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
View PSSM: cd04138
Aligned: 17 rows
Threshold Bit Score: 285.082
Threshold Setting Gi: 4291
Created: 1-Sep-2005
Updated: 17-Jan-2013
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
    View structure with Cn3D

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                #######         ### #  #                        #                      
1HE8_B        3 EYKLVVVGAVGVGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLDILDTAGQEEYSAMRDQYMRTGEGFLCVF 82
gi 1575028    3 EYKLVVVGAGGVGKSALTIQLIQNHFVEEYDPTIEDSYRKQMVIDGEICLLDILDTAGQEEYSAMRDQYMRTGEGFLCVF 82
gi 417589     4 LLKLVIVGDGGVGKSALTIQLTQNQFIAEYDPTIENSYRKQVNIDEEVYMLDILDTAGQEEYSAMRDQYIRSGRGFLIVY 83
gi 4291      10 EYKLVVVGGGGVGKSALTIQLTQSHFVDEYDPTIEDSYRKQVVIDDEVSILDILDTAGQEEYSAMREQYMRNGEGFLLVY 89
gi 62084144   9 EYKLVVVGGGGVGKSALTIQFIQSHFVDEYDPTIEDSYRKQCVIDDEVALLDVLDTAGQEEYGAMREQYMRTGEGFLLVY 88
gi 3074       8 EYKLVVVGGGGVGKSCLTIQLIQGHFLDEYDPTIEDSYRKQCTIDNEVALLDILDTAGQEEYSAMREQYMRTGEGFLLVF 87
gi 7299191    3 EYKLVVVGAGGVGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLDILDTAGQEEYSAMRDQYMRTGEGFLLVF 82
gi 2706488    9 KFKMVVVGAGGVGKSALTIQLIQNHFVEDYDPTIEDSYIKQVVVDGAICILDILDTAGQEEYSAMREHYMRTGEGFLCIF 88
gi 3881788    3 EYKLVVVGDGGVGKSALTIQLIQNHFVEEYDPTIEDSYRKQVVIDGETCLLDILDTAGQEEYSAMRDQYMRTGEGFLLVF 82
gi 50726950   3 EYKLVVVGAGGVGKSALTIQLIQNHFVEEYDPTIEDSYRKQVVIDGETCLLDILDTAGQEEYSAMRDQYMRTGEGFLCVF 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                        ## ##                          ##              
1HE8_B       83 AINNTKSFEDIHQYREQIKRVKDSDDVPMVLVGNKCDLAa--RTVESRQAQDLARSYGIPYIETSAKTRQGVEDAFYTLV 160
gi 1575028   83 AVNNSKSYDDINQYREQIKRVKDADEVPMVLVGNKVDLTn--RSVCTEEAKSLAHSYNIPYVETSAKTRQGVEDAFHKLV 160
gi 417589    84 SIISRASFEAVTTFREQILRVKDLSTYPIVIIGNKADLPdkdRKVPPMEGKELAKSFGAPFLETSAKSRVNVEEAFFTLV 163
gi 4291      90 SITSKSSLDELMTYYQQIPRVKDTDYVPIVVVGNKSDLEn-eKQVSYQDGLNMAKQMNAPFLETSAKQAINVEEAFYTLA 168
gi 62084144  89 SITSRNSFEEISTFHQQILRVKDQDSFPVIVVANKCDLEy-eRQVGMNEGRDLAKHFGCKFIETSAKNRINVDEAFSQLV 167
gi 3074      88 AINSRESFEEIRIYQQQILRVKDRDSFPMIIVGNKYDLRg-eRVVSEQEGQALAAEFGTKYIETSAKTQHNVENAFYDLV 166
gi 7299191   83 AVNSAKSFEDIGTYREQIKRVKDAEEVPMVLVGNKCDLAs--WNVNNEQAREVAKQYGIPYIETSAKTRMGVDDAFYTLV 160
gi 2706488   89 AVTSLKSFQEIDNFRTQALRVKDADKVPMVLVGNKVDLPk--RDVSTKDGNDKALSFGIPYVETSAKTKQGVEEAFFTLV 166
gi 3881788   83 AVNEAKSFENVANYREQIRRVKDSDDVPMVLVGNKCDLSs--RSVDFRTVSETAKGYGIPNVDTSAKTRMGVDEAFYTLV 160
gi 50726950  83 AVNNTKSFEDINQYREQIKRVKDADEVPMVLVGNKVDLPt--RTVGAKQARPVADSYNIPYVETSAKTRQGVDDAFYTLV 160

                ....
Feature 1           
1HE8_B      161 REIR 164
gi 1575028  161 REIR 164
gi 417589   164 REIK 167
gi 4291     169 RLVR 172
gi 62084144 168 REIR 171
gi 3074     167 REIR 170
gi 7299191  161 REIR 164
gi 2706488  167 REIL 170
gi 3881788  161 REIR 164
gi 50726950 161 REIR 164

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