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 21358003 141 PDIINEESSADLAVQEGEDATLTCKATGNPQPRVTWRREDGEMILIRKpgsRELMKVesyNGSSLRLLRLERRQMGAYLC 220
Cdd:cd20970   1 PVISTPQPSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNT---RYIVRE---NGTTLTIRNIRRSDMGIYLC 74

                        90
                ....*....|....*...
gi 21358003 221 IASNDVPPAVSKRVSLSV 238
Cdd:cd20970  75 IASNGVPGSVEKRITLQV 92

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 21358003  47 NVTYPAGREAILACSVRNLGKNKVGWLRASDQTVLALQGRVVTHNaRISVMHQDMHTWKLKISKLRESDRGCYMCQINTS 126
Cdd:cd05882   6 DETVAVGGTVTLKCGVKEHDNSSLQWSNTAQQTLYFGEKRALRDN-RIQLVKSTPTELIISISNVQLSDEGEYTCSIFTM 84

                ...
gi 21358003 127 PMK 129
Cdd:cd05882  85 PVR 87

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21358003 141 PDIINEESSADLAVQEGEDATLTCKATGNPQPRVTWRREDGEMILIRKpgsRELMKVesyNGSSLRLLRLERRQMGAYLC 220
Cdd:cd20970   1 PVISTPQPSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNT---RYIVRE---NGTTLTIRNIRRSDMGIYLC 74

                        90
                ....*....|....*...
gi 21358003 221 IASNDVPPAVSKRVSLSV 238
Cdd:cd20970  75 IASNGVPGSVEKRITLQV 92

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21358003    247 PSQLLGTPlGSDVQLECQVEASPSPVSYWLKgartsngfasvstaslesgsPGPEMLLDGPKYGITERRDGYRgvmlLVV 326
Cdd:smart00410   1 PPSVTVKE-GESVTLSCEASGSPPPEVTWYK--------------------QGGKLLAESGRFSVSRSGSTST----LTI 55

                           90       100
                   ....*....|....*....|....*....
gi 21358003    327 RSFSPSDVGTYHCVSTNSLGRAEGTLRLY 355
Cdd:smart00410  56 SNVTPEDSGTYTCAATNSSGSASSGTTLT 84

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21358003   256 GSDVQLECQVEASPSPVSYWLKGartsngfasvstaslesGSPgpemLLDGPKYGITERRDGYRgvmlLVVRSFSPSDVG 335
Cdd:pfam07679  15 GESARFTCTVTGTPDPEVSWFKD-----------------GQP----LRSSDRFKVTYEGGTYT----LTISNVQPDDSG 69

                          90
                  ....*....|....*....
gi 21358003   336 TYHCVSTNSLGRAEGTLRL 354
Cdd:pfam07679  70 KYTCVATNSAGEAEASAEL 88

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 21358003 256 GSDVQLECQVEASPSPVSYWLKGArtsngfasvstaslesgspgpEMLLDGPKYGITErrDGYrgvmlLVVRSFSPSDVG 335
Cdd:cd04969  17 GGDVIIECKPKASPKPTISWSKGT---------------------ELLTNSSRICILP--DGS-----LKIKNVTKSDEG 68

                        90
                ....*....|....*.
gi 21358003 336 TYHCVSTNSLGRAEGT 351
Cdd:cd04969  69 KYTCFAVNFFGKANST 84

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21358003    39 PEFIGFINNVTYPAGREAILACSVRNLGKNKVGWLRasdqtvlalQGRVVTHNARISVMHQDMHTwKLKISKLRESDRGC 118
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYK---------NGEPISSGSTRSRSLSGSNS-TLTISNVTRSDAGT 71

                  ....
gi 21358003   119 YMCQ 122
Cdd:pfam13927  72 YTCV 75

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21358003 141 PDIINEESSADLAVQEGEDATLTCKATGNPQPRVTWRREDGEMILIRKpgsRELMKVesyNGSSLRLLRLERRQMGAYLC 220
Cdd:cd20970   1 PVISTPQPSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNT---RYIVRE---NGTTLTIRNIRRSDMGIYLC 74

                        90
                ....*....|....*...
gi 21358003 221 IASNDVPPAVSKRVSLSV 238
Cdd:cd20970  75 IASNGVPGSVEKRITLQV 92

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21358003   140 PPDIINEESSadLAVQEGEDATLTCKATGNPQPRVTWRREDGEMIlirkpGSRELMKVESYNGSSLRLLRLERRQMGAYL 219
Cdd:pfam13927   1 KPVITVSPSS--VTVREGETVTLTCEATGSPPPTITWYKNGEPIS-----SGSTRSRSLSGSNSTLTISNVTRSDAGTYT 73

