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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 440214598  274 VIAGTRSHVTCTAIGARPPPEIIWSKAGQIVRGATSSTS--SDGN--TTISELMLIPVPEDNERQVVCSislnagITSQQ 349
Cdd:cd05759    12 LQAGVPYNLTCRARGAKPAAEIIWFRDGEQLEGAVYSKEllKDGKreTTVSTLLITPSDLDTGRTFTCR------ARNEA 85

                          90
                  ....*....|
gi 440214598  350 LHEGHTTVMT 359
Cdd:cd05759    86 IPNGKETSIT 95

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 440214598   178 LEGDSIDLTCLSSGGvPPPRVSWWRE-HALIDDSFQVLPDGSVRNVLRLKNIQRKDLLTmYTCQASN 243
Cdd:pfam13927   14 REGETVTLTCEATGS-PPPTITWYKNgEPISSGSTRSRSLSGSNSTLTISNVTRSDAGT-YTCVASN 78

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 440214598    719 PEPVKNCTAYNATANSLQIQCIPGYDGGIP---QHFHAQIYDELNRQILYNASYKYSEFTVKRLPSDSVFVIRITAVNAQ 795
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGITgyiVGYRVEYREEGSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVNGA 80

                    ...
gi 440214598    796 GAS 798
Cdd:smart00060   81 GEG 83

Second immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3 (also known as Neph2). This protein has five Ig-like domains, one transmembrane domain, and a cytoplasmic tail. Included in this group is mammalian Kirrel (Neph1), Kirrel2 (Neph3), and Drosophila RST (irregular chiasm C-roughest) protein. These proteins contain multiple Ig domains, have properties of cell adhesion molecules, and are important in organ development.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 440214598  274 VIAGTRSHVTCTAIGARPPPEIIWSKAGQIVRGATSSTS--SDGN--TTISELMLIPVPEDNERQVVCSislnagITSQQ 349
Cdd:cd05759    12 LQAGVPYNLTCRARGAKPAAEIIWFRDGEQLEGAVYSKEllKDGKreTTVSTLLITPSDLDTGRTFTCR------ARNEA 85

                          90
                  ....*....|
gi 440214598  350 LHEGHTTVMT 359
Cdd:cd05759    86 IPNGKETSIT 95

Immunoglobulin I-set domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 440214598   400 GTDVYLECDVKANPAITrVEWYHSDKQLHSSRGIIISN----QTLVLQGISKSSHGQYFCRASNLQGSVSS 466
Cdd:pfam07679   15 GESARFTCTVTGTPDPE-VSWFKDGQPLRSSDRFKVTYeggtYTLTISNVQPDDSGKYTCVATNSAGEAEA 84

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 440214598  399 KGTDVYLECDVKANPAITrVEWYHSDKQL-HSSRGIIISNQTLVLQGISKSSHGQYFCRASNLQGSVSSNEvYLDV 473
Cdd:cd04969    16 KGGDVIIECKPKASPKPT-ISWSKGTELLtNSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGKANSTG-SLSV 89

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

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 440214598    179 EGDSIDLTCLSSgGVPPPRVSWWREHA---LIDDSFQVLPDGSvRNVLRLKNIQRKDlLTMYTCQASNGH 245
Cdd:smart00410    8 EGESVTLSCEAS-GSPPPEVTWYKQGGkllAESGRFSVSRSGS-TSTLTISNVTPED-SGTYTCAATNSS 74

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 440214598    42 SEILTAVGSEVALPCDLVPGTgiVDKVQLVIWYRQGNVKPIYTFDARGRPLNlgipwaDESVFNKKAHFHHDTDPP--AL 119
Cdd:pfam07686    4 REVTVALGGSVTLPCTYSSSM--SEASTSVYWYRQPPGKGPTFLIAYYSNGS------EEGVKKGRFSGRGDPSNGdgSL 75

                           90       100       110
                   ....*....|....*....|....*....|....
gi 440214598   120 RIKNIQTSDAGLYKCRVDFHKSPTRNWRINVTVL 153
Cdd:pfam07686   76 TIQNLTLSDSGTYTCAVIPSGEGVFGKGTRLTVL 109

