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 149040699 134 PTVSIPSSVTIGNRAVLTCSEHDGSPPSEYSWFKDGVPMlTADAKKTRAFINSSYTIDPKSGDLVFDPVSAFDSGEYYCE 213
Cdd:cd20950    1 PTVNIPSSATIGNRAVLTCSEPDGSPPSEYTWFKDGVVM-PTNPKSTRAFSNSSYSLDPTTGELVFDPLSASDTGEYSCE 79

                         90
                 ....*....|....*...
gi 149040699 214 AQNGYGTAMRSEAVRMEA 231
Cdd:cd20950   80 ARNGYGTPMRSNAVRMEA 97

Second Ig-like domain of Junctional adhesion molecule-1 (JAM1); a member of the I-set of IgSF domains; The members here are composed of the second Ig-like domain of Junctional adhesion molecule-1 (JAM1). JAM1 is an immunoglobulin superfamily (IgSF) protein with two Ig-like domains in its extracellular region; it plays a role in the formation of endothelial and epithelial tight junction and acts as a receptor for mammalian reovirus sigma-1. The 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 second Ig-like domain of JAM1 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, the A strand of the I-set is discontinuous but lacks 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 149040699 134 PTVSIPSSVTIGNRAVLTCSEHDGSPPSEYSWFKDGVPMlTADAKKTRAFINSSYTIDPKSGDLVFDPVSAFDSGEYYCE 213
Cdd:cd20950    1 PTVNIPSSATIGNRAVLTCSEPDGSPPSEYTWFKDGVVM-PTNPKSTRAFSNSSYSLDPTTGELVFDPLSASDTGEYSCE 79

                         90
                 ....*....|....*...
gi 149040699 214 AQNGYGTAMRSEAVRMEA 231
Cdd:cd20950   80 ARNGYGTPMRSNAVRMEA 97

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149040699    37 VQVPENDSVKLPCIYSGFSSPRVEWKFvqgsttalvcyNNQITVPYADRVTFSSSG----ITFSSVTRKDNGEYTCMVSE 112
Cdd:smart00410   4 VTVKEGESVTLSCEASGSPPPEVTWYK-----------QGGKLLAESGRFSVSRSGststLTISNVTPEDSGTYTCAATN 72

                           90
                   ....*....|....*
gi 149040699   113 DGGQNYGEVsiHLTV 127
Cdd:smart00410  73 SSGSASSGT--TLTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149040699   29 SVYSPQTAVQVPENDSVKLPCIYSGFSSPRVEWKFvqgsttalvcyNNQITVPYADRVTFSSSG---ITFSSVTRKDNGE 105
Cdd:pfam13927   3 VITVSPSSVTVREGETVTLTCEATGSPPPTITWYK-----------NGEPISSGSTRSRSLSGSnstLTISNVTRSDAGT 71

                  ....*.
gi 149040699  106 YTCMVS 111
Cdd:pfam13927  72 YTCVAS 77

Second Ig-like domain of Junctional adhesion molecule-1 (JAM1); a member of the I-set of IgSF domains; The members here are composed of the second Ig-like domain of Junctional adhesion molecule-1 (JAM1). JAM1 is an immunoglobulin superfamily (IgSF) protein with two Ig-like domains in its extracellular region; it plays a role in the formation of endothelial and epithelial tight junction and acts as a receptor for mammalian reovirus sigma-1. The 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 second Ig-like domain of JAM1 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, the A strand of the I-set is discontinuous but lacks 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 149040699 134 PTVSIPSSVTIGNRAVLTCSEHDGSPPSEYSWFKDGVPMlTADAKKTRAFINSSYTIDPKSGDLVFDPVSAFDSGEYYCE 213
Cdd:cd20950    1 PTVNIPSSATIGNRAVLTCSEPDGSPPSEYTWFKDGVVM-PTNPKSTRAFSNSSYSLDPTTGELVFDPLSASDTGEYSCE 79

