The Sema domain, a protein interacting module, of semaphorins and plexins; Both semaphorins and plexins have a Sema domain on their N-termini. Plexins function as receptors for the semaphorins. Evolutionarily, plexins may be the ancestor of semaphorins. Semaphorins are regulatory molecules in the development of the nervous system and in axonal guidance. They also play important roles in other biological processes, such as angiogenesis, immune regulation, respiration systems, and cancer. Semaphorins can be divided into 7 classes. Vertebrates have members in classes 3-7, whereas classes 1 and 2 are known only in invertebrates. Class 2 and 3 semaphorins are secreted; classes 1 and 4 through 6 are transmembrane proteins; and class 7 is membrane associated via glycosylphosphatidylinositol (GPI) linkage. Plexins are a large family of transmembrane proteins, which are divided into four types (A-D) according to sequence similarity. In vertebrates, type A plexins serve as co-receptors for neuropilins to mediate the signalling of class 3 semaphorins. Plexins serve as direct receptors for several other members of the semaphorin family: class 6 semaphorins signal through type A plexins and class 4 semaphorins through type B plexins. This family also includes the MET and RON receptor tyrosine kinases. The Sema domain is located at the N-terminus and contains four disulfide bonds formed by eight conserved cysteine residues. It serves to recognize and bind receptors.

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gi 41393505   1 EPTAISAMELSTKQQQLYIGSTAGVAQLPLHRCD 34
Cdd:cd11249 460 EPTAISAMELSTKQQQLYIGSAIGVSQLPLHRCD 493

The Sema domain, a protein interacting module, of semaphorin 3A (Sema3A); Sema3A has been reported to inhibit the growth of certain experimental tumors and to regulate endothelial cell migration and apoptosis in vitro, as well as arteriogenesis in the muscle, skin vessel permeability, and tumor angiogenesis in vivo. The function of Sema3A is mediated through receptors neuropilin-1 (NP1) and plexins, although little is known about the requirement of specific plexins in its receptor complex. It is known however that Plexin-A4 is the receptor for Sema3A in the Toll-like receptor- and sepsis-induced cytokine storm during immune response. Sema3A is a member of the Class 3 semaphorin family of secreted proteins. Semaphorins are regulatory molecules in the development of the nervous system and in axonal guidance. They also play important roles in other biological processes, such as angiogenesis, immune regulation, respiration systems and cancer. The Sema domain is located at the N-terminus and contains four disulfide bonds formed by eight conserved cysteine residues. It serves as a receptor-recognition and -binding module.

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gi 41393505   1 EPTAISAMELSTKQQQLYIGSTAGVAQLPLHRCD 34
Cdd:cd11249 460 EPTAISAMELSTKQQQLYIGSAIGVSQLPLHRCD 493

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

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gi 41393505   103 GVENSSTFLECSPKSQRAL----VYWQFQRRNEERKEEI--------------RVD--DHIIRTDQGLLLRSLQQKDSGN 162
Cdd:pfam07686   8 VALGGSVTLPCTYSSSMSEastsVYWYRQPPGKGPTFLIayysngseegvkkgRFSgrGDPSNGDGSLTIQNLTLSDSGT 87

                          90       100
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gi 41393505   163 YLCHAVEHGFIQTLLKVTLEV 183
Cdd:pfam07686  88 YTCAVIPSGEGVFGKGTRLTV 108

Immunoglobulin (Ig)-like domain at the C-terminus of semaphorins; The members here are composed of the immunoglobulin (Ig)-like domain in semaphorins. Semaphorins are transmembrane protein that have important roles in a variety of tissues. Functionally, semaphorins were initially characterized for their importance in the development of the nervous system and in axonal guidance. Later they have been found to be important for the formation and functioning of the cardiovascular, endocrine, gastrointestinal, hepatic, immune, musculoskeletal, renal, reproductive, and respiratory systems. Semaphorins function through binding to their receptors and transmembrane semaphorins also serves as receptors themselves. Although molecular mechanism of semaphorins is poorly understood, the Ig-like domains may be involved in ligand binding or dimerization.