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 440214598    719 PEPVKNCTAYNATANSLQIQCIPGYDGGIP---QHFHAQIYDELNRQILYNASYKYSEFTVKRLPSDSVFVIRITAVNAQ 795
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGITgyiVGYRVEYREEGSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVNGA 80

                    ...
gi 440214598    796 GAS 798
Cdd:smart00060   81 GEG 83

Second immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3 (also known as Neph2). This protein has five Ig-like domains, one transmembrane domain, and a cytoplasmic tail. Included in this group is mammalian Kirrel (Neph1), Kirrel2 (Neph3), and Drosophila RST (irregular chiasm C-roughest) protein. These proteins contain multiple Ig domains, have properties of cell adhesion molecules, and are important in organ development.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 440214598  274 VIAGTRSHVTCTAIGARPPPEIIWSKAGQIVRGATSSTS--SDGN--TTISELMLIPVPEDNERQVVCSislnagITSQQ 349
Cdd:cd05759    12 LQAGVPYNLTCRARGAKPAAEIIWFRDGEQLEGAVYSKEllKDGKreTTVSTLLITPSDLDTGRTFTCR------ARNEA 85

                          90
                  ....*....|
gi 440214598  350 LHEGHTTVMT 359
Cdd:cd05759    86 IPNGKETSIT 95

Immunoglobulin I-set domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 440214598   400 GTDVYLECDVKANPAITrVEWYHSDKQLHSSRGIIISN----QTLVLQGISKSSHGQYFCRASNLQGSVSS 466
Cdd:pfam07679   15 GESARFTCTVTGTPDPE-VSWFKDGQPLRSSDRFKVTYeggtYTLTISNVQPDDSGKYTCVATNSAGEAEA 84

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 440214598  399 KGTDVYLECDVKANPAITrVEWYHSDKQL-HSSRGIIISNQTLVLQGISKSSHGQYFCRASNLQGSVSSNEvYLDV 473
Cdd:cd04969    16 KGGDVIIECKPKASPKPT-ISWSKGTELLtNSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGKANSTG-SLSV 89

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 440214598  403 VYLECDVKANPAITrVEWYHSDKQL----HSSRGIIISNQTLVLQGISKSSHGQYFCRASNLQGSVSSNEV 469
Cdd:cd00096     1 VTLTCSASGNPPPT-ITWYKNGKPLppssRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. 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. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 440214598  399 KGTDVYLECDVKANPaITRVEWYHSDKQLHSSRGIIISNQ----TLVLQGISKSSHGQYFCRASNLQGSVSSN-EVYL 471
Cdd:cd20972    15 EGSKVRLECRVTGNP-TPVVRWFCEGKELQNSPDIQIHQEgdlhSLIIAEAFEEDTGRYSCLATNSVGSDTTSaEIFV 91

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 440214598  400 GTDVYLECDVKANPaITRVEWYHSDKQLHSS-RGIIISNQTLVLQGISKSS-HGQYFCRASNLQGSVSSNEVYLDV 473
Cdd:cd20958    15 GQTLRLHCPVAGYP-ISSITWEKDGRRLPLNhRQRVFPNGTLVIENVQRSSdEGEYTCTARNQQGQSASRSVFVKV 89

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

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 440214598    179 EGDSIDLTCLSSgGVPPPRVSWWREHA---LIDDSFQVLPDGSvRNVLRLKNIQRKDlLTMYTCQASNGH 245
Cdd:smart00410    8 EGESVTLSCEAS-GSPPPEVTWYKQGGkllAESGRFSVSRSGS-TSTLTISNVTPED-SGTYTCAATNSS 74

Second immunoglobulin (Ig)-like domain of nectin-like molecule 2 (Necl-2); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molecule 2 (Necl-2; also known as cell adhesion molecule 1 (CADM1)). Nectin-like molecules (Necls) have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. Necl-2 has Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is expressed in a wide variety of tissues and is a putative tumour suppressor gene which is downregulated in aggressive neuroblastoma. Ig domains are likely to participate in ligand binding and recognition.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 440214598  260 LPPLSLLLQGLNHAVIAGTRSHVTCTAIGARPPPEIIWSKAGQIVRGATS--STSSDGNTTISELMLIPVPEDNERQVVC 337
Cdd:cd05883     2 VPPRNLVIDIQKDTAVEGEEIELNCTAMASKPAATIRWFKGNKELTGKSEveEWYSRMFTVTSQLMLKVTKEDDGVPVIC 81