                  ....*
gi 21358003   220 CIASN 224
Cdd:pfam13927  74 CVASN 78

Immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains NrCAM [Ng(neuronglia)CAM-related cell adhesion molecule], which is primarily expressed in the nervous system, and human neurofascin. 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 lacks a C" strand.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21358003 144 INEESSADLAVQEGEDATLTCKATGNPQPRVTWRReDGEMILIRKpGSRELMKVESYNGSSLRLLRLERRQMGAYLCIAS 223
Cdd:cd05733   3 ITEQSPKDYIVDPRDNITIKCEAKGNPQPTFRWTK-DGKFFDPAK-DPRVSMRRRSGTLVIDNHNGGPEDYQGEYQCYAS 80

                        90
                ....*....|...
gi 21358003 224 NDVPPAVSKRVSL 236
Cdd:cd05733  81 NELGTAISNEIRL 93

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21358003    247 PSQLLGTPlGSDVQLECQVEASPSPVSYWLKgartsngfasvstaslesgsPGPEMLLDGPKYGITERRDGYRgvmlLVV 326
Cdd:smart00410   1 PPSVTVKE-GESVTLSCEASGSPPPEVTWYK--------------------QGGKLLAESGRFSVSRSGSTST----LTI 55

                           90       100
                   ....*....|....*....|....*....
gi 21358003    327 RSFSPSDVGTYHCVSTNSLGRAEGTLRLY 355
Cdd:smart00410  56 SNVTPEDSGTYTCAATNSSGSASSGTTLT 84

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21358003   256 GSDVQLECQVEASPSPVSYWLKGartsngfasvstaslesGSPgpemLLDGPKYGITERRDGYRgvmlLVVRSFSPSDVG 335
Cdd:pfam07679  15 GESARFTCTVTGTPDPEVSWFKD-----------------GQP----LRSSDRFKVTYEGGTYT----LTISNVQPDDSG 69

                          90
                  ....*....|....*....
gi 21358003   336 TYHCVSTNSLGRAEGTLRL 354
Cdd:pfam07679  70 KYTCVATNSAGEAEASAEL 88

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 21358003 151 DLAVQEGEDATLTCKATGNPQPRVTWRReDGEMIlirKPGSRELMKVESYNGSSLRLLRLERRQMGAYLCIASN 224
Cdd:cd05744   9 DLEVQEGRLCRFDCKVSGLPTPDLFWQL-NGKPV---RPDSAHKMLVRENGRHSLIIEPVTKRDAGIYTCIARN 78

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 21358003 133 GCIDVQVPPDIINEESSADlavqegEDATLTCKATGNPQPRVTWRREDGEMILirKPGSRELMkvesYNGSSLRLLRLER 212
Cdd:cd04967   1 GPVFEEQPDDTIFPEDSDE------KKVALNCRARANPVPSYRWLMNGTEIDL--ESDYRYSL----VDGTLVISNPSKA 68

                        90       100
                ....*....|....*....|....*...
gi 21358003 213 RQMGAYLCIASNDVPPAVSKRVSLSVQF 240
Cdd:cd04967  69 KDAGHYQCLATNTVGSVLSREATLQFGY 96

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21358003   242 PMVRAPSQLLGTPLGSDVQLECQVEASPSPVSYWLK-GARTSNGFASVSTASLESGSpgpemlldgpkygiterrdgyrg 320
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKnGEPISSGSTRSRSLSGSNST----------------------- 58

                          90       100
                  ....*....|....*....|...
gi 21358003   321 vmlLVVRSFSPSDVGTYHCVSTN 343
Cdd:pfam13927  59 ---LTISNVTRSDAGTYTCVASN 78

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
                ....*....|....*....|....*....|....*.
gi 21358003 141 PDIINEESSAdLAVQEGEDATLTCKATGNPQPRVTW 176
Cdd:cd20978   1 PKFIQKPEKN-VVVKGGQDVTLPCQVTGVPQPKITW 35

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 21358003 256 GSDVQLECQVEASPSPVSYWLKGArtsngfasvstaslesgspgpEMLLDGPKYGITErrDGYrgvmlLVVRSFSPSDVG 335
Cdd:cd04969  17 GGDVIIECKPKASPKPTISWSKGT---------------------ELLTNSSRICILP--DGS-----LKIKNVTKSDEG 68

