Helically-extended SH3 domain; This domain is the 70 C-terminal residues of ADAP - Adhesion and de-granulation promoting adapter protein. It shows homology to SH3 domains; however, conserved residues of the fold are absent. It thus represents an altered SH3 domain fold. An N-terminal, amphipathic, helix makes extensive contacts to residues of the regular SH3 domain fold thereby creating a composite surface with unusual surface properties. The domain can no longer bind conventional proline-rich peptides. There are key phosphorylation sites within the two hSH3 domains and it would appear that binding at these sites does not materially affect the folding of these regions although the equilibrium towards the unfolded state may be slightly altered. The binding partners of the hSH3 domains are still unknown.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755550199  749 LRKKFKYDGEIRVLYSTKVASSLTSKKWGARDLQIKPGESLEVIQSTDDTKVLCRNEEGKYGYVLRSYLVDNDGEIYDDI 828
Cdd:pfam14603   1 FRKKFKYDGEIKVLYSMTVDPNLTIKKWGGKDLPVKPGEVLDVIQKTDDTKVLCRNEEGKYGYVLRSNLLQNDGEIYDDI 80

                  ....*....
gi 755550199  829 ADGCIYDND 837
Cdd:pfam14603  81 GDDCIYDND 89

Helically-extended SH3 domain; This domain is the 70 C-terminal residues of ADAP - Adhesion and de-granulation promoting adapter protein. It shows homology to SH3 domains; however, conserved residues of the fold are absent. It thus represents an altered SH3 domain fold. An N-terminal, amphipathic, helix makes extensive contacts to residues of the regular SH3 domain fold thereby creating a composite surface with unusual surface properties. The domain can no longer bind conventional proline-rich peptides. There are key phosphorylation sites within the two hSH3 domains and it would appear that binding at these sites does not materially affect the folding of these regions although the equilibrium towards the unfolded state may be slightly altered. The binding partners of the hSH3 domains are still unknown.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755550199  749 LRKKFKYDGEIRVLYSTKVASSLTSKKWGARDLQIKPGESLEVIQSTDDTKVLCRNEEGKYGYVLRSYLVDNDGEIYDDI 828
Cdd:pfam14603   1 FRKKFKYDGEIKVLYSMTVDPNLTIKKWGGKDLPVKPGEVLDVIQKTDDTKVLCRNEEGKYGYVLRSNLLQNDGEIYDDI 80

                  ....*....
gi 755550199  829 ADGCIYDND 837
Cdd:pfam14603  81 GDDCIYDND 89

Helically-extended SH3 domain; This domain is the 70 C-terminal residues of ADAP - Adhesion and de-granulation promoting adapter protein. It shows homology to SH3 domains; however, conserved residues of the fold are absent. It thus represents an altered SH3 domain fold. An N-terminal, amphipathic, helix makes extensive contacts to residues of the regular SH3 domain fold thereby creating a composite surface with unusual surface properties. The domain can no longer bind conventional proline-rich peptides. There are key phosphorylation sites within the two hSH3 domains and it would appear that binding at these sites does not materially affect the folding of these regions although the equilibrium towards the unfolded state may be slightly altered. The binding partners of the hSH3 domains are still unknown.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755550199  506 GPIQVIHHAK---ACCDVKGGKNELSFKQGEDIEIIRITDnpEGKWLGRTARGSYGYIKTTAveidydslkrkknslnav 582
Cdd:pfam14603   9 GEIKVLYSMTvdpNLTIKKWGGKDLPVKPGEVLDVIQKTD--DTKVLCRNEEGKYGYVLRSN------------------ 68

                          90
                  ....*....|....*....
gi 755550199  583 pprLVEDDQDVYDDVAEQD 601
Cdd:pfam14603  69 ---LLQNDGEIYDDIGDDC 84

Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, Abp1 (actin-binding protein 1), hematopoietic lineage cell-specific protein 1 (HS1), and similar proteins. These proteins are involved in regulating actin dynamics through direct or indirect interaction with the Arp2/3 complex, which is required to initiate actin polymerization. They all contain at least one C-terminal SH3 domain. Cortactin and HS1 bind Arp2/3 and actin through an N-terminal region that contains an acidic domain and several copies of a repeat domain found in cortactin and HS1. Abp1 binds actin via an N-terminal actin-depolymerizing factor (ADF) homology domain. Yeast Abp1 binds Arp2/3 directly through two acidic domains. Mammalian Abp1 does not directly interact with Arp2/3; instead, it regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. The C-terminal region of these proteins acts as an adaptor or scaffold that can connect membrane trafficking and signaling proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 755550199 513 HAKACCD-VKGGKNELSFKQGEDIEIIRITDnpEGKWLGRTARGSYGYIKTTAVEI 567
Cdd:cd11819    1 RAKALYDyQAAEDNEISFVEGDIITQIEQID--EGWWLGVNAKGQKGLFPANYVEL 54

