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 1008446962 265 PNDLLSIHKPQNVKCETSGSYPPAKLTWLLDGKPIRNAVVTEEV-TDSFTGSIIS---LNVVADNDGKDLVCRANNPRFP 340
Cdd:cd05759     8 PVISLQAGVPYNLTCRARGAKPAAEIIWFRDGEQLEGAVYSKELlKDGKRETTVStllITPSDLDTGRTFTCRARNEAIP 87

                  ..
gi 1008446962 341 GG 342
Cdd:cd05759    88 NG 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
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1008446962 169 GPFLEGDELFLSCQVTGGRPRPSLTWWHNNTLIDGVVD----SSETSFTIVNQLT 219
Cdd:cd05761    14 SPVVEGDEITLTCTTSGSKPAADIRWFKNDKELKGVKEvqesGAGKTFTVTSTLR 68

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1008446962 580 DGGLHQSFVLEVNDVtipspppgvttlsDQGEAKLLYRALGDKPMFRLHSLHPGREYQIMVYAENAKGRSEP 651
Cdd:cd00063    27 DGGPITGYVVEYREK-------------GSGDWKEVEVTPGSETSYTLTGLKPGTEYEFRVRAVNGGGESPP 85

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 1008446962 265 PNDLLSIHKPQNVKCETSGSYPPAKLTWLLDGKPIRNAVVTEEV-TDSFTGSIIS---LNVVADNDGKDLVCRANNPRFP 340
Cdd:cd05759     8 PVISLQAGVPYNLTCRARGAKPAAEIIWFRDGEQLEGAVYSKELlKDGKRETTVStllITPSDLDTGRTFTCRARNEAIP 87

                  ..
gi 1008446962 341 GG 342
Cdd:cd05759    88 NG 89

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 1008446962  32 PAKVIWGVLGKDVELPCDITPPIPSDNFkMVFWFKDTDGMPLYSLDARGGPLGEASHLamsddlGSRSYFIKDEQPSKAR 111
Cdd:pfam07686   2 TPREVTVALGGSVTLPCTYSSSMSEAST-SVYWYRQPPGKGPTFLIAYYSNGSEEGVK------KGRFSGRGDPSNGDGS 74

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1008446962 112 LRIRNVTIHDEGVFRCRVDFDNSPTRNFQVNLTLV 146
Cdd:pfam07686  75 LTIQNLTLSDSGTYTCAVIPSGEGVFGKGTRLTVL 109

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 1008446962 376 VTLRCDSSARPSPYgYRWYHDGHLVALNESGGVLPI--DHILTLKSIQKKSQGQYACFATNTEGGSYSSPF 444
Cdd:cd00096     1 VTLTCSASGNPPPT-ITWYKNGKPLPPSSRDSRRSElgNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

Second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 - Necl-4; member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 (also known as cell adhesion molecule 3 or CADM3), Necl-2 (also known as CADM1), Necl-3 (also known as CADM2) and Necl-4 (also known as CADM4). These 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. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1 and Necl-2 have Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue and is important to the formation of synapses, axon bundles, and myelinated axons. Necl-2 is expressed in a wide variety of tissues, and is a putative tumour suppressor gene, which is downregulated in aggressive neuroblastoma. 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. Necl-4 is expressed on Schwann cells, and plays a key part in initiating peripheral nervous system (PNS) myelination. Necl-4 participates in cell-cell adhesion and is proposed to play a role in tumor suppression.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1008446962 169 GPFLEGDELFLSCQVTGGRPRPSLTWWHNNTLIDGVVD----SSETSFTIVNQLT 219
Cdd:cd05761    14 SPVVEGDEITLTCTTSGSKPAADIRWFKNDKELKGVKEvqesGAGKTFTVTSTLR 68

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1008446962 172 LEGDELFLSCQVTGGrPRPSLTWWHNNTLIDGVVDSSETSFTIVNQLT 219
Cdd:pfam13927  14 REGETVTLTCEATGS-PPPTITWYKNGEPISSGSTRSRSLSGSNSTLT 60

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1008446962 580 DGGLHQSFVLEVNDVtipspppgvttlsDQGEAKLLYRALGDKPMFRLHSLHPGREYQIMVYAENAKGRSEP 651
Cdd:cd00063    27 DGGPITGYVVEYREK-------------GSGDWKEVEVTPGSETSYTLTGLKPGTEYEFRVRAVNGGGESPP 85

