Topoisomerase II-associated protein PAT1; Members of this family are necessary for accurate chromosome transmission during cell division.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68161500   395 QPSPPVARAAPVCETVPVHPLPQGEVQGLPPPPPPPPLPPPGIRPSSPVTVTALAHPPSGLHPTPSTAPGPHVPLMPPSP 474
Cdd:pfam09770 206 QAKKPAQQPAPAPAQPPAAPPAQQAQQQQQFPPQIQQQQQPQQQPQQPQQHPGQGHPVTILQRPQSPQPDPAQPSIQPQA 285

                          90
                  ....*....|....*
gi 68161500   475 PSQVIPASEPKRHPS 489
Cdd:pfam09770 286 QQFHQQPPPVPVQPT 300

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 68161500   494 ISDARSVLLEAIRKGIQLRKVEEQREQE 521
Cdd:pfam02205   1 GGGGRGALLADIRAGKKLKKVEETNDRS 28

Topoisomerase II-associated protein PAT1; Members of this family are necessary for accurate chromosome transmission during cell division.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68161500   395 QPSPPVARAAPVCETVPVHPLPQGEVQGLPPPPPPPPLPPPGIRPSSPVTVTALAHPPSGLHPTPSTAPGPHVPLMPPSP 474
Cdd:pfam09770 206 QAKKPAQQPAPAPAQPPAAPPAQQAQQQQQFPPQIQQQQQPQQQPQQPQQHPGQGHPVTILQRPQSPQPDPAQPSIQPQA 285

                          90
                  ....*....|....*
gi 68161500   475 PSQVIPASEPKRHPS 489
Cdd:pfam09770 286 QQFHQQPPPVPVQPT 300

Wiskott Aldrich syndrome homology region 2 (WH2 motif) found in Wiskott-Aldrich Syndrome Protein Family Member 3 (WASP-3 or WAVE3); This family contains the Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) found in the Wiskott-Aldrich syndrome protein (WASP) relative WAVE 3 (also called WASP-family verprolin homologous protein 3 or WASF3 or SCAR3 or WAVE3). WAVE3 is a downstream effector protein involved in the transmission of signals from tyrosine kinase receptors and small GTPases to the actin cytoskeleton. It plays a role in the regulation of cell morphology and cytoskeletal organization and is required in the control of cell shape. It forms a hetero-pentameric WAVE regulatory complex (WRC) with additional proteins in the cell (Sra1/Cyfip1, Nap1/Hem-2, Abi and HSPC300) that regulates actin filament reorganization via its interaction with the actin related protein (Arp)2/3 complex. The WRC is stimulated by the Rac GTPase, kinases and phosphatidylinositols, and binds and activates the Arp2/3 complex via WAVE3 C-terminal domain. It interacts with actin via the WH2 domain. This actin polymerization process is also involved in cancer cell invasion and metastasis. WASF3 has been shown to have a central role in cancer cell invasion and metastasis; elevated WAVE3 expression promotes metastasis in breast cancer and inactivation of WAVE3 in highly metastatic breast cancer cells has been shown to suppress invasion and metastasis. WAVE3 may also be pivotal in ovarian cancer cell motility, invasion and oncogenesis. In gastric cancer patients, WAVE3 expression correlates with poor outcome. In pancreatic cancer tissues, expression is prominently higher that in normal tissues and may be associated with lymphatic metastasis and poorly differentiated tumors; findings suggest that WAVE3 influences cell proliferation, migration and invasion via the AKT pathway.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 68161500 494 ISDARSVLLEAIRKGIQLRKVEEQREQEAKHERIENDVATILSRRIAVEYSDSEDDSEFDEVDW 557
Cdd:cd22073   1 ISDARSDLLAAIRMGIQLKKVQEQREQEAKREPVGNDVATILSRRIAVEYSDSEDESEFDENDW 64

Wiskott Aldrich syndrome homology region 2 (WH2 motif) found in Wiskott-Aldrich Syndrome Protein Family Member 2 (WASP2 or WAVE2 or WASF2 or SCAR2); This family contains the Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) found in the Wiskott-Aldrich syndrome protein (WASP) relative WAVE 2 (also called WASP-family verprolin homologous protein 2 or WASF2 or SCAR2 or WAVE2). WAVE2 is a downstream effector protein involved in the transmission of signals from tyrosine kinase receptors and small GTPases to the actin cytoskeleton. It participates in multiple processes related to actin dynamics, such as lamellipodia and filopodium formation, cell migration and protrusion, and embryogenesis. It regulates lamellipodia formation via a hetero-pentameric WAVE regulatory complex (WRC) with additional proteins in the cell (Sra1/Cyfip1, Nap1/Hem-2, Abi and HSPC300) that regulates actin filament reorganization via its interaction with the actin related protein (Arp)2/3 complex. The WRC is stimulated by the Rac GTPase, kinases and phosphatidylinositols, and binds and activates the Arp2/3 complex via WAVE2 C-terminal domain. It interacts with actin via the WH2 domain. WAVE2 can also be phosphorylated by MAPK and forms a complex with PKA that regulates membrane protrusion. In mouse oocyte, WAVE2 regulates meiotic spindle stability, peripheral positioning and polar body emission, probably via an actin-mediated pathway.

                        10        20        30
                ....*....|....*....|....*....|
gi 68161500 494 ISDARSVLLEAIRKGIQLRKVEEQREQEAK 523
Cdd:cd22072   1 VSDARSDLLSAIRQGFQLRKVEEQREQEKR 30

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

                           10
                   ....*....|....*...
gi 68161500    497 ARSVLLEAIRKGIQLRKV 514
Cdd:smart00246   1 ARSALLAQIRQGKKLKKV 18

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 68161500 495 SDARSVLLEAIRKGIQLRKVE 515
Cdd:cd21762   2 TSDRSALLSDIRKGKKLKKTV 22