Immunoglobulin Variable (IgV) domain at the N-terminus of CD33 and related Siglecs (sialic acid-binding Ig-like lectins); The members here are composed of the immunoglobulin (Ig) domain at the N-terminus of Cluster of Differentiation (CD) 33 and related Siglecs (sialic acid-binding Ig-like lectins). Siglec refers to a structurally related protein family that specifically recognizes sialic acid in oligosaccharide chains of glycoproteins and glycolipids. Siglecs are type I transmembrane proteins, 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, the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622895096  21 FWIRVEKLVMVQEGLCVSVSCSFNYPSRGWtESTPAYGYWFKAGTETETskDAPVATNNQNREVEMSTQGRFQLTGDPGK 100
Cdd:cd05712     1 WGLQMPKSVTVQEGLCVLIPCSFSYPADYW-VSNPVHGYWYRGGPYPKY--RPPVATNNRTREVHESTQGRFRLLGDPGK 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1622895096 101 KSCSLVIRDAQMWDEARYFFRVERGTYVRYNFMNNGFLLKVT 142
Cdd:cd05712    78 KNCSLSISDARPEDSGKYFFRVERGDSNKYSYLSNQLSLTVT 119

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
                  ....*....|....*....|....*....|....*..
gi 1622895096 141 VTVLSFTPSPQDHDTDLTCHVDFSRKGVSAQRTVRLR 177
Cdd:cd20987    58 SSVLTFTPRPEDHGTNLTCQVKFPGATVTTERTIQLN 94

Immunoglobulin Variable (IgV) domain at the N-terminus of CD33 and related Siglecs (sialic acid-binding Ig-like lectins); The members here are composed of the immunoglobulin (Ig) domain at the N-terminus of Cluster of Differentiation (CD) 33 and related Siglecs (sialic acid-binding Ig-like lectins). Siglec refers to a structurally related protein family that specifically recognizes sialic acid in oligosaccharide chains of glycoproteins and glycolipids. Siglecs are type I transmembrane proteins, 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, the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622895096  21 FWIRVEKLVMVQEGLCVSVSCSFNYPSRGWtESTPAYGYWFKAGTETETskDAPVATNNQNREVEMSTQGRFQLTGDPGK 100
Cdd:cd05712     1 WGLQMPKSVTVQEGLCVLIPCSFSYPADYW-VSNPVHGYWYRGGPYPKY--RPPVATNNRTREVHESTQGRFRLLGDPGK 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1622895096 101 KSCSLVIRDAQMWDEARYFFRVERGTYVRYNFMNNGFLLKVT 142
Cdd:cd05712    78 KNCSLSISDARPEDSGKYFFRVERGDSNKYSYLSNQLSLTVT 119

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
                  ....*....|....*....|....*....|....*..
gi 1622895096 141 VTVLSFTPSPQDHDTDLTCHVDFSRKGVSAQRTVRLR 177
Cdd:cd20987    58 SSVLTFTPRPEDHGTNLTCQVKFPGATVTTERTIQLN 94

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622895096  311 SLPVLEGQSLRLVCVTHSSPPARLSWT-QGGQTVGS------SQPSDPGVLELPRVQVEQEGEFTCHAQHPLGSQHVSLS 383
Cdd:smart00410   3 SVTVKEGESVTLSCEASGSPPPEVTWYkQGGKLLAEsgrfsvSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTT 82

                   ...
gi 1622895096  384 LSV 386
Cdd:smart00410  83 LTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1622895096 310 TSLPVLEGQSLRLVCVTHSSPPARLSWTQGGQTVGSSQPSDP------GVLELPRVQVEQEGEFTCHA 371
Cdd:pfam13927   9 SSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRslsgsnSTLTISNVTRSDAGTYTCVA 76

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622895096 208 LEAQKGQFLRLLCAADSQPPATLSWVLQDRVLSLSHP----WGPRTLGLELPGVKAGDSGHYTCRAENRLGSQQRALDLS 283
Cdd:pfam07679  10 VEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRfkvtYEGGTYTLTISNVQPDDSGKYTCVATNSAGEAEASAELT 89