                  ..
gi 440214598  338 SI 339
Cdd:cd05883    82 LV 83

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. 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. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 440214598  388 LGAPLDPDNLL--KGTDVYLECDVKANPAITrVEWYHSDKQL-HSSRGIIISNQTLVLQGISKSSHGQYFCRASN 459
Cdd:cd20957     2 LSATIDPPVQTvdFGRTAVFNCSVTGNPIHT-VLWMKDGKPLgHSSRVQILSEDVLVIPSVKREDKGMYQCFVRN 75

Second immunoglobulin (Ig) domain of Nectin-2 and Nectin-like protein 5, and similar domains; member of the C1-set of the Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig) domain of nectin-2 (also known as poliovirus receptor related protein 2 or Cluster of Differentiation 112 (CD112)), nectin-like protein 5 (CD155), and similar proteins. Nectins and Nectin-like molecules are a family of Ca(2+)-independent immunoglobulin-like transmembrane glycoproteins belonging to the class of adhesion receptors, consisting of nine members (nectins 1 through 4 and nectin-like proteins 1 through 5). Nectins are synaptic cell adhesion molecules (CAMs) which facilitate adhesion and signaling at various intracellular junctions. Nectins form homophilic cis-dimers, followed by homophilic and heterophilic trans-dimers involved in cell-cell adhesion. Nectin-2 and nectin-3 localize at Sertoli-spermatid junctions where they form heterophilic trans-interactions between the cells that are essential for the formation and maintenance of the junctions and for spermatid development. CD155 is the fifth member in the nectin-like molecule family, and functions as the receptor of poliovirus; therefore, CD155 is also referred to as Necl-5, or PVR. In contrast to all other family members, CD155 lacks self-adhesion capacity, yet it shares with nectins the feature to interact with other nectins. For instance, CD155 heterophilically trans-interacts with nectin-3, thereby contributing significantly to the establishment of adherens junctions between epithelial cells. This group belongs to the Constant 1 (C1)-set of IgSF domains, which has one beta-sheet that is formed by strands A-B-E-D and the other strands by G-F-C-C'.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 440214598  271 NHA----VIAGTRSHV--TCTAIGARPPPEIIWSKAGQIVRGATSSTSSDGNT-TI-SELMLIPVPEDNERQVVCSIS 340
Cdd:cd07703     3 NSAeaqeVQAGGIPVPvaRCVSANGRPPARISWSSTLNGNANTTQVPGPDSGTvTVtSEYSLVPTPEANGKEVTCKVE 80

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 440214598  398 LKGTDVYLECDVKANPAiTRVEWYHSDKQLHSSRGIIIS-NQTLVLQGISKSSHGQYFCRASNLQGSVS 465
Cdd:cd05731     8 LRGGVLLLECIAEGLPT-PDIRWIKLGGELPKGRTKFENfNKTLKIENVSEADSGEYQCTASNTMGSAR 75

First immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs), and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs). Interactions between IgG and FcgammaR are important to the initiation of cellular and humoral response. IgG binding to FcgammaR leads to a cascade of signals and ultimately to functions such as antibody-dependent-cellular-cytotoxicity (ADCC), endocytosis, phagocytosis, release of inflammatory mediators, etc. FcgammaR has two Ig-like domains. This group also contains FcepsilonRI which binds IgE with high affinity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 440214598  392 LDP--DNLLKGTDVYLECDVKANPAITRVEWYHSDKQLHSSRgiiiSNQTLVLQGISKSshGQYFCRAsnlQGSVSSNEV 469
Cdd:cd05752     5 LDPpwTTVFQGEKVTLTCQGFYSPEQNSTQWYHNGTLISSTS----SSYRIVAATVNDS--GEYRCQT---QGSSLSDPV 75

                  ....
gi 440214598  470 YLDV 473
Cdd:cd05752    76 HLEV 79

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. 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. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 440214598  178 LEGDSIDLTCLSSGGvPPPRVSWWREHALI---DDSFQVLPDGSvrnVLRLKNIQRKDlLTMYTCQASNGhVVPALTKKV 254
Cdd:cd20970    15 REGENATFMCRAEGS-PEPEISWTRNGNLIiefNTRYIVRENGT---TLTIRNIRRSD-MGIYLCIASNG-VPGSVEKRI 88

