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Conserved domains on  [gi|47086045|ref|NP_998397|]
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sprouty-related, EVH1 domain-containing protein 1 [Danio rerio]

Protein Classification

sprouty-related, EVH1 domain-containing protein( domain architecture ID 10180423)

sprouty-related, EVH1 domain-containing protein is a tyrosine kinase substrate that inhibits growth-factor-mediated activation of MAP kinase, and may negatively regulate Ras signaling pathways

Gene Ontology:  GO:0043409|GO:0019901
PubMed:  11911879

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
EVH1_SPRED-like cd10574
Sprouty-related EVH1 domain-containing-like proteins EVH1 domain; The Spred family has the ...
 12-123 3.00e-64

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.


:

Pssm-ID: 269978  Cd Length: 113  Bit Score: 200.62  E-value: 3.00e-64
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47086045  12 TYARVRAVVMTRDDSSGGWLPLGAGGLSCVTVHKISHTEPDAD-EFLIHGERLKDKTVLLDCSIRRDLVYNKVNPIFHHW 90
Cdd:cd10574   1 CLVRVRAVVMTRDDSSGGWLPLGGGGLSIVSVCKVMPEEGAPRtEYVIHGERIRDKTVVLECTLRKDLVYNKVMPTFHHW 80

                        90       100       110
                ....*....|....*....|....*....|...
gi 47086045  91 RIGSMKFGLTFQSPADARAFDRGIRRAMEDVTQ 123
Cdd:cd10574  81 RIGEKKFGLTFQSPADARAFDRGVRRALEDLSR 113
Sprouty pfam05210
Sprouty protein (Spry); This family consists of eukaryotic Sprouty protein homologs. Sprouty ...
 279-384 4.48e-36

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.


:

Pssm-ID: 461589  Cd Length: 101  Bit Score: 127.06  E-value: 4.48e-36
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47086045   279 RSRCIYCREMFNHEDNRRGQCQdapdpIKQCIYKVSCMLCAESMLYHCMSDSEGDFS-DPCSCdASEEQFCVRWLALLGL 357
Cdd:pfam05210   1 RCRCVYCQELFTEPRNLPGSCS-----AESCIDYVSCMCCAKGLFYHCMSDAEGDDScDPCSC-CSPHRCCKRWLALALL 74

                          90       100
                  ....*....|....*....|....*..
gi 47086045   358 SLLAPCLCCYPPLRLCHRCGEACRCCG 384
Cdd:pfam05210  75 SLLLPCLCCYPPLRACHKCCVACGCCG 101
 
Name Accession Description Interval E-value
EVH1_SPRED-like cd10574
Sprouty-related EVH1 domain-containing-like proteins EVH1 domain; The Spred family has the ...
 12-123 3.00e-64

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.


Pssm-ID: 269978  Cd Length: 113  Bit Score: 200.62  E-value: 3.00e-64
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47086045  12 TYARVRAVVMTRDDSSGGWLPLGAGGLSCVTVHKISHTEPDAD-EFLIHGERLKDKTVLLDCSIRRDLVYNKVNPIFHHW 90
Cdd:cd10574   1 CLVRVRAVVMTRDDSSGGWLPLGGGGLSIVSVCKVMPEEGAPRtEYVIHGERIRDKTVVLECTLRKDLVYNKVMPTFHHW 80

                        90       100       110
                ....*....|....*....|....*....|...
gi 47086045  91 RIGSMKFGLTFQSPADARAFDRGIRRAMEDVTQ 123
Cdd:cd10574  81 RIGEKKFGLTFQSPADARAFDRGVRRALEDLSR 113
Sprouty pfam05210
Sprouty protein (Spry); This family consists of eukaryotic Sprouty protein homologs. Sprouty ...
 279-384 4.48e-36

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.


