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 160333510  199 DIGTPSNFQHIGHVGWDPNTGFDlNNLDPELKNLFDMCGISEAQLKDRETSKVIYDFI 256
Cdd:pfam00786   1 MISAPTNFKHTVHVGFDPDTGFF-TGLPPEWAKLLDSSGITEDEQKENPKAVLDVLKF 57

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 160333510 425 VSCSGRDALLDQIRQGIQLKSVSDG 449
Cdd:cd22075    1 VSSSGRDALLDQIRQGIQLKSVPDG 25

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 160333510  37 TMSSAVVQLYAADRN-CMWSKK-CSGVACLVKDNPQRSYFLRIFDIKDGKLLWEQELYNNFVYNSPRGYFHTFAGDTCQV 114
Cdd:cd01205    1 ILAAAVARLYYAEPDpDSWSYTgLTGALCFVKDNAKRSYFFRLVDLKTRGVVWEQELYEGFEYNQDRPFFHTFEGDECMI 80

                         90       100
                 ....*....|....*....|.
gi 160333510 115 ALNFANEEEAKKFRKAVTDLL 135
Cdd:cd01205   81 GLNFADEDEAAAFYKKVQEKL 101

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 160333510  199 DIGTPSNFQHIGHVGWDPNTGFDlNNLDPELKNLFDMCGISEAQLKDRETSKVIYDFI 256
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 160333510 398 SSGNKAALLDQIREGAQLKKVEQNSRP 424
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 160333510   200 IGTPSNFQHIGHVGWDPNTGfDLNNLDPELKNLFDMC 236
Cdd:smart00285   1 ISTPTNFKHIAHVGFDGQTG-GFTGLPTEWKSLLKTS 36

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 160333510  399 SGNKAALLDQIREGAQLKKVEQN 421
Cdd:pfam02205   2 GGGRGALLADIRAGKKLKKVEET 24

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

                           10
                   ....*....|....*.
gi 160333510   403 AALLDQIREGAQLKKV 418
Cdd:smart00246   3 SALLAQIRQGKKLKKV 18

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 160333510  37 TMSSAVVQLYAADRN-CMWSKK-CSGVACLVKDNPQRSYFLRIFDIKDGKLLWEQELYNNFVYNSPRGYFHTFAGDTCQV 114
Cdd:cd01205    1 ILAAAVARLYYAEPDpDSWSYTgLTGALCFVKDNAKRSYFFRLVDLKTRGVVWEQELYEGFEYNQDRPFFHTFEGDECMI 80

                         90       100
                 ....*....|....*....|.
gi 160333510 115 ALNFANEEEAKKFRKAVTDLL 135
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 160333510    31 LGKKCVTMSSAVVQLYAADRNCmWSKKCSG-VACLVKDNPQRSYFLRIFDIKDG-KLLWEQELYNNFVYNSPRGYFHTFA 108
Cdd:smart00461   1 LGSQCIILARAVVQLYDADTKK-WVPTGEGgAANLVIDKNQRSYFFRIVGIKGQdKVIWNQELYKNFKYNQATPTFHQWA 79

                           90       100
                   ....*....|....*....|....*..
gi 160333510   109 GDTCQVALNFANEEEAKKFRKAVTDLL 135
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 160333510 198 ADIGTPSNFQHIGHVGWDPNtGFDLNNLDPELKNLFDMCGISE 240
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 160333510 425 VSCSGRDALLDQIRQGIQLKSVSDG 449
Cdd:cd22075    1 VSSSGRDALLDQIRQGIQLKSVPDG 25

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 160333510 426 SCSGRDALLDQIRQGIQLKSVSD 448
Cdd:cd22058    1 SCSGRDALLDQIRQGIQLKSVED 23

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. This subgroup of CRIB/PBD-domains is found N-terminal of Serine/Threonine kinase domains in PAK and PAK-like proteins.

                         10        20
                 ....*....|....*....|
gi 160333510 200 IGTPSNFQHIGHVGWDPNTG 219
Cdd:cd01093    3 ISSPTNFKHRVHVGFDPQTG 22

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 160333510  399 SGNKAALLDQIREGAQLKKVEQN 421
Cdd:pfam02205   2 GGGRGALLADIRAGKKLKKVEET 24

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 160333510  427 CSGRDALLDQIRQGIQLKSV 446
Cdd:pfam02205   2 GGGRGALLADIRAGKKLKKV 21

Wiskott-Aldrich Syndrome Homology (WASP) region 2 (WH2 motif), and similar proteins; This family contains the Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) as well as thymosin-beta (Tbeta; also called beta-thymosin or betaT) domains that are small, widespread intrinsically disordered actin-binding peptides displaying significant sequence variability and different regulations of actin self-assembly in motile and morphogenetic processes. These WH2/betaT peptides are identified by a central consensus actin-binding motif LKKT/V flanked by variable N-terminal and C-terminal extensions; the betaT shares a more extended and conserved C-terminal half than WH2. These single or repeated domains are found in actin-binding proteins (ABPs) such as the hematopoietic-specific protein WASP, its ubiquitously expressed ortholog neural-WASP (N-WASP), WASP-interacting protein (WAS/WASL-interacting protein family members 1 and 2), and WASP-family verprolin homologous protein (WAVE/SCAR) isoforms: WAVE1, WAVE2, and WAVE3. Also included are the WH2 domains found in inverted formin FH2 domain-containing protein (INF2), Cordon bleu (Cobl) protein, vasodilator-stimulated phosphoprotein (VASP) homology protein and actobindin (found in amoebae). These ABPs are commonly multidomain proteins that contain signaling domains and structurally conserved actin-binding motifs, the most important being the WH2 domain motif through which they bind actin in order to direct the location, rate, and timing for actin assembly in the cell into different structures, such as filopodia, lamellipodia, stress fibers, and focal adhesions. The WH2 domain motif is one of the most abundant actin-binding motifs in Wiskott-Aldrich syndrome proteins (WASPs) where they activate Arp2/3-dependent actin nucleation and branching in response to signals mediated by Rho-family GTPases. The thymosin beta (Tbeta) domains in metazoans act in cells as major actin-sequestering peptides; their complex with monomeric ATP-actin (G-ATP-actin) cannot polymerize at either filament (F-actin) end.

                         10        20
                 ....*....|....*....|..
gi 160333510 426 SCSGRDALLDQIRQGIQLKSVS 447
Cdd:cd21762    1 KTSDRSALLSDIRKGKKLKKTV 22