                  ..
gi 440214598  255 IL 256
Cdd:cd20970    89 TL 90

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 440214598    42 SEILTAVGSEVALPCDLVPGTgiVDKVQLVIWYRQGNVKPIYTFDARGRPLNlgipwaDESVFNKKAHFHHDTDPP--AL 119
Cdd:pfam07686    4 REVTVALGGSVTLPCTYSSSM--SEASTSVYWYRQPPGKGPTFLIAYYSNGS------EEGVKKGRFSGRGDPSNGdgSL 75

                           90       100       110
                   ....*....|....*....|....*....|....
gi 440214598   120 RIKNIQTSDAGLYKCRVDFHKSPTRNWRINVTVL 153
Cdd:pfam07686   76 TIQNLTLSDSGTYTCAVIPSGEGVFGKGTRLTVL 109

Third immunoglobulin domain in Cluster of Differentiation (CD) 22; member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain in Cluster of Differentiation (CD) 22 (also known as Siglec-2). CD22, a sialic-acid binding immunoglobulin type-lectin (Siglec) family member, is an inhibitory co-receptor of the B-cell receptor (BCR). The inhibitory function of CD22 and its restricted expression on B cells makes CD22 an attractive target against dysregulated B cells that cause autoimmune diseases and B-cell-derived cancers. CD22 plays a vital role in establishing a baseline level of B-cell inhibition, and thus is an important determinant of homeostasis in humoral immunity. Siglecs are primarily expressed on immune cells and recognize sialic acid-containing glycan ligands. Siglecs are organized as an extracellular module composed of Ig-like domains (an N-terminal variable set of Ig-like carbohydrate recognition domains, and 1 to 16 constant Ig-like domains), followed by transmembrane and short cytoplasmic domains. Human Siglecs are classified into two subgroups, one subgroup is comprised of sialoadhesin (Siglec-1), CD22 (Siglec-2), and MAG (Siglec-4, myelin-associated glycoprotein), the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11. 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. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 440214598  399 KGTDVYLECDVKA-NPAITRVEWYHSDKQLHSSRGIiisnqTLVLQGISKSSHGQYFCRASNLQGSVSSNEVYLDVKY 475
Cdd:cd20937    16 EGDSVTMTCEVSSsNPEYTTVSWLKDGTSLKKQNTF-----TLNLREVTKDQSGKYCCQVSNDVGPGRSEEVFLQVQY 88

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains, five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 440214598  398 LKGTDVYLECDVKANPAITrVEWYHSDKQLHSSRGIIIS-NQTLVLQGISKSSHGQYFCRASNLQGSV 464
Cdd:cd05876     8 LRGQSLVLECIAEGLPTPT-VKWLRPSGPLPPDRVKYQNhNKTLQLLNVGESDDGEYVCLAENSLGSA 74

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 440214598  396 NLLKGTDVYLECDVKANPAITrVEWYHSD-------KQLHSSRGI-IISNQTLVLQGISKSSHGQYFCRASNLQGSVSSN 467
Cdd:cd20954    12 NVAAGQDVMLHCQADGFPTPT-VTWKKATgstpgeyKDLLYDPNVrILPNGTLVFGHVQKENEGHYLCEAKNGIGSGLSK 90

                  ....*.
gi 440214598  468 EVYLDV 473
Cdd:cd20954    91 VIFLKV 96

Third immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F (also known as LAR), type IIa; member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains. Included in this group is Drosophila LAR (DLAR).

