1HE8,1XD2,1WQ1,1LFD,1NVX


Conserved Protein Domain Family
H_N_K_Ras_like

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cd04138: H_N_K_Ras_like 
Click on image for an interactive view with Cn3D
Ras GTPase family containing H-Ras,N-Ras and K-Ras4A/4B
H-Ras/N-Ras/K-Ras subfamily. H-Ras, N-Ras, and K-Ras4A/4B are the prototypical members of the Ras family. These isoforms generate distinct signal outputs despite interacting with a common set of activators and effectors, and are strongly associated with oncogenic progression in tumor initiation. Mutated versions of Ras that are insensitive to GAP stimulation (and are therefore constitutively active) are found in a significant fraction of human cancers. Many Ras guanine nucleotide exchange factors (GEFs) have been identified. They are sequestered in the cytosol until activation by growth factors triggers recruitment to the plasma membrane or Golgi, where the GEF colocalizes with Ras. Active (GTP-bound) Ras interacts with several effector proteins that stimulate a variety of diverse cytoplasmic signaling activities. Some are known to positively mediate the oncogenic properties of Ras, including Raf, phosphatidylinositol 3-kinase (PI3K), RalGEFs, and Tiam1. Others are proposed to play negative regulatory roles in oncogenesis, including RASSF and NORE/MST1. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.
Statistics
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PSSM-Id: 133338
Aligned: 17 rows
Threshold Bit Score: 285.082
Created: 1-Sep-2005
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
  next features
Conserved site includes 19 residues -Click on image for an interactive view with Cn3D
Feature 1:GTP/Mg2+ binding site [chemical binding site]
Evidence:
  • Structure:1HE8: Human Ras binds GppNHp, a GTP analog and Mg2+, defined using 3.5 A contacts

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1              #######         ### #  #                        #                      
1HE8_B      3 EYKLVVVGAVGVGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLDILDTAGQEEYSAMRDQYMRTGEGFLCVF 82  human
AAB09439    3 EYKLVVVGAGGVGKSALTIQLIQNHFVEEYDPTIEDSYRKQMVIDGEICLLDILDTAGQEEYSAMRDQYMRTGEGFLCVF 82  Schistosoma mansoni
P32253      4 LLKLVIVGDGGVGKSALTIQLTQNQFIAEYDPTIENSYRKQVNIDEEVYMLDILDTAGQEEYSAMRDQYIRSGRGFLIVY 83  Dictyostelium disc...
CAA25207   10 EYKLVVVGGGGVGKSALTIQLTQSHFVDEYDPTIEDSYRKQVVIDDEVSILDILDTAGQEEYSAMREQYMRNGEGFLLVY 89  baker's yeast
BAD91453    9 EYKLVVVGGGGVGKSALTIQFIQSHFVDEYDPTIEDSYRKQCVIDDEVALLDVLDTAGQEEYGAMREQYMRTGEGFLLVY 88  Trametes hirsuta
CAA37612    8 EYKLVVVGGGGVGKSCLTIQLIQGHFLDEYDPTIEDSYRKQCTIDNEVALLDILDTAGQEEYSAMREQYMRTGEGFLLVF 87  Neurospora crassa
AAF54388    3 EYKLVVVGAGGVGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLDILDTAGQEEYSAMRDQYMRTGEGFLLVF 82  fruit fly
CAA55332    9 KFKMVVVGAGGVGKSALTIQLIQNHFVEDYDPTIEDSYIKQVVVDGAICILDILDTAGQEEYSAMREHYMRTGEGFLCIF 88  Hydra vulgaris
CAA92630    3 EYKLVVVGDGGVGKSALTIQLIQNHFVEEYDPTIEDSYRKQVVIDGETCLLDILDTAGQEEYSAMRDQYMRTGEGFLLVF 82  nematode
AAT81171    3 EYKLVVVGAGGVGKSALTIQLIQNHFVEEYDPTIEDSYRKQVVIDGETCLLDILDTAGQEEYSAMRDQYMRTGEGFLCVF 82  blue mussel
Feature 1                                      ## ##                          ##              
1HE8_B     83 AINNTKSFEDIHQYREQIKRVKDSDDVPMVLVGNKCDLAa--RTVESRQAQDLARSYGIPYIETSAKTRQGVEDAFYTLV 160 human
AAB09439   83 AVNNSKSYDDINQYREQIKRVKDADEVPMVLVGNKVDLTn--RSVCTEEAKSLAHSYNIPYVETSAKTRQGVEDAFHKLV 160 Schistosoma mansoni
P32253     84 SIISRASFEAVTTFREQILRVKDLSTYPIVIIGNKADLPdkdRKVPPMEGKELAKSFGAPFLETSAKSRVNVEEAFFTLV 163 Dictyostelium disc...
CAA25207   90 SITSKSSLDELMTYYQQIPRVKDTDYVPIVVVGNKSDLEn-eKQVSYQDGLNMAKQMNAPFLETSAKQAINVEEAFYTLA 168 baker's yeast
BAD91453   89 SITSRNSFEEISTFHQQILRVKDQDSFPVIVVANKCDLEy-eRQVGMNEGRDLAKHFGCKFIETSAKNRINVDEAFSQLV 167 Trametes hirsuta
CAA37612   88 AINSRESFEEIRIYQQQILRVKDRDSFPMIIVGNKYDLRg-eRVVSEQEGQALAAEFGTKYIETSAKTQHNVENAFYDLV 166 Neurospora crassa
AAF54388   83 AVNSAKSFEDIGTYREQIKRVKDAEEVPMVLVGNKCDLAs--WNVNNEQAREVAKQYGIPYIETSAKTRMGVDDAFYTLV 160 fruit fly
CAA55332   89 AVTSLKSFQEIDNFRTQALRVKDADKVPMVLVGNKVDLPk--RDVSTKDGNDKALSFGIPYVETSAKTKQGVEEAFFTLV 166 Hydra vulgaris
CAA92630   83 AVNEAKSFENVANYREQIRRVKDSDDVPMVLVGNKCDLSs--RSVDFRTVSETAKGYGIPNVDTSAKTRMGVDEAFYTLV 160 nematode
AAT81171   83 AVNNTKSFEDINQYREQIKRVKDADEVPMVLVGNKVDLPt--RTVGAKQARPVADSYNIPYVETSAKTRQGVDDAFYTLV 160 blue mussel
Feature 1         
1HE8_B    161 REIR 164 human
AAB09439  161 REIR 164 Schistosoma mansoni
P32253    164 REIK 167 Dictyostelium discoideum
CAA25207  169 RLVR 172 baker's yeast
BAD91453  168 REIR 171 Trametes hirsuta
CAA37612  167 REIR 170 Neurospora crassa
AAF54388  161 REIR 164 fruit fly
CAA55332  167 REIL 170 Hydra vulgaris
CAA92630  161 REIR 164 nematode
AAT81171  161 REIR 164 blue mussel

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