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 24646192   259 ITAQMGNHAYMPCQIHRLSDKP---VSWVRMRDNH-------IISVDETTFIADERFQ-SIYQEDHDYtwSLQIKYVEPS 327
Cdd:pfam07686   6 VTVALGGSVTLPCTYSSSMSEAstsVYWYRQPPGKgptfliaYYSNGSEEGVKKGRFSgRGDPSNGDG--SLTIQNLTLS 83

                          90       100
                  ....*....|....*....|....*.
gi 24646192   328 DAGWYECQMATEPK--LSAKVHLQIV 351
Cdd:pfam07686  84 DSGTYTCAVIPSGEgvFGKGTRLTVL 109

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646192   365 VKAGSKVALHCIVRGtlDPPKYIIWFRGQKKISDSDERtgwytqldrnifgtVGDNQNTIGSLIIPLVRKEDSGNYTCQP 444
Cdd:pfam13927  13 VREGETVTLTCEATG--SPPPTITWYKNGEPISSGSTR--------------SRSLSGSNSTLTISNVTRSDAGTYTCVA 76

                  ..
gi 24646192   445 SN 446
Cdd:pfam13927  77 SN 78

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 24646192   259 ITAQMGNHAYMPCQIHRLSDKP---VSWVRMRDNH-------IISVDETTFIADERFQ-SIYQEDHDYtwSLQIKYVEPS 327
Cdd:pfam07686   6 VTVALGGSVTLPCTYSSSMSEAstsVYWYRQPPGKgptfliaYYSNGSEEGVKKGRFSgRGDPSNGDG--SLTIQNLTLS 83

                          90       100
                  ....*....|....*....|....*.
gi 24646192   328 DAGWYECQMATEPK--LSAKVHLQIV 351
Cdd:pfam07686  84 DSGTYTCAVIPSGEgvFGKGTRLTVL 109

First immunoglobulin (Ig)-like domain of Axl receptor tyrosine kinase (RTK), and similar domains; member of the I-set Ig domains; The members here are composed of the first immunoglobulin (Ig)-like domain of Axl receptor tyrosine kinase (RTK). Axl together with Tyro3 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. Ig superfamily 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 Axl 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 24646192 258 NITAQMGNHAYMPCQIHRLSDKP-VSWvrMRDNHIISVDETTfiadeRFQSIYQEDHDYTW----SLQIKYVEPSDAGWY 332
Cdd:cd20966   9 NITGARGLTGTLRCQLQVQGEPPeVHW--LRDGQILELADST-----QTQVPLGEDEQDDWivvsQLRITSLQLSDTGQY 81

                ..
gi 24646192 333 EC 334
Cdd:cd20966  82 QC 83

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646192   365 VKAGSKVALHCIVRGtlDPPKYIIWFRGQKKISDSDERtgwytqldrnifgtVGDNQNTIGSLIIPLVRKEDSGNYTCQP 444
Cdd:pfam13927  13 VREGETVTLTCEATG--SPPPTITWYKNGEPISSGSTR--------------SRSLSGSNSTLTISNVTRSDAGTYTCVA 76

                  ..
gi 24646192   445 SN 446
Cdd:pfam13927  77 SN 78

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646192   365 VKAGSKVALHCIVRGTldPPKYIIWFRGQKKISDSDERtgwytqldrnifgtVGDNQNTIGSLIIPLVRKEDSGNYTCQP 444
Cdd:pfam07679  12 VQEGESARFTCTVTGT--PDPEVSWFKDGQPLRSSDRF--------------KVTYEGGTYTLTISNVQPDDSGKYTCVA 75

                          90
                  ....*....|....*
gi 24646192   445 SNS---VSVSVDLHV 456
Cdd:pfam07679  76 TNSageAEASAELTV 90

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646192 365 VKAGSKVALHCIVRGtlDPPKYIIWFRGQKKISDSDERTgwytqldrnifgTVGDnqntiGSLIIPLVRKEDSGNYTCQP 444
Cdd:cd20978  13 VKGGQDVTLPCQVTG--VPQPKITWLHNGKPLQGPMERA------------TVED-----GTLTIINVQPEDTGYYGCVA 73

                        90
                ....*....|....*
gi 24646192 445 SNS---VSVSVDLHV 456
Cdd:cd20978  74 TNEigdIYTETLLHV 88

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646192 357 LIGDQSRFVKAGSKVALHCIVRGtlDPPKYIIWFRGQKKISDSDERtgwYTQLDRnifgtvgdnqntiGSLIIPLVRKED 436
Cdd:cd20952   3 LQGPQNQTVAVGGTVVLNCQATG--EPVPTISWLKDGVPLLGKDER---ITTLEN-------------GSLQIKGAEKSD 64

                        90       100
                ....*....|....*....|...
gi 24646192 437 SGNYTC---QPSNSVSVSVDLHV 456
Cdd:cd20952  65 TGEYTCvalNLSGEATWSAVLDV 87

