FYVE-related domain found in protein spire homolog 1 (Spire1) and similar proteins; Spire1 is encoded by gene spir-1, which is primarily found to be expressed in the developing nervous system and in neuronal cells of the adult brain, as well as in the fetal liver and in the adult spleen. It functions as a new essential factor in asymmetric division of oocytes. It mediates asymmetric spindle positioning by assembling a cytoplasmic actin network. It is also required for polar body extrusion by promoting assembly of the cleavage furrow. Moreover, it cooperates synergistically with Fmn2 to assemble F-actin in oocytes. Spire1 contains an N-terminal protein-interaction KIND domain, WH2 actin-binding domains, a Rab GTPase-interaction Spir-box, and a C-terminal FYVE membrane-binding domain. The FYVE domain resembles a FYVE-related domain that is structurally similar to the canonical FYVE domains but lack the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif, which form a binding pocket that specifically binds the phospholipid phosphatidylinositol 3-phosphate (PtdIns3P or PI3P).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1020532312 730 LKKGKLCFSCRTKKFSLFTWSYTCQFCKRPVCSQCCKKMKLPSKPHASLPISSLGPsilpkkestasaatekpsstsshk 809
Cdd:cd15767     1 LKKGKLCFSCRSKRFSLFTWSYTCQFCKRPVCSQCCKKMRLPSKPYSTLPIFSLGP------------------------ 56

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1020532312 810 rhslqrtmsrsskhaerssskdelelpeqftaDWSSMEVCVDCKKFINDIISNSR 864
Cdd:cd15767    57 --------------------------------DWSTMEVCVDCKKFISDIISSSR 79

first tandem Wiskott-Aldrich Syndrome Homology (WASP) region 2 (WH2 motif) repeat of protein Spire homologs 1 and 2; This family contains the first tandem Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) domain in human Spire family proteins Spire-1 (also called Spir1) and Spire-2 (Spir2) and related proteins. Spire is an actin nucleator essential for establishing an actin mesh during oogenesis. It was first identified as a Drosophila maternal effect gene essential to establishment of both the anterior/posterior and dorsal/ventral body axes in developing oocytes and embryos. It has been found to sever filaments and sequester monomers in addition to nucleating new filaments; it remains associated with the slow-growing pointed end of the new filament. Spire is involved in intracellular vesicle transport along actin fibers, providing a novel link between actin cytoskeleton dynamics and intracellular transport. It is required for asymmetric spindle positioning and asymmetric cell division during oocyte meiosis. Spire contains four tandem WH2 domains. The mammalian genome encodes two Spire proteins, namely Spire-1 and Spire-2. This model contains WH2 domain 1 of human Spire-1 and Spire-2 . Major expression of both spire genes have been detected during embryogenesis in the developing nervous system). In addition, spire1 expression is found in the fetal liver, while spire2 expression is seen in early stages of intestinal development. In adult tissues, the spire2 gene shows a rather broad expression pattern, which includes the epithelial cells of the digestive tract, testical spermatocytes, and neuronal cells of the nervous system. In contrast, spire1 is mainly expressed in neuronal cells of the nervous system. Minor expression levels were detected in testis and spleen. Spire also acts in the nucleus where, together with Spire-1 and Spire-2, it promotes assembly of nuclear actin filaments in response to DNA damage in order to facilitate movement of chromatin and repair factors after DNA damage. High levels of spire1 expression are restricted to the nervous system, oocytes, and testis. Since function of Spire-1 and Spire-2 in oocyte maturation is redundant, spire1 mutant mice are fertile, overall brain anatomy is not altered, and visual and motor functions remain normal; however, detailed behavioral studies of the spire1 mutant mice unveiled a very specific and highly significant phenotype in terms of fear learning in male mice.