                        90
                ....*....|....*.
gi 21358003 336 TYHCVSTNSLGRAEGT 351
Cdd:cd04969  69 KYTCFAVNFFGKANST 84

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 21358003 156 EGEDATLTCKATGNPQPRVTWRRE-DGEMILIRKPGSRelMKVESYNG-SSLRLLRLERRQMGAYLCIASN 224
Cdd:cd05732  15 ELEQITLTCEAEGDPIPEITWRRAtRGISFEEGDLDGR--IVVRGHARvSSLTLKDVQLTDAGRYDCEASN 83

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 21358003 256 GSDVQLECQVEASPSPVSYWLKGARTSNGFASVSTAsLESGSpgpemlldgpkygiterrdgyrgvmlLVVRSFSPSDVG 335
Cdd:cd20952  14 GGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITT-LENGS--------------------------LQIKGAEKSDTG 66

                        90
                ....*....|...
gi 21358003 336 TYHCVSTNSLGRA 348
Cdd:cd20952  67 EYTCVALNLSGEA 79

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band 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. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. 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 I1 domain of the titin I-band 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, 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 21358003 256 GSDVQLECQVEASPSPVSYWLKgartsNGFAsvstasLESGSpgpemllDGPKYGItERRDgyrGVMLLVVRSFSPSDVG 335
Cdd:cd20951  15 KSDAKLRVEVQGKPDPEVKWYK-----NGVP------IDPSS-------IPGKYKI-ESEY---GVHVLHIRRVTVEDSA 72

                        90
                ....*....|...
gi 21358003 336 TYHCVSTNSLGRA 348
Cdd:cd20951  73 VYSAVAKNIHGEA 85

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21358003 140 PPDIINEESSADLAVQEGEDATLTCKATGNPQPRVTWRReDGEmilirkPGSRELMKVE-SYNGSSLRLLRLERRQMGAY 218
Cdd:cd05730   1 PPTIRARQSEVNATANLGQSVTLACDADGFPEPTMTWTK-DGE------PIESGEEKYSfNEDGSEMTILDVDKLDEAEY 73

                ....*.
gi 21358003 219 LCIASN 224
Cdd:cd05730  74 TCIAEN 79

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 21358003 256 GSDVQLECQVEASPSPVSYWL-KGARTSNgfasvstaslesgSPGPEMLLDGPKYGiterrdgyrgvmLLVVRSFsPSDV 334
Cdd:cd20972  16 GSKVRLECRVTGNPTPVVRWFcEGKELQN-------------SPDIQIHQEGDLHS------------LIIAEAF-EEDT 69

                        90       100
                ....*....|....*....|.
gi 21358003 335 GTYHCVSTNSLGRAEGTLRLY 355
Cdd:cd20972  70 GRYSCLATNSVGSDTTSAEIF 90

First (N-terminal) immunoglobulin (Ig)-like domain of the nectin-like molecules; member of the V-set of Ig superfamily (IgSF) domains; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 (also known as cell adhesion molecule 3 (CADM3)), Necl-2 (CADM1), Necl-3 (CADM2), and similar proteins. At least five nectin-like molecules have been identified (Necl-1 to Necl-5). They all have an extracellular region containing three Ig-like domains, a transmembrane region, and a cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1, Necl-2, and Necl-3 have Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue, and is important to the formation of synapses, axon bundles, and myelinated axons. Necl-2 is expressed in a wide variety of tissues and is a putative tumour suppressor gene which is downregulated in aggressive neuroblastoma. Necl-3 accumulates in central and peripheral nervous system tissue and has been shown to selectively interact with oligodendrocytes. This group also contains Class-I MHC-restricted T-cell-associated molecule (CRTAM), whose expression pattern is consistent with its expression in Class-I MHC-restricted T-cells.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21358003  44 FINNVTYPAGREAILACSVRNLGKNKVGWLRASDQTVLALQGRVVtHNARISVMHQDMHTWKLKISKLRESDRGCYMCQI 123
Cdd:cd05717   2 HTQDVTVVEGETLTLKCQVSLRDDSSLQWLNPNGQTIYFNDKRAL-RDSRYQLLNHSASELSISVSNVTLSDEGVYTCLH 80

