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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24641984     51 NITGLVGKTVKLTCRVKNLGNRTVSWVRHRDIHLLTVGRYTYTSDQRfeamhsphaeDWTLRIRYAQRKDSGIYECQIST 130
Cdd:smart00410   3 SVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGS----------TSTLTISNVTPEDSGTYTCAATN 72

                   .
gi 24641984    131 T 131
Cdd:smart00410  73 S 73

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24641984     51 NITGLVGKTVKLTCRVKNLGNRTVSWVRHRDIHLLTVGRYTYTSDQRfeamhsphaeDWTLRIRYAQRKDSGIYECQIST 130
Cdd:smart00410   3 SVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGS----------TSTLTISNVTPEDSGTYTCAATN 72

                   .
gi 24641984    131 T 131
Cdd:smart00410  73 S 73

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24641984    42 PTFDTTIgTNITGLVGKTVKLTCRVKNLGNRTVSWvRHRDIHLLTVGRYTYTSDQrfeamhsphaEDWTLRIRYAQRKDS 121
Cdd:pfam07679   1 PKFTQKP-KDVEVQEGESARFTCTVTGTPDPEVSW-FKDGQPLRSSDRFKVTYEG----------GTYTLTISNVQPDDS 68

                  ....*.
gi 24641984   122 GIYECQ 127
Cdd:pfam07679  69 GKYTCV 74

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 24641984  56 VGKTVKLTCRVKNL-GNRTVSWVRHRD--------IHLLTVGRYTYTSDQRFEAMHSPhAEDWTLRIRYAQRKDSGIYEC 126
Cdd:cd00099  12 EGESVTLSCEVSSSfSSTYIYWYRQKPgqgpefliYLSSSKGKTKGGVPGRFSGSRDG-TSSFSLTISNLQPEDSGTYYC 90

                ....*.
gi 24641984 127 QISTTP 132
Cdd:cd00099  91 AVSESG 96

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24641984     51 NITGLVGKTVKLTCRVKNLGNRTVSWVRHRDIHLLTVGRYTYTSDQRfeamhsphaeDWTLRIRYAQRKDSGIYECQIST 130
Cdd:smart00410   3 SVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGS----------TSTLTISNVTPEDSGTYTCAATN 72

                   .
gi 24641984    131 T 131
Cdd:smart00410  73 S 73

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24641984    42 PTFDTTIgTNITGLVGKTVKLTCRVKNLGNRTVSWvRHRDIHLLTVGRYTYTSDQrfeamhsphaEDWTLRIRYAQRKDS 121
Cdd:pfam07679   1 PKFTQKP-KDVEVQEGESARFTCTVTGTPDPEVSW-FKDGQPLRSSDRFKVTYEG----------GTYTLTISNVQPDDS 68

                  ....*.
gi 24641984   122 GIYECQ 127
Cdd:pfam07679  69 GKYTCV 74

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24641984    153 PELHINRGSTINLTCIVKfaPEPPPTVIWSHNREIINFDSPRGGISLVTEKGVLTTSRLLVQkaitqDSGLYTCTPSNAN 232
Cdd:smart00410   2 PSVTVKEGESVTLSCEAS--GSPPPEVTWYKQGGKLLAESGRFSVSRSGSTSTLTISNVTPE-----DSGTYTCAATNSS 74

                           90
                   ....*....|.
gi 24641984    233 -----PTSVRV 238
Cdd:smart00410  75 gsassGTTLTV 85

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 24641984  56 VGKTVKLTCRVKNL-GNRTVSWVRHRD--------IHLLTVGRYTYTSDQRFEAMHSPhAEDWTLRIRYAQRKDSGIYEC 126
Cdd:cd00099  12 EGESVTLSCEVSSSfSSTYIYWYRQKPgqgpefliYLSSSKGKTKGGVPGRFSGSRDG-TSSFSLTISNLQPEDSGTYYC 90

                ....*.
gi 24641984 127 QISTTP 132
Cdd:cd00099  91 AVSESG 96

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 24641984 163 INLTCivKFAPEPPPTVIWSHNREIINFDSPRGGISlvtekgVLTTSRLLVQKAITQDSGLYTCTPSNANPTSVRVHI 240
Cdd:cd00096   1 VTLTC--SASGNPPPTITWYKNGKPLPPSSRDSRRS------ELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

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 24641984 155 LHINRGSTINLTCivKFAPEPPPTVIWSHNREIINFDSPRggISLVTEKGVLTtsrLLVQKAITQDSGLYTCTPSN 230
Cdd:cd05744  10 LEVQEGRLCRFDC--KVSGLPTPDLFWQLNGKPVRPDSAH--KMLVRENGRHS---LIIEPVTKRDAGIYTCIARN 78

