WASP family proteins EVH1 domain; The Wiskott-Aldrich Syndrome Protein (WASP; also called Bee1p) and its homolog N (neuronal)-WASP are signal transduction proteins that promote actin polymerization in response to upstream intracellular signals. WAS is an X-linked recessive disease, characterized by eczema, immunodeficiency, and thrombocytopenia. The majority of patients with WAS, or a milder version of the disorder, X-linked thrombocytopenia (XLT), have point mutations in the EVH1 domain of WASP. WASP is an actin regulatory protein consisting of an N-terminal EVH1 domain called WH1 which binds LPPPEP peptides, a basic region (B), a GTP binding domain (GBP), a proline rich region, a WH2 domain, and a verprolin-cofilin-acidic motif (VCA) which activates the actin-related protein (Arp)2/3 actin nucleating complex. The B, GBD, and the proline-rich region are involved in autoinhibitory interactions that repress or block the activity of the VCA. Yeast members lack the GTP binding domain. 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 62291053  40 TMSSAVVQLYAADRN-CMWSKK-CSGVACLVKDNPQRSYFLRIFDIKDGKLLWEQELYNNFVYNSPRGYFHTFAGDTCQV 117
Cdd:cd01205   1 ILAAAVARLYYAEPDpDSWSYTgLTGALCFVKDNAKRSYFFRLVDLKTRGVVWEQELYEGFEYNQDRPFFHTFEGDECMI 80

                        90       100
                ....*....|....*....|.
gi 62291053 118 ALNFANEEEAKKFRKAVTDLL 138
Cdd:cd01205  81 GLNFADEDEAAAFYKKVQEKL 101

first tandem Wiskott Aldrich syndrome homology region 2 (WH2 motif) repeat found in human Neural Wiskott-Aldrich syndrome protein (N-WASP) and related domains; This subfamily includes the first tandem Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) found in human Neural Wiskott-Aldrich syndrome protein (N-WASP or Neural WASP) and related domains. N-WASP integrates various extracellular signals to control actin dynamics and cytoskeletal reorganization through activation of the actin related protein (Arp)2/3 complex. It interacts with actin via the WH2 domain. N-WASP plays an important role in the deactivation or attenuation of B cell receptor signaling. N-WASP regulates filopodia formation and membrane invagination, as compared to WAVE proteins that serve as Rac1 effectors in the formation of lamellipodia. Filopodia are thin, actin-rich surface projections that are extended and maintained by N-WASP together with CDC42. N-WASP also plays a role in the nucleus by regulating gene transcription, probably by promoting nuclear actin polymerization. It binds to HSF1/HSTF1 and forms a complex on heat shock promoter elements (HSE) that negatively regulates HSP90 expression. It also plays a role in dendrite spine morphogenesis. Unphosphorylated N-WASP is preferentially localized in the nucleus and in the cytoplasm when phosphorylated; it is exported from the nucleus by a nuclear export signal (NES)-dependent mechanism to the cytoplasm.

                        10        20
                ....*....|....*....|....*..
gi 62291053 402 TAGNKAALLDQIREGAQLKKVEQNSRP 428
Cdd:cd22074   1 AAGNKSALLDQIREGAQLKKVEQNSRP 27

WASP family proteins EVH1 domain; The Wiskott-Aldrich Syndrome Protein (WASP; also called Bee1p) and its homolog N (neuronal)-WASP are signal transduction proteins that promote actin polymerization in response to upstream intracellular signals. WAS is an X-linked recessive disease, characterized by eczema, immunodeficiency, and thrombocytopenia. The majority of patients with WAS, or a milder version of the disorder, X-linked thrombocytopenia (XLT), have point mutations in the EVH1 domain of WASP. WASP is an actin regulatory protein consisting of an N-terminal EVH1 domain called WH1 which binds LPPPEP peptides, a basic region (B), a GTP binding domain (GBP), a proline rich region, a WH2 domain, and a verprolin-cofilin-acidic motif (VCA) which activates the actin-related protein (Arp)2/3 actin nucleating complex. The B, GBD, and the proline-rich region are involved in autoinhibitory interactions that repress or block the activity of the VCA. Yeast members lack the GTP binding domain. 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 62291053  40 TMSSAVVQLYAADRN-CMWSKK-CSGVACLVKDNPQRSYFLRIFDIKDGKLLWEQELYNNFVYNSPRGYFHTFAGDTCQV 117
Cdd:cd01205   1 ILAAAVARLYYAEPDpDSWSYTgLTGALCFVKDNAKRSYFFRLVDLKTRGVVWEQELYEGFEYNQDRPFFHTFEGDECMI 80

