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 768012242 139 VRVMGTLESGHPSNLTCSVPWVCEQGtPPIFSWMSAAPTSLGPR---------TTQSSVLTITPRPQDHSTNLTCQVTFP 209
Cdd:cd20987    3 IHVPEELEAGQEVTLTCSVPDNCPAL-SPEFSWLGAALTPLPPVlgrleeegtTTHSSVLTFTPRPEDHGTNLTCQVKFP 81

                         90
                 ....*....|...
gi 768012242 210 GAGVTMERTIQLN 222
Cdd:cd20987   82 GATVTTERTIQLN 94

Second immunoglobulin domain of Cluster of Differentiation (CD) 33 and related Siglecs; member of the C2-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig) domain of Cluster of Differentiation (CD) 33 (also known as sialic-acid binding immunoglobulin type-lectin 3 (Siglec-3)) and related Siglecs. CD33, a Siglec family member, is a well-known immunotherapeutic target in acute myeloid leukemia (AML). It is an inhibitory sialoadhesin expressed in human leukocytes of the myeloid lineage and some lymphoid subsets, including natural killer (NK) cells. Siglecs are primarily expressed on immune cells and recognize sialic acid-containing glycan ligands. Siglecs are organized as an extracellular module composed of Ig-like domains (an N-terminal variable set of Ig-like carbohydrate recognition domains, and 1 to 16 constant Ig-like domains), followed by transmembrane and short cytoplasmic domains. Human Siglecs are classified into two subgroups, one subgroup is comprised of sialoadhesin (Siglec-1), CD22 (Siglec-2), and MAG (Siglec-4, myelin-associated glycoprotein), the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11. CD33 (Siglec-3) is the smallest Siglec member. It preferentially binds to alpha2-6- and alpha2-3-sialylated glycans and strongly binds to sialylated ligands on leukemic cell lines. 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. This group includes CD33-related Siglecs which belong to the C2-set of IgSF domains. Unlike the C1-set, the C2-set structures do not have a D strand.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768012242 139 VRVMGTLESGHPSNLTCSVPWVCEQGtPPIFSWMSAAPTSLGPR---------TTQSSVLTITPRPQDHSTNLTCQVTFP 209
Cdd:cd20987    3 IHVPEELEAGQEVTLTCSVPDNCPAL-SPEFSWLGAALTPLPPVlgrleeegtTTHSSVLTFTPRPEDHGTNLTCQVKFP 81

                         90
                 ....*....|...
gi 768012242 210 GAGVTMERTIQLN 222
Cdd:cd20987   82 GATVTTERTIQLN 94

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768012242   34 EGPESLTVQEGLCVLVPCRLPTTLPASYYGYgYWFLEGADVP----VATNDPDEEvQEETRGRFHLLWDPRRKNCSLSIR 109
Cdd:pfam07686   1 QTPREVTVALGGSVTLPCTYSSSMSEASTSV-YWYRQPPGKGptflIAYYSNGSE-EGVKKGRFSGRGDPSNGDGSLTIQ 78

                          90       100       110
                  ....*....|....*....|....*....|..
gi 768012242  110 DARRRDNAAYFFRLKSKwmKYGYTSSKLSVRV 141
Cdd:pfam07686  79 NLTLSDSGTYTCAVIPS--GEGVFGKGTRLTV 108

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768012242   260 SSLPVLEGQALRLLCDADGNPPAHLSWFQGFPAL-------NATPISNTGVLELPQVGSAEEGDFTCRAQHPLGSLQISL 332
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLlaesgrfSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGT 81

                   ....
gi 768012242   333 SLFV 336
Cdd:smart00410  82 TLTV 85

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768012242    36 PESLTVQEGLCVLVPCRLPTTLPASYygygYWFLEGADVPVatndpdeevqeeTRGRFHLLWDPRrkNCSLSIRDARRRD 115
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEV----TWYKQGGKLLA------------ESGRFSVSRSGS--TSTLTISNVTPED 62

                           90       100
                   ....*....|....*....|....*.
gi 768012242   116 NAAYFFRLKSkwmKYGYTSSKLSVRV 141
Cdd:smart00410  63 SGTYTCAATN---SSGSASSGTTLTV 85

