Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034641939  47 PVIIARTDHIIVKEGNSALINCSVYGIPDPQFKWYnsigklLKEEEDEKERGGGKWQMHDSGLLNITKVSFSDRGKYTCV 126
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWY------KNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCV 75

                  ...
gi 1034641939 127 ASN 129
Cdd:pfam13927  76 ASN 78

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034641939  47 PVIIARTDHIIVKEGNSALINCSVYGIPDPQFKWYnsigklLKEEEDEKERGGGKWQMHDSGLLNITKVSFSDRGKYTCV 126
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWY------KNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCV 75

                  ...
gi 1034641939 127 ASN 129
Cdd:pfam13927  76 ASN 78

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 1034641939  64 ALINCSVYGIPDPQFKWYNSIGKLLKEEEDEKERGGGkwqmhdSGLLNITKVSFSDRGKYTCVASNIYGTVNNTVT 139
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELG------NGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034641939  47 PVIIARTDHIIVKEGNSALINCSVYGIPDPQFKWYnsigklLKEEEDEKERGGGKWQMHDSGLLNITKVSFSDRGKYTCV 126
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWY------KNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCV 75

                  ...
gi 1034641939 127 ASN 129
Cdd:pfam13927  76 ASN 78

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034641939  47 PVIIARTDHIIVKEGNSALINCSVYGIPDPQFKWYNsigkllkeeEDEKERGGGKWQMHDSG---LLNITKVSFSDRGKY 123
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFK---------DGQPLRSSDRFKVTYEGgtyTLTISNVQPDDSGKY 71

                          90
                  ....*....|....*....
gi 1034641939 124 TCVASNIYGTVNNTVTLRV 142
Cdd:pfam07679  72 TCVATNSAGEAEASAELTV 90

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034641939  56 IIVKEGNSALINCSVYGIPDPQFKWynSIGKLLKeeedekeRGGGKWQMHDSGLLNITKVSFSDRGKYTCVASNIYGTVN 135
Cdd:cd04969    12 ILAAKGGDVIIECKPKASPKPTISW--SKGTELL-------TNSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGKAN 82

                  ....*..
gi 1034641939 136 NTVTLRV 142
Cdd:cd04969    83 STGSLSV 89

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. 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. The Ig-like domain of the Twitchin is a member of the I-set 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. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034641939  56 IIVKEGNSALINCSVYGIPDPQFKWYNSigkllKEEEDEKERGGGKWQMHDSGLLnITKVSFSDRGKYTCVASNIYGTVN 135
Cdd:cd20949     9 TTVKEGQSATILCEVKGEPQPNVTWHFN-----GQPISASVADMSKYRILADGLL-INKVTQDDTGEYTCRAYQVNSIAS 82

                  ....*..
gi 1034641939 136 NTVTLRV 142
Cdd:cd20949    83 DMQERTV 89

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 1034641939  56 IIVKEGNSALINCSVYGIPDPQFKW-YNSIgkllkeeedEKERGGGKWQMHDSGLLnITKVSFSDRGKYTCVASNIYGTV 134
Cdd:cd20978    11 VVVKGGQDVTLPCQVTGVPQPKITWlHNGK---------PLQGPMERATVEDGTLT-IINVQPEDTGYYGCVATNEIGDI 80

                  ....*...
gi 1034641939 135 NNTVTLRV 142
Cdd:cd20978    81 YTETLLHV 88

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three IG-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034641939  58 VKEGNSALINCSVYGIPDPQFKWYNSigkllKEEEDEKERGGGKWQMHDSGLLNITKVSFSDRGKYTCVASNIYGTVNNT 137
Cdd:cd05857    16 VPAANTVKFRCPAAGNPTPTMRWLKN-----GKEFKQEHRIGGYKVRNQHWSLIMESVVPSDKGNYTCVVENEYGSINHT 90