                        90       100
                ....*....|....*....|.
gi 62291053 118 ALNFANEEEAKKFRKAVTDLL 138
Cdd:cd01205  81 GLNFADEDEAAAFYKKVQEKL 101

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 62291053     34 LGKKCVTMSSAVVQLYAADRNCmWSKKCSG-VACLVKDNPQRSYFLRIFDIKDG-KLLWEQELYNNFVYNSPRGYFHTFA 111
Cdd:smart00461   1 LGSQCIILARAVVQLYDADTKK-WVPTGEGgAANLVIDKNQRSYFFRIVGIKGQdKVIWNQELYKNFKYNQATPTFHQWA 79

                           90       100
                   ....*....|....*....|....*..
gi 62291053    112 GDTCQVALNFANEEEAKKFRKAVTDLL 138
Cdd:smart00461  80 DDKCVYGLNFASEEEAKKFRKKVLKAL 106

PAK (p21 activated kinase) Binding Domain (PBD), binds Cdc42p- and/or Rho-like small GTPases; also known as the Cdc42/Rac interactive binding (CRIB) motif; has been shown to inhibit transcriptional activation and cell transformation mediated by the Ras-Rac pathway. CRIB-containing effector proteins are functionally diverse and include serine/threonine kinases, tyrosine kinases, actin-binding proteins, and adapter molecules.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 62291053 201 ADIGTPSNFQHIGHVGWDPNtGFDLNNLDPELKNLFDMCGISE 243
Cdd:cd00132   1 MEISTPTDFKHISHVGWDGV-GFDGANLPPDLQSLFQTAGISA 42

second tandem Wiskott Aldrich syndrome homology region 2 (WH2 motif) repeat found in human Neural Wiskott-Aldrich syndrome protein (N-WASP) and related domains; This subfamily includes the second tandem Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) found in human Neural Wiskott-Aldrich syndrome protein (N-WASP or Neural WASP). N-WASP integrates various extracellular signals to control actin dynamics and cytoskeletal reorganization through activation of the actin related protein (Arp)2/3 complex. It interacts with actin via the WH2 domain. N-WASP plays an important role in the deactivation or attenuation of B cell receptor signaling. N-WASP regulates filopodia formation and membrane invagination, as compared to WAVE proteins that serve as Rac1 effectors in the formation of lamellipodia. Filopodia are thin, actin-rich surface projections that are extended and maintained by N-WASP together with CDC42. N-WASP also plays a role in the nucleus by regulating gene transcription, probably by promoting nuclear actin polymerization. It binds to HSF1/HSTF1 and forms a complex on heat shock promoter elements (HSE) that negatively regulates HSP90 expression. It also plays a role in dendrite spine morphogenesis. Unphosphorylated N-WASP is preferentially localized in the nucleus and in the cytoplasm when phosphorylated; it is exported from the nucleus by a nuclear export signal (NES)-dependent mechanism to the cytoplasm. This subfamily includes both tandem WH2 domains of mouse N-WASP.

                        10        20
                ....*....|....*....|....*
gi 62291053 429 VSCSGRDALLDQIRQGIQLKSVADG 453
Cdd:cd22075   1 VSSSGRDALLDQIRQGIQLKSVPDG 25

Wiskott Aldrich syndrome homology region 2; Wiskott Aldrich syndrome homology region 2 / actin-binding motif

                           10
                   ....*....|....*...
gi 62291053    433 GRDALLDQIRQGIQLKSV 450
Cdd:smart00246   1 ARSALLAQIRQGKKLKKV 18

WH2 motif; The WH2 motif (for Wiskott Aldrich syndrome homology region 2) has been shown in WASP and Scar1 (mammalian homolog) to be the region that interacts with actin.