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 1008446962 265 PNDLLSIHKPQNVKCETSGSYPPAKLTWLLDGKPIRNAVVTEEV-TDSFTGSIIS---LNVVADNDGKDLVCRANNPRFP 340
Cdd:cd05759     8 PVISLQAGVPYNLTCRARGAKPAAEIIWFRDGEQLEGAVYSKELlKDGKRETTVStllITPSDLDTGRTFTCRARNEAIP 87

                  ..
gi 1008446962 341 GG 342
Cdd:cd05759    88 NG 89

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 1008446962  32 PAKVIWGVLGKDVELPCDITPPIPSDNFkMVFWFKDTDGMPLYSLDARGGPLGEASHLamsddlGSRSYFIKDEQPSKAR 111
Cdd:pfam07686   2 TPREVTVALGGSVTLPCTYSSSMSEAST-SVYWYRQPPGKGPTFLIAYYSNGSEEGVK------KGRFSGRGDPSNGDGS 74

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1008446962 112 LRIRNVTIHDEGVFRCRVDFDNSPTRNFQVNLTLV 146
Cdd:pfam07686  75 LTIQNLTLSDSGTYTCAVIPSGEGVFGKGTRLTVL 109

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1008446962 368 SPVKEGTDVTLRCDSSARPsPYGYRWYHDGHlvALNESGGVLpidhiltLKSIQKKSQGQYACFATNTEGGSYSSPFDLI 447
Cdd:pfam13895   9 TVVTEGEPVTLTCSAPGNP-PPSYTWYKDGS--AISSSPNFF-------TLSVSAEDSGTYTCVARNGRGGKVSNPVELT 78

                  .
gi 1008446962 448 I 448
Cdd:pfam13895  79 V 79

Second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 - Necl-4; member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 (also known as cell adhesion molecule 3 or CADM3), Necl-2 (also known as CADM1), Necl-3 (also known as CADM2) and Necl-4 (also known as CADM4). These 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. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1 and Necl-2 have Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue and is important to the formation of synapses, axon bundles, and myelinated axons. Necl-2 is expressed in a wide variety of tissues, and is a putative tumour suppressor gene, which is downregulated in aggressive neuroblastoma. 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. Necl-4 is expressed on Schwann cells, and plays a key part in initiating peripheral nervous system (PNS) myelination. Necl-4 participates in cell-cell adhesion and is proposed to play a role in tumor suppression.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1008446962 277 VKCETSGSYPPAKLTWLLDGKPIRNA--VVTEEVTDSFT-GSIISLNVVADNDGKDLVCRANNPRFPGGSLEDRRQIHV 352
Cdd:cd05761    24 LTCTTSGSKPAADIRWFKNDKELKGVkeVQESGAGKTFTvTSTLRFRVDRDDDGVAVICRVDHESLTSTPKQTQQVLEV 102

Immunoglobulin (Ig)-like domain of myelin oligodendrocyte glycoprotein (MOG); The members here are composed of the immunoglobulin (Ig)-like domain of myelin oligodendrocyte glycoprotein (MOG). MOG, a minor component of the myelin sheath, is an important CNS-specific autoantigen, linked to the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). It is a transmembrane protein having an extracellular Ig domain. MOG is expressed in the CNS on the outermost lamellae of the myelin sheath, and on the surface of oligodendrocytes, and may participate in the completion, compaction, and/or maintenance of myelin. This group also includes butyrophilin (BTN). BTN is the most abundant protein in bovine milk-fat globule membrane (MFGM).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1008446962  32 PAKVIWGVLGKDVELPCDITPPIPSDNFKmVFWFKDTDGMP--LYsldaRGGPlgEASHLAMSDDLGsRSYFIKD--EQP 107
Cdd:cd05713     6 PTEPILALVGEDAELPCHLSPKMSAEHME-VRWFRSQFSPVvhLY----RDGQ--DQEEEQMPEYRG-RTELLKDaiAEG 77

                          90       100
                  ....*....|....*....|....*..
gi 1008446962 108 SKArLRIRNVTIHDEGVFRCRVDFDNS 134
Cdd:cd05713    78 SVA-LRIHNVRPSDEGQYTCFFRSGSF 103

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. 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. The fourth Ig-like domain of hemolin 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 domains, members of the I-set have a discontinuous A strand but lack a C" strand. 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 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 1008446962 356 PKVSVKLDSGVNspVKEGTDVTLRCDSSARPSPYgYRWYHDG-HLVALNESGGVlpIDHILTLKSIQKKSQGQYACFATN 434
Cdd:cd20978     1 PKFIQKPEKNVV--VKGGQDVTLPCQVTGVPQPK-ITWLHNGkPLQGPMERATV--EDGTLTIINVQPEDTGYYGCVATN 75