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gi 41393505  95 SPEERIIYGvENSSTFLECSPKSQRALVYWQFQRRNEERKeeiRVDDHIIRTDQGLLLRSLQQKDSGNYLCHAVEHGFIQ 174
Cdd:cd04979   1 TSFKQISVK-EGDTVILSCSVKSNNAPVTWIHNGKKVPRY---RSPRLVLKTERGLLIRSAQEADAGVYECHSGERVLGS 76

                        90
                ....*....|..
gi 41393505 175 TLLKVTLEVIDT 186
Cdd:cd04979  77 TLRSVTLHVLER 88

The Sema domain, a protein interacting module, of class 3 semaphorins; Class 3 semaphorins (Sema3s) are secreted regulator molecules involved in the development of the nervous system, vasculogenesis, angiogenesis,and tumorigenesis. There are 7 distinct subfamilies named Sema3A to 3G. Sema3s function as repellent signals during axon guidance by repelling neurons away from the source of Sema3s. However, Sema3s that are secreted by tumor cells play an inhibitory role in tumor growth and angiogenesis (specifically Sema3B and Sema3F). Sema3s functions by forming complexes with neuropilins and A-type plexins, where neuropilins serve as the ligand binding moiety and the plexins function as signal transduction component. Sema3s primarily inhibit the cell motility and migration of tumor and endothelial cells by inducing collapse of the actin cytoskeleton via neuropilins and plexins. The Sema domain is located at the N-terminus and contains four disulfide bonds formed by eight conserved cysteine residues. It serves as a receptor-recognition and -binding module.

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gi 41393505   1 EPTAISAMELSTKQQQLYIGSTAGVAQLPLHRC 33
Cdd:cd11239 439 HPSPITSMEISSKRQQLYVGSAEGVVQLPLHRC 471

The Sema domain, a protein interacting module, of semaphorin 3D (Sema3D); Sema3D is a secreted semaphorin expressed during the development of the nervous system. In zebrafish, Sema3D is expressed in the ventral tectum. It guides retinal axons along the dorsoventral axis of the tectum and guides the laterality of retinal ganglion cell (RGC) projections. Both Sema3D knockdown or its ubiquitous overexpression induced aberrant ipsilateral projections. Proper balance of Sema3D is needed at the midline for the progression of RGC axons from the chiasm midline into the contralateral optic tract. Sema3D is a member of the class 3 semaphorin family of proteins. Semaphorins are regulatory molecules in the development of the nervous system and in axonal guidance. They also play important roles in other biological processes, such as angiogenesis, immune regulation, respiration systems and cancer. The Sema domain is located at the N-terminus and contains four disulfide bonds formed by eight conserved cysteine residues. It serves as a receptor-recognition and -binding module.

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gi 41393505   1 EPTAISAMELSTKQQQLYIGSTAGVAQLPLHRC 33
Cdd:cd11252 442 HPSPILNMELSLKQQQLYIGSRDGLVQLSLHRC 474

The Sema domain, a protein interacting module, of semaphorin 3F (Sema3F); Sema3F is coexpressed with semaphorin3B. Both Sema3B and Sema3F proteins are candidate tumor suppressors that are down-regulated in highly metastatic tumors. Two receptor families, the neuropilins and plexins, have been implicated in mediating the actions of semaphorins 3B and 3F. Sema3F is a member of the class 3 semaphorin family of proteins. Semaphorins are regulatory molecules in the development of the nervous system and in axonal guidance. They also play important roles in other biological processes, such as angiogenesis, immune regulation, respiration systems and cancer. The Sema domain is located at the N-terminus and contains four disulfide bonds formed by eight conserved cysteine residues. It serves as a receptor-recognition and -binding module.

