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 133778997   5 SICQARAAVMVYDDANKKWVPAGGSTGFSRVHIYHHTGNNTFRVVGRKIQDHQVVINCAIPKGLKYNQATQTFHQWRDAR 84
Cdd:cd01207    1 SVASARASVMVYDDENKRWVPSGGSQGLSRVQIYHNTRNNTFRVVGRKLQDHEVVINCAILKGLKYNQATPTFHQWRDAR 80

                         90       100
                 ....*....|....*....|....*...
gi 133778997  85 QVYGLNFGSKEDANVFASAMMHALEVLN 112
Cdd:cd01207   81 QVYGLNFASKEEATEFAQAMLLALERLN 108

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 133778997 356 DNRPLTGLAAAIAGAKLRKVSRVEDGS 382
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 133778997   5 SICQARAAVMVYDDANKKWVPAGGSTGFSRVHIYHHTGNNTFRVVGRKIQDHQVVINCAIPKGLKYNQATQTFHQWRDAR 84
Cdd:cd01207    1 SVASARASVMVYDDENKRWVPSGGSQGLSRVQIYHNTRNNTFRVVGRKLQDHEVVINCAILKGLKYNQATPTFHQWRDAR 80

                         90       100
                 ....*....|....*....|....*...
gi 133778997  85 QVYGLNFGSKEDANVFASAMMHALEVLN 112
Cdd:cd01207   81 QVYGLNFASKEEATEFAQAMLLALERLN 108

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 133778997     1 MSEQSICQARAAVMVYDDANKKWVPAGGStGFSRVHIYHHTGNNTFRVVGRKIQDhQVVINCAIPKGLKYNQATQTFHQW 80
Cdd:smart00461   1 LGSQCIILARAVVQLYDADTKKWVPTGEG-GAANLVIDKNQRSYFFRIVGIKGQD-KVIWNQELYKNFKYNQATPTFHQW 78

                           90       100
                   ....*....|....*....|....*...
gi 133778997    81 RDARQVYGLNFGSKEDANVFASAMMHAL 108
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 133778997 356 DNRPLTGLAAAIAGAKLRKVSRVEDGS 382
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 133778997   5 SICQARAAVMVYDDANKKWVPAGGSTGFSRVHIYHHTGNNTFRVVGRKIQDHQVVINCAIPKGLKYNQATQTFHQWRDAR 84
Cdd:cd01207    1 SVASARASVMVYDDENKRWVPSGGSQGLSRVQIYHNTRNNTFRVVGRKLQDHEVVINCAILKGLKYNQATPTFHQWRDAR 80

                         90       100
                 ....*....|....*....|....*...
gi 133778997  85 QVYGLNFGSKEDANVFASAMMHALEVLN 112
Cdd:cd01207   81 QVYGLNFASKEEATEFAQAMLLALERLN 108

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 133778997    4 QSICQARAAVMVYDDANKK-WVPAGGstgFSRVHIYHHTGNNTFRVVGRKIQDHQVVINCAIPKGLKYNQATQTFHQWRD 82
Cdd:pfam00568   9 QTICTAVAQVYLADPDNKRhWIKAKH---SGVVCFVKDSPQNSYFIRLVDIQDGKVIWNQEIYPNMEYNQARPFFHTFAD 85

                          90       100
                  ....*....|....*....|....*.
gi 133778997   83 ARQVYGLNFGSKEDANVFASAMMHAL 108
Cdd:pfam00568  86 SRCVYGLNFASEEEATKFAKAVQEAL 111

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 133778997   5 SICQARAAVMVYDDANKKWVPAGGStGFSRVHIY-----HHTGNNTFRVVGRKIQDHQVVINCAIPKGLKYNQATQTFHQ 79
Cdd:cd10574    1 CLVRVRAVVMTRDDSSGGWLPLGGG-GLSIVSVCkvmpeEGAPRTEYVIHGERIRDKTVVLECTLRKDLVYNKVMPTFHH 79

                         90       100       110
                 ....*....|....*....|....*....|..
gi 133778997  80 WRDARQVYGLNFGSKEDANVFASAMMHALEVL 111
Cdd:cd10574   80 WRIGEKKFGLTFQSPADARAFDRGVRRALEDL 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 133778997  503 LDYDRLKQDILDEMRKELAKLKEELIDAIRQELSK 537
Cdd:pfam08776   1 SDLERLKQEILEEVRKELQKVKEEIIDAIRQELNR 35

Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133778997   7 CQARAAVMVYDDankkwvpagGSTGFSRVHIYHHtgnntfRVVGRKIQDHQVVINCAIPKGLKYNQATQT----FHQWR- 81
Cdd:cd00900    1 LKFRAVRVYREP---------TKRVEGTLYITSD------RLILRDKNDGGLELSIPISDIVNVNVSPQGpssrYLVLVl 65

                         90       100
                 ....*....|....*....|....
gi 133778997  82 -DARQVYGLNFGSKEDANVFASAM 104
Cdd:cd00900   66 kDRGEFVGFSFPKEEDAIEISDAL 89

Ran-binding protein 2, Ran binding domain repeat 4; RanBP2 (also called E3 SUMO-protein ligase RanBP2, 358 kDa nucleoporin, and nuclear pore complex (NPC) protein Nup358) is a giant nucleoporin that localizes to the cytosolic face of the NPC. RanBP2 contains a leucine-rich region, 8 zinc-finger motifs, a cyclophilin A homologous domain, and 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. All eukaryotic cells contain RanBP1, but in vertebrates however, the main RanBP seems to be RanBP2. There is no RanBP2 ortholog in yeast. Transport complex disassembly is accomplished by a small ubiquitin-related modifier-1 (SUMO-1)-modified version of RanGAP that is bound to RanBP2. RanBP1 acts as a second line of defense against exported RanGTP-importin complexes which have escaped from dissociation by RanBP2. RanBP2 also interacts with the importin subunit beta-1. RabBD shares structural similarity to the PH domain, but lacks detectable sequence similarity. The members here include insects and nematodes. RanBD repeat 4 is present in this hierarchy.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 133778997  10 RAAVMVYDDANKKWVPAGgsTGfsRVHIYHHTGNNTFRVVGRKIQDHQVVINCAIPKGLK 69
Cdd:cd13174   13 RAKLYRFDADTKEWKERG--VG--EMKILYHPELNTYRLLMRREQVHKVVLNMLITSDLQ 68

Nucleoporin 50 Ran-binding domain; NUP50 acts as a cofactor for the importin-alpha:importin-beta heterodimer, which allows for transportation of many nuclear-targeted proteins through nuclear pore complexes. It is thought to function primarily at the terminal stages of nuclear protein import to coordinate import complex disassembly and importin recycling. NUP50 is composed of a N-terminal NUP50 domain which binds the C-terminus of importin-beta, a central domain which binds importin-beta, and a C-terminal RanBD which binds importin-beta through Ran-GTP. NUP50:importin-alpha then binds cargo and can stimulate nuclear import. The N-terminal domain of NUP50 is also able to displace nuclear localization signals from importin-alpha. NUP50 interacts with cyclin-dependent kinase inhibitor 1B which binds to cyclin E-CDK2 or cyclin D-CDK4 complexes and prevents its activation, thereby controling the cell cycle progression at G1. Fungal Nup2 transiently associates with nuclear pore complexes (NPCs) and when artificially tethered to DNA, can prevent the spread of transcriptional activation or repression between flanking genes, a function termed boundary activity (BA). Nup2 and the Ran guanylyl-nucleotide exchange factor, Prp20, interact at specific chromatin regions and enable the NPC to play an active role in chromatin organization. Nup60p, the nup responsible for anchoring Nup2 and the Mlp proteins to the NPC is required for Nup2-dependent BA. Nup2 contains an N-terminal Nup50 family domain and a C-terminal RanBD. 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. RabBD shares structural similarity to the PH domain, but lacks detectable sequence similarity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133778997   3 EQSICQARAAVMVYDDaNKKWVPAGgsTGFsrVHIYHHTGNNTFRVVGRKIQDHQVVINCAIPKGLKY-----NQATQTF 77
Cdd:cd13170    6 EDTVFEVRAKLFKKKD-DGEWKDKG--VGT--LRLKKHKTTGKARILVRADTLGKILLNFLLYKGMPYsvagkNNVFVGC 80

                         90       100
                 ....*....|....*....|....*..
gi 133778997  78 HQWRDARQVYGLNFGSKEDANVFASAM 104
Cdd:cd13170   81 VPNPGKPVTYLLRVKTAEDADELAKAL 107