                  .
gi 1622895096 284 V 284
Cdd:pfam07679  90 V 90

Immunoglobulin Variable (IgV) domain at the N-terminus of CD33 and related Siglecs (sialic acid-binding Ig-like lectins); The members here are composed of the immunoglobulin (Ig) domain at the N-terminus of Cluster of Differentiation (CD) 33 and related Siglecs (sialic acid-binding Ig-like lectins). Siglec refers to a structurally related protein family that specifically recognizes sialic acid in oligosaccharide chains of glycoproteins and glycolipids. Siglecs are type I transmembrane proteins, 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, the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622895096  21 FWIRVEKLVMVQEGLCVSVSCSFNYPSRGWtESTPAYGYWFKAGTETETskDAPVATNNQNREVEMSTQGRFQLTGDPGK 100
Cdd:cd05712     1 WGLQMPKSVTVQEGLCVLIPCSFSYPADYW-VSNPVHGYWYRGGPYPKY--RPPVATNNRTREVHESTQGRFRLLGDPGK 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1622895096 101 KSCSLVIRDAQMWDEARYFFRVERGTYVRYNFMNNGFLLKVT 142
Cdd:cd05712    78 KNCSLSISDARPEDSGKYFFRVERGDSNKYSYLSNQLSLTVT 119

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
                  ....*....|....*....|....*....|....*..
gi 1622895096 141 VTVLSFTPSPQDHDTDLTCHVDFSRKGVSAQRTVRLR 177
Cdd:cd20987    58 SSVLTFTPRPEDHGTNLTCQVKFPGATVTTERTIQLN 94

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622895096  311 SLPVLEGQSLRLVCVTHSSPPARLSWT-QGGQTVGS------SQPSDPGVLELPRVQVEQEGEFTCHAQHPLGSQHVSLS 383
Cdd:smart00410   3 SVTVKEGESVTLSCEASGSPPPEVTWYkQGGKLLAEsgrfsvSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTT 82

                   ...
gi 1622895096  384 LSV 386
Cdd:smart00410  83 LTV 85

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 1622895096 216 LRLLCAADSQPPATLSWVLQDRVLSLSHPWGPRTLG----LELPGVKAGDSGHYTCRAENRLGSQQRA 279
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELgngtLTISNVTLEDSGTYTCVASNSAGGSASA 68

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 1622895096  25 VEKLVMVQEGLCVSVSCSFnypSRGWTESTPAYgYWFKagTETETSKDAPVATNNQNREVEmSTQGRFQLTGDPGKKSCS 104
Cdd:pfam07686   2 TPREVTVALGGSVTLPCTY---SSSMSEASTSV-YWYR--QPPGKGPTFLIAYYSNGSEEG-VKKGRFSGRGDPSNGDGS 74

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1622895096 105 LVIRDAQMWDEARYFFRVergTYVRYNFMNNGFLLKVT 142
Cdd:pfam07686  75 LTIQNLTLSDSGTYTCAV---IPSGEGVFGKGTRLTVL 109

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622895096 208 LEAQKGQFLRLLCAADSQPPATLSWVLQDRVLSLSHP----WGPRTLGLELPGVKAGDSGHYTCRAENRLGSQQRALDLS 283
Cdd:pfam07679  10 VEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRfkvtYEGGTYTLTISNVQPDDSGKYTCVATNSAGEAEASAELT 89

                  .
gi 1622895096 284 V 284
Cdd:pfam07679  90 V 90

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1622895096 316 EGQSLRLVCVTHSSPPARLSWTQGGQTVG---SSQPSDPGVLELPRVQVEQEGEFTCHAQHPLGSQHVSLSLSV 386
Cdd:cd05745     1 EGQTVDFLCEAQGYPQPVIAWTKGGSQLSvdrRHLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622895096 200 QPQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQDRVLslshPWGPRTLgleLPGVKAGDSGHYTCRAENRLGSQQRA 279
Cdd:pfam13895   1 KPVLTPSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDGSAI----SSSPNFF---TLSVSAEDSGTYTCVARNGRGGKVSN 73

