NCBI Conserved Domain Search

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 79.53 E-value: 1.13e-18

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24653061   134 PPVISdNSTQSVVASEGSEVQMECYASGYPTPTITWRRENNAILPTDSATYV----GNTLRIKSVKKEDRGTYYCVADN 208
Cdd:pfam13927   1 KPVIT-VSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSlsgsNSTLTISNVTRSDAGTYTCVASN 78

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 72.54 E-value: 4.07e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061    143 QSVVASEGSEVQMECYASGYPTPTITWRRENNAILPTD---SATYVGN--TLRIKSVKKEDRGTYYCVADNGvSKGDRRN 217
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESgrfSVSRSGStsTLTISNVTPEDSGTYTCAATNS-SGSASSG 80


                   ....*
gi 24653061    218 INVEV 222
Cdd:smart00410  81 TTLTV 85

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.

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 71.29 E-value: 1.01e-15

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 141 STQSVVASEGSEVQMECYASGYPTPTITWRRENNAiLPTDSATY--VGNTLRIKSVKKEDRGTYYCVADNGVSKGdRRNI 218
Cdd:cd05731   1 SESSTMVLRGGVLLLECIAEGLPTPDIRWIKLGGE-LPKGRTKFenFNKTLKIENVSEADSGEYQCTASNTMGSA-RHTI 78


                ....*
gi 24653061 219 NVEVE 223
Cdd:cd05731  79 SVTVE 83

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 71.13 E-value: 1.37e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061   227 VITVPRP---RLGQALqydmDLECHIEAYPPPAIVWTKDDIQLANNQHYSIshfaTADEYTdSTLRVITVEKRQYGDYVC 303
Cdd:pfam07679   3 FTQKPKDvevQEGESA----RFTCTVTGTPDPEVSWFKDGQPLRSSDRFKV----TYEGGT-YTLTISNVQPDDSGKYTC 73

                          90
                  ....*....|....*
gi 24653061   304 KATNRFGEAEARVNL 318
Cdd:pfam07679  74 VATNSAGEAEASAEL 88

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

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 71.39 E-value: 1.59e-15

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 135 PVISDNSTQS-VVASEGSEVQMECYASGYPTPTITWRRENNAILPTDSATYV---GNTLRIKSVKKEDRGTYYCVADNGV 210
Cdd:cd20970   1 PVISTPQPSFtVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRYIVrenGTTLTIRNIRRSDMGIYLCIASNGV 80

                        90
                ....*....|..
gi 24653061 211 SKGDRRNINVEV 222
Cdd:cd20970  81 PGSVEKRITLQV 92

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.

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 68.34 E-value: 1.34e-14

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24653061 135 PVISDNSTQSVVASEGSEVQMECYASGYPTPTITWRRENNAILPTDSATYVGNTLRIKSVKKEDRGTYYCVADNgvSKG 213
Cdd:cd04968   1 PSIKVRFPADTYALKGQTVTLECFALGNPVPQIKWRKVDGSPSSQWEITTSEPVLEIPNVQFEDEGTYECEAEN--SRG 77

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); 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, five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409460 [Multi-domain] Cd Length: 83 Bit Score: 66.86 E-value: 5.17e-14

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 141 STQSVVASEGSEVQMECYASGYPTPTITWRRENNAiLPTDSATYVGN--TLRIKSVKKEDRGTYYCVADNGVSKGdRRNI 218
Cdd:cd05876   1 SSSSLVALRGQSLVLECIAEGLPTPTVKWLRPSGP-LPPDRVKYQNHnkTLQLLNVGESDDGEYVCLAENSLGSA-RHAY 78


                ....*
gi 24653061 219 NVEVE 223
Cdd:cd05876  79 YVTVE 83

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 65.74 E-value: 1.22e-13

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 24653061   143 QSVVASEGSEVQMECYASGYPTPTITWRRENNAILPTD--SATYVGN--TLRIKSVKKEDRGTYYCVADNGVSK 212
Cdd:pfam07679   8 KDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDrfKVTYEGGtyTLTISNVQPDDSGKYTCVATNSAGE 81

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.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 61.58 E-value: 2.82e-12

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 153 VQMECYASGYPTPTITWRRENNAILPTDSATY----VGNTLRIKSVKKEDRGTYYCVADNGVSKGDRRNI 218
Cdd:cd00096   1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRrselGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

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.