                         90
                 ....*....|....*...
gi 149040699 214 AQNGYGTAMRSEAVRMEA 231
Cdd:cd20950   80 ARNGYGTPMRSNAVRMEA 97

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149040699    37 VQVPENDSVKLPCIYSGFSSPRVEWKFvqgsttalvcyNNQITVPYADRVTFSSSG----ITFSSVTRKDNGEYTCMVSE 112
Cdd:smart00410   4 VTVKEGESVTLSCEASGSPPPEVTWYK-----------QGGKLLAESGRFSVSRSGststLTISNVTPEDSGTYTCAATN 72

                           90
                   ....*....|....*
gi 149040699   113 DGGQNYGEVsiHLTV 127
Cdd:smart00410  73 SSGSASSGT--TLTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149040699   29 SVYSPQTAVQVPENDSVKLPCIYSGFSSPRVEWKFvqgsttalvcyNNQITVPYADRVTFSSSG---ITFSSVTRKDNGE 105
Cdd:pfam13927   3 VITVSPSSVTVREGETVTLTCEATGSPPPTITWYK-----------NGEPISSGSTRSRSLSGSnstLTISNVTRSDAGT 71

                  ....*.
gi 149040699  106 YTCMVS 111
Cdd:pfam13927  72 YTCVAS 77

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 149040699 148 AVLTCsEHDGSPPSEYSWFKDGVPMLTADakktrafiNSSYTIDPKSGDLVFDPVSAFDSGEYYCEAQNGYGTAMRSEA 226
Cdd:cd00096    1 VTLTC-SASGNPPPTITWYKNGKPLPPSS--------RDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

Sixth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the sixth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 149040699 143 TIGNRAVLTCSEHDGSPPSEYSWFKDGVPMLTADAKKTRafinssyTIDPKSGDLVFDPVSAFDSGEYYCEAQNGYGTA 221
Cdd:cd20959   15 QVGMRAQLHCGVPGGDLPLNIRWTLDGQPISDDLGITVS-------RLGRRSSILSIDSLEASHAGNYTCHARNSAGSA 86

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149040699  135 TVSIPSSVTIGNRAVLTCsEHDGSPPSEYSWFKDGVPMLTadakktrafiNSSYTIDPKSGD--LVFDPVSAFDSGEYYC 212
Cdd:pfam07679   5 QKPKDVEVQEGESARFTC-TVTGTPDPEVSWFKDGQPLRS----------SDRFKVTYEGGTytLTISNVQPDDSGKYTC 73

                  ....*....
gi 149040699  213 EAQNGYGTA 221
Cdd:pfam07679  74 VATNSAGEA 82

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149040699 147 RAVLTCseH-DGSPPSEYSWFKDGVPMltADAKktrafinSSYTIDPKSGDLVFDPVSAFDSGEYYCEAQNGYGTAMRSE 225
Cdd:cd05760   18 RVTLRC--HiDGHPRPTYQWFRDGTPL--SDGQ-------GNYSVSSKERTLTLRSAGPDDSGLYYCCAHNAFGSVCSSQ 86

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 149040699 149 VLTCsEHDGSPPSEYSWFKDGVPM-LTADAKKTRAFINSSYTIDPKSGdlvfdPVSAFDsGEYYCEAQNGYGTAMRSEAV 227
Cdd:cd05733   20 TIKC-EAKGNPQPTFRWTKDGKFFdPAKDPRVSMRRRSGTLVIDNHNG-----GPEDYQ-GEYQCYASNELGTAISNEIR 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 149040699  45 VKLPCIYSGFSSPRVEWKFVQGSttalvcynNQITVPYADRVTFSSSGITFSSVTRKDNGEYTCMVSEDGG 115
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKP--------LPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAG 63

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149040699    44 SVKLPCIYSGFSSPRVEWKFVQ---GSTTALVCYNNQITVPYA-----DRVTFSSSG------ITFSSVTRKDNGEYTCM 109
Cdd:smart00406   1 SVTLSCKFSGSTFSSYYVSWVRqppGKGLEWLGYIGSNGSSYYqesykGRFTISKDTskndvsLTISNLRVEDTGTYYCA 80

