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Conserved domains on  [gi|2217293479|ref|XP_047286016|]
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actin-binding protein WASF3 isoform X1 [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
WH2_WAVE-3 cd22073
Wiskott Aldrich syndrome homology region 2 (WH2 motif) found in Wiskott-Aldrich Syndrome ...
437-502 2.80e-27

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.


:

Pssm-ID: 409216  Cd Length: 66  Bit Score: 104.05  E-value: 2.80e-27
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2217293479 437 ISDARSDLLAAIRMGIQLKKVQEQREQEAKREPVGNDVATILSRRIAVEYSDSDDDSEFDENDWSD 502
Cdd:cd22073     1 ISDARSDLLAAIRMGIQLKKVQEQREQEAKREPVGNDVATILSRRIAVEYSDSEDESEFDENDWSD 66
 
Name Accession Description Interval E-value
WH2_WAVE-3 cd22073
Wiskott Aldrich syndrome homology region 2 (WH2 motif) found in Wiskott-Aldrich Syndrome ...
437-502 2.80e-27

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.


Pssm-ID: 409216  Cd Length: 66  Bit Score: 104.05  E-value: 2.80e-27
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2217293479 437 ISDARSDLLAAIRMGIQLKKVQEQREQEAKREPVGNDVATILSRRIAVEYSDSDDDSEFDENDWSD 502
Cdd:cd22073     1 ISDARSDLLAAIRMGIQLKKVQEQREQEAKREPVGNDVATILSRRIAVEYSDSEDESEFDENDWSD 66
WH2 pfam02205
WH2 motif; The WH2 motif (for Wiskott Aldrich syndrome homology region 2) has been shown in ...
437-464 7.13e-05

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.


Pssm-ID: 460490  Cd Length: 28  Bit Score: 39.79  E-value: 7.13e-05
                          10        20
                  ....*....|....*....|....*...
gi 2217293479 437 ISDARSDLLAAIRMGIQLKKVQEQREQE 464
Cdd:pfam02205   1 GGGGRGALLADIRAGKKLKKVEETNDRS 28
WH2 smart00246
Wiskott Aldrich syndrome homology region 2; Wiskott Aldrich syndrome homology region 2 / ...
440-457 3.52e-04

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


Pssm-ID: 128542  Cd Length: 18  Bit Score: 37.56  E-value: 3.52e-04
                           10
                   ....*....|....*...
gi 2217293479  440 ARSDLLAAIRMGIQLKKV 457
Cdd:smart00246   1 ARSALLAQIRQGKKLKKV 18
 
Name Accession Description Interval E-value
WH2_WAVE-3 cd22073
Wiskott Aldrich syndrome homology region 2 (WH2 motif) found in Wiskott-Aldrich Syndrome ...
437-502 2.80e-27

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.


Pssm-ID: 409216  Cd Length: 66  Bit Score: 104.05  E-value: 2.80e-27
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2217293479 437 ISDARSDLLAAIRMGIQLKKVQEQREQEAKREPVGNDVATILSRRIAVEYSDSDDDSEFDENDWSD 502
Cdd:cd22073     1 ISDARSDLLAAIRMGIQLKKVQEQREQEAKREPVGNDVATILSRRIAVEYSDSEDESEFDENDWSD 66
WH2_WAVE-1 cd22071
Wiskott Aldrich syndrome homology region 2 (WH2 motif) found in Wiskott-Aldrich Syndrome ...
428-500 9.76e-24

Wiskott Aldrich syndrome homology region 2 (WH2 motif) found in Wiskott-Aldrich Syndrome Protein Family Member 1 (WASP1 or WAVE1 or WASF1 or SCAR1); This family contains the Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) found in the Wiskott-Aldrich syndrome protein (WASP) relative WAVE 1 (also called WASP-family verprolin homologous protein 1 or SCAR1 or WAVE1). WAVE1 is a downstream effector protein involved in the transmission of signals from tyrosine kinase receptors and small GTPases to the actin cytoskeleton. 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 binding to CYFIP protein, allowing the release of WAVE1 from the complex. WAVE1 then binds and activates the Arp2/3 complex via its C-terminal domain. It interacts with actin via the WH2 domain. WAVE1 has been shown to be necessary for efficient transcriptional reprogramming in Xenopus oocytes and for normal development.


