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Conserved domains on  [gi|1828054684|ref|NP_001366383|]
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actin-binding protein WASF1 isoform 2 [Mus musculus]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
WH2_WAVE-1 cd22071
Wiskott Aldrich syndrome homology region 2 (WH2 motif) found in Wiskott-Aldrich Syndrome ...
 484-558 5.78e-50

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: 166.45  E-value: 5.78e-50
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1828054684 484 KRHPSTLPVISDARSVLLEAIRKGIQLRKVEEQREQEAKHERIENDVATILSRRIAVEYSDSEDDSEFDEVDWLE 558
Cdd:cd22071     1 KRHPSTLPVISDARSVLLEAIRKGIQLRKVEEQREQEAKHERIENDVATILSRRIAVEYSDSEDDSEFDEVDWLE 75
PAT1 super family cl37801
Topoisomerase II-associated protein PAT1; Members of this family are necessary for accurate ...
 394-488 4.29e-04

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


The actual alignment was detected with superfamily member pfam09770:

Pssm-ID: 401645 [Multi-domain]  Cd Length: 846  Bit Score: 43.10  E-value: 4.29e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1828054684 394 QPSPPVARAAPVCETVPVHPLPQGEVQGLPPPPPPPPLPPPGIRPSSPVAVAALAHPPSGLHPAPSTAPGPHAPLMPPSP 473
Cdd:pfam09770 206 QAKKPAQQPAPAPAQPPAAPPAQQAQQQQQFPPQIQQQQQPQQQPQQPQQHPGQGHPVTILQRPQSPQPDPAQPSIQPQA 285

                          90
                  ....*....|....*
gi 1828054684 474 PSQVLPASEPKRHPS 488
Cdd:pfam09770 286 QQFHQQPPPVPVQPT 300
 
Name Accession Description Interval E-value
WH2_WAVE-1 cd22071
Wiskott Aldrich syndrome homology region 2 (WH2 motif) found in Wiskott-Aldrich Syndrome ...
 484-558 5.78e-50

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: 166.45  E-value: 5.78e-50
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1828054684 484 KRHPSTLPVISDARSVLLEAIRKGIQLRKVEEQREQEAKHERIENDVATILSRRIAVEYSDSEDDSEFDEVDWLE 558
Cdd:cd22071     1 KRHPSTLPVISDARSVLLEAIRKGIQLRKVEEQREQEAKHERIENDVATILSRRIAVEYSDSEDDSEFDEVDWLE 75
WH2 pfam02205
WH2 motif; The WH2 motif (for Wiskott Aldrich syndrome homology region 2) has been shown in ...
 493-520 2.00e-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: 41.33  E-value: 2.00e-05
                          10        20
                  ....*....|....*....|....*...
gi 1828054684 493 ISDARSVLLEAIRKGIQLRKVEEQREQE 520
Cdd:pfam02205   1 GGGGRGALLADIRAGKKLKKVEETNDRS 28
WH2 smart00246
Wiskott Aldrich syndrome homology region 2; Wiskott Aldrich syndrome homology region 2 / ...
 496-513 4.25e-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: 4.25e-04
                           10
                   ....*....|....*...
gi 1828054684  496 ARSVLLEAIRKGIQLRKV 513
Cdd:smart00246   1 ARSALLAQIRQGKKLKKV 18
PAT1 pfam09770
Topoisomerase II-associated protein PAT1; Members of this family are necessary for accurate ...
 394-488 4.29e-04

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


Pssm-ID: 401645 [Multi-domain]  Cd Length: 846  Bit Score: 43.10  E-value: 4.29e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1828054684 394 QPSPPVARAAPVCETVPVHPLPQGEVQGLPPPPPPPPLPPPGIRPSSPVAVAALAHPPSGLHPAPSTAPGPHAPLMPPSP 473
Cdd:pfam09770 206 QAKKPAQQPAPAPAQPPAAPPAQQAQQQQQFPPQIQQQQQPQQQPQQPQQHPGQGHPVTILQRPQSPQPDPAQPSIQPQA 285

                          90
                  ....*....|....*
gi 1828054684 474 PSQVLPASEPKRHPS 488
Cdd:pfam09770 286 QQFHQQPPPVPVQPT 300
 
Name Accession Description Interval E-value
WH2_WAVE-1 cd22071
Wiskott Aldrich syndrome homology region 2 (WH2 motif) found in Wiskott-Aldrich Syndrome ...
 484-558 5.78e-50