                  ....*.
gi 1622895096 280 -LDLSV 284
Cdd:pfam13895  74 pVELTV 79

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622895096 317 GQSLRLVC-VTHSSPPARLSWTQGGQTVgssqPSDPG-----------VLELPRVQVEQEGEFTCHAQHPLGSQHVSLSL 384
Cdd:cd20959    17 GMRAQLHCgVPGGDLPLNIRWTLDGQPI----SDDLGitvsrlgrrssILSIDSLEASHAGNYTCHARNSAGSASYTAPL 92

                  ..
gi 1622895096 385 SV 386
Cdd:cd20959    93 TV 94

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 1622895096 208 LEAQKGQFLRLLCAADSQPPATLSWVLQDRVLSLSHPWGPR----TLGLELPGVKAGDSGHYTCRAENRLGSQQRALDLS 283
Cdd:cd20949     9 TTVKEGQSATILCEVKGEPQPNVTWHFNGQPISASVADMSKyrilADGLLINKVTQDDTGEYTCRAYQVNSIASDMQERT 88

                  .
gi 1622895096 284 V 284
Cdd:cd20949    89 V 89

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 1622895096 310 TSLPVLEGQSLRLVCVTH--SSPPARLSWTQGGQTVGSSQPSDPGV------------LELPRVQVEQEGEFTCHAQHPL 375
Cdd:cd00098     7 PSPEEKGGGKVTLVCLVSgfYPKDITVTWLKNGVPLTSGVSTSSPVepndgtysvtssLTVPPSDWDEGATYTCVVTHES 86

                  ....*....
gi 1622895096 376 GSQHVSLSL 384
Cdd:cd00098    87 LKSPLSKTW 95

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1622895096 213 GQFLRLLCAADSQPPATLSWVLQDRVLSLS--HPWGPRTLglELPGVKAGDSGHYTCRAENRLGS 275
Cdd:cd05725    12 DDSAEFQCEVGGDPVPTVRWRKEDGELPKGryEILDDHSL--KIRKVTAGDMGSYTCVAENMVGK 74

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1622895096 202 QGNVPYLEAQKGQFLrLLCAADSQPPATLSWVLQDRVLSLSHPwGPRTL---GLELPGVKAGDSGHYTCRAENRLGS 275
Cdd:cd20952     4 QGPQNQTVAVGGTVV-LNCQATGEPVPTISWLKDGVPLLGKDE-RITTLengSLQIKGAEKSDTGEYTCVALNLSGE 78

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1622895096 206 PYLEAQKGQFLRLLC-AADSQPPATLSWVLQDRVLSLSHPWGP-----RTLGLELPGVKAGDSGHYTCRAENRLGSQQR 278
Cdd:pfam00047   4 PTVTVLEGDSATLTCsASTGSPGPDVTWSKEGGTLIESLKVKHdngrtTQSSLLISNVTKEDAGTYTCVVNNPGGSATL 82

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1622895096 313 PVLEGQSLRLVCVTHSSPPARLSWTQGGQTVGSSQPS----DPGVLELPRVQVEQEGEFTCHAQHPLGSQHVSLSLSV 386
Cdd:cd20952    10 TVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERittlENGSLQIKGAEKSDTGEYTCVALNLSGEATWSAVLDV 87

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1622895096 210 AQKGQFLRLLCAADSQPPATLSWVLQDRVLSLSHPwgpRTL----GLELPGVKAGDSGHYTCRAENRLGSQQRALDLSV 284
Cdd:cd20978    13 VKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPME---RATvedgTLTIINVQPEDTGYYGCVATNEIGDIYTETLLHV 88

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1622895096 213 GQFLRLLCAADSQPPATLSWVLQDRVLSLSHPWGPR--TLGLELPGVKAGDSGHYTCRAENRLG 274
Cdd:cd05856    19 GSSVRLKCVASGNPRPDITWLKDNKPLTPPEIGENKkkKWTLSLKNLKPEDSGKYTCHVSNRAG 82

