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 1370453830  267 SICQARAAVMVYDDANKKWVPAGGSTGFSRVHIYHHTGNNTFRVVGRKIQDHQVVINCAIPKGLKYNQATQTFHQWRDAR 346
Cdd:cd01207      1 SVASARASVMVYDDENKRWVPSGGSQGLSRVQIYHNTRNNTFRVVGRKLQDHEVVINCAILKGLKYNQATPTFHQWRDAR 80

                           90       100
                   ....*....|....*....|....*...
gi 1370453830  347 QVYGLNFGSKEDANVFASAMMHALEVLN 374
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 1370453830  898 DNRPLTGLAAAIAGAKLRKVSRMEDTS 924
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 1370453830  267 SICQARAAVMVYDDANKKWVPAGGSTGFSRVHIYHHTGNNTFRVVGRKIQDHQVVINCAIPKGLKYNQATQTFHQWRDAR 346
Cdd:cd01207      1 SVASARASVMVYDDENKRWVPSGGSQGLSRVQIYHNTRNNTFRVVGRKLQDHEVVINCAILKGLKYNQATPTFHQWRDAR 80

                           90       100
                   ....*....|....*....|....*...
gi 1370453830  347 QVYGLNFGSKEDANVFASAMMHALEVLN 374
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 1370453830   265 EQSICQARAAVMVYDDANKKWVPAGGStGFSRVHIYHHTGNNTFRVVGRKIQDhQVVINCAIPKGLKYNQATQTFHQWRD 344
Cdd:smart00461    3 SQCIILARAVVQLYDADTKKWVPTGEG-GAANLVIDKNQRSYFFRIVGIKGQD-KVIWNQELYKNFKYNQATPTFHQWAD 80

                            90       100
                    ....*....|....*....|....*.
gi 1370453830   345 ARQVYGLNFGSKEDANVFASAMMHAL 370
Cdd:smart00461   81 DKCVYGLNFASEEEAKKFRKKVLKAL 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 1370453830  898 DNRPLTGLAAAIAGAKLRKVSRMEDTS 924
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 1370453830  267 SICQARAAVMVYDDANKKWVPAGGSTGFSRVHIYHHTGNNTFRVVGRKIQDHQVVINCAIPKGLKYNQATQTFHQWRDAR 346
Cdd:cd01207      1 SVASARASVMVYDDENKRWVPSGGSQGLSRVQIYHNTRNNTFRVVGRKLQDHEVVINCAILKGLKYNQATPTFHQWRDAR 80

                           90       100
                   ....*....|....*....|....*...
gi 1370453830  347 QVYGLNFGSKEDANVFASAMMHALEVLN 374
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 1370453830  266 QSICQARAAVMVYDDANKK-WVPAGGstgFSRVHIYHHTGNNTFRVVGRKIQDHQVVINCAIPKGLKYNQATQTFHQWRD 344
Cdd:pfam00568    9 QTICTAVAQVYLADPDNKRhWIKAKH---SGVVCFVKDSPQNSYFIRLVDIQDGKVIWNQEIYPNMEYNQARPFFHTFAD 85

                           90       100
                   ....*....|....*....|....*.
gi 1370453830  345 ARQVYGLNFGSKEDANVFASAMMHAL 370
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 1370453830  267 SICQARAAVMVYDDANKKWVPAGGStGFSRVHIY-----HHTGNNTFRVVGRKIQDHQVVINCAIPKGLKYNQATQTFHQ 341
Cdd:cd10574      1 CLVRVRAVVMTRDDSSGGWLPLGGG-GLSIVSVCkvmpeEGAPRTEYVIHGERIRDKTVVLECTLRKDLVYNKVMPTFHH 79

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1370453830  342 WRDARQVYGLNFGSKEDANVFASAMMHALEVL 373
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 1370453830 1045 LDYDRLKQDILDEMRKELTKLKEELIDAIRQELSK 1079
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 1370453830  269 CQARAAVMVYDDankkwvpagGSTGFSRVHIYHHtgnntfRVVGRKIQDHQVVINCAIPKGLKYNQATQT----FHQWR- 343
Cdd:cd00900      1 LKFRAVRVYREP---------TKRVEGTLYITSD------RLILRDKNDGGLELSIPISDIVNVNVSPQGpssrYLVLVl 65

                           90       100
                   ....*....|....*....|....
gi 1370453830  344 -DARQVYGLNFGSKEDANVFASAM 366
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 1370453830  272 RAAVMVYDDANKKWVPAGgsTGfsRVHIYHHTGNNTFRVVGRKIQDHQVVINCAIPKGLK 331
Cdd:cd13174     13 RAKLYRFDADTKEWKERG--VG--EMKILYHPELNTYRLLMRREQVHKVVLNMLITSDLQ 68

large tegument protein UL36; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370453830  614 RHSATRFATSLGSAFHPVLPHYATVPR-------PLNKNSRPSSPVNTPSSQPPATKPC------------AWSTSNFSP 674
Cdd:PHA03247  2660 RVSRPRRARRLGRAAQASSPPQRPRRRaarptvgSLTSLADPPPPPPTPEPAPHALVSAtplppgpaaarqASPALPAAP 2739

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370453830  675 LPPSPPIMISSPPGKATGPRPVLPVCVSSP----VPQMPPSPTAPNGLVDSVTYPVSPPPTSGPAAPPPPPPLPSLASLS 750
Cdd:PHA03247  2740 APPAVPAGPATPGGPARPARPPTTAGPPAPappaAPAAGPPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALP 2819

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370453830  751 HCGSQASP-PPSTPIASTPSSKPSvlpspsaAAPASVETPLNSVL--GDSSASEPGLQAASQPAeTPSQQGIVLGPLAPP 827
Cdd:PHA03247  2820 PAASPAGPlPPPTSAQPTAPPPPP-------GPPPPSLPLGGSVApgGDVRRRPPSRSPAAKPA-APARPPVRRLARPAV 2891

                          250       260
                   ....*....|....*....|..
gi 1370453830  828 PPPPLPPGPAQASVALPPPPGP 849
Cdd:PHA03247  2892 SRSTESFALPPDQPERPPQPQA 2913