                ....*.
gi 21358003 124 NTSPMK 129
Cdd:cd05717  81 YTDPVS 86

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. 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 21358003 147 ESSADLAVQEGEDATLTCKATGNPQPRVTWRReDGEMIlirKPGSRELMKVESYNGSSLRLLRLERRQMGAYLCIASN 224
Cdd:cd20990   5 QAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQL-DGKPI---RPDSAHKMLVRENGVHSLIIEPVTSRDAGIYTCIATN 78

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21358003 150 ADLAVQEGEDATLTCKA-TGNPQPRVTWRReDGEMILIRKPGSRELmkvesyNGSSLRLLRLERRQMGAYLCIASNDVPP 228
Cdd:cd05724   5 SDTQVAVGEMAVLECSPpRGHPEPTVSWRK-DGQPLNLDNERVRIV------DDGNLLIAEARKSDEGTYKCVATNMVGE 77

                        90
                ....*....|
gi 21358003 229 AVSKRVSLSV 238
Cdd:cd05724  78 RESRAARLSV 87

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 21358003 147 ESSADLAVQEGEDATLTCKATGNPQPRVTWRREDGEMILIRKPGSRelmkvesYNGSSLRLLRLERRQ--MGAYLCIASN 224
Cdd:cd20949   4 ENAYVTTVKEGQSATILCEVKGEPQPNVTWHFNGQPISASVADMSK-------YRILADGLLINKVTQddTGEYTCRAYQ 76

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth 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
                ....*....|....*....|....*....|....*....|....*.
gi 21358003 151 DLAVQEGEDATLTCKATGNPQPRVTWRREDGEMILI----RKPGSR 192
Cdd:cd05726   8 DQVVALGRTVTFQCETKGNPQPAIFWQKEGSQNLLFpyqpPQPSSR 53

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21358003   154 VQEGEDATLTCKATGNPQPRVTWRREDGEMilirKPGSRELMKVESYNGSslrllrlerrqmGAYLCIASNDVPPAVSKR 233
Cdd:pfam13895  11 VTEGEPVTLTCSAPGNPPPSYTWYKDGSAI----SSSPNFFTLSVSAEDS------------GTYTCVARNGRGGKVSNP 74

                  ....*
gi 21358003   234 VSLSV 238
Cdd:pfam13895  75 VELTV 79

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; 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 and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. 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 21358003 139 VPPDIINEESSadLAVQEGEDATLTCKATGNPQPRVTWRREdGEMI 184
Cdd:cd05747   2 LPATILTKPRS--LTVSEGESARFSCDVDGEPAPTVTWMRE-GQII 44

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 21358003   148 SSADLAVQEGEDATLTCKA-TGNPQPRVTWRREDGemiliRKPGSRELMKVESYNG-SSLRLLRLERRQMGAYLCIASND 225
Cdd:pfam00047   2 APPTVTVLEGDSATLTCSAsTGSPGPDVTWSKEGG-----TLIESLKVKHDNGRTTqSSLLISNVTKEDAGTYTCVVNNP 76

                          90
                  ....*....|
gi 21358003   226 VPPAVSKRVS 235
Cdd:pfam00047  77 GGSATLSTSL 86

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band 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. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. 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 I1 domain of the titin I-band 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, 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
                ....*....|....*....|....*....|....*....
gi 21358003 141 PDIINEESSadLAVQEGEDATLTCKATGNPQPRVTWRRE 179
Cdd:cd20951   1 PEFIIRLQS--HTVWEKSDAKLRVEVQGKPDPEVKWYKN 37

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.

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 21358003 140 PPDIINeeSSADLAVQEGEDATLTCKATGNPQPRVTWRR 178
Cdd:cd20976   1 APSFSS--VPKDLEAVEGQDFVAQCSARGKPVPRITWIR 37

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
                ....*....|....*....|....*....|....*...
gi 21358003 153 AVQEGEDATLTCKATGNPQPRVTWRRE-DGEMILIRKP 189
Cdd:cd05765  11 TVKVGETASFHCDVTGRPQPEITWEKQvPGKENLIMRP 48

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21358003 157 GEDATLTCKATGNPQPRVTWRREDGEMILIRKPGSRELMKVESYNGSSLRLLRLERRQMGAYLCIASNDVPPAVSKRVSL 236
Cdd:cd05734  16 GKAVVLNCSADGYPPPTIVWKHSKGSGVPQFQHIVPLNGRIQLLSNGSLLIKHVLEEDSGYYLCKVSNDVGADISKSMYL 95

                ..
gi 21358003 237 SV 238
Cdd:cd05734  96 TV 97