                   .
gi 149040699   110 V 110
Cdd:smart00406  81 V 81

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) 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, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), 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 Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149040699 139 PSSVTI--GNRAVLTCsEHDGSPPSEYSWFKDGVPMltadakKTRAFINSSYTIDPKSGDLVFDPV-----SAFDSGEYY 211
Cdd:cd07693    7 PSDLIVskGDPATLNC-KAEGRPTPTIQWLKNGQPL------ETDKDDPRSHRIVLPSGSLFFLRVvhgrkGRSDEGVYV 79

                         90
                 ....*....|....*
gi 149040699 212 CEAQNGYGTAMRSEA 226
Cdd:cd07693   80 CVAHNSLGEAVSRNA 94

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 149040699 157 GSPPSEYSWFKDGVPMltadakktrafiNSSYTIDPKSGDLVFDPVSAFDSGEYYCEAQNGYGTAMRSEAVRM 229
Cdd:cd05728   25 GNPRPAYRWLKNGQPL------------ASENRIEVEAGDLRITKLSLSDSGMYQCVAENKHGTIYASAELAV 85

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 149040699 133 KPTVSipsSVTIGNRAVLTCsEHDGSPPSEYSWFKDGVPmLTADAKKTRAFINSSYtidpksgDLVFDPVSAFDSGEYYC 212
Cdd:cd20949    5 NAYVT---TVKEGQSATILC-EVKGEPQPNVTWHFNGQP-ISASVADMSKYRILAD-------GLLINKVTQDDTGEYTC 72

                         90       100
                 ....*....|....*....|....
gi 149040699 213 EAQNGYGTAmrseavrMEAVELNV 236
Cdd:cd20949   73 RAYQVNSIA-------SDMQERTV 89

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; 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 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, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149040699  33 PQTAVQVPENDSVKLPCIYSGFSSPRVEWKFVQGSTtalvcynnqitvpYADRVTFSSSGITF--SSVTRKDNGEYTCMV 110
Cdd:cd05731    1 SESSTMVLRGGVLLLECIAEGLPTPDIRWIKLGGEL-------------PKGRTKFENFNKTLkiENVSEADSGEYQCTA 67

                         90
                 ....*....|....
gi 149040699 111 SEDGGQNYGEVSIH 124
Cdd:cd05731   68 SNTMGSARHTISVT 81

First 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 first 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 first 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 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, including vascular (VCAM), intercellular (ICAM), neural (NCAM) and mucosal addressin (MADCAM) cell adhesion molecules, as well as junction adhesion molecules (JAM).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 149040699 145 GNRAVLTCSEHDGSPPSEYSWFKDGVPMltadakktrAFINSSYTIDPKSGDLVFDPVSAFDSGEYYCEAQNGYGTA 221
Cdd:cd20979   15 GQPTVLECVTEGGDQGVKYSWLKDGKSF---------NWQEHNVAQRKDEGSLVFLKPQASDEGQYQCFAETPAGVA 82

Immunoglobulin (Ig) constant domain of the complement receptor of the immunoglobulin superfamily (CRIg); The members here are composed of the Immunoglobulin (Ig) constant domain of the complement receptor of the immunoglobulin superfamily (CRIg). The N-terminal domain of CRIg (also referred to as Z39Ig and V-set and Ig domain-containing 4 (VSIG4)) belongs to the IgV family of immunoglobulin-like domains while the C-terminal domain of CRIg belongs to the IgC family of immunoglobulin-like domains. CRIg plays a role in the complement system, an inhibitor of the alternative pathway convertases, and a negative regulator of T cell activation. 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 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149040699 141 SVTIGNRAVLTCsEHDGSPPSEYSWFK----DGVPMLTADakktrafinssytidpkSGDLVFDPVSAFDSGEYYCEAQN 216
Cdd:cd16082    9 TVPQGMRISLQC-QAWGSPPISYVWYKeqtnNQEPIKVAA-----------------LSTLLFKPAVVADSGSYFCTAKG 70

