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 530537263   5 VICSSRATVMLYDDSNKRWLPAGtGPQAFSRVQIYHNPTANSFRVVGRKMQpDQQVVINCAIIRGVKYNQATPIFHQWRD 84
Cdd:cd01207    1 SVASARASVMVYDDENKRWVPSG-GSQGLSRVQIYHNTRNNTFRVVGRKLQ-DHEVVINCAILKGLKYNQATPTFHQWRD 78

                         90       100
                 ....*....|....*....|
gi 530537263  85 ARQVWGLNFGSKEDAIQFAT 104
Cdd:cd01207   79 ARQVYGLNFASKEEATEFAQ 98

Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) of human Vasodilator-stimulated phosphoprotein and related proteins; This family contains the Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) of Ena/VASP family members including Protein enabled homolog (also known as Mena, mammalian enabled), VASP (vasodilator-stimulated phosphoprotein) and EVL (Ena-VASP-like or Enabled VASP or Ena/VASP). These are actin-associated proteins involved in a range of processes dependent on cytoskeleton remodeling and cell polarity such as axon guidance and lamellipodial and filopodial dynamics in migrating cells, platelet activation and cell migration. Ena/VASP proteins processively elongate F-actin barbed ends, promoting dissociation of barbed end assembly antagonists (uncapping). WH2 domains are small, widespread intrinsically disordered actin-binding peptides displaying significant sequence variability and different regulations of actin self-assembly in motile and morphogenetic processes. WH2 domains are identified by a central consensus actin-binding motif LKKT/V flanked by variable N-terminal and C-terminal extensions.

                         10        20
                 ....*....|....*....|....*..
gi 530537263 205 GGSGAPGLAAAIAGAKLRKVSKQEEAS 231
Cdd:cd22185    1 GGSGAPGLAAAIAGAKLRKVSKQEEAS 27

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 530537263   5 VICSSRATVMLYDDSNKRWLPAGtGPQAFSRVQIYHNPTANSFRVVGRKMQpDQQVVINCAIIRGVKYNQATPIFHQWRD 84
Cdd:cd01207    1 SVASARASVMVYDDENKRWVPSG-GSQGLSRVQIYHNTRNNTFRVVGRKLQ-DHEVVINCAILKGLKYNQATPTFHQWRD 78

                         90       100
                 ....*....|....*....|
gi 530537263  85 ARQVWGLNFGSKEDAIQFAT 104
Cdd:cd01207   79 ARQVYGLNFASKEEATEFAQ 98

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530537263    4 TVICSSRATVMLYDDSNKR-WLPAgtgpQAFSRVQIYHNPTANSFRVVGRKMQpDQQVVINCAIIRGVKYNQATPIFHQW 82
Cdd:pfam00568   9 QTICTAVAQVYLADPDNKRhWIKA----KHSGVVCFVKDSPQNSYFIRLVDIQ-DGKVIWNQEIYPNMEYNQARPFFHTF 83

                          90       100
                  ....*....|....*....|.
gi 530537263   83 RDARQVWGLNFGSKEDAIQFA 103
Cdd:pfam00568  84 ADSRCVYGLNFASEEEATKFA 104

Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) of human Vasodilator-stimulated phosphoprotein and related proteins; This family contains the Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) of Ena/VASP family members including Protein enabled homolog (also known as Mena, mammalian enabled), VASP (vasodilator-stimulated phosphoprotein) and EVL (Ena-VASP-like or Enabled VASP or Ena/VASP). These are actin-associated proteins involved in a range of processes dependent on cytoskeleton remodeling and cell polarity such as axon guidance and lamellipodial and filopodial dynamics in migrating cells, platelet activation and cell migration. Ena/VASP proteins processively elongate F-actin barbed ends, promoting dissociation of barbed end assembly antagonists (uncapping). WH2 domains are small, widespread intrinsically disordered actin-binding peptides displaying significant sequence variability and different regulations of actin self-assembly in motile and morphogenetic processes. WH2 domains are identified by a central consensus actin-binding motif LKKT/V flanked by variable N-terminal and C-terminal extensions.

                         10        20
                 ....*....|....*....|....*..
gi 530537263 205 GGSGAPGLAAAIAGAKLRKVSKQEEAS 231
Cdd:cd22185    1 GGSGAPGLAAAIAGAKLRKVSKQEEAS 27

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 530537263   5 VICSSRATVMLYDDSNKRWLPAGtGPQAFSRVQIYHNPTANSFRVVGRKMQpDQQVVINCAIIRGVKYNQATPIFHQWRD 84
Cdd:cd01207    1 SVASARASVMVYDDENKRWVPSG-GSQGLSRVQIYHNTRNNTFRVVGRKLQ-DHEVVINCAILKGLKYNQATPTFHQWRD 78

                         90       100
                 ....*....|....*....|
gi 530537263  85 ARQVWGLNFGSKEDAIQFAT 104
Cdd:cd01207   79 ARQVYGLNFASKEEATEFAQ 98

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530537263    4 TVICSSRATVMLYDDSNKR-WLPAgtgpQAFSRVQIYHNPTANSFRVVGRKMQpDQQVVINCAIIRGVKYNQATPIFHQW 82
Cdd:pfam00568   9 QTICTAVAQVYLADPDNKRhWIKA----KHSGVVCFVKDSPQNSYFIRLVDIQ-DGKVIWNQEIYPNMEYNQARPFFHTF 83