                  ....*....
gi 1008446962 435 TEGGSYSSP 443
Cdd:cd20978    76 EIGDIYTET 84

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1008446962 373 GTDVTLRCdssarpsPY-GY-----RWYHDGHLvalnesggvLPIDH--------ILTLKSIQKKS-QGQYACFATNTEG 437
Cdd:cd20958    15 GQTLRLHC-------PVaGYpissiTWEKDGRR---------LPLNHrqrvfpngTLVIENVQRSSdEGEYTCTARNQQG 78

                          90
                  ....*....|.
gi 1008446962 438 GSYSSPFDLII 448
Cdd:cd20958    79 QSASRSVFVKV 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1008446962 276 NVKCETSGsYPPAKLTWLLDGKPIRNAVVTEEVTDSFTGSIISLNVVADNDGKdLVCRANNP 337
Cdd:cd00096     2 TLTCSASG-NPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGT-YTCVASNS 61

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1008446962 356 PKVSVKLDSGVnspVKEGTDVTLRCDSSARPSPyGYRWYHDGHLvaLNESGGVL----PIDHILTLKSIQKKSQGQYACF 431
Cdd:pfam07679   1 PKFTQKPKDVE---VQEGESARFTCTVTGTPDP-EVSWFKDGQP--LRSSDRFKvtyeGGTYTLTISNVQPDDSGKYTCV 74

                          90
                  ....*....|....*..
gi 1008446962 432 ATNtEGGSYSSPFDLII 448
Cdd:pfam07679  75 ATN-SAGEAEASAELTV 90

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF 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 1008446962 370 VKEGTDVTLRCDSSARPSPYGYrWYHDGHLVA--------LNESGgvlpiDHILTLKSIQKKSQGQYACFATNTEG 437
Cdd:cd05744    12 VQEGRLCRFDCKVSGLPTPDLF-WQLNGKPVRpdsahkmlVRENG-----RHSLIIEPVTKRDAGIYTCIARNRAG 81

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 1008446962 358 VSVKLDSGVNSpVKEGTDVTLRCDSSARPSpYGYRWYHDGHLVALNESGGVLPIDhILTLKSIQKKSQGQYACFATN 434
Cdd:cd20957     2 LSATIDPPVQT-VDFGRTAVFNCSVTGNPI-HTVLWMKDGKPLGHSSRVQILSED-VLVIPSVKREDKGMYQCFVRN 75

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1008446962 172 LEGDELFLSCQVTGGrPRPSLTWWHNNTLIDGVVDSSETSFTIVNQLT 219
Cdd:pfam13927  14 REGETVTLTCEATGS-PPPTITWYKNGEPISSGSTRSRSLSGSNSTLT 60

Sixth immunoglobulin (Ig) domain of contactin; The members here are composed of the sixth 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1008446962 367 NSPVKEGTDVTLRCDSSARPS-PYGYRWYHDGHLVALNESGG------VLPIDHILTLKSIQKKSQGQYACFAtNTEGGS 439
Cdd:cd04970    11 NADITVGENATLQCHASHDPTlDLTFTWSFNGVPIDLEKIEGhyrrryGKDSNGDLEIVNAQLKHAGRYTCTA-QTVVDS 89

                          90
                  ....*....|...
gi 1008446962 440 YSSPFDLIIQYAP 452
Cdd:cd04970    90 DSASATLVVRGPP 102

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 1008446962  44 VELPCDIT-PPIPSdnfkmVFWFKDtdgmplysldarGGPLGEASHLAMSDDLGSrsyfikdeqpskARLRIRNVTIHDE 122
Cdd:cd00096     1 VTLTCSASgNPPPT-----ITWYKN------------GKPLPPSSRDSRRSELGN------------GTLTISNVTLEDS 51

                  ....*..
gi 1008446962 123 GVFRCRV 129
Cdd:cd00096    52 GTYTCVA 58

CD80-like C2-set immunoglobulin domain; These domains belong to the immunoglobulin superfamily.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1008446962 173 EGDELFLSCQVTGGRPRPSLTWWHNNTLIDGVVDSSETS-----FTIVNQLtrRHTPRSFWKSH-LECRASSSAIAGD 244
Cdd:pfam08205  13 EGPEVVATCSSAGGKPAPRITWYLDGKPLEAAETSSEQDpesglVTVTSEL--KLVPSRSDHGQsLTCQVSYGALRGS 88

