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Conserved domains on  [gi|18959210|ref|NP_573571|]
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WAS/WASL-interacting protein family member 2 [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
WH2_WAS_WASL-2_3 cd22077
Wiskott Aldrich syndrome homology region 2 (WH2 motif) in WAS/WASL-interacting protein (WIP) ...
 33-62 3.51e-10

Wiskott Aldrich syndrome homology region 2 (WH2 motif) in WAS/WASL-interacting protein (WIP) family members 2 and 3; WASF2 (WAS protein family, member 2), This family contains the Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) in WAS/WASL-interacting protein family (WIPF, also known as WASP-interacting protein or WIP) members 2 (WIPF2; also known as WIRE/WICH) and 3 (WIPF3). WIPF2 may be an important regulator of the actin cytoskeleton. It binds to N-WASP, regulating actin dynamics close to the plasma membrane; N-WASP in turn controls the second phase insulin secretion through the regulation of the Arp2/3 complex. Pathogenic properties of Shigella flexneri, a causative agent of intestinal infections worldwide, rely on its ability to invade the human colon where it spreads from cell to cell; WIPF2 has been shown to promote this via its contribution to the efficiency of actin-based motility in the cytosol and the resolution of the membrane protrusions into vacuoles. WIPF3, along with LIPA (lysosomal acid lipase A), are expressed in microphages and are involved in pathological abdominal aortic aneurysm (AAA), a serious condition of the aorta.


:

Pssm-ID: 409220  Cd Length: 30  Bit Score: 54.91  E-value: 3.51e-10
                        10        20        30
                ....*....|....*....|....*....|
gi 18959210  33 EQRGRGALLQDICKGTKLKKVTNINDRSAP 62
Cdd:cd22077   1 EQKGRNALLADIQKGARLKKVTQINDRSAP 30
PHA03247 super family cl33720
large tegument protein UL36; Provisional
 96-308 4.59e-04

large tegument protein UL36; Provisional


The actual alignment was detected with superfamily member PHA03247:

Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 43.00  E-value: 4.59e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18959210    96 RPVGAKDGSENLAGKPALQIPSSRAAAPRPPVSAASGRPQDDTDSSRASLPELPRMQR-PSLPDLSRPNTTSSTGMKHSS 174
Cdd:PHA03247 2597 RPRAPVDDRGDPRGPAPPSPLPPDTHAPDPPPPSPSPAANEPDPHPPPTVPPPERPRDdPAPGRVSRPRRARRLGRAAQA 2676

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18959210   175 SAPPPPPpgRRANAPPTPLPMHSSKAPAynrekPLPPTPGQRLHPGREGPPAPPPVKpppspvnirtgpSGQSLAPPPPP 254
Cdd:PHA03247 2677 SSPPQRP--RRRAARPTVGSLTSLADPP-----PPPPTPEPAPHALVSATPLPPGPA------------AARQASPALPA 2737

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 18959210   255 YRQPPGVPNGPSSPTNESAPELPQRHNSLHRKTP------GPVRGLAPPPPTSASPSLLS 308
Cdd:PHA03247 2738 APAPPAVPAGPATPGGPARPARPPTTAGPPAPAPpaapaaGPPRRLTRPAVASLSESRES 2797
 
Name Accession Description Interval E-value
WH2_WAS_WASL-2_3 cd22077
Wiskott Aldrich syndrome homology region 2 (WH2 motif) in WAS/WASL-interacting protein (WIP) ...
 33-62 3.51e-10

Wiskott Aldrich syndrome homology region 2 (WH2 motif) in WAS/WASL-interacting protein (WIP) family members 2 and 3; WASF2 (WAS protein family, member 2), This family contains the Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) in WAS/WASL-interacting protein family (WIPF, also known as WASP-interacting protein or WIP) members 2 (WIPF2; also known as WIRE/WICH) and 3 (WIPF3). WIPF2 may be an important regulator of the actin cytoskeleton. It binds to N-WASP, regulating actin dynamics close to the plasma membrane; N-WASP in turn controls the second phase insulin secretion through the regulation of the Arp2/3 complex. Pathogenic properties of Shigella flexneri, a causative agent of intestinal infections worldwide, rely on its ability to invade the human colon where it spreads from cell to cell; WIPF2 has been shown to promote this via its contribution to the efficiency of actin-based motility in the cytosol and the resolution of the membrane protrusions into vacuoles. WIPF3, along with LIPA (lysosomal acid lipase A), are expressed in microphages and are involved in pathological abdominal aortic aneurysm (AAA), a serious condition of the aorta.