                          10        20
                  ....*....|....*....|.
gi 62291053   431 CSGRDALLDQIRQGIQLKSVA 451
Cdd:pfam02205   2 GGGRGALLADIRAGKKLKKVE 22

WASP family proteins EVH1 domain; The Wiskott-Aldrich Syndrome Protein (WASP; also called Bee1p) and its homolog N (neuronal)-WASP are signal transduction proteins that promote actin polymerization in response to upstream intracellular signals. WAS is an X-linked recessive disease, characterized by eczema, immunodeficiency, and thrombocytopenia. The majority of patients with WAS, or a milder version of the disorder, X-linked thrombocytopenia (XLT), have point mutations in the EVH1 domain of WASP. WASP is an actin regulatory protein consisting of an N-terminal EVH1 domain called WH1 which binds LPPPEP peptides, a basic region (B), a GTP binding domain (GBP), a proline rich region, a WH2 domain, and a verprolin-cofilin-acidic motif (VCA) which activates the actin-related protein (Arp)2/3 actin nucleating complex. The B, GBD, and the proline-rich region are involved in autoinhibitory interactions that repress or block the activity of the VCA. Yeast members lack the GTP binding domain. 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 62291053  40 TMSSAVVQLYAADRN-CMWSKK-CSGVACLVKDNPQRSYFLRIFDIKDGKLLWEQELYNNFVYNSPRGYFHTFAGDTCQV 117
Cdd:cd01205   1 ILAAAVARLYYAEPDpDSWSYTgLTGALCFVKDNAKRSYFFRLVDLKTRGVVWEQELYEGFEYNQDRPFFHTFEGDECMI 80

                        90       100
                ....*....|....*....|.
gi 62291053 118 ALNFANEEEAKKFRKAVTDLL 138
Cdd:cd01205  81 GLNFADEDEAAAFYKKVQEKL 101

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 62291053  40 TMSSAVVQLYAADR-NCMWSK---KCSGVACLVKDNPQRSYFLRIFDIKDGKLLWEQELYNNFVYNSPRGYFHTFAGDTC 115
Cdd:cd00837   1 SIFSARAHVMQIDDsNKNWVPaggKGASRVSYFKDTTRNSFRIIGVDIKDKKVVINCTITKNLVYNKATQTFHQWADDRT 80

                        90       100
                ....*....|....*....|...
gi 62291053 116 QVALNFANEEEAKKFRKAVTDLL 138
Cdd:cd00837  81 VFGLNFASEEDATKFAEAVQEAL 103

P21-Rho-binding domain; Small domains that bind Cdc42p- and/or Rho-like small GTPases. Also known as the Cdc42/Rac interactive binding (CRIB).

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 62291053   202 DIGTPSNFQHIGHVGWDPNTGFDlNNLDPELKNLFDMCGISEAQLKDRETSKVIYDFI 259
Cdd:pfam00786   1 MISAPTNFKHTVHVGFDPDTGFF-TGLPPEWAKLLDSSGITEDEQKENPKAVLDVLKF 57

first tandem Wiskott Aldrich syndrome homology region 2 (WH2 motif) repeat found in human Neural Wiskott-Aldrich syndrome protein (N-WASP) and related domains; This subfamily includes the first tandem Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) found in human Neural Wiskott-Aldrich syndrome protein (N-WASP or Neural WASP) and related domains. N-WASP integrates various extracellular signals to control actin dynamics and cytoskeletal reorganization through activation of the actin related protein (Arp)2/3 complex. It interacts with actin via the WH2 domain. N-WASP plays an important role in the deactivation or attenuation of B cell receptor signaling. N-WASP regulates filopodia formation and membrane invagination, as compared to WAVE proteins that serve as Rac1 effectors in the formation of lamellipodia. Filopodia are thin, actin-rich surface projections that are extended and maintained by N-WASP together with CDC42. N-WASP also plays a role in the nucleus by regulating gene transcription, probably by promoting nuclear actin polymerization. It binds to HSF1/HSTF1 and forms a complex on heat shock promoter elements (HSE) that negatively regulates HSP90 expression. It also plays a role in dendrite spine morphogenesis. Unphosphorylated N-WASP is preferentially localized in the nucleus and in the cytoplasm when phosphorylated; it is exported from the nucleus by a nuclear export signal (NES)-dependent mechanism to the cytoplasm.

                        10        20
                ....*....|....*....|....*..
gi 62291053 402 TAGNKAALLDQIREGAQLKKVEQNSRP 428
Cdd:cd22074   1 AAGNKSALLDQIREGAQLKKVEQNSRP 27

P21-Rho-binding domain; Small domains that bind Cdc42p- and/or Rho-like small GTPases. Also known as the Cdc42/Rac interactive binding (CRIB).