                  ....*
gi 1034641939 138 VTLRV 142
Cdd:cd05857    91 YHLDV 95

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (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 1034641939  47 PVIIARTDHIIVKEGNSALINCSVYGIPDPQFKWYNSIGKLLKEEEDEKergggkwqMHDSGLLNITKVSFSDRGKYTCV 126
Cdd:cd05764     1 PLITRHTHELRVLEGQRATLRCKARGDPEPAIHWISPEGKLISNSSRTL--------VYDNGTLDILITTVKDTGAFTCI 72

                          90
                  ....*....|....*.
gi 1034641939 127 ASNIYGTVNNTVTLRV 142
Cdd:cd05764    73 ASNPAGEATARVELHI 88

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup 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. 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. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin 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. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034641939  55 HIIVKEGNSALINCSVYGIPDPQFKWYNSIGKLLKEEEdekergggKWQMH---DSGLLNITKVSFSDRGKYTCVASNIY 131
Cdd:cd05763     8 DITIRAGSTARLECAATGHPTPQIAWQKDGGTDFPAAR--------ERRMHvmpEDDVFFIVDVKIEDTGVYSCTAQNSA 79

                          90
                  ....*....|..
gi 1034641939 132 GTVNNTVTLRVI 143
Cdd:cd05763    80 GSISANATLTVL 91

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 1034641939  58 VKEGNSALINC-SVYGIPDPQFKWYNSiGKLLKEEEDEKERGGGKwqmHDSGLLNITKVSFSDRGKYTCVASNIYGTVNN 136
Cdd:cd05750    11 VQEGSKLVLKCeATSENPSPRYRWFKD-GKELNRKRPKNIKIRNK---KKNSELQINKAKLEDSGEYTCVVENILGKDTV 86

                  ....*.
gi 1034641939 137 TVTLRV 142
Cdd:cd05750    87 TGNVTV 92

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034641939  58 VKEGNSALINCSV-YGIPDPQFKWYNSIGKLLKEEEDEKERGGgkwQMHDSglLNITKVSFSDRGKYTCVASNIYGTVNN 136
Cdd:pfam00047   8 VLEGDSATLTCSAsTGSPGPDVTWSKEGGTLIESLKVKHDNGR---TTQSS--LLISNVTKEDAGTYTCVVNNPGGSATL 82

                  ....
gi 1034641939 137 TVTL 140
Cdd:pfam00047  83 STSL 86

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, 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 found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034641939  61 GNSALINCSVYGIPDPQFKWY-NSIGKLLKEEEDEKERGGGKwqmhdsgLLNITKVSFSDRGKYTCVASNIYGTVNNTVT 139
Cdd:cd05736    15 GVEASLRCHAEGIPLPRVQWLkNGMDINPKLSKQLTLIANGS-------ELHISNVRYEDTGAYTCIAKNEGGVDEDISS 87

                  ...
gi 1034641939 140 LRV 142
Cdd:cd05736    88 LFV 90

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034641939  60 EGNSALINCSVYGIPDPQFKWynsigkllkeeedekERGGG------KWQMHDSGLLNITKVSFSDRGKYTCVASNIYGT 133
Cdd:cd05745     1 EGQTVDFLCEAQGYPQPVIAW---------------TKGGSqlsvdrRHLVLSSGTLRISRVALHDQGQYECQAVNIVGS 65

                  ....*....
gi 1034641939 134 VNNTVTLRV 142
Cdd:cd05745    66 QRTVAQLTV 74

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 1034641939  58 VKEGNSALINCSVYGIPDPQFKWYNSigkllkeeeDEKERGGG-KWQMHDSGLLNITKVSFSDRGKYTCVASNIYGTVNN 136
Cdd:cd20952    11 VAVGGTVVLNCQATGEPVPTISWLKD---------GVPLLGKDeRITTLENGSLQIKGAEKSDTGEYTCVALNLSGEATW 81

                  ....*.
gi 1034641939 137 TVTLRV 142
Cdd:cd20952    82 SAVLDV 87

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034641939  55 HIIVKEGNSALINCSVYGIPDPQFKWYNSIGKLLKEEedekerggGKWQMHDSgLLNITKVSFSDRGKYTCVASNIYGTV 134
Cdd:cd05876     4 SLVALRGQSLVLECIAEGLPTPTVKWLRPSGPLPPDR--------VKYQNHNK-TLQLLNVGESDDGEYVCLAENSLGSA 74