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 1622895096 208 LEAQKGQFLRLLCAADSQPPATLSWVLQDRVLSLSHPWGPRTL----GLELPGVKAGDSGHYTCRAENRLGSQQRALDLS 283
Cdd:cd05747    13 LTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQITSTeyksTFEISKVQMSDEGNYTVVVENSEGKQEAQFTLT 92

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 1622895096 200 QPQ--GNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQDRVLSLSH---PWGPRTLGLELPGVKAGDSGHYTCRAENRLG 274
Cdd:cd20976     1 APSfsSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAAdrsTCEAGVGELHIQDVLPEDHGTYTCLAKNAAG 80

                          90
                  ....*....|
gi 1622895096 275 SQQRALDLSV 284
Cdd:cd20976    81 QVSCSAWVTV 90

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1622895096 212 KGQFLRLLCAADSQPPATLSWVlqdRVLSlSHPWGPRTLG-----LELPGVKAGDSGHYTCRAENRLGSQQ 277
Cdd:cd05731     9 RGGVLLLECIAEGLPTPDIRWI---KLGG-ELPKGRTKFEnfnktLKIENVSEADSGEYQCTASNTMGSAR 75

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1622895096 209 EAQKGQFLRLLCAADSQPPA-TLSWVLQDRVLSLSHPW------GPRTLGLELPGVKAGDSGHYTCRAENRLG 274
Cdd:cd05750    10 TVQEGSKLVLKCEATSENPSpRYRWFKDGKELNRKRPKnikirnKKKNSELQINKAKLEDSGEYTCVVENILG 82

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622895096 199 LQPQGNvpyLEAQKGQFLRLLCAADSQPPATLSWVLQDRVL--SLSHPWGPRTLGLE---LPGVKAGDSGHYTCRAENRL 273
Cdd:cd20990     4 LQAPGD---LTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIrpDSAHKMLVRENGVHsliIEPVTSRDAGIYTCIATNRA 80

                          90
                  ....*....|.
gi 1622895096 274 GSQQRALDLSV 284
Cdd:cd20990    81 GQNSFNLELVV 91

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622895096 213 GQFLRLLCaadSQPP--ATLSWVLQDRVLSLSHP----WGPRTlGLELPGVKAGDSGHYTCRAENR-LGSQQRALDLSVQ 285
Cdd:cd04979    11 GDTVILSC---SVKSnnAPVTWIHNGKKVPRYRSprlvLKTER-GLLIRSAQEADAGVYECHSGERvLGSTLRSVTLHVL 86

                  ..
gi 1622895096 286 YP 287
Cdd:cd04979    87 ER 88

Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor 2 (FGFR2); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain of human fibroblast growth factor receptor 2 (FGFR2). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for FGFs. FGFR2 is required for male sex determination. 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 1622895096 314 VLEGQSLRLVCVTHSSPPARLSWTQGGQTVGSSQPSD----------PGV---------LELPRVQVEQEGEFTCHAQHP 374
Cdd:cd05858    13 VVVGTDAEFVCKVYSDAQPHIQWLKHVEKNGSKYGPDglpyvevlktAGVnttdkeievLYLRNVTFEDAGEYTCLAGNS 92

                          90
                  ....*....|...
gi 1622895096 375 LGSQHVSLSLSVH 387
Cdd:cd05858    93 IGISHHSAWLTVL 105

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622895096   29 VMVQEGLCVSVSCSFNYPSrgwtestPAYGYWFKagtetetskdapvatnnqNREVEMSTQGRFQLTGDPGkkSCSLVIR 108
Cdd:smart00410   4 VTVKEGESVTLSCEASGSP-------PPEVTWYK------------------QGGKLLAESGRFSVSRSGS--TSTLTIS 56

                           90
                   ....*....|....*
gi 1622895096  109 DAQMWDEARYFFRVE 123
Cdd:smart00410  57 NVTPEDSGTYTCAAT 71