                          10        20        30
                  ....*....|....*....|....*....|..
gi 1020532312 250 DLNELQNADWARFWVQVMRDLRHGVKLKKVQE 281
Cdd:cd22065     1 ELDELQNTDWARLWVQVMRELRNGVKLKKVQE 32

third tandem Wiskott-Aldrich Syndrome Homology (WASP) region 2 (WH2 motif) repeat of protein Spire homologs 1 and 2; This family contains the third tandem Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) domain in human Spire family protein Spire-1 (also called Spir1) and Spire-2 (Spir2) and related proteins. Spire is an actin nucleator essential for establishing an actin mesh during oogenesis. It was first identified as a Drosophila maternal effect gene essential to establishment of both the anterior/posterior and dorsal/ventral body axes in developing oocytes and embryos. It has been found to sever filaments and sequester monomers in addition to nucleating new filaments; it remains associated with the slow-growing pointed end of the new filament. Spire is involved in intracellular vesicle transport along actin fibers, providing a novel link between actin cytoskeleton dynamics and intracellular transport. It is required for asymmetric spindle positioning and asymmetric cell division during oocyte meiosis. Spire contains four tandem WH2 domains. The mammalian genome encodes two Spire proteins, namely Spire-1 (Spir1) and Spire-2 (Spir2). This model contains WH2 domain 3 of human Spire-1 and Spire-2 . Major expression of both spire genes have been detected during embryogenesis in the developing nervous system). In addition, spire1 expression is found in the fetal liver, while spire2 expression is seen in early stages of intestinal development. In adult tissues, the spire2 gene shows a rather broad expression pattern, which includes the epithelial cells of the digestive tract, testical spermatocytes, and neuronal cells of the nervous system. In contrast, spire1 is mainly expressed in neuronal cells of the nervous system. Minor expression levels were detected in testis and spleen. Spire also acts in the nucleus where, together with Spire-1 and Spire-2, it promotes assembly of nuclear actin filaments in response to DNA damage in order to facilitate movement of chromatin and repair factors after DNA damage. High levels of spire1 expression are restricted to the nervous system, oocytes, and testis. Since function of Spire-1 and Spire-2 in oocyte maturation is redundant, spire1 mutant mice are fertile, overall brain anatomy is not altered, and visual and motor functions remain normal; however, detailed behavioral studies of the spire1 mutant mice unveiled a very specific and highly significant phenotype in terms of fear learning in male mice.

                          10        20
                  ....*....|....*....|...
gi 1020532312 324 KKSAHEIILEFIRSRPPLNPVSA 346
Cdd:cd22186     1 KKSAHELILDFIRSRPPLNPVSA 23

FYVE-related domain found in protein spire homolog 1 (Spire1) and similar proteins; Spire1 is encoded by gene spir-1, which is primarily found to be expressed in the developing nervous system and in neuronal cells of the adult brain, as well as in the fetal liver and in the adult spleen. It functions as a new essential factor in asymmetric division of oocytes. It mediates asymmetric spindle positioning by assembling a cytoplasmic actin network. It is also required for polar body extrusion by promoting assembly of the cleavage furrow. Moreover, it cooperates synergistically with Fmn2 to assemble F-actin in oocytes. Spire1 contains an N-terminal protein-interaction KIND domain, WH2 actin-binding domains, a Rab GTPase-interaction Spir-box, and a C-terminal FYVE membrane-binding domain. The FYVE domain resembles a FYVE-related domain that is structurally similar to the canonical FYVE domains but lack the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif, which form a binding pocket that specifically binds the phospholipid phosphatidylinositol 3-phosphate (PtdIns3P or PI3P).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1020532312 730 LKKGKLCFSCRTKKFSLFTWSYTCQFCKRPVCSQCCKKMKLPSKPHASLPISSLGPsilpkkestasaatekpsstsshk 809
Cdd:cd15767     1 LKKGKLCFSCRSKRFSLFTWSYTCQFCKRPVCSQCCKKMRLPSKPYSTLPIFSLGP------------------------ 56

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1020532312 810 rhslqrtmsrsskhaerssskdelelpeqftaDWSSMEVCVDCKKFINDIISNSR 864
Cdd:cd15767    57 --------------------------------DWSTMEVCVDCKKFISDIISSSR 79

FYVE-related domain found in protein spire homolog 1 (Spire1) and similar proteins; Spire1 is encoded by gene spir-1, which is primarily found to be expressed in the developing nervous system and in neuronal cells of the adult brain, as well as in the fetal liver and in the adult spleen. It functions as a new essential factor in asymmetric division of oocytes. It mediates asymmetric spindle positioning by assembling a cytoplasmic actin network. It is also required for polar body extrusion by promoting assembly of the cleavage furrow. Moreover, it cooperates synergistically with Fmn2 to assemble F-actin in oocytes. Spire1 contains an N-terminal protein-interaction KIND domain, WH2 actin-binding domains, a Rab GTPase-interaction Spir-box, and a C-terminal FYVE membrane-binding domain. The FYVE domain resembles a FYVE-related domain that is structurally similar to the canonical FYVE domains but lack the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif, which form a binding pocket that specifically binds the phospholipid phosphatidylinositol 3-phosphate (PtdIns3P or PI3P).