First immunoglobulin variable (IgV) domain of poliovirus receptor (PVR, also known as CD155 and necl-5), and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of poliovirus receptor (PVR, also known as CD155 and nectin-like protein 5 (necl-5)). Poliovirus (PV) binds to its cellular receptor (PVR/CD155) to initiate infection. CD155 is a membrane-anchored, single-span glycoprotein; its extracellular region has three Ig-like domains. There are four different isotypes of CD155 (referred to as alpha, beta, gamma, and delta), that result from alternate splicing of the CD155 mRNA, and have identical extracellular domains. CD155-beta and CD155-gamma are secreted; CD155-alpha and CD155-delta are membrane-bound and function as PV receptors. The virus recognition site is contained in the amino-terminal domain, D1. Having the virus attachment site on the receptor distal from the plasma membrane may be important for successful initiation of infection of cells by the virus. CD155 binds in the poliovirus "canyon" with a footprint similar to that of the intercellular adhesion molecule-1 receptor on human rhinoviruses. This group also includes the first Ig-like domain of nectin-1 (also known as poliovirus receptor related protein(PVRL)1; CD111), nectin-3 (also known as PVRL 3), nectin-4 (also known as PVRL4; LNIR receptor)and DNAX accessory molecule 1 (DNAM-1; CD226).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24641984  50 TNITGLVGKTVKLTCRVKNLGNRT---VSWVRHRDIHLLTVGRYTYT--------SDQRFEAMHSPHA-EDWTLRIRYAQ 117
Cdd:cd05718   7 TEVTGFLGGSVTLPCSLTSPGTTKitqVTWMKIGAGSSQNVAVFHPQygpsvpnpYAERVEFLAARLGlRNATLRIRNLR 86

                        90
                ....*....|....*
gi 24641984 118 RKDSGIYECQISTTP 132
Cdd:cd05718  87 VEDEGNYICEFATFP 101

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24641984    50 TNITGLVGKTVKLTCRVKNLGNRTVSWVRHrdihlltvGRYTYTSDQRFEAMHSPHAedwTLRIRYAQRKDSGIYECQIS 129
Cdd:pfam13927   9 SSVTVREGETVTLTCEATGSPPPTITWYKN--------GEPISSGSTRSRSLSGSNS---TLTISNVTRSDAGTYTCVAS 77

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24641984 159 RGSTINLTCIVKFAPEPpptVIWSHN-REIINFDSPRGGIslVTEKGvlttsrLLVQKAITQDSGLYTC 226
Cdd:cd04979  10 EGDTVILSCSVKSNNAP---VTWIHNgKKVPRYRSPRLVL--KTERG------LLIRSAQEADAGVYEC 67

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. 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, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -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, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -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 is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 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. 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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24641984  51 NITGLVGKTVKLTCRVKNLGNRTVSWVRHrdihlltvGRYTYTSDQRFEAMhsphaEDWTLRIRYAQRKDSGIYECQIST 130
Cdd:cd20952   8 NQTVAVGGTVVLNCQATGEPVPTISWLKD--------GVPLLGKDERITTL-----ENGSLQIKGAEKSDTGEYTCVALN 74

                .
gi 24641984 131 T 131
Cdd:cd20952  75 L 75

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 24641984 147 TDIIGGP-ELHINRGSTINLTCIVKFAPEPPPTVIWSHNREIINFDSPRGGISLVTekGVLTTSRLLVQKAITQDSGLYT 225
Cdd:cd04970   3 TRITLAPsNADITVGENATLQCHASHDPTLDLTFTWSFNGVPIDLEKIEGHYRRRY--GKDSNGDLEIVNAQLKHAGRYT 80

                ..
gi 24641984 226 CT 227
Cdd:cd04970  81 CT 82

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24641984   149 IIGGPELHINRGSTINLTCIVKFAPepPPTVIWSHNREIINfdsprggislvtekgvlTTSRLLVQKAITQDSGLYTCTP 228
Cdd:pfam13895   3 VLTPSPTVVTEGEPVTLTCSAPGNP--PPSYTWYKDGSAIS-----------------SSPNFFTLSVSAEDSGTYTCVA 63

                  ..
gi 24641984   229 SN 230
Cdd:pfam13895  64 RN 65

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 24641984  52 ITGLVGKTVKLTCRVKNLGNRTVSWVrHRDIHLLTV---GRYTYTSDQrfeamhsphaedwTLRIRYAQRKDSGIYEC 126
Cdd:cd20969  12 VFVDEGHTVQFVCRADGDPPPAILWL-SPRKHLVSAksnGRLTVFPDG-------------TLEVRYAQVQDNGTYLC 75

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24641984 157 INRGSTINLTCivKFAPEPPPTVIWSHNREIINFDSPRGGISLVTEkGVLTTSRLLVQkaitqDSGLYTCTPSNA---NP 233
Cdd:cd20969  14 VDEGHTVQFVC--RADGDPPPAILWLSPRKHLVSAKSNGRLTVFPD-GTLEVRYAQVQ-----DNGTYLCIAANAggnDS 85

