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 21704168  20 YSLSVTGSVTVQEGLCVFVACQVQYP---NSKGPVFGYWFREGANIFSGSPVATNDPQRSVLKEAQGRFYLMGKENSHNC 96
Cdd:cd05712   1 WGLQMPKSVTVQEGLCVLIPCSFSYPadyWVSNPVHGYWYRGGPYPKYRPPVATNNRTREVHESTQGRFRLLGDPGKKNC 80

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 21704168  97 SLDIRDAQKIDTGTYFFRLD--GSVKYSFQKSMLSVLVI 133
Cdd:cd05712  81 SLSISDARPEDSGKYFFRVErgDSNKYSYLSNQLSLTVT 119

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21704168    252 SLQIQEGESLSLVCMADSNPPAVLSWERPTQKP------FQLS---TPAELQLPRAELEDQGKYICQAQNSQGAQTASVS 322
Cdd:smart00410   3 SVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLlaesgrFSVSrsgSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTT 82

                   ...
gi 21704168    323 LSI 325
Cdd:smart00410  83 LTV 85

Immunoglobulin Variable (IgV) domain at the N-terminus of CD33 and related Siglecs (sialic acid-binding Ig-like lectins); The members here are composed of the immunoglobulin (Ig) domain at the N-terminus of Cluster of Differentiation (CD) 33 and related Siglecs (sialic acid-binding Ig-like lectins). Siglec refers to a structurally related protein family that specifically recognizes sialic acid in oligosaccharide chains of glycoproteins and glycolipids. Siglecs are type I transmembrane proteins, 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, the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21704168  20 YSLSVTGSVTVQEGLCVFVACQVQYP---NSKGPVFGYWFREGANIFSGSPVATNDPQRSVLKEAQGRFYLMGKENSHNC 96
Cdd:cd05712   1 WGLQMPKSVTVQEGLCVLIPCSFSYPadyWVSNPVHGYWYRGGPYPKYRPPVATNNRTREVHESTQGRFRLLGDPGKKNC 80

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 21704168  97 SLDIRDAQKIDTGTYFFRLD--GSVKYSFQKSMLSVLVI 133
Cdd:cd05712  81 SLSISDARPEDSGKYFFRVErgDSNKYSYLSNQLSLTVT 119

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21704168    252 SLQIQEGESLSLVCMADSNPPAVLSWERPTQKP------FQLS---TPAELQLPRAELEDQGKYICQAQNSQGAQTASVS 322
Cdd:smart00410   3 SVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLlaesgrFSVSrsgSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTT 82

                   ...
gi 21704168    323 LSI 325
Cdd:smart00410  83 LTV 85

Fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains; member of the C2-set IgSF domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains. The CEA family is a group of anchored or secreted glycoproteins, expressed by epithelial cells, leukocytes, endothelial cells and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), also known as CD66e (Cluster of Differentiation 66e), is a cell surface glycoprotein that plays a role in cell adhesion, intracellular signaling and tumor progression. Diseases associated with CEACAM5 include lung cancer and rectum cancer. 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 21704168 249 SGASLQIQEGESLSLVCMADSNPPAVLSWErpTQKPFQLSTpAELQLPRAELEDQGKYICQAQNSQGAQTASVSLSI 325
Cdd:cd20948   1 SPSDTYYLSGENLNLSCHAASNPPAQYSWT--INGTFQTSS-QELFLPAITENNEGTYTCSAHNSLTGKNISLVLSV 74

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21704168   133 IALTEVPNIQVTSTLVSGNStKLLCSVPWacEQGTPPIFSWMSSALTSLGHRT-TLSSELNLTPRPQDNGTNLTCQVNLP 211
Cdd:pfam08205   7 ASLLEGEGPEVVATCSSAGG-KPAPRITW--YLDGKPLEAAETSSEQDPESGLvTVTSELKLVPSRSDHGQSLTCQVSYG 83

