the gene product of VHL, is a critical regulator of the ubiquitous oxygen-sensing pathway. It is conserved throughout evolution, as its homologs are found in organisms ranging from mammals to the Drosophila melanogaster, Anopheles gambiae insects and the Caenorhabditis elegans nematode. pVHL acts as the substrate recognition component of an E3 ubiquitin ligase complex. Several proteins have been identified as pVHL-binding proteins that are subject to ubiquitin-mediated proteolysis; the best characterized putative substrates are the alpha subunits of the hypoxia-inducible factor (HIF1alpha, HIF2alpha, and HIF3alpha). In addition to HIF degradation, pVHL has been implicated to be involved in HIF independent cellular processes. Germline VHL mutations cause renal cell carcinomas, hemangioblastomas and pheochromocytomas in humans. pVHL can bind to and direct the proper deposition of fibronectin and collagen IV within the extracellular matrix. It works to stabilize microtubules and foster the maintenance of primary cilium. It also has been reported to promote the stabilization and activation of p53 in a HIF-independent manner and, in neuronal cells, promote apoptosis by down-regulation of Jun-B.
Statistics
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PSSM-Id: 176472
View PSSM: cd05468
Aligned: 39 rows
Threshold Bit Score: 77.5097
Threshold Setting Gi: 99082530
Created: 26-Apr-2007
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
pVHL-HIF-1alphapVHL-ElonginB..
Conserved site includes 20 residues -Click on image for an interactive view with Cn3D
Feature 1:pVHL-HIF-1alpha interaction [polypeptide binding site]
Evidence:
  • Comment:For ubiquitination of the hypoxia-inducible factor (HIF) by the von Hippel-Lindau tumor suppressor (pVHL) to occur, pVHL binds to HIF only when a conserved proline in HIF is hydroxylated, a modification that is oxygen-dependent.
  • Structure:1LM8: Human von Hippel-Lindau tumor suppressor (pVHL) bound to 20 residue HIF-1alpha peptide; contacts at 4.0A
    View structure with Cn3D

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1            # #      # ###        #  #      ##     ########  # #                         
1LM8_V         11 RSVNSRep-sqVIFCNRsprvVLPVWLNFdGEPQPYPTLppgTGRRIHSYrGHLWLFRDagtHDGLLvn-----qtELFV 84   human
XP_001703428   55 RSMGWTve-seLTVLNDlehpIKIYWLNYdGDAELFGSLnpgSVFTVKTYeSHAWRFVDsstGYTVA---------EHVA 124  Chlamydomonas...
XP_001221196  131 VSDNAGdp-agVNIVNKtevaVKVFWIDGsGKAVQYATVqpgREMRIETYaGHVWRVEGe-gGEQAVyra---legEGFI 205  Chaetomium gl...
XP_387534     125 ASSHSHia-vtVDFVNRtgktLKVYWIDWdGKPVYYRTItngQTKRQITYtGHVWRLVDl-sDEKFRavfe-apdvGIYV 201  Gibberella ze...
EEU46439      126 PSSNGDte-itVDFVNRtgttIKAFWIDWdGEPIWYHTIhngGTVRQETYvGHVWRFVDa-lDERFR---------AIYA 194  Nectria haema...
XP_001694179   53 RSVNSNvr-srATFVNDctepVTMVWLDYnGQEVVYGALrpgQSKVYDSYaSHPWVFRCsttDKRMMagg----rmAHYM 127  Chlamydomonas...
XP_001701489   46 HSRRSDvp-csLTIRNRsamvVEARWVNYdGDEEPYATIppgHEWTVDTFeTHPWRFRDartGGLVV---------EYVA 115  Chlamydomonas...
YP_614684     195 ASGASTtp-ttLTVTNSadgpIELWWIDEtGTAQYYATLqpgDTRNQSTFeEHNWILRHp--DGWYLeyiegapnqTVNF 271  Silicibacter ...
NP_864730     130 RSGRSSeahteITFVNKtdqaLQLFWVDSsGKRVKYEVIpagETFVRTTFaGHVWELVGd--NETKF---------GYFV 198  Rhodopirellul...
YP_003369558  130 RSQAGGva-sgLRFSNTldrkVQLWWIDPqGELVEYETIdagAKHQQPSYhRHQWLLRDe-aGTDLA---------RIEV 198  Pirellula sta...
Feature 1                                                                                         
1LM8_V         85 Pslnv--------dgqPIFANITLpvy-------------tlKERCLQVVRSlvk----------peNYRRLdi-----v 128  human
XP_001703428  125 Aagqqv------vrvaSKTGGVVAyttaqs------pglaapQQRTLAGRGS---------------GGAGLaq-----q 172  Chlamydomonas...
XP_001221196  206 Vveg---------wglRKEGSGEIlaerk---------vpvkEEKEVQEIREl--------------ADGGIfvr---dg 250  Chaetomium gl...
XP_387534     202 AiiedlsdsiteaspsSDDGKSSA------------------DEDTAELENGt-------------cHVKEF-------- 242  Gibberella ze...
EEU46439      195 Apdqr-------tdvvVIKNLVDLdeeasss-----nnddniEEDEEDESTAs-------------tTEPQLyvk---ns 246  Nectria haema...
XP_001694179  128 Ep--------------PPPGDTGLl----------------lSSSARRQAANp--------------EPPRVhitpppvl 163  Chlamydomonas...
XP_001701489  116 A---------------RGPRLLQLtdtgaaea---epagssaQGRGARQSQAsds----------paTRTGSgsp--ham 165  Chlamydomonas...
YP_614684     272 G---------------SAGLNDTVy-----------------AGAGNDLIDGmygddl----lygegNNDTIygd--ygs 313  Silicibacter ...
NP_864730     199 Adi------------ePARVEVSAparvtq-------veperRGRRRRDFRRgddwsagvpapdndkVLARLsdg---rl 256  Rhodopirellul...
YP_003369558  199 Gpt-----------irEVLIDGEAenevrerraprggggqspDRKWVAYVEE---------------GNLLLrn----rd 248  Pirellula sta...
Feature 1                                              
1LM8_V        129 RSLYEDLEdhp---------------nvqKDLERLTQ 150  human
XP_001703428  173 EQLAAPSAte-----------------ppRPLEPSSP 192  Chlamydomonas reinhardtii
XP_001221196  251 DVWIRDADgehritt-------ndepglqYDPNRLMA 280  Chaetomium globosum CBS 148.51
XP_387534     243 NIWYKDDDg--------------------QDVQLSKD 259  Gibberella zeae PH-1
EEU46439      247 NVWFGKKDgq------------------dKQLSEYGS 265  Nectria haematococca mpVI 77-13-4
XP_001694179  164 QHTVSERDpgarnavnaaltaaqptlqamQPLEMSSP 200  Chlamydomonas reinhardtii
XP_001701489  166 DDVYADEDgsse--------------gavTALQPEPP 188  Chlamydomonas reinhardtii
YP_614684     314 DTIYGGAG---------------------DDLLYGGD 329  Silicibacter sp. TM1040
NP_864730     257 QLKHAEVDdda---------------aewKTLIEESR 278  Rhodopirellula baltica SH 1
YP_003369558  249 SGVIQPLK---------------------TDLDPQYP 264  Pirellula staleyi DSM 6068

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