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1020532312 561 LKKGKLCFSCRTKKFSLFTWSYTCQF-----CLFVHSAMKLPSKPHASLPISSLGP 611
Cdd:cd15767     1 LKKGKLCFSCRSKRFSLFTWSYTCQFckrpvCSQCCKKMRLPSKPYSTLPIFSLGP 56

second tandem Wiskott-Aldrich Syndrome Homology (WASP) region 2 (WH2 motif) repeat of protein Spire homolog 1 (Spir1), and related proteins; This family contains the second tandem Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) domain in human Spire family protein Spire-1 (also called Spir1) and related proteins. Spire is an actin nucleator essential for establishing an actin mesh during oogenesis. It was first identified as a Drosophila maternal effect gene essential to establishment of both the anterior/posterior and dorsal/ventral body axes in developing oocytes and embryos. It has been found to sever filaments and sequester monomers in addition to nucleating new filaments; it remains associated with the slow-growing pointed end of the new filament. Spire is involved in intracellular vesicle transport along actin fibers, providing a novel link between actin cytoskeleton dynamics and intracellular transport. It is required for asymmetric spindle positioning and asymmetric cell division during oocyte meiosis. Spire contains four tandem WH2 domains. The mammalian genome encodes two Spire proteins, namely Spire-1 (Spir1) and Spire-2 (Spir2). This model contains WH2 domain 2 of human Spire-1 protein. Major expression of both spire genes have been detected during embryogenesis in the developing nervous system). In addition, spire1 expression is found in the fetal liver, and in adult tissues, spire1 is mainly expressed in neuronal cells of the nervous system. Minor expression levels were detected in testis and spleen. Spire also acts in the nucleus where, together with Spire-1 and Spire-2, it promotes assembly of nuclear actin filaments in response to DNA damage in order to facilitate movement of chromatin and repair factors after DNA damage. High levels of spire1 expression are restricted to the nervous system, oocytes, and testis. Since function of Spire-1 and Spire-2 in oocyte maturation is redundant, spire1 mutant mice are fertile, overall brain anatomy is not altered, and visual and motor functions remain normal; however, detailed behavioral studies of the spire1 mutant mice unveiled a very specific and highly significant phenotype in terms of fear learning in male mice. This family also contains the second of four tandem repeats of WH2 in Drosophila melanogaster Spire (also called Spir), an actin nucleator essential for establishing an actin mesh during oogenesis.

                          10        20        30
                  ....*....|....*....|....*....|..
gi 1020532312 290 EFQLTPYEMLMDDIRSKRYKLRKVMVNGNIPP 321
Cdd:cd22078     1 EYELTPYEMLMDDIRSKRYTLRKVMVNGDIPP 32

fourth tandem Wiskott-Aldrich Syndrome Homology (WASP) region 2 (WH2 motif) repeat of protein Spire homolog 1; This family contains the fourth tandem Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) domain in human Spire family protein Spire-1 (also called Spir1) and related proteins. Spire is an actin nucleator essential for establishing an actin mesh during oogenesis. It was first identified as a Drosophila maternal effect gene essential to establishment of both the anterior/posterior and dorsal/ventral body axes in developing oocytes and embryos. It has been found to sever filaments and sequester monomers in addition to nucleating new filaments; it remains associated with the slow-growing pointed end of the new filament. Spire is involved in intracellular vesicle transport along actin fibers, providing a novel link between actin cytoskeleton dynamics and intracellular transport. It is required for asymmetric spindle positioning and asymmetric cell division during oocyte meiosis. Spire contains four tandem WH2 domains. The mammalian genome encodes two Spire proteins, namely Spire-1 (Spir1) and Spire-2 (Spir2). This model contains WH2 domain 4 of Spire-1 protein. Major expression of both spire genes have been detected during embryogenesis in the developing nervous system). In addition, spire1 expression is found in the fetal liver, and in adult tissues, spire1 is mainly expressed in neuronal cells of the nervous system. Minor expression levels were detected in testis and spleen. Spire also acts in the nucleus where, together with Spire-1 and Spire-2, it promotes assembly of nuclear actin filaments in response to DNA damage in order to facilitate movement of chromatin and repair factors after DNA damage. High levels of spire1 expression are restricted to the nervous system, oocytes, and testis. Since function of Spire-1 and Spire-2 in oocyte maturation is redundant, spire1 mutant mice are fertile, overall brain anatomy is not altered, and visual and motor functions remain normal; however, detailed behavioral studies of the spire1 mutant mice unveiled a very specific and highly significant phenotype in terms of fear learning in male mice.