                  .
gi 21704168   212 G 212
Cdd:pfam08205  84 A 84

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21704168     26 GSVTVQEGLCVFVACQVqypNSKGPVFGYWFREGanifsGSPVATNdpqrsvlkeaqGRFYLmgKENSHNCSLDIRDAQK 105
Cdd:smart00410   2 PSVTVKEGESVTLSCEA---SGSPPPEVTWYKQG-----GKLLAES-----------GRFSV--SRSGSTSTLTISNVTP 60

                           90       100
                   ....*....|....*....|....*
gi 21704168    106 IDTGTYFFRLDGSVKYSFQKSMLSV 130
Cdd:smart00410  61 EDSGTYTCAATNSSGSASSGTTLTV 85

Immunoglobulin Variable (IgV) domain at the N-terminus of CD33 and related Siglecs (sialic acid-binding Ig-like lectins); The members here are composed of the immunoglobulin (Ig) domain at the N-terminus of Cluster of Differentiation (CD) 33 and related Siglecs (sialic acid-binding Ig-like lectins). Siglec refers to a structurally related protein family that specifically recognizes sialic acid in oligosaccharide chains of glycoproteins and glycolipids. Siglecs are type I transmembrane proteins, 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, the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21704168  20 YSLSVTGSVTVQEGLCVFVACQVQYP---NSKGPVFGYWFREGANIFSGSPVATNDPQRSVLKEAQGRFYLMGKENSHNC 96
Cdd:cd05712   1 WGLQMPKSVTVQEGLCVLIPCSFSYPadyWVSNPVHGYWYRGGPYPKYRPPVATNNRTREVHESTQGRFRLLGDPGKKNC 80

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 21704168  97 SLDIRDAQKIDTGTYFFRLD--GSVKYSFQKSMLSVLVI 133
Cdd:cd05712  81 SLSISDARPEDSGKYFFRVErgDSNKYSYLSNQLSLTVT 119

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21704168    252 SLQIQEGESLSLVCMADSNPPAVLSWERPTQKP------FQLS---TPAELQLPRAELEDQGKYICQAQNSQGAQTASVS 322
Cdd:smart00410   3 SVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLlaesgrFSVSrsgSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTT 82

                   ...
gi 21704168    323 LSI 325
Cdd:smart00410  83 LTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 21704168   245 KVLQSGASLQIQEGESLSLVCMADSNPPAVLSWER--------PTQKPFQLSTPAELQLPRAELEDQGKYICQAQN 312
Cdd:pfam13927   3 VITVSPSSVTVREGETVTLTCEATGSPPPTITWYKngepissgSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

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 21704168    26 GSVTVQEGLCVFVACQVQYPNSKGPVFGYWFREGANIFSGSPVATNDPQRSVLKEaQGRFYLMGKENSHNCSLDIRDAQK 105
Cdd:pfam07686   4 REVTVALGGSVTLPCTYSSSMSEASTSVYWYRQPPGKGPTFLIAYYSNGSEEGVK-KGRFSGRGDPSNGDGSLTIQNLTL 82

                          90       100
                  ....*....|....*....|....*..
gi 21704168   106 IDTGTYFFRLDGSVKYSFQKSM-LSVL 131
Cdd:pfam07686  83 SDSGTYTCAVIPSGEGVFGKGTrLTVL 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 21704168 261 LSLVCMADSNPPAVLSWER--------PTQKPFQLSTPAELQLPRAELEDQGKYICQAQNSQGAQTAS 320
Cdd:cd00096   1 VTLTCSASGNPPPTITWYKngkplppsSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASA 68

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third 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. This group belongs to the I-set of IgSF domains.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 21704168 258 GESLSLVCMADSNPPAVLSWERPTQKPF----QLSTPAELQLPRAELEDQGKYICQAQNSQGAQTA 319
Cdd:cd04968  16 GQTVTLECFALGNPVPQIKWRKVDGSPSsqweITTSEPVLEIPNVQFEDEGTYECEAENSRGKDTV 81