                  ....*...
gi 1034641939 135 NNTVTLRV 142
Cdd:cd05876    75 RHAYYVTV 82

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034641939  55 HIIVKEGNSALINCSVYGIPDPQFKWYnsigkllkeeedekeRGG------GKWQMH---DSGLLNITKVSFSDRGKYTC 125
Cdd:cd05748     1 TIVVRAGESLRLDIPIKGRPTPTVTWS---------------KDGqplketGRVQIEttaSSTSLVIKNAKRSDSGKYTL 65

                          90
                  ....*....|....*..
gi 1034641939 126 VASNIYGTVNNTVTLRV 142
Cdd:cd05748    66 TLKNSAGEKSATINVKV 82

Second 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 second 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 the 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, and 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, 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 Slit-2 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 1034641939  61 GNSALINCSV-YGIPDPQFKWYNSIGKLLKEEEDEKERGGGKwqmhdsglLNITKVSFSDRGKYTCVASNIYGT 133
Cdd:cd05724    12 GEMAVLECSPpRGHPEPTVSWRKDGQPLNLDNERVRIVDDGN--------LLIAEARKSDEGTYKCVATNMVGE 77

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first 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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034641939  47 PVIIARTDHIIVKEGNS---ALINCSVYGIPDPQFKWYNSIGKLLKEEEDekergggKWQMHDSGLLNITKVSFSDRGKY 123
Cdd:cd04967     2 PVFEEQPDDTIFPEDSDekkVALNCRARANPVPSYRWLMNGTEIDLESDY-------RYSLVDGTLVISNPSKAKDAGHY 74

                          90       100
                  ....*....|....*....|..
gi 1034641939 124 TCVASNIYGTVNNT-VTLRVIF 144
Cdd:cd04967    75 QCLATNTVGSVLSReATLQFGY 96

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first 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 1034641939  47 PVIIARTDHIIVKEGNSALINCSVYGIPDPQFKWY---NSIGKLLKEEEDEKERGGgkwqmhdSGLLNITKVSFSDRGKY 123
Cdd:cd20974     1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFrdgQVISTSTLPGVQISFSDG-------RAKLSIPAVTKANSGRY 73

                          90
                  ....*....|....*....
gi 1034641939 124 TCVASNIYGTVNNTVTLRV 142
Cdd:cd20974    74 SLTATNGSGQATSTAELLV 92

First immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. 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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034641939  66 INCSVYGIPDPQFKWYNSIGKLLKEEEDEKERGGGkwqmhdsgLLNITKVSFSDRGKYTCVASNIYGTVNNT 137
Cdd:cd05849    24 VNCRARANPFPIYKWRKNNLDIDLTNDRYSMVGGN--------LVINNPDKYKDAGRYVCIVSNIYGKVRSR 87

Third immunoglobulin domain of the hematopoietic colony-stimulating factor 1 receptor (CSF-1R), and similar domains; member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the hematopoietic colony-stimulating factor 1 receptor (CSF-1R) and similar proteins. CSF-1R, a class III receptor tyrosine kinase (RTKIII), is critical to the survival, proliferation, and differentiation of mononuclear phagocytic cells such as monocytes, tissue macrophages, muscularis macrophages, microglia, osteoclasts, Paneth cells, and myeloid dendritic cells. Human colony-stimulating factor 1 receptor (hCSF-1R) is unique among the hematopoietic receptors because it is activated by two distinct cytokines, CSF-1 and interleukin-34 (IL-34). The Ig superfamily (IgSF) 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, 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. 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 I-set of IgSF domains.