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 62.33 E-value: 2.96e-12

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24653061 147 ASEGSEVQMECYASGYPTPTITWRR-------ENNAILPTDSATYVGN-TLRIKSVKKEDRGTYYCVADNGVSKG 213
Cdd:cd20954  13 VAAGQDVMLHCQADGFPTPTVTWKKatgstpgEYKDLLYDPNVRILPNgTLVFGHVQKENEGHYLCEAKNGIGSG 87

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

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 61.36 E-value: 4.74e-12

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 141 STQSVVASEGSEVQMECYASGYPTPTITWRRENNAILPTDS-ATYVGN-TLRIKSVKKEDRGTYYCVADN 208
Cdd:cd20952   5 GPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDErITTLENgSLQIKGAEKSDTGEYTCVALN 74

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.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 60.48 E-value: 8.56e-12

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 134 PPVISDNSTQsVVASEGSEVQMECYASGYPTPTITWRRENNAIL-PTDSATYVGNTLRIKSVKKEDRGTYYCVADNgvSK 212
Cdd:cd20978   1 PKFIQKPEKN-VVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQgPMERATVEDGTLTIINVQPEDTGYYGCVATN--EI 77

                        90
                ....*....|.
gi 24653061 213 GD-RRNINVEV 222
Cdd:cd20978  78 GDiYTETLLHV 88

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.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 58.95 E-value: 3.01e-11

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 131 VRRPpvisdnstQSVVASEGSEVQMECYASGYPTPTITWRRENNAiLPtDSATYV--GNTLRIKSVKKEDRGTYYCVADN 208
Cdd:cd05725   1 VKRP--------QNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGE-LP-KGRYEIldDHSLKIRKVTAGDMGSYTCVAEN 70


                ....
gi 24653061 209 GVSK 212
Cdd:cd05725  71 MVGK 74

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 58.79 E-value: 3.68e-11

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 131 VRRPPVisdnstqSVVASEGSEVQMECYASGYPTPTITW------RRENNAILPTDSATyvgntLRIKSVKKEDRGTYYC 204
Cdd:cd20968   2 ITRPPT-------NVTIIEGLKAVLPCTTMGNPKPSVSWikgddlIKENNRIAVLESGS-----LRIHNVQKEDAGQYRC 69

                        90
                ....*....|....*....
gi 24653061 205 VADNGVSKGDRRNINVEVE 223
Cdd:cd20968  70 VAKNSLGIAYSKPVTIEVE 88

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 58.73 E-value: 3.70e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061   226 PVITVPRPRLGQALQYDMDLECHIEAYPPPAIVWTKDDIQLANNQHYSISHfatadEYTDSTLRVITVEKRQYGDYVCKA 305
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSL-----SGSNSTLTISNVTRSDAGTYTCVA 76


                  ..
gi 24653061   306 TN 307
Cdd:pfam13927  77 SN 78

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 58.67 E-value: 4.02e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061     36 QEQIKDIGGTVEFDCSVQYAKEYNVLFLKTdsdpvflstGSTLVIKDSRFSLRYDPNSSTykLQIKDIQETDAGTYTCQV 115
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQ---------GGKLLAESGRFSVSRSGSTST--LTISNVTPEDSGTYTCAA 70

                           90
                   ....*....|....*.
gi 24653061    116 ViSTVHKVSAEVKLSV 131
Cdd:smart00410  71 T-NSSGSASSGTTLTV 85

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. 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.

Pssm-ID: 143259 Cd Length: 88 Bit Score: 58.11 E-value: 6.38e-11

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24653061 134 PPVISdNSTQSVVASEGSEVQMECYASGYPTPTITWRRENNAILPTDSATYVGNTLRIKSVKKEDRGTYYCVADN 208
Cdd:cd05851   1 PADIN-VKFKDTYALKGQNVTLECFALGNPVPVIRWRKILEPMPATAEISMSGAVLKIFNIQPEDEGTYECEAEN 74

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 57.02 E-value: 1.46e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061   135 PVISDNSTqsvVASEGSEVQMECYASGYPTPTITWRRENNAILPTDSATyvgntlrIKSVKKEDRGTYYCVADNGVSKGD 214
Cdd:pfam13895   2 PVLTPSPT---VVTEGEPVTLTCSAPGNPPPSYTWYKDGSAISSSPNFF-------TLSVSAEDSGTYTCVARNGRGGKV 71


                  ....*...
gi 24653061   215 RRNINVEV 222
Cdd:pfam13895  72 SNPVELTV 79

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

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 57.22 E-value: 1.49e-10

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 24653061 147 ASEGSEVQMECYASGYPTPTITWRReNNAILPTDSATYV-GNTLRIKSVKKEDRGTYYCVADN 208
Cdd:cd05728  11 ADIGSSLRWECKASGNPRPAYRWLK-NGQPLASENRIEVeAGDLRITKLSLSDSGMYQCVAEN 72

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

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 55.71 E-value: 5.57e-10

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 134 PPVI-SDNSTQSVVASEGSEVQMECYASGYPTPTITWRRENNAILPTD---SATYVGNTLRIKSVKKEDRGTYYCVADNG 209
Cdd:cd05730   1 PPTIrARQSEVNATANLGQSVTLACDADGFPEPTMTWTKDGEPIESGEekySFNEDGSEMTILDVDKLDEAEYTCIAENK 80


                ....*
gi 24653061 210 VSKGD 214
Cdd:cd05730  81 AGEQE 85

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. 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.