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gi 41393505   1 EPTAISAMELSTKQQQLYIGSTAGVAQLPLHRC 33
Cdd:cd11254 438 VPAPIKTMKISSKRQQLYVSSAVGVTHLSLHRC 470

The Sema domain, a protein interacting module, of semaphorin 3E (Sema3E); Sema3E is a secreted molecule implicated in axonal path finding and inhibition of developmental and postischemic angiogenesis. It is also highly expressed in metastatic cancer cells. Sema3E signaling, through its high affinity functional receptor Plexin D1, drives cancer cell invasiveness and metastatic spreading. Sema3E is a member of the class 3 semaphorin family of proteins. Semaphorins are regulatory molecules in the development of the nervous system and in axonal guidance. They also play important roles in other biological processes, such as angiogenesis, immune regulation, respiration systems and cancer. The Sema domain is located at the N-terminus and contains four disulfide bonds formed by eight conserved cysteine residues. It serves as a receptor-recognition and -binding module.

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gi 41393505   2 PTAISAMELSTKQQQLYIGSTAGVAQLPLHRC 33
Cdd:cd11253 440 PVPIISMEISSKRQQLYIGSESGVAQIRFHQC 471

The Sema domain, a protein interacting module, of Plexin A2; Plexin A2 serves as a receptor for class 6 semaphorins. Interactions between Plexin A2, A4 and semaphorins 6A and 6B control the lamina-restricted projection of hippocampal mossy fibers. Sema6B also repels the growth of mossy fibers in a Plexin A4 dependent manner. Plexin A2 does not suppress Sema6B function. In addition, studies have shown that Plexin A2 may be related to anxiety and other psychiatric disorders. The Sema domain is located at the N-terminus and contains four disulfide bonds formed by eight conserved cysteine residues. It serves as a ligand-recognition and -binding module.

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gi 41393505   8 MELSTKQQQLYIGSTAGVAQLPLHRCDIYgKACAECCLARDPYCAWDG--SACSR 60
Cdd:cd11272 449 MAFSIDHKYLYVMSERQVSRVPVESCEQY-TTCGECLSSGDPHCGWCAlhNMCSR 502

Immunoglobulin (Ig)-like domain of semaphorin 4D (Sema4D) and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of semaphorin 4D (Sema4D) and similar proteins. Sema4D is a Class IV semaphorin. Semaphorins are classified based on structural features additional to the Sema domain. Sema4D has extracellular Sema and Ig domains, a transmembrane domain, and a short cytoplasmic domain. Sema4D plays a part in the development of GABAergic synapses. Sema4D in addition is an immune semaphorin. It is abundant on resting T cells; its expression is weak on resting B cells and antigen presenting cells (APCs), but is upregulated by various stimuli. The receptor used by Sema4D in the immune system is CD72. Sem4D enhances the activation of B cells and DCs through binding CD72, perhaps by reducing CD72s inhibitory signals. The receptor used by Sema4D in the non-lymphatic tissues is plexin-B1. Sem4D is anchored to the cell surface but its extracellular domain can be released from the cell surface by a metalloprotease-dependent process. Sem4D may mediate its effects in its membrane-bound form and/or its cleaved form.

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gi 41393505 111 LECSPKSQRALVYWQFQR---RNEERKEEIrvddhiirTDQGLLLRSLQQKDSGNYLCHAVEHG----FIQTLLKVTLEV 183
Cdd:cd05873  16 LKCSPKSNLARVVWKFQGkvlKAESPKYGL--------YGDGLLIFNASEADAGRYQCLSVEKSkaktFFQTVAKYVLEV 87

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

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gi 41393505 111 LECSPKSQRAL-VYWQfqRRNEERKEEIRVDDHIIRTDQGLLLRSLQQKDSGNYLCHA 167
Cdd:cd00096   3 LTCSASGNPPPtITWY--KNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVA 58

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 41393505    101 IYGVENSSTFLECSPKSQR-ALVYWQFQRrneerKEEIRVDDHIIRTDQG----LLLRSLQQKDSGNYLCHA 167
Cdd:smart00410   4 VTVKEGESVTLSCEASGSPpPEVTWYKQG-----GKLLAESGRFSVSRSGststLTISNVTPEDSGTYTCAA 70