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. 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 21704168 258 GESLSLVCMADSNPPAVLSWER-----PTQKpFQLSTPAELQLPRAELEDQGKYICQAQNSQGAQTASVSLSI 325
Cdd:cd05725  12 DDSAEFQCEVGGDPVPTVRWRKedgelPKGR-YEILDDHSLKIRKVTAGDMGSYTCVAENMVGKIEASATLTV 83

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21704168 255 IQEGESLSLVCMADSNPPAV-LSW-----ERPTQKPFQLSTP-----AELQLPRAELEDQGKYICQAQNSQGAQTASVSL 323
Cdd:cd05750  11 VQEGSKLVLKCEATSENPSPrYRWfkdgkELNRKRPKNIKIRnkkknSELQINKAKLEDSGEYTCVVENILGKDTVTGNV 90

                ..
gi 21704168 324 SI 325
Cdd:cd05750  91 TV 92

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. 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 Lingo-1 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 21704168 257 EGESLSLVCMADSNPPAVLSWERPTQKPFQLST--------PAELQLPRAELEDQGKYICQAQNSQGAQTASVSLSI 325
Cdd:cd20969  16 EGHTVQFVCRADGDPPPAILWLSPRKHLVSAKSngrltvfpDGTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHLHV 92

Immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1; The members here are composed of the immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. NRG-1 belongs to the neuregulin gene family which is comprised of four genes. This group represents NRG-1. NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, and heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. The NRG-1 protein binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. NRG-1 has multiple functions, for example, in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21704168 247 LQSGASLQIQEGESLSLVCMADSNPPAV-LSWER------PTQKPFQLSTP-----AELQLPRAELEDQGKYICQAQNSQ 314
Cdd:cd05895   3 LKEMKSQEVAAGSKLVLRCETSSEYPSLrFKWFKngkeinRKNKPENIKIQkkkkkSELRINKASLADSGEYMCKVSSKL 82

                        90
                ....*....|.
gi 21704168 315 GAQTASVSLSI 325
Cdd:cd05895  83 GNDSASANVTI 93

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21704168   133 IALTEVPNIQVTSTLVSGNStKLLCSVPWacEQGTPPIFSWMSSALTSLGHRT-TLSSELNLTPRPQDNGTNLTCQVNLP 211
Cdd:pfam08205   7 ASLLEGEGPEVVATCSSAGG-KPAPRITW--YLDGKPLEAAETSSEQDPESGLvTVTSELKLVPSRSDHGQSLTCQVSYG 83

                  .
gi 21704168   212 G 212
Cdd:pfam08205  84 A 84

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 21704168 247 LQSGASLQIQEGESLSLVCMADSNPPAVLSW-----ERPTQKPFQLSTPAELQ---LPRAELEDQGKYICQAQNSQGAQT 318
Cdd:cd20972   5 IQKLRSQEVAEGSKVRLECRVTGNPTPVVRWfcegkELQNSPDIQIHQEGDLHsliIAEAFEEDTGRYSCLATNSVGSDT 84

                ....*..
gi 21704168 319 ASVSLSI 325
Cdd:cd20972  85 TSAEIFV 91

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as 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. 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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21704168 255 IQEGESLSLVCMADSNPPAVLSWERPTQ-------KPFQL------STPAELQLPRAELEDQGKYICQAQNSQGAQTASV 321
Cdd:cd05765  12 VKVGETASFHCDVTGRPQPEITWEKQVPgkenlimRPNHVrgnvvvTNIGQLVIYNAQPQDAGLYTCTARNSGGLLRANF 91

                ....
gi 21704168 322 SLSI 325
Cdd:cd05765  92 PLSV 95

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 21704168 258 GESLSLVCMADSNPPAVLSWER-----PTQKPFQLSTpAELQLPRAELEDQGKYICQAQNSQGAQTASVSLSI 325
Cdd:cd05728  14 GSSLRWECKASGNPRPAYRWLKngqplASENRIEVEA-GDLRITKLSLSDSGMYQCVAENKHGTIYASAELAV 85