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: 166.45  E-value: 5.78e-50
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1828054684 484 KRHPSTLPVISDARSVLLEAIRKGIQLRKVEEQREQEAKHERIENDVATILSRRIAVEYSDSEDDSEFDEVDWLE 558
Cdd:cd22071     1 KRHPSTLPVISDARSVLLEAIRKGIQLRKVEEQREQEAKHERIENDVATILSRRIAVEYSDSEDDSEFDEVDWLE 75
WH2_WAVE-3 cd22073
Wiskott Aldrich syndrome homology region 2 (WH2 motif) found in Wiskott-Aldrich Syndrome ...
 493-556 1.44e-28

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: 107.91  E-value: 1.44e-28
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1828054684 493 ISDARSVLLEAIRKGIQLRKVEEQREQEAKHERIENDVATILSRRIAVEYSDSEDDSEFDEVDW 556
Cdd:cd22073     1 ISDARSDLLAAIRMGIQLKKVQEQREQEAKREPVGNDVATILSRRIAVEYSDSEDESEFDENDW 64
WH2_WAVE cd22057
Wiskott Aldrich syndrome homology region 2 (WH2 motif) found in Wiskott-Aldrich Syndrome ...
 493-520 3.44e-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: 3.44e-10
                          10        20
                  ....*....|....*....|....*...
gi 1828054684 493 ISDARSVLLEAIRKGIQLRKVEEQREQE 520
Cdd:cd22057     1 VTDPRSDLLSAIREGIKLRKVEKQEEKE 28
WH2_WAVE-2 cd22072
Wiskott Aldrich syndrome homology region 2 (WH2 motif) found in Wiskott-Aldrich Syndrome ...
 493-522 5.45e-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: 5.45e-09
                          10        20        30
                  ....*....|....*....|....*....|
gi 1828054684 493 ISDARSVLLEAIRKGIQLRKVEEQREQEAK 522
Cdd:cd22072     1 VSDARSDLLSAIRQGFQLRKVEEQREQEKR 30
WH2 pfam02205
WH2 motif; The WH2 motif (for Wiskott Aldrich syndrome homology region 2) has been shown in ...
 493-520 2.00e-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: 41.33  E-value: 2.00e-05
                          10        20
                  ....*....|....*....|....*...
gi 1828054684 493 ISDARSVLLEAIRKGIQLRKVEEQREQE 520
Cdd:pfam02205   1 GGGGRGALLADIRAGKKLKKVEETNDRS 28
WH2 smart00246
Wiskott Aldrich syndrome homology region 2; Wiskott Aldrich syndrome homology region 2 / ...
 496-513 4.25e-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: 4.25e-04
                           10
                   ....*....|....*...
gi 1828054684  496 ARSVLLEAIRKGIQLRKV 513
Cdd:smart00246   1 ARSALLAQIRQGKKLKKV 18
PAT1 pfam09770
Topoisomerase II-associated protein PAT1; Members of this family are necessary for accurate ...
 394-488 4.29e-04

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


Pssm-ID: 401645 [Multi-domain]  Cd Length: 846  Bit Score: 43.10  E-value: 4.29e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1828054684 394 QPSPPVARAAPVCETVPVHPLPQGEVQGLPPPPPPPPLPPPGIRPSSPVAVAALAHPPSGLHPAPSTAPGPHAPLMPPSP 473
Cdd:pfam09770 206 QAKKPAQQPAPAPAQPPAAPPAQQAQQQQQFPPQIQQQQQPQQQPQQPQQHPGQGHPVTILQRPQSPQPDPAQPSIQPQA 285

                          90
                  ....*....|....*
gi 1828054684 474 PSQVLPASEPKRHPS 488
Cdd:pfam09770 286 QQFHQQPPPVPVQPT 300
Atrophin-1 pfam03154
Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian ...
 443-499 1.49e-03

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.


Pssm-ID: 460830 [Multi-domain]  Cd Length: 991  Bit Score: 41.68  E-value: 1.49e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1828054684 443 AVAALAHPPSGLHPAPSTAPGPHAPLMPPSPPSQVLPASEPKRHPSTLPVISDARSV 499
Cdd:pfam03154 442 PPAASHPPTSGLHQVPSQSPFPQHPFVPGGPPPITPPSGPPTSTSSAMPGIQPPSSA 498
WH2 cd21762
Wiskott-Aldrich Syndrome Homology (WASP) region 2 (WH2 motif), and similar proteins; This ...
 494-514 2.40e-03

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.


Pssm-ID: 409196  Cd Length: 22  Bit Score: 35.26  E-value: 2.40e-03
                          10        20
                  ....*....|....*....|.
gi 1828054684 494 SDARSVLLEAIRKGIQLRKVE 514
Cdd:cd21762     2 TSDRSALLSDIRKGKKLKKTV 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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