Second immunoglobulin domain of Cluster of Differentiation (CD) 33 and related Siglecs; member of the C2-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig) domain of Cluster of Differentiation (CD) 33 (also known as sialic-acid binding immunoglobulin type-lectin 3 (Siglec-3)) and related Siglecs. CD33, a Siglec family member, is a well-known immunotherapeutic target in acute myeloid leukemia (AML). It is an inhibitory sialoadhesin expressed in human leukocytes of the myeloid lineage and some lymphoid subsets, including natural killer (NK) cells. Siglecs are primarily expressed on immune cells and recognize sialic acid-containing glycan ligands. Siglecs are organized as an extracellular module composed of Ig-like domains (an N-terminal variable set of Ig-like carbohydrate recognition domains, and 1 to 16 constant Ig-like domains), followed by transmembrane and short cytoplasmic domains. Human Siglecs are classified into two subgroups, one subgroup is comprised of sialoadhesin (Siglec-1), CD22 (Siglec-2), and MAG (Siglec-4, myelin-associated glycoprotein), the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11. CD33 (Siglec-3) is the smallest Siglec member. It preferentially binds to alpha2-6- and alpha2-3-sialylated glycans and strongly binds to sialylated ligands on leukemic cell lines. 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. This group includes CD33-related Siglecs which belong to the C2-set of IgSF domains. Unlike the C1-set, the C2-set structures do not have a D strand.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768012242 139 VRVMGTLESGHPSNLTCSVPWVCEQGtPPIFSWMSAAPTSLGPR---------TTQSSVLTITPRPQDHSTNLTCQVTFP 209
Cdd:cd20987    3 IHVPEELEAGQEVTLTCSVPDNCPAL-SPEFSWLGAALTPLPPVlgrleeegtTTHSSVLTFTPRPEDHGTNLTCQVKFP 81

                         90
                 ....*....|...
gi 768012242 210 GAGVTMERTIQLN 222
Cdd:cd20987   82 GATVTTERTIQLN 94

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768012242   34 EGPESLTVQEGLCVLVPCRLPTTLPASYYGYgYWFLEGADVP----VATNDPDEEvQEETRGRFHLLWDPRRKNCSLSIR 109
Cdd:pfam07686   1 QTPREVTVALGGSVTLPCTYSSSMSEASTSV-YWYRQPPGKGptflIAYYSNGSE-EGVKKGRFSGRGDPSNGDGSLTIQ 78

                          90       100       110
                  ....*....|....*....|....*....|..
gi 768012242  110 DARRRDNAAYFFRLKSKwmKYGYTSSKLSVRV 141
Cdd:pfam07686  79 NLTLSDSGTYTCAVIPS--GEGVFGKGTRLTV 108

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768012242   260 SSLPVLEGQALRLLCDADGNPPAHLSWFQGFPAL-------NATPISNTGVLELPQVGSAEEGDFTCRAQHPLGSLQISL 332
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLlaesgrfSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGT 81

                   ....
gi 768012242   333 SLFV 336
Cdd:smart00410  82 TLTV 85

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 768012242 266 EGQALRLLCDADGNPPAHLSWFQGFPALNATP---ISNTGVLELPQVGSAEEGDFTCRAQHPLGSLQISLSLFV 336
Cdd:cd05745    1 EGQTVDFLCEAQGYPQPVIAWTKGGSQLSVDRrhlVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 768012242 270 LRLLCDADGNPPAHLSWF------QGFPALNATPISNTGVLELPQVGSAEEGDFTCRAQHPLG 326
Cdd:cd00096    1 VTLTCSASGNPPPTITWYkngkplPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAG 63

Second immunoglobulin domain of Cluster of Differentiation (CD) 22; member of the Constant 1 (C1)-set of IgSF domains; The members here are composed of the second immunoglobulin domain of clusters of differentiation (CD) 22 (also known as Siglec-2). CD22, a sialic-acid binding immunoglobulin type-lectin (Siglec) family member, is an inhibitory co-receptor of the B-cell receptor (BCR). The inhibitory function of CD22 and its restricted expression on B cells makes CD22 an attractive target against dysregulated B cells that cause autoimmune diseases and B-cell-derived cancers. CD22 plays a vital role in establishing a baseline level of B-cell inhibition, and thus is an important determinant of homeostasis in humoral immunity. Siglecs are primarily expressed on immune cells and recognize sialic acid-containing glycan ligands. Siglecs are organized as an extracellular module composed of Ig-like domains (an N-terminal variable set of Ig-like carbohydrate recognition domains, and 1 to 16 constant Ig-like domains), followed by transmembrane and short cytoplasmic domains. Human Siglecs are classified into two subgroups, one subgroup is comprised of sialoadhesin (Siglec-1), CD22 (Siglec-2), and MAG (Siglec-4, myelin-associated glycoprotein), the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C1-set of IgSF domains.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768012242 153 LTCSVPWVCeQGTPPIFSW-MSAAPTSLGPRTTQS---------SVLTITPRPQDHSTNLTCQVTFPGAGVTMERTIQLN 222
Cdd:cd20938   19 LTCLLNFSC-YGYPIQLQWlLEGSPMRQAAVTSTSltiksvftrSELKFQPKWSHHGKIVTCQLQDADGKVLSEDTVQLN 97