Fourth 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 fourth 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 24646192 362 SRFVKAGSKVALHCIVRGTldPPKYIIWFRGQKKISDSDE-RTGWYTQLDrnifGTVgdnqntIGSLIIPLVRKEDSGNY 440
Cdd:cd20956  10 EQTLQPGPSVSLKCVASGN--PLPQITWTLDGFPIPESPRfRVGDYVTSD----GDV------VSYVNISSVRVEDGGEY 77

                ....*....
gi 24646192 441 TCQPSNSVS 449
Cdd:cd20956  78 TCTATNDVG 86

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24646192    258 NITAQMGNHAYMPCQIHRLSDKPVSWVRMRDNHIISvdettfiaDERFQSIYQedhDYTWSLQIKYVEPSDAGWYECQ 335
Cdd:smart00410   3 SVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAE--------SGRFSVSRS---GSTSTLTISNVTPEDSGTYTCA 69

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 24646192 362 SRFVKAGSKVALHCIVRGTLDPpkyIIW-FRGQKKISDSDERTGWYTqlDRNifgtvgdnqntigsLIIPLVRKEDSGNY 440
Cdd:cd04979   5 QISVKEGDTVILSCSVKSNNAP---VTWiHNGKKVPRYRSPRLVLKT--ERG--------------LLIRSAQEADAGVY 65

                        90       100
                ....*....|....*....|.
gi 24646192 441 TCQPSN----SVSVSVDLHVL 457
Cdd:cd04979  66 ECHSGErvlgSTLRSVTLHVL 86

Immunoglobulin variable domain (IgV); The members here are composed of the immunoglobulin variable domain (IgV). The IgV family contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology, and are components of immunoglobulin (Ig) and T cell receptors. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. Within the variable domain, there are regions of even more variability called the hypervariable or complementarity-determining regions (CDRs) which are responsible for antigen binding. A predominant feature of most Ig domains is the disulfide bridge connecting 2 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" strands in the other.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646192 361 QSRFVKAGSKVALHCIVRgTLDPPKYIIWFRGQK-------KISDSDERTGWYTQLDRniFGTVGDNQNTIgSLIIPLVR 433
Cdd:cd00099   6 RSLSVQEGESVTLSCEVS-SSFSSTYIYWYRQKPgqgpeflIYLSSSKGKTKGGVPGR--FSGSRDGTSSF-SLTISNLQ 81

                        90
                ....*....|
gi 24646192 434 KEDSGNYTCQ 443
Cdd:cd00099  82 PEDSGTYYCA 91

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 24646192 365 VKAGSKVALHCIVRGTldPPKYIIWfrgqKKISDS------DERTGWYTQLDRNifgtvgdnqntiGSLIIPLVRKEDSG 438
Cdd:cd20954  13 VAAGQDVMLHCQADGF--PTPTVTW----KKATGStpgeykDLLYDPNVRILPN------------GTLVFGHVQKENEG 74

                        90
                ....*....|.
gi 24646192 439 NYTCQPSNSVS 449
Cdd:cd20954  75 HYLCEAKNGIG 85

First immunoglobulin (Ig)-like domain of Axl receptor tyrosine kinase (RTK), and similar domains; member of the I-set Ig domains; The members here are composed of the first immunoglobulin (Ig)-like domain of Axl receptor tyrosine kinase (RTK). Axl together with Tyro3 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. Ig superfamily 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 Axl 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 24646192 258 NITAQMGNHAYMPCQIHRLSDKP-VSWvrMRDNHIISVDETTfiadeRFQSIYQEDHDYTW----SLQIKYVEPSDAGWY 332
Cdd:cd20966   9 NITGARGLTGTLRCQLQVQGEPPeVHW--LRDGQILELADST-----QTQVPLGEDEQDDWivvsQLRITSLQLSDTGQY 81

                ..
gi 24646192 333 EC 334
Cdd:cd20966  82 QC 83

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24646192 383 PPKYIIWFRGQKKISDSDERtgwytqldrniFGTVGDnqntiGSLIIPLVRKEDSGNYTCQPSNSV 448
Cdd:cd05724  26 PEPTVSWRKDGQPLNLDNER-----------VRIVDD-----GNLLIAEARKSDEGTYKCVATNMV 75

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646192 365 VKAGSKVALHCIVRGTldPPKYIIWfrgQKKISDSDERTGWYTQLDRNIFGTvgdnqnTIGSLIIPLVRKEDSGNYTCQP 444
Cdd:cd05765  12 VKVGETASFHCDVTGR--PQPEITW---EKQVPGKENLIMRPNHVRGNVVVT------NIGQLVIYNAQPQDAGLYTCTA 80

                ...
gi 24646192 445 SNS 447
Cdd:cd05765  81 RNS 83