Sprouty-related EVH1 domain-containing-like proteins EVH1 domain; The Spred family has the following domains: an N-terminal EVH1 domain, a unique KBD (c-Kit kinase binding) domain which that is phosphorylated by the stem cell factor receptor c-Kit, and a C-terminal cysteine-rich SPR (Sprouty-related) domain which is involved in membrane localization. There are 3 Spred proteins: Spred1 which interacts with both Ras and Raf through its SPR domain; Spred2 which is the most abundant isoform; and Spred3 which has a non-functional KBD and maintains the inhibitory action on Raf. Legius syndrome is caused by heterozygous mutations in Spred1. Both EVH1 and SPR domains are involved in the inhibition of the MAP kinase pathway by Spred proteins. The specific function of the Spred2 EVH1 domain is unknown and there are no known interacting proteins to date. It is thought that its EVH1 domain will have a fourth distinct peptide binding mechanism within the EVH1 family. The EVH1 domains are part of the PH domain superamily. There are 5 EVH1 subfamilies: Enables/VASP, Homer/Vesl, WASP, Dcp1, and Spred. Ligands are known for three of the EVH1 subfamilies, all of which bind proline-rich sequences: the Enabled/VASP family binds to FPPPP peptides, the Homer/Vesl family binds PPxxF peptides, and the WASP family binds LPPPEP peptides. EVH1 has a PH-like fold, despite having minimal sequence similarity to PH or PTB domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039776880  93 YMVRVRAVVMARDDSSGGWLPVGGGGLSQVSVCRVRgarPEGGARQGHYVIHGERLRDQKTTLECTLRPGLVYNKVNPIF 172
Cdd:cd10574     1 CLVRVRAVVMTRDDSSGGWLPLGGGGLSIVSVCKVM---PEEGAPRTEYVIHGERIRDKTVVLECTLRKDLVYNKVMPTF 77

                          90       100
                  ....*....|....*....|....*.
gi 1039776880 173 HHWSLGDCKFGLTFQSPAEADEFQKS 198
Cdd:cd10574    78 HHWRIGEKKFGLTFQSPADARAFDRG 103

Sprouty-related EVH1 domain-containing-like proteins EVH1 domain; The Spred family has the following domains: an N-terminal EVH1 domain, a unique KBD (c-Kit kinase binding) domain which that is phosphorylated by the stem cell factor receptor c-Kit, and a C-terminal cysteine-rich SPR (Sprouty-related) domain which is involved in membrane localization. There are 3 Spred proteins: Spred1 which interacts with both Ras and Raf through its SPR domain; Spred2 which is the most abundant isoform; and Spred3 which has a non-functional KBD and maintains the inhibitory action on Raf. Legius syndrome is caused by heterozygous mutations in Spred1. Both EVH1 and SPR domains are involved in the inhibition of the MAP kinase pathway by Spred proteins. The specific function of the Spred2 EVH1 domain is unknown and there are no known interacting proteins to date. It is thought that its EVH1 domain will have a fourth distinct peptide binding mechanism within the EVH1 family. The EVH1 domains are part of the PH domain superamily. There are 5 EVH1 subfamilies: Enables/VASP, Homer/Vesl, WASP, Dcp1, and Spred. Ligands are known for three of the EVH1 subfamilies, all of which bind proline-rich sequences: the Enabled/VASP family binds to FPPPP peptides, the Homer/Vesl family binds PPxxF peptides, and the WASP family binds LPPPEP peptides. EVH1 has a PH-like fold, despite having minimal sequence similarity to PH or PTB domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039776880  93 YMVRVRAVVMARDDSSGGWLPVGGGGLSQVSVCRVRgarPEGGARQGHYVIHGERLRDQKTTLECTLRPGLVYNKVNPIF 172
Cdd:cd10574     1 CLVRVRAVVMTRDDSSGGWLPLGGGGLSIVSVCKVM---PEEGAPRTEYVIHGERIRDKTVVLECTLRKDLVYNKVMPTF 77

                          90       100
                  ....*....|....*....|....*.
gi 1039776880 173 HHWSLGDCKFGLTFQSPAEADEFQKS 198
Cdd:cd10574    78 HHWRIGEKKFGLTFQSPADARAFDRG 103

WH1 domain; WASp Homology domain 1 (WH1) domain. WASP is the protein that is defective in Wiskott-Aldrich syndrome (WAS). The majority of point mutations occur within the amino- terminal WH1 domain. The metabotropic glutamate receptors mGluR1alpha and mGluR5 bind a protein called homer, which is a WH1 domain homolog. A subset of WH1 domains has been termed a "EVH1" domain and appear to bind a polyproline motif.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1039776880 141 YVIHGERLRDQKTTLECTLRPGLVYNKVNPIFHHWSLGDCKFGLTFQSPAEADEFQK 197
Cdd:pfam00568  49 YFIRLVDIQDGKVIWNQEIYPNMEYNQARPFFHTFADSRCVYGLNFASEEEATKFAK 105