                          10        20
                  ....*....|....*....|....
gi 1020532312 355 RPPSLHERILEGIRSERKLRPVSP 378
Cdd:cd22080     1 RPRSLHERILEEIKAERKLRPVSP 24

FYVE-related domain found in protein spire homolog 1 (Spire1) and similar proteins; Spire1 is encoded by gene spir-1, which is primarily found to be expressed in the developing nervous system and in neuronal cells of the adult brain, as well as in the fetal liver and in the adult spleen. It functions as a new essential factor in asymmetric division of oocytes. It mediates asymmetric spindle positioning by assembling a cytoplasmic actin network. It is also required for polar body extrusion by promoting assembly of the cleavage furrow. Moreover, it cooperates synergistically with Fmn2 to assemble F-actin in oocytes. Spire1 contains an N-terminal protein-interaction KIND domain, WH2 actin-binding domains, a Rab GTPase-interaction Spir-box, and a C-terminal FYVE membrane-binding domain. The FYVE domain resembles a FYVE-related domain that is structurally similar to the canonical FYVE domains but lack the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif, which form a binding pocket that specifically binds the phospholipid phosphatidylinositol 3-phosphate (PtdIns3P or PI3P).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1020532312 730 LKKGKLCFSCRTKKFSLFTWSYTCQFCKRPVCSQCCKKMKLPSKPHASLPISSLGPsilpkkestasaatekpsstsshk 809
Cdd:cd15767     1 LKKGKLCFSCRSKRFSLFTWSYTCQFCKRPVCSQCCKKMRLPSKPYSTLPIFSLGP------------------------ 56

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1020532312 810 rhslqrtmsrsskhaerssskdelelpeqftaDWSSMEVCVDCKKFINDIISNSR 864
Cdd:cd15767    57 --------------------------------DWSTMEVCVDCKKFISDIISSSR 79

FYVE-related domain found in protein spire homolog 2 (Spire2) and similar proteins; Spire2 is encoded by gene spir-2, which is expressed in the nervous system and highly expressed in the colonic epithelium. It functions as a new essential factor in asymmetric division of oocytes. It mediates asymmetric spindle positioning by assembling a cytoplasmic actin network. It is also required for polar body extrusion by promoting assembly of the cleavage furrow. Moreover, it cooperates synergistically with Fmn2 to assemble F-actin in oocytes. Spire2 contains an N-terminal protein-interaction KIND domain, WH2 actin-binding domains, a Rab GTPase-interaction Spir-box, and a C-terminal FYVE membrane-binding domain. The FYVE domain resembles a FYVE-related domain that is structurally similar to the canonical FYVE domains but lacks the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif, which form a binding pocket that specifically binds the phospholipid phosphatidylinositol 3-phosphate (PtdIns3P or PI3P).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1020532312 730 LKKGKLCFSCRTKkFSLFTWSYTCQFCKRPVCSQCCKKMKLPSKPHASLPISSLGPSILPKKESTASAATEKPSSTSSHK 809
Cdd:cd15768     1 LKKGKICCCCRVK-FPLFSWPSNCLFCKRSVCSSCSMKMKMPSKKLAHIPVYTVGFESPPRSTSAKANARRWTDSLHGPS 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020532312 810 RHSLqrtmsrsskhaerssskdELELPEQFTADWSSMEVCVDCKKFINDII 860
Cdd:cd15768    80 WRSV------------------EEEFPHIYAQGSVLKDVCSDCTGFVADVV 112