Pssm-ID: 409388 Cd Length: 84 Bit Score: 55.28 E-value: 6.66e-10

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24653061 144 SVVASEGSEVQMECYASGYPTPTITWRRENNAILPTDSATYVG-NTLRIKSVKKEDRGTYYCVADNGV 210
Cdd:cd05723   6 NIYAHESMDIVFECEVTGKPTPTVKWVKNGDVVIPSDYFKIVKeHNLQVLGLVKSDEGFYQCIAENDV 73

Fifth 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 fifth 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.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 54.88 E-value: 1.03e-09

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 134 PPVISDNSTQSVVAseGSEVQMECYASGYPTPTITWRRENNaILPTDSATYVGN--TLRIKSV-KKEDRGTYYCVADNGV 210
Cdd:cd20958   1 PPFIRPMGNLTAVA--GQTLRLHCPVAGYPISSITWEKDGR-RLPLNHRQRVFPngTLVIENVqRSSDEGEYTCTARNQQ 77

                        90
                ....*....|..
gi 24653061 211 SKGDRRNINVEV 222
Cdd:cd20958  78 GQSASRSVFVKV 89

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.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 54.33 E-value: 1.41e-09

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24653061 144 SVVASEGSEVQMECYAS-GYPTPTITWRRENNAILPTDSATYV--GNTLRIKSVKKEDRGTYYCVADNGVskGDRR 216
Cdd:cd05724   6 DTQVAVGEMAVLECSPPrGHPEPTVSWRKDGQPLNLDNERVRIvdDGNLLIAEARKSDEGTYKCVATNMV--GERE 79

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

Pssm-ID: 462230 Cd Length: 109 Bit Score: 54.39 E-value: 2.09e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061    43 GGTVEFDCSVQYAKEYNVL-----FLKTDSDPVFL----STGSTLVIKDSRFSLRYDPNSSTYKLQIKDIQETDAGTYTC 113
Cdd:pfam07686  11 GGSVTLPCTYSSSMSEASTsvywyRQPPGKGPTFLiayySNGSEEGVKKGRFSGRGDPSNGDGSLTIQNLTLSDSGTYTC 90

                          90
                  ....*....|....*....
gi 24653061   114 QVVISTVHKVSAEVKLSVR 132
Cdd:pfam07686  91 AVIPSGEGVFGKGTRLTVL 109

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.

Pssm-ID: 409442 Cd Length: 92 Bit Score: 53.71 E-value: 2.34e-09

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24653061 150 GSEVQMECYASGYPTPTITWRRENNAILPTDSATYVGN--TLRIKSVKKEDRGTYYCVADNgvsKGDRRNINVEVE 223
Cdd:cd05856  19 GSSVRLKCVASGNPRPDITWLKDNKPLTPPEIGENKKKkwTLSLKNLKPEDSGKYTCHVSN---RAGEINATYKVD 91

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.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 53.10 E-value: 2.45e-09

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 24653061 245 LECHIEAYPPPAIVWTKDDIQLANNQHYSISHfatadEYTDSTLRVITVEKRQYGDYVCKATNRFGEAEAR 315
Cdd:cd00096   3 LTCSASGNPPPTITWYKNGKPLPPSSRDSRRS-----ELGNGTLTISNVTLEDSGTYTCVASNSAGGSASA 68

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 53.28 E-value: 3.01e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24653061    245 LECHIEAYPPPAIVWTKDDIQ-LANNQHYSISHfatadEYTDSTLRVITVEKRQYGDYVCKATNRFGEAEARVNL 318
Cdd:smart00410  14 LSCEASGSPPPEVTWYKQGGKlLAESGRFSVSR-----SGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTTL 83

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

Pssm-ID: 409561 Cd Length: 92 Bit Score: 52.78 E-value: 5.18e-09

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 134 PPVISDNSTQSVVASEGSEVQMECYASGYPTPTITW---RRENNAILPTDSATYV-GNTLRIKSVKKEDRGTYYCVADNG 209
Cdd:cd20969   1 RAAIRDRKAQQVFVDEGHTVQFVCRADGDPPPAILWlspRKHLVSAKSNGRLTVFpDGTLEVRYAQVQDNGTYLCIAANA 80

                        90
                ....*....|...
gi 24653061 210 VSKgDRRNINVEV 222
Cdd:cd20969  81 GGN-DSMPAHLHV 92