Sprouty-related EVH1 domain-containing-like proteins EVH1 domain; The Spred family has the following domains: an N-terminal EVH1 domain, a unique KBD (c-Kit kinase binding) domain which that is phosphorylated by the stem cell factor receptor c-Kit, and a C-terminal cysteine-rich SPR (Sprouty-related) domain which is involved in membrane localization. There are 3 Spred proteins: Spred1 which interacts with both Ras and Raf through its SPR domain; Spred2 which is the most abundant isoform; and Spred3 which has a non-functional KBD and maintains the inhibitory action on Raf. Legius syndrome is caused by heterozygous mutations in Spred1. Both EVH1 and SPR domains are involved in the inhibition of the MAP kinase pathway by Spred proteins. The specific function of the Spred2 EVH1 domain is unknown and there are no known interacting proteins to date. It is thought that its EVH1 domain will have a fourth distinct peptide binding mechanism within the EVH1 family. The EVH1 domains are part of the PH domain superamily. There are 5 EVH1 subfamilies: Enables/VASP, Homer/Vesl, WASP, Dcp1, and Spred. Ligands are known for three of the EVH1 subfamilies, all of which bind proline-rich sequences: the Enabled/VASP family binds to FPPPP peptides, the Homer/Vesl family binds PPxxF peptides, and the WASP family binds LPPPEP peptides. EVH1 has a PH-like fold, despite having minimal sequence similarity to PH or PTB domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039776880  93 YMVRVRAVVMARDDSSGGWLPVGGGGLSQVSVCRVRgarPEGGARQGHYVIHGERLRDQKTTLECTLRPGLVYNKVNPIF 172
Cdd:cd10574     1 CLVRVRAVVMTRDDSSGGWLPLGGGGLSIVSVCKVM---PEEGAPRTEYVIHGERIRDKTVVLECTLRKDLVYNKVMPTF 77

                          90       100
                  ....*....|....*....|....*.
gi 1039776880 173 HHWSLGDCKFGLTFQSPAEADEFQKS 198
Cdd:cd10574    78 HHWRIGEKKFGLTFQSPADARAFDRG 103

WASP homology region 1; Region of the Wiskott-Aldrich syndrome protein (WASp) that contains point mutations in the majority of patients with WAS. Unknown function. Ena-like WH1 domains bind polyproline-containing peptides, and that Homer contains a WH1 domain.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039776880   97 VRAVVMARDDSSGGWLPVGGGGLSQVsVCRVRgarpeggARQGHYVIHGERLRDQkTTLECTLRPGLVYNKVNPIFHHWS 176
Cdd:smart00461   9 ARAVVQLYDADTKKWVPTGEGGAANL-VIDKN-------QRSYFFRIVGIKGQDK-VIWNQELYKNFKYNQATPTFHQWA 79

                           90       100
                   ....*....|....*....|..
gi 1039776880  177 LGDCKFGLTFQSPAEADEFQKS 198
Cdd:smart00461  80 DDKCVYGLNFASEEEAKKFRKK 101

Enabled/VASP family EVH1 domain; Ena/VASP family includes proteins such as: Vasodilator-stimulated phosphoprotein (VASP), enabled gene product from Drosophila (Ena), mammalian enabled (Mena) and Ena/VASP-Like protein (EVL) localize to focal adhesions and to sites of actin filament dynamics. These proteins share a common modular organization with a highly conserved N- and C-terminal domains, termed Ena/VASP homology domains 1 and 2 (EVH1 and EVH2), that are separated by a central proline-rich domain. The EVH1 domain binds to other proteins at proline rich sequences. The majority of Ena-VASP type EVH1 domains recognize FPPPP motifs such as in the focal adhesion proteins zyxin and vinculin, and the ActA surface protein of Listeria monocytogenes, however the LIM3 domain of Tes lacks the FPPPP motif but still binds the EVH1 domain of Mena. It has a PH-like fold, despite having minimal sequence similarity to PH or PTB domains. EVH2 mediates oligomerization within the family. The proline-rich region binds SH3 and WW domains as well as profilin, a protein that regulates actin filament dynamics. The EVH1 domains are part of the PH domain superamily. There are 5 EVH1 subfamilies: Enables/VASP, Homer/Vesl, WASP, Dcp1, and Spred. Ligands are known for three of the EVH1 subfamilies, all of which bind proline-rich sequences: the Enabled/VASP family binds to FPPPP peptides, the Homer/Vesl family binds PPxxF peptides, and the WASP family binds LPPPEP peptides. EVH1 has a PH-like fold, despite having minimal sequence similarity to PH or PTB domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039776880  97 VRAVVMARDDSSGG-WLPVGGGGLSQVSV--CRVRGArpeggarqghYVIHGERLRDQKTTLECTLRPGLVYNKVNPIFH 173
Cdd:cd01207     5 ARASVMVYDDENKRwVPSGGSQGLSRVQIyhNTRNNT----------FRVVGRKLQDHEVVINCAILKGLKYNQATPTFH 74

                          90       100
                  ....*....|....*....|....
gi 1039776880 174 HWSlgDCK--FGLTFQSPAEADEF 195
Cdd:cd01207    75 QWR--DARqvYGLNFASKEEATEF 96