first tandem Wiskott-Aldrich Syndrome Homology (WASP) region 2 (WH2 motif) repeat of protein Spire homologs 1 and 2; This family contains the first tandem Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) domain in human Spire family proteins Spire-1 (also called Spir1) and Spire-2 (Spir2) and related proteins. Spire is an actin nucleator essential for establishing an actin mesh during oogenesis. It was first identified as a Drosophila maternal effect gene essential to establishment of both the anterior/posterior and dorsal/ventral body axes in developing oocytes and embryos. It has been found to sever filaments and sequester monomers in addition to nucleating new filaments; it remains associated with the slow-growing pointed end of the new filament. Spire is involved in intracellular vesicle transport along actin fibers, providing a novel link between actin cytoskeleton dynamics and intracellular transport. It is required for asymmetric spindle positioning and asymmetric cell division during oocyte meiosis. Spire contains four tandem WH2 domains. The mammalian genome encodes two Spire proteins, namely Spire-1 and Spire-2. This model contains WH2 domain 1 of human Spire-1 and Spire-2 . Major expression of both spire genes have been detected during embryogenesis in the developing nervous system). In addition, spire1 expression is found in the fetal liver, while spire2 expression is seen in early stages of intestinal development. In adult tissues, the spire2 gene shows a rather broad expression pattern, which includes the epithelial cells of the digestive tract, testical spermatocytes, and neuronal cells of the nervous system. In contrast, spire1 is mainly expressed in neuronal cells of the nervous system. Minor expression levels were detected in testis and spleen. Spire also acts in the nucleus where, together with Spire-1 and Spire-2, it promotes assembly of nuclear actin filaments in response to DNA damage in order to facilitate movement of chromatin and repair factors after DNA damage. High levels of spire1 expression are restricted to the nervous system, oocytes, and testis. Since function of Spire-1 and Spire-2 in oocyte maturation is redundant, spire1 mutant mice are fertile, overall brain anatomy is not altered, and visual and motor functions remain normal; however, detailed behavioral studies of the spire1 mutant mice unveiled a very specific and highly significant phenotype in terms of fear learning in male mice.

                          10        20        30
                  ....*....|....*....|....*....|..
gi 1020532312 250 DLNELQNADWARFWVQVMRDLRHGVKLKKVQE 281
Cdd:cd22065     1 ELDELQNTDWARLWVQVMRELRNGVKLKKVQE 32

FYVE-related domain found in Spir proteins, Spire1 and Spire2; Spir proteins were originally discovered as the protein products of the Drosophila spire gene. They are Jun N-terminal kinase (JNK)-interacting proteins that have exclusively been identified in metazoans. They may play roles in membrane trafficking and cortical filament crosslinking. This family includes Spire1 and Spire2, which function as new essential factors in asymmetric division of oocytes. They mediate asymmetric spindle positioning by assembling a cytoplasmic actin network. They are also required for polar body extrusion by promoting assembly of the cleavage furrow. Moreover, they cooperate synergistically with Fmn2 to assemble F-actin in oocytes. Both Spire1 and Spire2 contain an N-terminal protein-interaction KIND domain, WH2 actin-binding domains, a Rab GTPase-interaction Spir-box, and a C-terminal FYVE membrane-binding domain. Their FYVE domains resemble FYVE-related domains that are structurally similar to the canonical FYVE domains but lack the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif, which form a binding pocket that specifically bind the phospholipid phosphatidylinositol 3-phosphate (PtdIns3P or PI3P).

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1020532312 732 KGKLCFSCRTKKFSLFTWSYTCQFCKRPVCSQCCK 766
Cdd:cd15748     1 KGKVCFCCKKKKFSFFTWPNTCKLCKRVVCSKCCR 35

FYVE-related domain found in protein spire homolog 2 (Spire2) and similar proteins; Spire2 is encoded by gene spir-2, which is expressed in the nervous system and highly expressed in the colonic epithelium. It functions as a new essential factor in asymmetric division of oocytes. It mediates asymmetric spindle positioning by assembling a cytoplasmic actin network. It is also required for polar body extrusion by promoting assembly of the cleavage furrow. Moreover, it cooperates synergistically with Fmn2 to assemble F-actin in oocytes. Spire2 contains an N-terminal protein-interaction KIND domain, WH2 actin-binding domains, a Rab GTPase-interaction Spir-box, and a C-terminal FYVE membrane-binding domain. The FYVE domain resembles a FYVE-related domain that is structurally similar to the canonical FYVE domains but lacks the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif, which form a binding pocket that specifically binds the phospholipid phosphatidylinositol 3-phosphate (PtdIns3P or PI3P).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1020532312 561 LKKGKLCFSCRTKkFSLFTWSYTCQFC-LFVHSA----MKLPSKPHASLPISSLGPSILPKKESTASAATEKPSSTSSHK 635
Cdd:cd15768     1 LKKGKICCCCRVK-FPLFSWPSNCLFCkRSVCSScsmkMKMPSKKLAHIPVYTVGFESPPRSTSAKANARRWTDSLHGPS 79