Second immunoglobulin domain of Cluster of Differentiation (CD) 22; member of the Constant 1 (C1)-set of IgSF domains; The members here are composed of the second immunoglobulin domain of clusters 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 C1-set of IgSF domains.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21704168 139 PNIQVTSTLVSGNSTKLLCSVPWACeQGTPPIFSWM-------SSALTSLGHRTT---LSSELNLTPRPQDNGTNLTCQV 208
Cdd:cd20938   3 PHIQLPPEIQESQEVTLTCLLNFSC-YGYPIQLQWLlegspmrQAAVTSTSLTIKsvfTRSELKFQPKWSHHGKIVTCQL 81

                        90
                ....*....|....*..
gi 21704168 209 NLPGTGVTVERTQQLSV 225
Cdd:cd20938  82 QDADGKVLSEDTVQLNV 98

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 21704168 249 SGASLQIQEGESLSLVCMADSNPPAVLSWER-----PTQKPFQLSTPAELQLPRAELEDQGKYICQAQNSQGA 316
Cdd:cd05876   1 SSSSLVALRGQSLVLECIAEGLPTPTVKWLRpsgplPPDRVKYQNHNKTLQLLNVGESDDGEYVCLAENSLGS 73

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and similar proteins; member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and related proteins. The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. The VEGFR family consists of three members: VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1) and VEGFR-3 (Flt-4). VEGF-A interacts with both VEGFR-1 and VEGFR-2. VEGFR-1 binds strongest to VEGF; VEGF-2 binds more weakly. VEGFR-3 appears not to bind VEGF, but binds other members of the VEGF family (VEGF-C and -D). VEGFRs bind VEGFs with high affinity with the IG-like domains. VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-2 is a major mediator of the mitogenic, angiogenic, and microvascular permeability-enhancing effects of VEGF-A. VEGFR-1 may play an inhibitory part in these processes by binding VEGF and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. VEGFR-3 has been shown to be involved in tumor angiogenesis and growth. This group also contains alpha-type platelet-derived growth factor receptor precursor (PDGFR)-alpha (CD140a), and PDGFR-beta (CD140b). PDGFRs alpha and beta have an extracellular component with five Ig-like domains, a transmembrane segment, and a cytoplasmic portion that has protein tyrosine kinase activity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21704168 258 GESLSLVCMADSNPPAV--LSWERPTQKPFQLSTPAE---------------LQLPRAELEDQGKYICQAqnSQGAQTAS 320
Cdd:cd05742  17 GETLVLNCTANVNLNEVvdFQWTYPSEKEGKLALLKPdikvdwsepgefvstLTIPEATLKDSGTYTCAA--RSGVMKKE 94

                ....*.
gi 21704168 321 VSLSIR 326
Cdd:cd05742  95 KQTSVS 100

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. 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 this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus 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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21704168 253 LQIQEGESLSLVCMADSNPPAVLSW---ERPTQKPFQLSTP----AELQLPRAELEDQGKYICQAQNSQGAQTASVSLSI 325
Cdd:cd20976  11 LEAVEGQDFVAQCSARGKPVPRITWirnAQPLQYAADRSTCeagvGELHIQDVLPEDHGTYTCLAKNAAGQVSCSAWVTV 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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 21704168 255 IQEGESLSLVCMADSNPPAVLSWERPTQkpfqlSTPAE-----------------LQLPRAELEDQGKYICQAQNSQGA 316
Cdd:cd20954  13 VAAGQDVMLHCQADGFPTPTVTWKKATG-----STPGEykdllydpnvrilpngtLVFGHVQKENEGHYLCEAKNGIGS 86

Fifth 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 fifth 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 (also known as Neph1), Kirrel2 (also known as Neph3), and Drosophila RST (also known as 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 21704168 337 SFEGQGLHCSCSSRAWPAP-SLRWRLGEGVLEGNSSnGSFTVKSSSAGQWANSSLILSMEFSSNHRLS--CEAW 407
Cdd:cd05758  13 AILGEKARLECLVFSSPPPdRIVWSWDEGFLESGSS-GRFSVETFPTEPGVISVLHISGTQRSDFQTSfnCSAW 85