                          90       100
                  ....*....|....*....|.
gi 530537263   83 RDARQVWGLNFGSKEDAIQFA 103
Cdd:pfam00568  84 ADSRCVYGLNFASEEEATKFA 104

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 530537263   6 ICSSRATVMLYDDSNKRWLPAGTGpqAFSRVQIYHNPTANS-----FRVVGRKMQpDQQVVINCAIIRGVKYNQATPIFH 80
Cdd:cd10574    2 LVRVRAVVMTRDDSSGGWLPLGGG--GLSIVSVCKVMPEEGaprteYVIHGERIR-DKTVVLECTLRKDLVYNKVMPTFH 78

                         90       100
                 ....*....|....*....|..
gi 530537263  81 QWRDARQVWGLNFGSKEDAIQF 102
Cdd:cd10574   79 HWRIGEKKFGLTFQSPADARAF 100

Homer/Vesl family proteins EVH1 domain; Homer/Vesl proteins are synaptic scaffolding proteins, required for long-term potentiation, a form of synaptic plasticity thought to underlie memory formation. They contains an N-terminal EVH1 domain and bind to both neurotransmitter receptors, such as the metabotropic group 1 glutamate receptor (mGluR) and to other scaffolding proteins via PPXXF motifs, in order to target them to the synaptic junction. These mGluRs possess a long C-terminal intracellular tail that may be important for subcellular localization of the receptor. The C-terminus is also the site of binding by the immediate early gene (IEG), Homer 1a. In contrast to Homer 1a, other Homer members additionally encode a C-terminal coiled-coil (CC) domain and form multivalent complexes that bind group 1 mGluRs. Homer 1a competes with constitutively expressed CC-Homers to modify the association of group 1 mGluRs with CC-Homer complexes. Since Homer proteins are strikingly enriched at the postsynaptic density (PSD), these observations suggest a role for the Homer family in regulating synaptic metabotropic receptor function. PSD-Zip45 (also named Homer 1c/Vesl-1L) has an EVH1 domain with a longer alpha-helix and its linking part included in the conserved region of Homer 1 (CRH1) interacts with the EVH1 domain of the neighbour CRH1 molecule in the crystal, suggesting that the EVH1 domain recognizes the PPXXF motif found in the binding partners, and the SPLTP sequence (P-motif) in the linking region of the CRH1. The two types of binding are partly overlapped in the EVH1 domain, implying a mechanism to regulate multimerization of Homer 1 family proteins. Homer 2 and Homer 3 are negative regulators of T cell activation. They bind the nuclear factor of activated T cells (NFAT) and compete with calcineurin binding. NFAT plays a critical role in calcium-dependent signaling in other cell types, including muscle and neurons. Homer-NFAT binding is also antagonized by active serine-threonine kinase AKT, enhancing TCR signaling via calcineurin-dependent dephosphorylation of NFAT resulting in changes in cytokine expression and an increase in effector-memory T cell populations in Homer-deficient mice. 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 530537263   3 ETVICSSRATVMLYDDSNKR-WLPAGTgpQAFsRVQIYHNPTANSFRVVGRKmqpDQQVVINCAIIRGVKYNQATPIFHQ 81
Cdd:cd01206    1 EQPIFTTQAHVFQIDPQTKKsWIPASK--QAV-TVSFFYDSTRNTYRIISVE---GSKAIINSTITPNMTFTKTSQKFGQ 74

                         90       100
                 ....*....|....*....|....
gi 530537263  82 WRDAR--QVWGLNFGSKEDAIQFA 103
Cdd:cd01206   75 WADSRanTVYGLGFASEAELTKFA 98

Ran-binding domain; The RanBD is present in RanBP1, RanBP2, RanBP3, Nuc2, and Nuc50. Most of these proteins have a single RanBD, with the exception of RanBP2 which has 4 RanBDs. Ran is a Ras-like nuclear small GTPase, which regulates receptor-mediated transport between the nucleus and the cytoplasm. RanGTP hydrolysis is stimulated by RanGAP together with the Ran-binding domain containing acessory proteins RanBP1 and RanBP2. These accessory proteins stabilize the active GTP-bound form of Ran. The Ran-binding domain is found in multiple copies in Nuclear pore complex proteins. RabBD shares structural similarity to the PH domain, but lacks detectable sequence similarity. The RanBD proteins of the nuclear pore complex (NPC): nucleoporin 1 (NUP1), NUP2, NUP61, and Nuclear Pore complex Protein 9 (npp-9) are present in the parent, but specific models were not made due to lineage. To date there been no reports of inositol phosphate or phosphoinositide binding by Ran-binding proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530537263   3 ETVICSSRATVMLYDDSNKRWLPAGTGPqafsrVQIYHNPTANSFRVVgrkMQPDQ--QVVINCAIIRGVKYNQATPIFH 80
Cdd:cd00835    6 EEVLFEKRAKLFRFDKETKEWKERGVGD-----LKILKNKDTGKYRIV---MRRDQvlKLCCNHYILPDMKLTKMGNNDR 77

                         90       100       110
                 ....*....|....*....|....*....|...
gi 530537263  81 QWR-----------DARQVWGLNFGSKEDAIQF 102
Cdd:cd00835   78 AWVwtamddsedgeGKPETFAVRFKTAEDAEEF 110