                         90
                 ....*....|..
gi 149040699 217 GYGTAMRSEAVR 228
Cdd:cd16082   71 RVGSEQRSDIVK 82

First immunoglobulin (Ig)-like domain of Tyro3 receptor tyrosine kinase (RTK), and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain of Tyro3 receptor tyrosine kinase (RTK). Tyro3 together with Axl and Mer form the Axl/Tyro3 family of receptor tyrosine kinases (RTKs). This family includes Axl (also known as Ark, Ufo, and Tyro7), Tyro3 (also known as Sky, Rse, Brt, Dtk, and Tif), and Mer (also known as Nyk, c-Eyk, and Tyro12). Axl/Tyro3 family receptors have an extracellular portion with two Ig-like domains followed by two fibronectin-types III (FNIII) domains, a membrane-spanning single helix, and a cytoplasmic tyrosine kinase domain. Axl, Tyro3 and Mer are widely expressed in adult tissues, though they show higher expression in the brain, in the lymphatic and vascular systems, and in the testis. Axl, Tyro3, and Mer bind the vitamin K dependent protein Gas6 with high affinity, and in doing so activate their tyrosine kinase activity. Axl/Gas6 signaling may play a part in cell adhesion processes, prevention of apoptosis, and cell proliferation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149040699  37 VQVPENDSVKLPCIYSGFSSPRVEWKfvqgSTTALVCYNNQITVPYADR--VTFsssgITFSSVTRKDNGEYTCMVsEDG 114
Cdd:cd20961    3 LTVSQGQPVKLNCSVEGMEEPDIQWV----KDGAVVQNLDQLYIPVSEQhwIGF----LSLKSVERSDAGRYWCQV-EDG 73

                         90
                 ....*....|...
gi 149040699 115 GQNYGEVSIHLTV 127
Cdd:cd20961   74 GETEISQPVWLTV 86

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        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149040699 130 PPSKPTVSIPSSVTIGNRAVLTCSEHdGSPPSEYSWFKDGVPMLTADAKktrafinssYTIDPKSGDLVFDPVSAFDSGE 209
Cdd:cd20976    1 APSFSSVPKDLEAVEGQDFVAQCSAR-GKPVPRITWIRNAQPLQYAADR---------STCEAGVGELHIQDVLPEDHGT 70

                         90
                 ....*....|....*...
gi 149040699 210 YYCEAQNGYGTAMRSEAV 227
Cdd:cd20976   71 YTCLAKNAAGQVSCSAWV 88

Immunoglobulin (Ig)-like domain of human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) domains 2, 4, and 6, and similar domains; The members here are composed of the second, fourth, and sixth immunoglobulin (Ig)-like domains in human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) protein subfamily. The CEA family is a group of anchored or secreted glycoproteins expressed by epithelial cells, leukocytes, endothelial cells, and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. This group represents the CEACAM subfamily. CEACAM1 has many important cellular functions; it is a cell adhesion molecule and a signaling molecule that regulates the growth of tumor cells, an angiogenic factor, and a receptor for bacterial and viral pathogens, including mouse hepatitis virus (MHV). In mice, four isoforms of CEACAM1 generated by alternative splicing have either two [D1, D4] or four [D1-D4] Ig-like domains on the cell surface.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149040699 133 KPTVSIPSSVTIGNR--AVLTCSEHDgsPPSEYSWFKDGVPMLTADakktrafinsSYTIDPKSGDLVFDPVSAFDSGEY 210
Cdd:cd05740    1 KPFISSNNSNPVEDKdaVTLTCEPET--QNTSYLWWFNGQSLPVTP----------RLTLSNGNRTLTLLNVTREDAGAY 68

                         90
                 ....*....|....*..
gi 149040699 211 YCEAQNGYgTAMRSEAV 227
Cdd:cd05740   69 QCEISNPV-SANRSDPV 84

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149040699 140 SSVTIGNRAVLTCsEHDGSPPSEYSWfKDGVPMLTADAKKtraFINSSYTIDPKSGDLVFDPVSAFDSGEYYCEAQNGYG 219
Cdd:cd20954   11 ANVAAGQDVMLHC-QADGFPTPTVTW-KKATGSTPGEYKD---LLYDPNVRILPNGTLVFGHVQKENEGHYLCEAKNGIG 85

