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 197927358   6 VICSSRATVMLYDDSNKRWLPAGtGPQAFSRVQIYHNPTANSFRVVGRKLQpDQQVVINCAIIRGVKYNQATPIFHQWRD 85
Cdd:cd01207    1 SVASARASVMVYDDENKRWVPSG-GSQGLSRVQIYHNTRNNTFRVVGRKLQ-DHEVVINCAILKGLKYNQATPTFHQWRD 78

                         90       100
                 ....*....|....*....|....*....
gi 197927358  86 ARQVWGLNFGSKEDAAQFAIGMANALEAL 114
Cdd:cd01207   79 ARQVYGLNFASKEEATEFAQAMLLALERL 107

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 197927358 216 GGSGAPGLAAAIAGAKLRKVSKEE 239
Cdd:cd22185    1 GGSGAPGLAAAIAGAKLRKVSKQE 24

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 197927358   6 VICSSRATVMLYDDSNKRWLPAGtGPQAFSRVQIYHNPTANSFRVVGRKLQpDQQVVINCAIIRGVKYNQATPIFHQWRD 85
Cdd:cd01207    1 SVASARASVMVYDDENKRWVPSG-GSQGLSRVQIYHNTRNNTFRVVGRKLQ-DHEVVINCAILKGLKYNQATPTFHQWRD 78

                         90       100
                 ....*....|....*....|....*....
gi 197927358  86 ARQVWGLNFGSKEDAAQFAIGMANALEAL 114
Cdd:cd01207   79 ARQVYGLNFASKEEATEFAQAMLLALERL 107

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 197927358     4 ETVICSSRATVMLYDDSNKRWLPAGTGPqaFSRVQIYHNPTANSFRVVGRKLQPdqQVVINCAIIRGVKYNQATPIFHQW 83
Cdd:smart00461   3 SQCIILARAVVQLYDADTKKWVPTGEGG--AANLVIDKNQRSYFFRIVGIKGQD--KVIWNQELYKNFKYNQATPTFHQW 78

                           90       100
                   ....*....|....*....|....*...
gi 197927358    84 RDARQVWGLNFGSKEDAAQFAIGMANAL 111
Cdd:smart00461  79 ADDKCVYGLNFASEEEAKKFRKKVLKAL 106

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 197927358 216 GGSGAPGLAAAIAGAKLRKVSKEE 239
Cdd:cd22185    1 GGSGAPGLAAAIAGAKLRKVSKQE 24

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 197927358   6 VICSSRATVMLYDDSNKRWLPAGtGPQAFSRVQIYHNPTANSFRVVGRKLQpDQQVVINCAIIRGVKYNQATPIFHQWRD 85
Cdd:cd01207    1 SVASARASVMVYDDENKRWVPSG-GSQGLSRVQIYHNTRNNTFRVVGRKLQ-DHEVVINCAILKGLKYNQATPTFHQWRD 78

                         90       100
                 ....*....|....*....|....*....
gi 197927358  86 ARQVWGLNFGSKEDAAQFAIGMANALEAL 114
Cdd:cd01207   79 ARQVYGLNFASKEEATEFAQAMLLALERL 107

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 197927358   7 ICSSRATVMLYDDSNKRWLPAGTGpqAFSRVQIYHNPTANSFRVVGRKLQpDQQVVINCAIIRGVKYNQATPIFHQWRDA 86
Cdd:cd00837    2 IFSARAHVMQIDDSNKNWVPAGGK--GASRVSYFKDTTRNSFRIIGVDIK-DKKVVINCTITKNLVYNKATQTFHQWADD 78

                         90       100
                 ....*....|....*....|....*
gi 197927358  87 RQVWGLNFGSKEDAAQFAIGMANAL 111
Cdd:cd00837   79 RTVFGLNFASEEDATKFAEAVQEAL 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 197927358   7 ICSSRATVMLYDDSNKRWLPAGTGpqAFSRVQIYHNPTANS-----FRVVGRKLQpDQQVVINCAIIRGVKYNQATPIFH 81
Cdd:cd10574    2 LVRVRAVVMTRDDSSGGWLPLGGG--GLSIVSVCKVMPEEGaprteYVIHGERIR-DKTVVLECTLRKDLVYNKVMPTFH 78

                         90       100       110
                 ....*....|....*....|....*....|...
gi 197927358  82 QWRDARQVWGLNFGSKEDAAQFAIGMANALEAL 114
Cdd:cd10574   79 HWRIGEKKFGLTFQSPADARAFDRGVRRALEDL 111

VASP tetramerization domain; Vasodilator-stimulated phosphoprotein (VASP) is an actin cytoskeletal regulatory protein. This region corresponds to the tetramerization domain which forms a right handed alpha helical coiled coil structure.

                          10        20        30
                  ....*....|....*....|....*....|...
gi 197927358  340 LERVKQELVEEVRKELQKMKEEIIEVFVQELRK 372
Cdd:pfam08776   3 LERLKQEILEEVRKELQKVKEEIIDAIRQELNR 35

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 197927358   3 NETVICSSRATVMLYDDSNKRWLPAGTGPqafsrVQIYHNPTANSFRVVGRKlqpDQ--QVVINCAIIRGVKYNQATPIF 80
Cdd:cd00835    5 NEEVLFEKRAKLFRFDKETKEWKERGVGD-----LKILKNKDTGKYRIVMRR---DQvlKLCCNHYILPDMKLTKMGNND 76

                         90       100       110
                 ....*....|....*....|....*....|....
gi 197927358  81 HQWR-----------DARQVWGLNFGSKEDAAQF 103
Cdd:cd00835   77 RAWVwtamddsedgeGKPETFAVRFKTAEDAEEF 110