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 110225353   2 VRVRAVVMARDDSSGGWLPVGGGGLSQVSVCRVRgarPEGGARQGHYVIHGERLRDQKTTLECTLKPGLVYNKVNPIFHH 81
Cdd:cd10574    3 VRVRAVVMTRDDSSGGWLPLGGGGLSIVSVCKVM---PEEGAPRTEYVIHGERIRDKTVVLECTLRKDLVYNKVMPTFHH 79

                         90       100
                 ....*....|....*....|....
gi 110225353  82 WSLGDCKFGLTFQSPAEADEFQKS 105
Cdd:cd10574   80 WRIGEKKFGLTFQSPADARAFDRG 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 110225353   2 VRVRAVVMARDDSSGGWLPVGGGGLSQVSVCRVRgarPEGGARQGHYVIHGERLRDQKTTLECTLKPGLVYNKVNPIFHH 81
Cdd:cd10574    3 VRVRAVVMTRDDSSGGWLPLGGGGLSIVSVCKVM---PEEGAPRTEYVIHGERIRDKTVVLECTLRKDLVYNKVMPTFHH 79

                         90       100
                 ....*....|....*....|....
gi 110225353  82 WSLGDCKFGLTFQSPAEADEFQKS 105
Cdd:cd10574   80 WRIGEKKFGLTFQSPADARAFDRG 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 110225353     4 VRAVVMARDDSSGGWLPVGGGGLSQVsVCRVRgarpeggARQGHYVIHGERLRDQkTTLECTLKPGLVYNKVNPIFHHWS 83
Cdd:smart00461   9 ARAVVQLYDADTKKWVPTGEGGAANL-VIDKN-------QRSYFFRIVGIKGQDK-VIWNQELYKNFKYNQATPTFHQWA 79

                           90       100
                   ....*....|....*....|..
gi 110225353    84 LGDCKFGLTFQSPAEADEFQKS 105
Cdd:smart00461  80 DDKCVYGLNFASEEEAKKFRKK 101

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 110225353   2 VRVRAVVMARDDSSGGWLPVGGGGLSQVSVCRVRgarPEGGARQGHYVIHGERLRDQKTTLECTLKPGLVYNKVNPIFHH 81
Cdd:cd10574    3 VRVRAVVMTRDDSSGGWLPLGGGGLSIVSVCKVM---PEEGAPRTEYVIHGERIRDKTVVLECTLRKDLVYNKVMPTFHH 79

                         90       100
                 ....*....|....*....|....
gi 110225353  82 WSLGDCKFGLTFQSPAEADEFQKS 105
Cdd:cd10574   80 WRIGEKKFGLTFQSPADARAFDRG 103

Sprouty protein (Spry); This family consists of eukaryotic Sprouty protein homologs. Sprouty proteins have been revealed as inhibitors of the Ras/mitogen-activated protein kinase (MAPK) cascade, a pathway crucial for developmental processes initiated by activation of various receptor tyrosine kinases. The sprouty gene has found to be expressed in the the brain, cochlea, nasal organs, teeth, salivary gland, lungs, digestive tract, kidneys and limb buds in mice.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110225353  296 RCVHCRALFRRRADGRGGRCAEApdpgrlLVRRLSCLWCAESLLYHCLSDAEGDFS-DPCACePGHPRPAARWAALAALS 374
Cdd:pfam05210   3 RCVYCQELFTEPRNLPGSCSAES------CIDYVSCMCCAKGLFYHCMSDAEGDDScDPCSC-CSPHRCCKRWLALALLS 75

                          90       100
                  ....*....|....*....|....*.
gi 110225353  375 LAVPCLCCYAPLRACHWVAARCGCAG 400
Cdd:pfam05210  76 LLLPCLCCYPPLRACHKCCVACGCCG 101

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 110225353   48 YVIHGERLRDQKTTLECTLKPGLVYNKVNPIFHHWSLGDCKFGLTFQSPAEADEFQK 104
Cdd:pfam00568  49 YFIRLVDIQDGKVIWNQEIYPNMEYNQARPFFHTFADSRCVYGLNFASEEEATKFAK 105

WASP family proteins EVH1 domain; The Wiskott-Aldrich Syndrome Protein (WASP; also called Bee1p) and its homolog N (neuronal)-WASP are signal transduction proteins that promote actin polymerization in response to upstream intracellular signals. WAS is an X-linked recessive disease, characterized by eczema, immunodeficiency, and thrombocytopenia. The majority of patients with WAS, or a milder version of the disorder, X-linked thrombocytopenia (XLT), have point mutations in the EVH1 domain of WASP. WASP is an actin regulatory protein consisting of an N-terminal EVH1 domain called WH1 which binds LPPPEP peptides, a basic region (B), a GTP binding domain (GBP), a proline rich region, a WH2 domain, and a verprolin-cofilin-acidic motif (VCA) which activates the actin-related protein (Arp)2/3 actin nucleating complex. The B, GBD, and the proline-rich region are involved in autoinhibitory interactions that repress or block the activity of the VCA. Yeast members lack the GTP binding domain. 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
                 ....*....|....*....|....*....|....*....|....*....|
gi 110225353  55 LRDQKTTLECTLKPGLVYNKVNPIFHHWSLGDCKFGLTFQSPAEADEFQK 104
Cdd:cd01205   46 LKTRGVVWEQELYEGFEYNQDRPFFHTFEGDECMIGLNFADEDEAAAFYK 95