Pssm-ID: 409220  Cd Length: 30  Bit Score: 54.91  E-value: 3.51e-10
                        10        20        30
                ....*....|....*....|....*....|
gi 18959210  33 EQRGRGALLQDICKGTKLKKVTNINDRSAP 62
Cdd:cd22077   1 EQKGRNALLADIQKGARLKKVTQINDRSAP 30
WH2 pfam02205
WH2 motif; The WH2 motif (for Wiskott Aldrich syndrome homology region 2) has been shown in ...
 36-60 7.18e-06

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: 42.49  E-value: 7.18e-06
                          10        20
                  ....*....|....*....|....*
gi 18959210    36 GRGALLQDICKGTKLKKVTNINDRS 60
Cdd:pfam02205   4 GRGALLADIRAGKKLKKVEETNDRS 28
PHA03247 PHA03247
large tegument protein UL36; Provisional
 96-308 4.59e-04

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 43.00  E-value: 4.59e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18959210    96 RPVGAKDGSENLAGKPALQIPSSRAAAPRPPVSAASGRPQDDTDSSRASLPELPRMQR-PSLPDLSRPNTTSSTGMKHSS 174
Cdd:PHA03247 2597 RPRAPVDDRGDPRGPAPPSPLPPDTHAPDPPPPSPSPAANEPDPHPPPTVPPPERPRDdPAPGRVSRPRRARRLGRAAQA 2676

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18959210   175 SAPPPPPpgRRANAPPTPLPMHSSKAPAynrekPLPPTPGQRLHPGREGPPAPPPVKpppspvnirtgpSGQSLAPPPPP 254
Cdd:PHA03247 2677 SSPPQRP--RRRAARPTVGSLTSLADPP-----PPPPTPEPAPHALVSATPLPPGPA------------AARQASPALPA 2737

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 18959210   255 YRQPPGVPNGPSSPTNESAPELPQRHNSLHRKTP------GPVRGLAPPPPTSASPSLLS 308
Cdd:PHA03247 2738 APAPPAVPAGPATPGGPARPARPPTTAGPPAPAPpaapaaGPPRRLTRPAVASLSESRES 2797
WH2 smart00246
Wiskott Aldrich syndrome homology region 2; Wiskott Aldrich syndrome homology region 2 / ...
 36-53 3.48e-03

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


Pssm-ID: 128542  Cd Length: 18  Bit Score: 34.87  E-value: 3.48e-03
                           10
                   ....*....|....*...
gi 18959210     36 GRGALLQDICKGTKLKKV 53
Cdd:smart00246   1 ARSALLAQIRQGKKLKKV 18
 
Name Accession Description Interval E-value
WH2_WAS_WASL-2_3 cd22077
Wiskott Aldrich syndrome homology region 2 (WH2 motif) in WAS/WASL-interacting protein (WIP) ...
 33-62 3.51e-10

Wiskott Aldrich syndrome homology region 2 (WH2 motif) in WAS/WASL-interacting protein (WIP) family members 2 and 3; WASF2 (WAS protein family, member 2), This family contains the Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) in WAS/WASL-interacting protein family (WIPF, also known as WASP-interacting protein or WIP) members 2 (WIPF2; also known as WIRE/WICH) and 3 (WIPF3). WIPF2 may be an important regulator of the actin cytoskeleton. It binds to N-WASP, regulating actin dynamics close to the plasma membrane; N-WASP in turn controls the second phase insulin secretion through the regulation of the Arp2/3 complex. Pathogenic properties of Shigella flexneri, a causative agent of intestinal infections worldwide, rely on its ability to invade the human colon where it spreads from cell to cell; WIPF2 has been shown to promote this via its contribution to the efficiency of actin-based motility in the cytosol and the resolution of the membrane protrusions into vacuoles. WIPF3, along with LIPA (lysosomal acid lipase A), are expressed in microphages and are involved in pathological abdominal aortic aneurysm (AAA), a serious condition of the aorta.


Pssm-ID: 409220  Cd Length: 30  Bit Score: 54.91  E-value: 3.51e-10
                        10        20        30
                ....*....|....*....|....*....|
gi 18959210  33 EQRGRGALLQDICKGTKLKKVTNINDRSAP 62
Cdd:cd22077   1 EQKGRNALLADIQKGARLKKVTQINDRSAP 30
WH2_WAS_WASL-1 cd22076
Wiskott Aldrich syndrome homology region 2 (WH2 motif) in WAS/WASL-interacting protein family ...
 33-65 5.07e-07

Wiskott Aldrich syndrome homology region 2 (WH2 motif) in WAS/WASL-interacting protein family member 1; This family contains the Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) in WAS/WASL-interacting protein family (WIPF, also known as WASP-interacting protein or WIP) member 1 (WIPF1). WIPF1 is a ubiquitously expressed proline-rich multidomain protein and is a binding partner and chaperone of WASP. It stabilizes actin filaments and regulates actin organization and polymerization which are associated with cell migration and invasion. Mutations in the WIPF1 binding site of WASP or in WIPF1 itself cause Wiskott-Aldrich syndrome (WAS), a rare X-linked recessive disease characterized by eczema, thrombocytopenia, immune deficiency, and bloody diarrhea. Aberrant expression of WIPF1 contributes to the invasion and metastasis of several malignancies such breast cancer, glioma and colorectal cancer; it has been identified as an oncoprotein in human pancreatic ductal adenocarcinoma (PDAC) and is associated with poor survival.