                ....*..
gi 24641984 234 TSVRVHI 240
Cdd:cd20969  86 MPAHLHV 92

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24641984 160 GSTINLTCIVkfAPEPPPTVIW---SHNRE--IINFDSPRGGIsLVTEKGvlttsRLLVQKAITQDSGLYTCTPSNA 231
Cdd:cd05765  15 GETASFHCDV--TGRPQPEITWekqVPGKEnlIMRPNHVRGNV-VVTNIG-----QLVIYNAQPQDAGLYTCTARNS 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 24641984 144 EPVtdIIGGPELHINRGSTINLTCiVKFAPEPPPTVIWSHNREIINfdsprGGIS----LVTEKGVLTTSRLLVQKAITQ 219
Cdd:cd05759   1 DPV--IEGGPVISLQAGVPYNLTC-RARGAKPAAEIIWFRDGEQLE-----GAVYskelLKDGKRETTVSTLLITPSDLD 72

                        90
                ....*....|....*.
gi 24641984 220 DSGLYTCTPSN-ANPT 234
Cdd:cd05759  73 TGRTFTCRARNeAIPN 88

C-terminal immunoglobulin (Ig)-like domain of M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of M-protein (also known as myomesin-2). M-protein is a structural protein localized to the M-band, a transverse structure in the center of the sarcomere, and is a candidate for M-band bridges. M-protein is modular consisting mainly of repetitive IG-like and fibronectin type III (FnIII) domains and has a muscle-type specific expression pattern. M-protein is present in fast fibers.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24641984 149 IIGG-PEL-HINRGSTINLTCIVkfAPEPPPTVIWSHNREIInfdSPRGGISLVTEKGVLTTsrLLVQKAITQDSGLYTC 226
Cdd:cd05891   3 VIGGlPDVvTIMEGKTLNLTCTV--FGNPDPEVIWFKNDQDI---ELSEHYSVKLEQGKYAS--LTIKGVTSEDSGKYSI 75

                ....
gi 24641984 227 TPSN 230
Cdd:cd05891  76 NVKN 79

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.

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gi 24641984  51 NITGLVGKTVKLTCRVKNLGNRTVSWvrHRDIHLLTVGRYtytsDQRfeamhsphaEDWTLRIRYAQRKDSGIYECQ 127
Cdd:cd05725   6 NQVVLVDDSAEFQCEVGGDPVPTVRW--RKEDGELPKGRY----EIL---------DDHSLKIRKVTAGDMGSYTCV 67

CD19 (Cluster of Differentiation 19), a unique double immunoglobulin (Ig)-fold protodomain 3 and 4; CD19, also known as B-Lymphocyte Surface Antigen B4, T-Cell Surface Antigen Leu-12, and CVID3, is a transmembrane receptor present on various types of B cells, including progenitor, naive, and memory B cells, as well as plasmablasts. Until recently, it was believed to comprise two extracellular immunoglobulin (Ig) structural domains arranged in tandem with C2 topology. However, recent crystal structures have shown that the CD19 extracellular domain contains a unique double Ig domain that is responsible for its binding to proteins such as CD21, CD81, and CD225, which regulate B cell activation and survival. A recent analysis of the CD19 extracellular domain sequence reveals two "Ig domains", but the structure demonstrates that these two domains are not folded independently and connected in tandem. Rather, they fold together as one intertwined domain that can be referred to as a "double Ig" domain. Each of the two regular Ig domain sequences has a noticeably short linker that forms a loop between strands C' and D, rather than allowing the formation of a C" strand. Additionally, the two Ig-domain sequences are separated by a long linker that is structured as a small insertion domain, enabling both Ig sequences to fold together as a unique double Ig-domain. The CD19 domain comprises four "protodomains": two formed by A'B-CC' strands and two by DE-FG strands that interdigitate to form a novel double Ig fold. When analyzing this double Ig domain in terms of the usual Ig-fold, A'B-CC' protodomain of the first Ig sequence combines with DE-FG protodomain of the second, and vice versa. Hence, the second combined Ig fold is inverted, with DE-FG protodomain of the first Ig sequence combining with A'B-CC' protodomain of the second Ig sequence and in that order, as if it were a circular permutation, obtained only through structural folding. This group contains the protodomains 3 and 4 of the CD19 double Ig domain.

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gi 24641984 154 ELHINRGSTINLTCIVKFAPEPPPTVIWSHNReiinfdSPRGGISL----------VTEKGVLTTSR----LLVQKAITQ 219
Cdd:cd23998   2 DLTVAPGSTLWLSCGVPPDSGTRGPISWTHVH------PKPSNTSLlslelkedrpAREKWVLGTLRggalLLLPRATAQ 75

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gi 24641984 220 DSGLYTCTPSN 230
Cdd:cd23998  76 DAGIYHCHLGN 86

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.

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gi 24641984  56 VGKTVKLTCRVKNLGNRTVSWvRHRDIHLLTVGRYTYTSDQRfeamhsphaedwtLRIRYAQRKDSGIYEC 126
Cdd:cd20957  15 FGRTAVFNCSVTGNPIHTVLW-MKDGKPLGHSSRVQILSEDV-------------LVIPSVKREDKGMYQC 71