                  ....*
gi 1020532312 636 RHSLQ 640
Cdd:cd15768    80 WRSVE 84

fourth tandem Wiskott-Aldrich Syndrome Homology (WASP) region 2 (WH2 motif) repeat of protein Spire homolog 1; This family contains the fourth tandem Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) domain in human Spire family protein Spire-1 (also called Spir1) and related proteins. Spire is an actin nucleator essential for establishing an actin mesh during oogenesis. It was first identified as a Drosophila maternal effect gene essential to establishment of both the anterior/posterior and dorsal/ventral body axes in developing oocytes and embryos. It has been found to sever filaments and sequester monomers in addition to nucleating new filaments; it remains associated with the slow-growing pointed end of the new filament. Spire is involved in intracellular vesicle transport along actin fibers, providing a novel link between actin cytoskeleton dynamics and intracellular transport. It is required for asymmetric spindle positioning and asymmetric cell division during oocyte meiosis. Spire contains four tandem WH2 domains. The mammalian genome encodes two Spire proteins, namely Spire-1 (Spir1) and Spire-2 (Spir2). This model contains WH2 domain 4 of Spire-1 protein. Major expression of both spire genes have been detected during embryogenesis in the developing nervous system). In addition, spire1 expression is found in the fetal liver, and in adult tissues, spire1 is mainly expressed in neuronal cells of the nervous system. Minor expression levels were detected in testis and spleen. Spire also acts in the nucleus where, together with Spire-1 and Spire-2, it promotes assembly of nuclear actin filaments in response to DNA damage in order to facilitate movement of chromatin and repair factors after DNA damage. High levels of spire1 expression are restricted to the nervous system, oocytes, and testis. Since function of Spire-1 and Spire-2 in oocyte maturation is redundant, spire1 mutant mice are fertile, overall brain anatomy is not altered, and visual and motor functions remain normal; however, detailed behavioral studies of the spire1 mutant mice unveiled a very specific and highly significant phenotype in terms of fear learning in male mice.

                          10        20
                  ....*....|....*....|....
gi 1020532312 355 RPPSLHERILEGIRSERKLRPVSP 378
Cdd:cd22080     1 RPRSLHERILEEIKAERKLRPVSP 24

first tandem Wiskott-Aldrich Syndrome Homology (WASP) region 2 (WH2 motif) repeat found in Drosophila melanogaster Spire, and similar proteins; This family contains the first of four tandem repeats of Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) in Drosophila melanogaster Spire (also called Spir), an actin nucleator essential for establishing an actin mesh during oogenesis. Spire was first identified as a Drosophila maternal effect gene essential to establishment of both the anterior/posterior and dorsal/ventral body axes in developing oocytes and embryos. It has been found to sever filaments and sequester monomers in addition to nucleating new filaments; it remains associated with the slow-growing pointed end of the new filament. Spire promotes dissociation of the actin nucleator Cappuccino (Capu) from the barbed end of actin filaments. Spire is involved in intracellular vesicle transport along actin fibers, providing a link between actin cytoskeleton dynamics and intracellular transport. Drosophila Spire contains four tandem WH2 domains which appear to function by determining the size of filament nuclei according to the number of WH2 repeats, suggesting that the WH2 domains of Spire line up actin subunits along a filament strand of the actin double helix, thereby generating nuclei for actin assembly. This model contains the first tandem WH2 domain of Spire (also called Spir-A or WH2-A).

                          10        20
                  ....*....|....*....|....*..
gi 1020532312 249 RDLNELQNADWARFWVQVMRDLRHGVK 275
Cdd:cd22067     1 QELAKLGFNDWARFWVQVIDELRRGVR 27

third tandem Wiskott-Aldrich Syndrome Homology (WASP) region 2 (WH2 motif) repeat found in Drosophila melanogaster Spire, and similar proteins; This family contains the third of four tandem repeats of Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) in Drosophila melanogaster Spire (also called Spir), an actin nucleator essential for establishing an actin mesh during oogenesis. Spire was first identified as a Drosophila maternal effect gene essential to establishment of both the anterior/posterior and dorsal/ventral body axes in developing oocytes and embryos. It has been found to sever filaments and sequester monomers in addition to nucleating new filaments; it remains associated with the slow-growing pointed end of the new filament. Spire promotes dissociation of the actin nucleator Cappuccino (Capu) from the barbed end of actin filaments. Spire is involved in intracellular vesicle transport along actin fibers, providing a link between actin cytoskeleton dynamics and intracellular transport. Drosophila Spire contains four tandem WH2 domains which appear to function by determining the size of filament nuclei according to the number of WH2 repeats, suggesting that the WH2 domains of Spire line up actin subunits along a filament strand of the actin double helix, thereby generating nuclei for actin assembly. This model contains the third tandem WH2 domain of Spire (also called Spir-C or WH2-C), which plays a unique role whereby two critical residues have been identified for activity for binding to actin with positive cooperativity.