                 .
gi 768012242 223 V 223
Cdd:cd20938   98 V 98

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        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768012242 254 KILQNTSSLPVLEGQALRLLCDADGNPPAHLSWFQGFPALNATP---ISNT---GVLELPQVGSAEEGDFTCRAQHPLGS 327
Cdd:cd05747    5 TILTKPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQrhqITSTeykSTFEISKVQMSDEGNYTVVVENSEGK 84

                 ....*..
gi 768012242 328 LQISLSL 334
Cdd:cd05747   85 QEAQFTL 91

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 768012242  259 TSSLPVLEGQALRLLCDA-DGNPPAHLSWF---QGFPALNATPISNTGV----LELPQVGSAEEGDFTCRAQHPLGSLQI 330
Cdd:pfam00047   3 PPTVTVLEGDSATLTCSAsTGSPGPDVTWSkegGTLIESLKVKHDNGRTtqssLLISNVTKEDAGTYTCVVNNPGGSATL 82

                  ....
gi 768012242  331 SLSL 334
Cdd:pfam00047  83 STSL 86

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 768012242 261 SLPVLEGQALRLLCDADGNPPAHLSW--FQGFPALNATPISNTGVLELPQVGSAEEGDFTCRAQHPLG 326
Cdd:cd04968   10 DTYALKGQTVTLECFALGNPVPQIKWrkVDGSPSSQWEITTSEPVLEIPNVQFEDEGTYECEAENSRG 77

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 768012242 267 GQALRLLCD-ADGNPPAHLSWF---QGFPALNATPISNTG----VLELPQVGSAEEGDFTCRAQHPLGSLQISLSLFV 336
Cdd:cd20959   17 GMRAQLHCGvPGGDLPLNIRWTldgQPISDDLGITVSRLGrrssILSIDSLEASHAGNYTCHARNSAGSASYTAPLTV 94

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768012242 255 ILQNTSSLPVLEGQALRLLCDADGNPPAHLSWFqgFPalNATPISNT--------GVLELPQVGSAEEGDFTCRAQHPLG 326
Cdd:cd05764    3 ITRHTHELRVLEGQRATLRCKARGDPEPAIHWI--SP--EGKLISNSsrtlvydnGTLDILITTVKDTGAFTCIASNPAG 78

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768012242 260 SSLPVLEGQALRLLCDADGNPPAHLSWFQGFPALnatPISNTGV-----LELPQVGSAEEGDFTCRAQHPLGSLQISLSL 334
Cdd:cd05725    5 QNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGEL---PKGRYEIlddhsLKIRKVTAGDMGSYTCVAENMVGKIEASATL 81

                 ..
gi 768012242 335 FV 336
Cdd:cd05725   82 TV 83

Immunoglobulin Constant-1 (C1)-set domain; The members here are composed of C1-set domains, classical Ig-like domains resembling the antibody constant domain. Members of the IgC1 family are components of immunoglobulin, T-cell receptors, CD1 cell surface glycoproteins, secretory glycoproteins A/C, and major histocompatibility complex (MHC) class I/II molecules. In immunoglobulins, each chain is composed of one variable domain (IgV) and one or more IgC domains. These names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. The IgV domain is responsible for antigen binding, while the IgC domain is involved in oligomerization and molecular interactions. 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 strands by G, F, C, and C'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768012242 144 TLESGHPSNLTCSV----P------WvcEQGTPPIFSWMSAAPTSLGPRTT--QSSVLTITPRPQDHSTNLTCQVTFPGA 211
Cdd:cd00098   10 EEKGGGKVTLVCLVsgfyPkditvtW--LKNGVPLTSGVSTSSPVEPNDGTysVTSSLTVPPSDWDEGATYTCVVTHESL 87

                 ....*...
gi 768012242 212 GVTMERTI 219
Cdd:cd00098   88 KSPLSKTW 95