Helically-extended SH3 domain; This domain is the 70 C-terminal residues of ADAP - Adhesion and de-granulation promoting adapter protein. It shows homology to SH3 domains; however, conserved residues of the fold are absent. It thus represents an altered SH3 domain fold. An N-terminal, amphipathic, helix makes extensive contacts to residues of the regular SH3 domain fold thereby creating a composite surface with unusual surface properties. The domain can no longer bind conventional proline-rich peptides. There are key phosphorylation sites within the two hSH3 domains and it would appear that binding at these sites does not materially affect the folding of these regions although the equilibrium towards the unfolded state may be slightly altered. The binding partners of the hSH3 domains are still unknown.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755550199  749 LRKKFKYDGEIRVLYSTKVASSLTSKKWGARDLQIKPGESLEVIQSTDDTKVLCRNEEGKYGYVLRSYLVDNDGEIYDDI 828
Cdd:pfam14603   1 FRKKFKYDGEIKVLYSMTVDPNLTIKKWGGKDLPVKPGEVLDVIQKTDDTKVLCRNEEGKYGYVLRSNLLQNDGEIYDDI 80

                  ....*....
gi 755550199  829 ADGCIYDND 837
Cdd:pfam14603  81 GDDCIYDND 89

Helically-extended SH3 domain; This domain is the 70 C-terminal residues of ADAP - Adhesion and de-granulation promoting adapter protein. It shows homology to SH3 domains; however, conserved residues of the fold are absent. It thus represents an altered SH3 domain fold. An N-terminal, amphipathic, helix makes extensive contacts to residues of the regular SH3 domain fold thereby creating a composite surface with unusual surface properties. The domain can no longer bind conventional proline-rich peptides. There are key phosphorylation sites within the two hSH3 domains and it would appear that binding at these sites does not materially affect the folding of these regions although the equilibrium towards the unfolded state may be slightly altered. The binding partners of the hSH3 domains are still unknown.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755550199  506 GPIQVIHHAK---ACCDVKGGKNELSFKQGEDIEIIRITDnpEGKWLGRTARGSYGYIKTTAveidydslkrkknslnav 582
Cdd:pfam14603   9 GEIKVLYSMTvdpNLTIKKWGGKDLPVKPGEVLDVIQKTD--DTKVLCRNEEGKYGYVLRSN------------------ 68

                          90
                  ....*....|....*....
gi 755550199  583 pprLVEDDQDVYDDVAEQD 601
Cdd:pfam14603  69 ---LLQNDGEIYDDIGDDC 84

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 755550199  513 HAKACCDVKG-GKNELSFKQGEdieIIRITD-NPEGKWLGRTaRGSYGYIKTTAVEID 568
Cdd:pfam07653   1 YGRVIFDYVGtDKNGLTLKKGD---VVKVLGkDNDGWWEGET-GGRVGLVPSTAVEEI 54

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 755550199 513 HAKACCDVKGGK-NELSFKQGEDIEIIRITDnpEGKWLGRTARGSYGYI 560
Cdd:cd00174    1 YARALYDYEAQDdDELSFKKGDIITVLEKDD--DGWWEGELNGGREGLF 47

Third Src Homology 3 domain of Nck adaptor proteins; This group contains the third SH3 domain of Nck, the first SH3 domain of Caenorhabditis elegans Ced-2 (Cell death abnormality protein 2), and similar domains. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. Ced-2 is a cell corpse engulfment protein that interacts with Ced-5 in a pathway that regulates the activation of Ced-10, a Rac small GTPase.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 755550199 526 ELSFKQGEDIEIIRITDNPEGKWLGRTARGSYGYIKTTAVEI 567
Cdd:cd11767   15 ELSFEKGERLEIIEKPEDDPDWWKARNALGTTGLVPRNYVEV 56

Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the peroxisomal membrane, contains two transmembrane regions and a C-terminal SH3 domain. It binds to the peroxisomal targeting type I (PTS1) receptor Pex5p and the docking factor Pex14p through its SH3 domain. It is essential for both PTS1 and PTS2 protein import pathways into the peroxisomal matrix. Pex13p binds Pex14p, which contains a PxxP motif, in a classical fashion to the proline-rich ligand binding site of its SH3 domain. It binds the WxxxF/Y motif of Pex5p in a novel site that does not compete with Pex14p binding. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 755550199 524 KNELSFKQGEDIEIIRITD---NPEGKWLGRTARGSYGYIKTTAVEI 567
Cdd:cd11771   14 EMELSLKKGDIVAVLSKTDplgRDSEWWKGRTRDGRIGWFPSNYVEV 60