Conserved Protein Domain Family
SH2_nSH2_p85_like

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cd09942: SH2_nSH2_p85_like 
Click on image for an interactive view with Cn3D
N-terminal Src homology 2 (nSH2) domain found in p85
Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. p110, the catalytic subunit, is composed of an adaptor-binding domain, a Ras-binding domain, a C2 domain, a helical domain, and a kinase domain. The regulatory unit is called p85 and is composed of an SH3 domain, a RhoGap domain, a N-terminal SH2 (nSH2) domain, an internal SH2 (iSH2) domain, and C-terminal (cSH2) domain. There are 2 inhibitory interactions between p110alpha and p85 of P13K: (1) p85 nSH2 domain with the C2, helical, and kinase domains of p110alpha and (2) p85 iSH2 domain with C2 domain of p110alpha. There are 3 inhibitory interactions between p110beta and p85 of P13K: (1) p85 nSH2 domain with the C2, helical, and kinase domains of p110beta, (2) p85 iSH2 domain with C2 domain of p110alpha, and (3) p85 cSH2 domain with the kinase domain of p110alpha. It is interesting to note that p110beta is oncogenic as a wild type protein while p110alpha lacks this ability. One explanation is the idea that the regulation of p110beta by p85 is unique because of the addition of inhibitory contacts from the cSH2 domain and the loss of contacts in the iSH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.
Statistics
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PSSM-Id: 198195
View PSSM: cd09942
Aligned: 15 rows
Threshold Bit Score: 183.294
Threshold Setting Gi: 17510927
Created: 8-Mar-2011
Updated: 17-Jan-2013
Structure
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Program:
Drawing:
Aligned Rows:
 
phosphotyrosinehydrophobic
Conserved site includes 4 residues -Click on image for an interactive view with Cn3D
Feature 1:phosphotyrosine binding pocket [polypeptide binding site]
Evidence:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                        #                 #                     # #                      
2IUG_A          5 NMSLQNAEWYWGDISREEVNEKLRDTADGTFLVRDAStkmHGDYTLTLRKggNNKLIKIFHRDGKYGFS--DPLTFSSVV 82
gi 17137398    24 EDELRMAPWYWGRISREEAKSILHGKPDGSFLVRDALs-mKGEYTLTLMKdgCEKLIKICHMDRKYGFI--ETDLFNSVV 100
gi 17510927    12 THSLMEQGWYWADADRSAVSKALSDQPDGSFIVRNASt--PGDYTLSVKFaaQVKLLRIVVKDGKCGFNt-DSLTHDSVV 88
gi 32483418   322 DSLLSEAEWYWGDISREEVNEKMRDTPDGTFLVRDASskvHGEYTLTLRKggNNKLIKIFHRGGKYGFS--EPLTFLSVV 399
gi 158593164    9 THGLQQQEWYWANASKEEIASAICDCPNGTFCVRDASt--KGNYTLTLRYgeRNRLIRIIVAGEHCGFTe-DMLKFESVV 85
gi 316972870  198 KQQSAHPAWYWGDASRDEVNVQMRDQPDGTFCVRNSSt--VGDYTLTVRTggCNKMIRIYQRDGKFGFSpeTSMQFTSLE 275
gi 322795970  389 PRTLQEAEWYWGDITREEVNEMMIDSPDGTFLVRNASs-kGGEYTLTLRKggTNKLIKISHRNGKYGFS--DPYNFHSVI 465
gi 312377934  727 PQELRDAEWYWGKISRDVAKEKMMDAPDGSFLVRDAI---SDAGEYTLDG--TDRTIKIFHKGGRCGFT--HECTYDSLV 799
gi 324514803   33 SRGLANQTWYWGDSSKDLIASAMSGCENGTFCVRDASt--KGDYTLTLRFgeSNKLIKIIVSKGRCGFAp-EELKFDSVV 109
gi 189181684  191 EHSLEAAEWYWGDITRDEANEKLRDTRDGTFLVRNASn-kDSGYTLTVRKggANKLIKIYHHEGRYGFR--EPFEFKSVV 267
                          90       100       110
                  ....*....|....*....|....*....|...
Feature 1                                          
2IUG_A         83 ELINHYRNESLAQYNPKLDVKLLYPVSKYQQDQ 115
gi 17137398   101 EMINYYKENSLSMYNKTLDITLSNPIVRAREDE 133
gi 17510927    89 RLIEFHRNISLNIFNDALDVRLLYPVSVRRNSQ 121
gi 32483418   400 ELINHYRHESLAQYNAKLDSHLLFPVSKYQQDQ 432
gi 158593164   86 SLIDYYRRNSLLEYNRQLSTELLYPLRKPNFQQ 118
gi 316972870  276 DFVKHYSSNSLSAYNRNLNLVLQKPLSRRMRFT 308
gi 322795970  466 ELVDYYRNCSLAQYNSVLDIKLLYPVSRFQQED 498
gi 312377934  800 ALINEFRTTTLKEYNTILDTCLLHPISRFEDDL 832
gi 324514803  110 QLIDYYKRNSLKEYNRQLEVGLIYPLRRPNIDK 142
gi 189181684  268 DLVCYYSEYSLATCNSSLDIKLLYPLSRHQENE 300

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