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 440214598  180 GDSIDLTCLSSGGvPPPRVSWWREHALIDDSFQvLPDGsvRNVLRLKNIQRKdllTMYTCQA 241
Cdd:cd05739    12 GGSVNLTCVAVGA-PMPYVKWMKGGEELTKEDE-MPVG--RNVLELTNIYES---ANYTCVA 66

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

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 440214598     42 SEILTAVGSEVALPCDlVPGtgivDKVQLVIWYRQGNVKPIYtfdargrplnlgipwadesvfNKKAHFHHDTDPPALRI 121
Cdd:smart00410    2 PSVTVKEGESVTLSCE-ASG----SPPPEVTWYKQGGKLLAE---------------------SGRFSVSRSGSTSTLTI 55

                            90       100       110
                    ....*....|....*....|....*....|.
gi 440214598    122 KNIQTSDAGLYKCRVDFhKSPTRNWRINVTV 152
Cdd:smart00410   56 SNVTPEDSGTYTCAATN-SSGSASSGTTLTV 85

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 440214598  169 IRDQTAGPYLEGDSIDLTCLSsGGVPPPRVSWwrehaLIDDSF-QVLPDGSVRNV----LRLKNIQRKDLlTMYTCQASN 243
Cdd:cd04978     3 IIEPPSLVLSPGETGELICEA-EGNPQPTITW-----RLNGVPiEPAPEDMRRTVdgrtLIFSNLQPNDT-AVYQCNASN 75

                  ..
gi 440214598  244 GH 245
Cdd:cd04978    76 VH 77

Second immunoglobulin (Ig)-like domain of nectin-like molecule-3 (Necl-3); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molecule-3 (Necl-3; also known as cell adhesion molecule 2 (CADM2)). Nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. Necl-3 has been shown to accumulate in tissues of the central and peripheral nervous system where it is expressed in ependymal cells and myelinated axons. It is observed at the interface between the axon shaft and the myelin sheath. Ig domains are likely to participate in ligand binding and recognition.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 440214598  176 PYLEGDSIDLTCLSSGGVPPPRVSWWREHALIDDSFQVLPDGSVRNVLRLKN-----IQRKDLLTMYTCQ 240
Cdd:cd05884    16 PVMEGDHIQLTCKTSGSKPAADIRWFKNDKEVKDVKYLKAEDANRKTFTVSSsldfhVDRDDDGVAITCR 85

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 440214598  192 GVPPPRVSWWREHALIDDSFQV--LPDGSvrnvLRLKNIQRKDLlTMYTCQASN 243
Cdd:cd04969    28 ASPKPTISWSKGTELLTNSSRIciLPDGS----LKIKNVTKSDE-GKYTCFAVN 76

Immunoglobulin variable domain (IgV); The members here are composed of the immunoglobulin variable domain (IgV). The IgV family contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology, and are components of immunoglobulin (Ig) and T cell receptors. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. Within the variable domain, there are regions of even more variability called the hypervariable or complementarity-determining regions (CDRs) which are responsible for antigen binding. A predominant feature of most Ig domains is the disulfide bridge connecting 2 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" strands in the other.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 440214598   30 EQHPATadegplseILTAVGSEVALPCDlVPGTGIVDKVQlviWYRQgnvKP------IYTFDARGRPLNLGIPWADESV 103
Cdd:cd00099     2 TQSPRS--------LSVQEGESVTLSCE-VSSSFSSTYIY---WYRQ---KPgqgpefLIYLSSSKGKTKGGVPGRFSGS 66

                          90       100       110
                  ....*....|....*....|....*....|.
gi 440214598  104 FNKKAHFHhdtdppaLRIKNIQTSDAGLYKC 134
Cdd:cd00099    67 RDGTSSFS-------LTISNLQPEDSGTYYC 90

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 440214598  180 GDSIDLTCLSSGgVPPPRVSWWREHA---------LIDDSFQVLPDGSvrnvLRLKNIQrKDLLTMYTCQASNGhVVPAL 250
Cdd:cd20954    16 GQDVMLHCQADG-FPTPTVTWKKATGstpgeykdlLYDPNVRILPNGT----LVFGHVQ-KENEGHYLCEAKNG-IGSGL 88

                  ....*.
gi 440214598  251 TKKVIL 256
Cdd:cd20954    89 SKVIFL 94

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. 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. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 440214598  178 LEGDSIDLTCLSSGGvPPPRVSWWREHALI--DDSFQVLPDGSvrnvLRLKNIQRKDlLTMYTCQASN 243
Cdd:cd20968    12 IEGLKAVLPCTTMGN-PKPSVSWIKGDDLIkeNNRIAVLESGS----LRIHNVQKED-AGQYRCVAKN 73