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 62291053    203 IGTPSNFQHIGHVGWDPNTGfDLNNLDPELKNLFDMC 239
Cdd:smart00285   1 ISTPTNFKHIAHVGFDGQTG-GFTGLPTEWKSLLKTS 36

first and second of two tandem Wiskott Aldrich syndrome homology region 2 (WH2 motif) repeats found in Neural Wiskott-Aldrich syndrome protein (N-WASP); This family contains both tandem Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) repeats found in the Neural Wiskott-Aldrich syndrome protein (N-WASP or Neural WASP); N-WASP contains two tandem WH2 domains. N-WASP integrates various extracellular signals to control actin dynamics and cytoskeletal reorganization through activation of the actin related protein (Arp)2/3 complex. It interacts with actin via the WH2 domain. N-WASP plays an important role in the deactivation or attenuation of B cell receptor signaling. N-WASP regulates filopodia formation and membrane invagination, as compared to WAVE proteins that serve as Rac1 effectors in the formation of lamellipodia. Filopodia are thin, actin-rich surface projections that are extended and maintained by N-WASP together with CDC42. N-WASP also plays a role in the nucleus by regulating gene transcription, probably by promoting nuclear actin polymerization. It binds to HSF1/HSTF1 and forms a complex on heat shock promoter elements (HSE) that negatively regulates HSP90 expression. It also plays a role in dendrite spine morphogenesis. Unphosphorylated N-WASP is preferentially localized in the nucleus and in the cytoplasm when phosphorylated; it is exported from the nucleus by a nuclear export signal (NES)-dependent mechanism to the cytoplasm.

                        10        20
                ....*....|....*....|...
gi 62291053 402 TAGNKAALLDQIREGAQLKKVEQ 424
Cdd:cd22058   1 SCSGRDALLDQIRQGIQLKSVED 23

Wiskott Aldrich syndrome homology region 2; Wiskott Aldrich syndrome homology region 2 / actin-binding motif

                           10
                   ....*....|....*...
gi 62291053    433 GRDALLDQIRQGIQLKSV 450
Cdd:smart00246   1 ARSALLAQIRQGKKLKKV 18

WH2 motif; The WH2 motif (for Wiskott Aldrich syndrome homology region 2) has been shown in WASP and Scar1 (mammalian homolog) to be the region that interacts with actin.

                          10        20
                  ....*....|....*....|.
gi 62291053   431 CSGRDALLDQIRQGIQLKSVA 451
Cdd:pfam02205   2 GGGRGALLADIRAGKKLKKVE 22

second tandem Wiskott Aldrich syndrome homology region 2 (WH2 motif) repeat found in human Neural Wiskott-Aldrich syndrome protein (N-WASP) and related domains; This subfamily includes the second tandem Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) found in human Neural Wiskott-Aldrich syndrome protein (N-WASP or Neural WASP). N-WASP integrates various extracellular signals to control actin dynamics and cytoskeletal reorganization through activation of the actin related protein (Arp)2/3 complex. It interacts with actin via the WH2 domain. N-WASP plays an important role in the deactivation or attenuation of B cell receptor signaling. N-WASP regulates filopodia formation and membrane invagination, as compared to WAVE proteins that serve as Rac1 effectors in the formation of lamellipodia. Filopodia are thin, actin-rich surface projections that are extended and maintained by N-WASP together with CDC42. N-WASP also plays a role in the nucleus by regulating gene transcription, probably by promoting nuclear actin polymerization. It binds to HSF1/HSTF1 and forms a complex on heat shock promoter elements (HSE) that negatively regulates HSP90 expression. It also plays a role in dendrite spine morphogenesis. Unphosphorylated N-WASP is preferentially localized in the nucleus and in the cytoplasm when phosphorylated; it is exported from the nucleus by a nuclear export signal (NES)-dependent mechanism to the cytoplasm. This subfamily includes both tandem WH2 domains of mouse N-WASP.

                        10        20
                ....*....|....*....|....*
gi 62291053 401 TTAGNKAALLDQIREGAQLKKVEQN 425
Cdd:cd22075   1 VSSSGRDALLDQIRQGIQLKSVPDG 25