Pssm-ID: 461589  Cd Length: 101  Bit Score: 127.06  E-value: 4.48e-36
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47086045   279 RSRCIYCREMFNHEDNRRGQCQdapdpIKQCIYKVSCMLCAESMLYHCMSDSEGDFS-DPCSCdASEEQFCVRWLALLGL 357
Cdd:pfam05210   1 RCRCVYCQELFTEPRNLPGSCS-----AESCIDYVSCMCCAKGLFYHCMSDAEGDDScDPCSC-CSPHRCCKRWLALALL 74

                          90       100
                  ....*....|....*....|....*..
gi 47086045   358 SLLAPCLCCYPPLRLCHRCGEACRCCG 384
Cdd:pfam05210  75 SLLLPCLCCYPPLRACHKCCVACGCCG 101
WH1 smart00461
WASP homology region 1; Region of the Wiskott-Aldrich syndrome protein (WASp) that contains ...
 16-117 1.03e-19

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.


Pssm-ID: 214674  Cd Length: 106  Bit Score: 83.56  E-value: 1.03e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47086045     16 VRAVVMTRDDSSGGWLPLGAGGLSCVTvhkISHTEPDADeFLIHGERLKDKtVLLDCSIRRDLVYNKVNPIFHHWRIGSM 95
Cdd:smart00461   9 ARAVVQLYDADTKKWVPTGEGGAANLV---IDKNQRSYF-FRIVGIKGQDK-VIWNQELYKNFKYNQATPTFHQWADDKC 83

                           90       100
                   ....*....|....*....|..
gi 47086045     96 KFGLTFQSPADARAFDRGIRRA 117
Cdd:smart00461  84 VYGLNFASEEEAKKFRKKVLKA 105
WH1 pfam00568
WH1 domain; WASp Homology domain 1 (WH1) domain. WASP is the protein that is defective in ...
 14-121 1.22e-06

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.


Pssm-ID: 395450  Cd Length: 111  Bit Score: 46.67  E-value: 1.22e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47086045    14 ARVRaVVMTRDDSSGGWLPLGAGGLSCVtVHkishtEPDADEFLIHGERLKDKTVLLDCSIRRDLVYNKVNPIFHHWRIG 93
Cdd:pfam00568  14 AVAQ-VYLADPDNKRHWIKAKHSGVVCF-VK-----DSPQNSYFIRLVDIQDGKVIWNQEIYPNMEYNQARPFFHTFADS 86

                          90       100
                  ....*....|....*....|....*...
gi 47086045    94 SMKFGLTFQSPADARAFdrgiRRAMEDV 121
Cdd:pfam00568  87 RCVYGLNFASEEEATKF----AKAVQEA 110
 
Name Accession Description Interval E-value
EVH1_SPRED-like cd10574
Sprouty-related EVH1 domain-containing-like proteins EVH1 domain; The Spred family has the ...
 12-123 3.00e-64

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.


Pssm-ID: 269978  Cd Length: 113  Bit Score: 200.62  E-value: 3.00e-64
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47086045  12 TYARVRAVVMTRDDSSGGWLPLGAGGLSCVTVHKISHTEPDAD-EFLIHGERLKDKTVLLDCSIRRDLVYNKVNPIFHHW 90
Cdd:cd10574   1 CLVRVRAVVMTRDDSSGGWLPLGGGGLSIVSVCKVMPEEGAPRtEYVIHGERIRDKTVVLECTLRKDLVYNKVMPTFHHW 80

                        90       100       110
                ....*....|....*....|....*....|...
gi 47086045  91 RIGSMKFGLTFQSPADARAFDRGIRRAMEDVTQ 123
Cdd:cd10574  81 RIGEKKFGLTFQSPADARAFDRGVRRALEDLSR 113
EVH1_family cd00837
EVH1 (Drosophila Enabled (Ena)/Vasodilator-stimulated phosphoprotein (VASP) homology 1) domain; ...
 12-118 7.03e-43

EVH1 (Drosophila Enabled (Ena)/Vasodilator-stimulated phosphoprotein (VASP) homology 1) domain; The EVH1 domains are part of the PH domain superfamily. EVH1 subfamilies include Enables/VASP, Homer/Vesl, WASP, 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.