Pssm-ID: 409219 [Multi-domain]  Cd Length: 32  Bit Score: 45.73  E-value: 5.07e-07
                        10        20        30
                ....*....|....*....|....*....|...
gi 18959210  33 EQRGRGALLQDICKGTKLKKvTNINDRSAPILE 65
Cdd:cd22076   1 EQAGRNALLSDINKGKKLKK-TVTNDRSAPILD 32
WH2_WAS_WASL cd22064
Wiskott Aldrich syndrome homology region 2 (WH2 motif) in WAS/WASL-interacting protein (WIP); ...
 33-62 6.40e-06

Wiskott Aldrich syndrome homology region 2 (WH2 motif) in WAS/WASL-interacting protein (WIP); This family contains the Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) found in WAS/WASL-interacting protein family (WIPF, also known as WASP-interacting protein or WIP). Human WIP protein is proline rich and has high sequence similarity to yeast protein verprolin (included in this model). WIP forms complexes with WASP/N-WASP and modulates their function in vivo. It is involved in the regulation of endocytosis and participates in several cellular processes, some of which are relevant in cancer and may be dependent on different oncogenic stimuli. WIP interacts directly with mammalian actin-binding protein-1 (mABP1) via the SH3 domain during platelet-derived growth factor (PDGF)-mediated dorsal ruffle formation. WIP family includes members 1 (WAS/WASL-interacting protein family member 1) or WIPF1), 2 (WIPF2) and 3 (WIPF3). Aberrant expression of WIPF1 contributes to the invasion and metastasis of several malignancies such breast cancer, glioma and colorectal cancer; it has been identified as an oncoprotein in human pancreatic ductal adenocarcinoma (PDAC) and is associated with poor survival. WIPF2 may be an important regulator of the actin cytoskeleton. WIPF2 binds to N-WASP, regulating actin dynamics close to the plasma membrane; N-WASP in turn controls the second phase insulin secretion through the regulation of the Arp2/3 complex. WIPF3, along with LIPA (lysosomal acid lipase A), are expressed in microphages and are involved in pathological abdominal aortic aneurysm (AAA), a serious condition of the aorta. In yeast, verprolin is involved in cytoskeletal organization and cellular growth. It may exert its effects on the cytoskeleton directly, or indirectly via proline-binding proteins, such as profilin, or via proteins possessing SH3 domains.


Pssm-ID: 409207 [Multi-domain]  Cd Length: 29  Bit Score: 42.46  E-value: 6.40e-06
                        10        20        30
                ....*....|....*....|....*....|
gi 18959210  33 EQRGRGALLQDICKGTKLKKVTNiNDRSAP 62
Cdd:cd22064   1 EQKGRGALLGDIRKGMKLKKTVT-NDRSAP 29
WH2 pfam02205
WH2 motif; The WH2 motif (for Wiskott Aldrich syndrome homology region 2) has been shown in ...
 36-60 7.18e-06

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: 42.49  E-value: 7.18e-06
                          10        20
                  ....*....|....*....|....*
gi 18959210    36 GRGALLQDICKGTKLKKVTNINDRS 60
Cdd:pfam02205   4 GRGALLADIRAGKKLKKVEETNDRS 28
PHA03247 PHA03247
large tegument protein UL36; Provisional
 96-308 4.59e-04

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 43.00  E-value: 4.59e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18959210    96 RPVGAKDGSENLAGKPALQIPSSRAAAPRPPVSAASGRPQDDTDSSRASLPELPRMQR-PSLPDLSRPNTTSSTGMKHSS 174
Cdd:PHA03247 2597 RPRAPVDDRGDPRGPAPPSPLPPDTHAPDPPPPSPSPAANEPDPHPPPTVPPPERPRDdPAPGRVSRPRRARRLGRAAQA 2676

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18959210   175 SAPPPPPpgRRANAPPTPLPMHSSKAPAynrekPLPPTPGQRLHPGREGPPAPPPVKpppspvnirtgpSGQSLAPPPPP 254
Cdd:PHA03247 2677 SSPPQRP--RRRAARPTVGSLTSLADPP-----PPPPTPEPAPHALVSATPLPPGPA------------AARQASPALPA 2737

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 18959210   255 YRQPPGVPNGPSSPTNESAPELPQRHNSLHRKTP------GPVRGLAPPPPTSASPSLLS 308
Cdd:PHA03247 2738 APAPPAVPAGPATPGGPARPARPPTTAGPPAPAPpaapaaGPPRRLTRPAVASLSESRES 2797
WH2 cd21762
Wiskott-Aldrich Syndrome Homology (WASP) region 2 (WH2 motif), and similar proteins; This ...
 35-54 3.34e-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: 34.87  E-value: 3.34e-03
                        10        20
                ....*....|....*....|
gi 18959210  35 RGRGALLQDICKGTKLKKVT 54
Cdd:cd21762   3 SDRSALLSDIRKGKKLKKTV 22
WH2 smart00246
Wiskott Aldrich syndrome homology region 2; Wiskott Aldrich syndrome homology region 2 / ...
 36-53 3.48e-03

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


Pssm-ID: 128542  Cd Length: 18  Bit Score: 34.87  E-value: 3.48e-03
                           10
                   ....*....|....*...
gi 18959210     36 GRGALLQDICKGTKLKKV 53
Cdd:smart00246   1 ARSALLAQIRQGKKLKKV 18
 
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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