                 .
gi 149040699 220 T 220
Cdd:cd20954   86 S 86

First immunoglobulin (Ig) domain of contactin-2; 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-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module by contacts between IG domains 1 and 4, and domains 2 and 3. 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-2 is also expressed in retinal amacrine cells in the developing chick retina, corresponding to the period of formation and maturation of AC processes. This group belongs to the I-set of IgSF domains.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149040699 134 PTVSIPSSVTIGNRAvltcsehDGSPPSEYSWFKDGVPMLTADakktrafiNSSYTIdpKSGDLVF-DPVSAFDSGEYYC 212
Cdd:cd05850   15 PEGSAEEKVTLACRA-------RASPPATYRWKMNGTELKMEP--------DSRYRL--VAGNLVIsNPVKAKDAGSYQC 77

                         90
                 ....*....|....
gi 149040699 213 EAQNGYGTAMRSEA 226
Cdd:cd05850   78 LASNRRGTVVSREA 91

Immunoglobulin (Ig)-like domain of human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) domains 2, 4, and 6, and similar domains; The members here are composed of the second, fourth, and sixth immunoglobulin (Ig)-like domains in human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) protein subfamily. The CEA family is a group of anchored or secreted glycoproteins expressed by epithelial cells, leukocytes, endothelial cells, and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. This group represents the CEACAM subfamily. CEACAM1 has many important cellular functions; it is a cell adhesion molecule and a signaling molecule that regulates the growth of tumor cells, an angiogenic factor, and a receptor for bacterial and viral pathogens, including mouse hepatitis virus (MHV). In mice, four isoforms of CEACAM1 generated by alternative splicing have either two [D1, D4] or four [D1-D4] Ig-like domains on the cell surface.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 149040699  48 PCIYSGFSSPRVEWKFVQ-------GSTTALVCYNNQiTVPYADRVTFSSSG--ITFSSVTRKDNGEYTCMVS 111
Cdd:cd05740    2 PFISSNNSNPVEDKDAVTltcepetQNTSYLWWFNGQ-SLPVTPRLTLSNGNrtLTLLNVTREDAGAYQCEIS 73

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 149040699 134 PTVSIPSS-----VTIGNRAVLTCSEhDGSPPSEYSWFKDGVPMLTADakkTRAFINSSYTidpksgDLVFDPVSAFDSG 208
Cdd:cd20970    1 PVISTPQPsftvtAREGENATFMCRA-EGSPEPEISWTRNGNLIIEFN---TRYIVRENGT------TLTIRNIRRSDMG 70

                         90
                 ....*....|....*...
gi 149040699 209 EYYCEAQNGYGTAMRSEA 226
Cdd:cd20970   71 IYLCIASNGVPGSVEKRI 88

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the Lingo-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 149040699 145 GNRAVLTCsEHDGSPPSEYSWFKDGVPMLTADAkktrafiNSSYTIDPkSGDLVFDPVSAFDSGEYYCEAQNGYGTA 221
Cdd:cd20969   17 GHTVQFVC-RADGDPPPAILWLSPRKHLVSAKS-------NGRLTVFP-DGTLEVRYAQVQDNGTYLCIAANAGGND 84

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; 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 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, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149040699 140 SSVTI--GNRAVLTCSEhDGSPPSEYSWFKDGVPmLTADAKKTRAFINSsytidpksgdLVFDPVSAFDSGEYYCEAQNG 217
Cdd:cd05731    3 SSTMVlrGGVLLLECIA-EGLPTPDIRWIKLGGE-LPKGRTKFENFNKT----------LKIENVSEADSGEYQCTASNT 70

                         90
                 ....*....|...
gi 149040699 218 YGTAMRSEAVRME 230
Cdd:cd05731   71 MGSARHTISVTVE 83

Fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 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, and 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 149040699 145 GNRAVLTCsEHDGSPPSEYSWFKDGVPMLTADAKKTRAFinssytidpKSGDLVFDPVSAFDSGEYYCEAQNGYG 219
Cdd:cd05867   14 GETARLDC-QVEGIPTPNITWSINGAPIEGTDPDPRRHV---------SSGALILTDVQPSDTAVYQCEARNRHG 78