                          10        20        30
                  ....*....|....*....|....*....|...
gi 1034641939 110 LNITKVSFSDRGKYTCVASNIYGTVNNTVTLRV 142
Cdd:cd20936    61 LNLDQVDFQDAGNYSCVASNVQGKHSASMFFRV 93

First immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. 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 1034641939  56 IIVKEGNSALINCSVYGIPDPQFKWYNSiGKLLKEEEDEkergggKWQMHDSGLLNITKVSFS-----DRGKYTCVASN- 129
Cdd:cd05722    11 IVAMRGGPVVLNCSAESDPPPKIEWKKD-GVLLNLVSDE------RRQQLPNGSLLITSVVHSkhnkpDEGFYQCVAQNe 83

                  ....*
gi 1034641939 130 IYGTV 134
Cdd:cd05722    84 SLGSI 88

C-terminal immunoglobulin (Ig)-like domain of myomesin and 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 myomesin and M-protein (also known as myomesin-2). Myomesin and M-protein are both structural proteins localized to the M-band, a transverse structure in the center of the sarcomere, and are candidates for M-band bridges. Both proteins are modular, consisting mainly of repetitive Ig-like and fibronectin type III (FnIII) domains. Myomesin is expressed in all types of vertebrate striated muscle; M-protein has a muscle-type specific expression pattern. Myomesin is present in both slow and fast fibers; M-protein is present only in fast fibers. It has been suggested that myomesin acts as a molecular spring with alternative splicing as a means of modifying its elasticity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034641939  42 VLGSVPviiartDHIIVKEGNSALINCSVYGIPDPQFKWYNSigkllKEEEDEKERGGGKWQMHDSGLLNITKVSFSDRG 121
Cdd:cd05737     3 VLGGLP------DVVTIMEGKTLNLTCNVWGDPPPEVSWLKN-----DQALAFLDHCNLKVEAGRTVYFTINGVSSEDSG 71

                          90       100
                  ....*....|....*....|.
gi 1034641939 122 KYTCVASNIYGTVNNTVTLRV 142
Cdd:cd05737    72 KYGLVVKNKYGSETSDVTVSV 92

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034641939  47 PVIIARTDHIIVKEGNSALINCSVYGIPDPQFKW-YNSIGKLLKEEEDEKERGGGKwqmHDsglLNITKVSFSDRGKYTC 125
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWqLNGKPVRPDSAHKMLVRENGR---HS---LIIEPVTKRDAGIYTC 74

                          90
                  ....*....|....*..
gi 1034641939 126 VASNIYGTVNNTVTLRV 142
Cdd:cd05744    75 IARNRAGENSFNAELVV 91

Immunoglobulin (Ig)-like domain found in Perlecan and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in Perlecan. Perlecan is a large multi-domain heparin sulfate proteoglycan, important in tissue development and organogenesis. Perlecan can be represented as 5 major portions; its fourth major portion (domain IV) is a tandem repeat of immunoglobulin-like domains (Ig2-Ig15) which can vary in size due to alternative splicing. Perlecan binds many cellular and extracellular ligands. Its domain IV region has many binding sites. Some of these have been mapped at the level of individual Ig-like domains, including a site restricted to the Ig5 domain for heparin/sulfatide, a site restricted to the Ig3 domain for nidogen-1 and nidogen-2, a site restricted to Ig4-5 for fibronectin, and sites restricted to Ig2 and to Ig13-15 for fibulin-2. 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
                  ....*....|....*....|....*....|....*....|....*..
gi 1034641939  97 RGGGKW--QMHDS-GLLNITKVSFSDRGKYTCVASNIYGTVNNTVTL 140
Cdd:cd05754    38 RVNGTLpsRAMDFnGILTIRNVQLSDAGTYVCTGSNMLDTDEATATL 84

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 1034641939  56 IIVKEGNSALINCSV---YGIPDPQFKWY---------NSIGKLLKEEEDEKERGGGKWQMHDS---GLLNITKVSFSDR 120
Cdd:pfam07686   6 VTVALGGSVTLPCTYsssMSEASTSVYWYrqppgkgptFLIAYYSNGSEEGVKKGRFSGRGDPSngdGSLTIQNLTLSDS 85

                          90       100
                  ....*....|....*....|...
gi 1034641939 121 GKYTC-VASNIYGTVNNTVTLRV 142
Cdd:pfam07686  86 GTYTCaVIPSGEGVFGKGTRLTV 108