                          10        20
                  ....*....|....*....|....*
gi 1020532312 324 KKSAHEIILEFIRSRPPLNPVSARK 348
Cdd:cd22068     2 KKDAHAMILEFIRSRPPLKKASDRQ 26

second, third, and fourth, tandem Wiskott-Aldrich Syndrome Homology (WASP) region 2 (WH2 motif) repeats of protein Spire; This family contains the Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) repeats 2-4 in human Spire (also called Spir), Drosophila Spire, and related proteins. Spire is an actin nucleator essential for establishing an actin mesh during oogenesis. This WH2-containing actin nucleator was first identified as a Drosophila maternal effect gene essential to establishment of both the anterior/posterior and dorsal/ventral body axes in developing oocytes and embryos. It has been found to sever filaments and sequester monomers in addition to nucleating new filaments; it remains associated with the slow-growing pointed end of the new filament. Spire is involved in intracellular vesicle transport along actin fibers, providing a novel link between actin cytoskeleton dynamics and intracellular transport. It is required for asymmetric spindle positioning and asymmetric cell division during oocyte meiosis. Spire contains four tandem WH2 domains. Several spire gene family members have been identified, including paralogs Spire-1 (Spir1) and Spire-2 (Spir2) in higher eukaryotes. Spire acts in the nucleus where, together with Spire-1 and Spire-2, it promotes assembly of nuclear actin filaments in response to DNA damage in order to facilitate movement of chromatin and repair factors after DNA damage. Spire-1 and Spire-2 encode a modified Fab1/YOTB/Vac1/EEA1 (FYVE)-type zinc finger membrane-binding domain at their C-termini that promiscuously interacts with negatively charged lipids and the interaction of these proteins with additional factors may provide the specificity for its targeting to the correct subpopulation of vesicles.

                          10        20
                  ....*....|....*....|...
gi 1020532312 292 QLTPYEMLMDDIRsKRYKLRKVM 314
Cdd:cd22066     1 QKSPHEMILEFIR-SRPPLKKVS 22

fourth tandem Wiskott-Aldrich Syndrome Homology (WASP) region 2 (WH2 motif) repeat of protein Spire homolog 2; This family contains the fourth tandem Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) domain in human Spire family protein Spire-2 (also called Spir2) and related proteins. Spire is an actin nucleator essential for establishing an actin mesh during oogenesis. It was first identified as a Drosophila maternal effect gene essential to establishment of both the anterior/posterior and dorsal/ventral body axes in developing oocytes and embryos. It has been found to sever filaments and sequester monomers in addition to nucleating new filaments; it remains associated with the slow-growing pointed end of the new filament. Spire is involved in intracellular vesicle transport along actin fibers, providing a novel link between actin cytoskeleton dynamics and intracellular transport. It is required for asymmetric spindle positioning and asymmetric cell division during oocyte meiosis. Spire contains four tandem WH2 domains. The mammalian genome encodes two Spire proteins, namely Spire-1 (Spir1) and Spire-2 (Spir2). This model contains WH2 domain 4 of Spire-2. Major expression of both spire genes have been detected during embryogenesis in the developing nervous system). In addition, spire2 expression is seen in early stages of intestinal development. In adult tissues, the spire2 gene shows a rather broad expression pattern, which includes the epithelial cells of the digestive tract, testical spermatocytes, and neuronal cells of the nervous system. Spire also acts in the nucleus where, together with Spire-1 and Spire-2, it promotes assembly of nuclear actin filaments in response to DNA damage in order to facilitate movement of chromatin and repair factors after DNA damage.

                          10
                  ....*....|....*....
gi 1020532312 358 SLHERILEGIRSERKLRPV 376
Cdd:cd22081     3 SLHEKILEEIKQERKLRPV 21