Pssm-ID: 409214  Cd Length: 75  Bit Score: 94.42  E-value: 9.76e-24
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2217293479 428 KRQEPAQPPISDARSDLLAAIRMGIQLKKVQEQREQEAKREPVGNDVATILSRRIAVEYSDSDDDSEFDENDW 500
Cdd:cd22071     1 KRHPSTLPVISDARSVLLEAIRKGIQLRKVEEQREQEAKHERIENDVATILSRRIAVEYSDSEDDSEFDEVDW 73
WH2_WAVE cd22057
Wiskott Aldrich syndrome homology region 2 (WH2 motif) found in Wiskott-Aldrich Syndrome ...
437-464 3.63e-10

Wiskott Aldrich syndrome homology region 2 (WH2 motif) found in Wiskott-Aldrich Syndrome Protein Family members 1 (WASP1 or WAVE1), 2 (WASP2 or WAVE2) and 3 (WASP3 or WAVE3); This family contains the Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) found in three Wiskott-Aldrich syndrome protein (WASP) family verprolin homologous protein (SCAR/WAVE) isoforms: WAVE1, WAVE2, and WAVE3. Members of this family activate actin related protein (Arp)2/3-dependent actin nucleation and branching in response to signals mediated by Rho-family GTPases. The domain structure of these proteins varies, reflecting different modes of regulation; however, they all share a common C-terminal WH2 region which constitutes the smallest fragment necessary for Arp2/3 activation. These proteins interact with actin via their WH2 domain.


Pssm-ID: 409200  Cd Length: 28  Bit Score: 54.79  E-value: 3.63e-10
                          10        20
                  ....*....|....*....|....*...
gi 2217293479 437 ISDARSDLLAAIRMGIQLKKVQEQREQE 464
Cdd:cd22057     1 VTDPRSDLLSAIREGIKLRKVEKQEEKE 28
WH2_WAVE-2 cd22072
Wiskott Aldrich syndrome homology region 2 (WH2 motif) found in Wiskott-Aldrich Syndrome ...
437-466 5.11e-09

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.


Pssm-ID: 409215  Cd Length: 30  Bit Score: 51.56  E-value: 5.11e-09
                          10        20        30
                  ....*....|....*....|....*....|
gi 2217293479 437 ISDARSDLLAAIRMGIQLKKVQEQREQEAK 466
Cdd:cd22072     1 VSDARSDLLSAIRQGFQLRKVEEQREQEKR 30
WH2 pfam02205
WH2 motif; The WH2 motif (for Wiskott Aldrich syndrome homology region 2) has been shown in ...
437-464 7.13e-05

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.


Pssm-ID: 460490  Cd Length: 28  Bit Score: 39.79  E-value: 7.13e-05
                          10        20
                  ....*....|....*....|....*...
gi 2217293479 437 ISDARSDLLAAIRMGIQLKKVQEQREQE 464
Cdd:pfam02205   1 GGGGRGALLADIRAGKKLKKVEETNDRS 28
WH2 smart00246
Wiskott Aldrich syndrome homology region 2; Wiskott Aldrich syndrome homology region 2 / ...
440-457 3.52e-04

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


Pssm-ID: 128542  Cd Length: 18  Bit Score: 37.56  E-value: 3.52e-04
                           10
                   ....*....|....*...
gi 2217293479  440 ARSDLLAAIRMGIQLKKV 457
Cdd:smart00246   1 ARSALLAQIRQGKKLKKV 18
WH2_Pan1-like cd22070
Wiskott-Aldrich Syndrome Homology (WASP) region 2 (WH2 motif) domain found in Actin ...
439-458 1.05e-03

Wiskott-Aldrich Syndrome Homology (WASP) region 2 (WH2 motif) domain found in Actin cytoskeleton-regulatory complex protein Pan1, and similar proteins; This family contains the Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) found in actin cytoskeleton-regulatory complex protein Pan1, and similar proteins. Pan1 actin cytoskeleton-regulatory complex is a multi-domain scaffold that is required for the internalization of endosomes during actin-coupled endocytosis. It links the site of endocytosis to the cell membrane-associated actin cytoskeleton. Pan1 mediates uptake of external molecules and vacuolar degradation of plasma membrane proteins, may play a role in the proper organization of the cell membrane-associated actin cytoskeleton, and promotes its destabilization.


Pssm-ID: 409213  Cd Length: 22  Bit Score: 36.51  E-value: 1.05e-03
                          10        20
                  ....*....|....*....|
gi 2217293479 439 DARSDLLAAIRMGIQLKKVQ 458
Cdd:cd22070     3 DGRGALLASIRAGKQLRKVQ 22
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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