Pssm-ID: 269909  Cd Length: 103  Bit Score: 145.30  E-value: 7.03e-43
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47086045  12 TYARVRAVVMTRDDSSGGWLPLGAGGLSCVTVHKISHTepdaDEFLIHGERLKDKTVLLDCSIRRDLVYNKVNPIFHHWR 91
Cdd:cd00837   1 SIFSARAHVMQIDDSNKNWVPAGGKGASRVSYFKDTTR----NSFRIIGVDIKDKKVVINCTITKNLVYNKATQTFHQWA 76

                        90       100
                ....*....|....*....|....*..
gi 47086045  92 IGSMKFGLTFQSPADARAFDRGIRRAM 118
Cdd:cd00837  77 DDRTVFGLNFASEEDATKFAEAVQEAL 103
Sprouty pfam05210
Sprouty protein (Spry); This family consists of eukaryotic Sprouty protein homologs. Sprouty ...
 279-384 4.48e-36

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.


Pssm-ID: 461589  Cd Length: 101  Bit Score: 127.06  E-value: 4.48e-36
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47086045   279 RSRCIYCREMFNHEDNRRGQCQdapdpIKQCIYKVSCMLCAESMLYHCMSDSEGDFS-DPCSCdASEEQFCVRWLALLGL 357
Cdd:pfam05210   1 RCRCVYCQELFTEPRNLPGSCS-----AESCIDYVSCMCCAKGLFYHCMSDAEGDDScDPCSC-CSPHRCCKRWLALALL 74

                          90       100
                  ....*....|....*....|....*..
gi 47086045   358 SLLAPCLCCYPPLRLCHRCGEACRCCG 384
Cdd:pfam05210  75 SLLLPCLCCYPPLRACHKCCVACGCCG 101
EVH1_Ena_VASP-like cd01207
Enabled/VASP family EVH1 domain; Ena/VASP family includes proteins such as: ...
 14-122 9.28e-22

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.


Pssm-ID: 269918  Cd Length: 108  Bit Score: 89.29  E-value: 9.28e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47086045  14 ARVRAVVMTRDDSSGGWLPLGAG-GLSCVTvhkISHtEPDADEFLIHGERLKDKTVLLDCSIRRDLVYNKVNPIFHHWRI 92
Cdd:cd01207   3 ASARASVMVYDDENKRWVPSGGSqGLSRVQ---IYH-NTRNNTFRVVGRKLQDHEVVINCAILKGLKYNQATPTFHQWRD 78

                        90       100       110
                ....*....|....*....|....*....|
gi 47086045  93 GSMKFGLTFQSPADARAFDRGIRRAMEDVT 122
Cdd:cd01207  79 ARQVYGLNFASKEEATEFAQAMLLALERLN 108
WH1 smart00461
WASP homology region 1; Region of the Wiskott-Aldrich syndrome protein (WASp) that contains ...
 16-117 1.03e-19

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.


Pssm-ID: 214674  Cd Length: 106  Bit Score: 83.56  E-value: 1.03e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47086045     16 VRAVVMTRDDSSGGWLPLGAGGLSCVTvhkISHTEPDADeFLIHGERLKDKtVLLDCSIRRDLVYNKVNPIFHHWRIGSM 95
Cdd:smart00461   9 ARAVVQLYDADTKKWVPTGEGGAANLV---IDKNQRSYF-FRIVGIKGQDK-VIWNQELYKNFKYNQATPTFHQWADDKC 83

                           90       100
                   ....*....|....*....|..
gi 47086045     96 KFGLTFQSPADARAFDRGIRRA 117
Cdd:smart00461  84 VYGLNFASEEEAKKFRKKVLKA 105
WH1 pfam00568
WH1 domain; WASp Homology domain 1 (WH1) domain. WASP is the protein that is defective in ...
 14-121 1.22e-06

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.


Pssm-ID: 395450  Cd Length: 111  Bit Score: 46.67  E-value: 1.22e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47086045    14 ARVRaVVMTRDDSSGGWLPLGAGGLSCVtVHkishtEPDADEFLIHGERLKDKTVLLDCSIRRDLVYNKVNPIFHHWRIG 93
Cdd:pfam00568  14 AVAQ-VYLADPDNKRHWIKAKHSGVVCF-VK-----DSPQNSYFIRLVDIQDGKVIWNQEIYPNMEYNQARPFFHTFADS 86

                          90       100
                  ....*....|....*....|....*...
gi 47086045    94 SMKFGLTFQSPADARAFdrgiRRAMEDV 121
Cdd:pfam00568  87 RCVYGLNFASEEEATKF----AKAVQEA 110
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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