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule 1(NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-non-NCAM) interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1008446962 376 VTLRCDSSARPSPyGYRWYHDGHLVALNES---GGVLPIDHI----LTLKSIQKKSQGQYACFATNTEG 437
Cdd:cd05869    20 ITLTCEASGDPIP-SITWRTSTRNISSEEKtldGHIVVRSHArvssLTLKYIQYTDAGEYLCTASNTIG 87

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1008446962 356 PKVSVKLDSGvNSPVKEGTDVTLRCD-SSARPSPYGYRWYHDGhlVALNESGGVLpidhiLTLKSIQKKSQGQYACFATN 434
Cdd:cd20937     1 PKLEIKVTPS-DAIVREGDSVTMTCEvSSSNPEYTTVSWLKDG--TSLKKQNTFT-----LNLREVTKDQSGKYCCQVSN 72

                          90
                  ....*....|....*.
gi 1008446962 435 TEGGSYSSPFDLIIQY 450
Cdd:cd20937    73 DVGPGRSEEVFLQVQY 88

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
                  ....*....|....*....|....*....|....*....|....*.
gi 1008446962 171 FLEGDELFLSCQVTGGRPRPSLTWWHNNTLIdgvvDSSETSFTIVN 216
Cdd:cd05752    12 VFQGEKVTLTCQGFYSPEQNSTQWYHNGTLI----SSTSSSYRIVA 53

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1008446962 355 PPKVSVKLDSgvnSPVKEGTDVTLRCDSSARPSPYgYRWYHDGHL------VALNESGGVlpidHILTLKSIQKKSQGQY 428
Cdd:cd20972     1 PPQFIQKLRS---QEVAEGSKVRLECRVTGNPTPV-VRWFCEGKElqnspdIQIHQEGDL----HSLIIAEAFEEDTGRY 72

                          90
                  ....*....|....
gi 1008446962 429 ACFATNTEGGSYSS 442
Cdd:cd20972    73 SCLATNSVGSDTTS 86

Fibronectin type III domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1008446962 608 DQGEAKLLYRALGDKPMFRLHSLHPGREYQIMVYAENAKGRSEP 651
Cdd:pfam00041  41 NSGEPWNEITVPGTTTSVTLTGLKPGTEYEVRVQAVNGGGEGPP 84

Second immunoglobulin (Ig)-like domain of protein tyrosine kinase (PTK) 7; The members here are composed of the second immunoglobulin (Ig)-like domain in protein tyrosine kinase (PTK) 7, also known as CCK4. PTK7 is a subfamily of the receptor protein tyrosine kinase family, and is referred to as an RPTK-like molecule. RPTKs transduce extracellular signals across the cell membrane and play important roles in regulating cell proliferation, migration, and differentiation. PTK7 is organized as an extracellular portion having seven Ig-like domains, a single transmembrane region, and a cytoplasmic tyrosine kinase-like domain. PTK7 is considered a pseudokinase as it has several unusual residues in some of the highly conserved tyrosine kinase (TK) motifs; it is predicted to lack TK activity. PTK7 may function as a cell-adhesion molecule. PTK7 mRNA is expressed at high levels in placenta, melanocytes, liver, lung, pancreas, and kidney. PTK7 is overexpressed in several cancers, including melanoma and colon cancer lines.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1008446962 368 SPVKEGTDVTLRCDSSARPSPYgYRWYHDGhlVALNESGGVLPI---DHILTLKSIQKKSQGQYACFATNTEGGSYSS 442
Cdd:cd05760    11 AEIQPSSRVTLRCHIDGHPRPT-YQWFRDG--TPLSDGQGNYSVsskERTLTLRSAGPDDSGLYYCCAHNAFGSVCSS 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1008446962  39 VLGKDVELPCDIT-PPIPSdnfkmVFWFKDtdgmplysldarGGPLGEASHLAMSDDLGSRSyfikdeqpskarLRIRNV 117
Cdd:pfam13927  14 REGETVTLTCEATgSPPPT-----ITWYKN------------GEPISSGSTRSRSLSGSNST------------LTISNV 64

                          90
                  ....*....|..
gi 1008446962 118 TIHDEGVFRCRV 129
Cdd:pfam13927  65 TRSDAGTYTCVA 76