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 52.45 E-value: 6.59e-09

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 143 QSVVASEGSEVQMECYASGYPTPTITWRRENNAI--LPTDSATYV-GNTLRIKSVKKEDRGTYYCVADNG 209
Cdd:cd04978   7 PSLVLSPGETGELICEAEGNPQPTITWRLNGVPIepAPEDMRRTVdGRTLIFSNLQPNDTAVYQCNASNV 76

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

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 52.46 E-value: 7.95e-09

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24653061 143 QSVVASEGSEVQMECYASGYPTPTITWRRENNAILPTDSATYVGN-TLRIKSVKKEDRGTYYCVADN 208
Cdd:cd04969  10 KKILAAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICILPDgSLKIKNVTKSDEGKYTCFAVN 76

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.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 52.18 E-value: 9.54e-09

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 150 GSEVQMECYASGYPTPTITWRRENNAILPTDSAT---YVGNT------LRIKSVKKEDRGTYYCVADNGVSK-GDRRNIN 219
Cdd:cd20956  16 GPSVSLKCVASGNPLPQITWTLDGFPIPESPRFRvgdYVTSDgdvvsyVNISSVRVEDGGEYTCTATNDVGSvSHSARIN 95


                .
gi 24653061 220 V 220
Cdd:cd20956  96 V 96

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 51.73 E-value: 1.28e-08

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24653061 149 EGSEVQMECYASGYPTPTITWRRENNAILPTDS-ATYVGN----TLRIKSVKKEDRGTYYCVADN 208
Cdd:cd05744  14 EGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAhKMLVREngrhSLIIEPVTKRDAGIYTCIARN 78

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 51.49 E-value: 1.51e-08

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 24653061 150 GSEVQMECYASGYPTPTITWRRENNAILPTDSATYV----GNTLRIKSVKKEDRGTYYCVADN 208
Cdd:cd05736  15 GVEASLRCHAEGIPLPRVQWLKNGMDINPKLSKQLTlianGSELHISNVRYEDTGAYTCIAKN 77

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third 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. 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 C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 51.38 E-value: 1.52e-08

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24653061 142 TQSVVAseGSEVQMECYASGYPTPTITWRRENNAiLPTDS--ATYVGNTLRIKSVKKEDRGTYYCVADN 208
Cdd:cd20957  10 VQTVDF--GRTAVFNCSVTGNPIHTVLWMKDGKP-LGHSSrvQILSEDVLVIPSVKREDKGMYQCFVRN 75

Immunoglobulin (Ig)-like domain found in Perlecan and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in Perlecan. Perlecan is a large multi-domain heparin sulfate proteoglycan, important in tissue development and organogenesis. Perlecan can be represented as 5 major portions; its fourth major portion (domain IV) is a tandem repeat of immunoglobulin-like domains (Ig2-Ig15) which can vary in size due to alternative splicing. Perlecan binds many cellular and extracellular ligands. Its domain IV region has many binding sites. Some of these have been mapped at the level of individual Ig-like domains, including a site restricted to the Ig5 domain for heparin/sulfatide, a site restricted to the Ig3 domain for nidogen-1 and nidogen-2, a site restricted to Ig4-5 for fibronectin, and sites restricted to Ig2 and to Ig13-15 for fibulin-2. 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.

Pssm-ID: 409412 Cd Length: 85 Bit Score: 51.02 E-value: 2.10e-08

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 24653061 136 VISDNSTQSVvaSEGSEVQMECYA-SGYPTPTITWRReNNAILPTdSATYVGNTLRIKSVKKEDRGTYYCVADN 208
Cdd:cd05754   4 TVEEPRSQEV--RPGADVSFICRAkSKSPAYTLVWTR-VNGTLPS-RAMDFNGILTIRNVQLSDAGTYVCTGSN 73

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; 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. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). 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.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 50.68 E-value: 3.82e-08

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 24653061 150 GSEVQMECYASGYPTPTITWRRENNAILPTD--SATYVGN---TLRIKSVKKEDRGTYYCVADN 208
Cdd:cd05729  19 ANKVRLECGAGGNPMPNITWLKDGKEFKKEHriGGTKVEEkgwSLIIERAIPRDKGKYTCIVEN 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.

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 50.43 E-value: 3.97e-08

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 24653061 143 QSVVASEGSEVQMECYASGYPTPTITWRRENNAILPTD----SATYVGNTLRIKSVKKEDRGTYYCVADNGVSK 212
Cdd:cd05747  11 RSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQrhqiTSTEYKSTFEISKVQMSDEGNYTVVVENSEGK 84

First immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. 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.

Pssm-ID: 409436 [Multi-domain] Cd Length: 95 Bit Score: 49.57 E-value: 8.75e-08

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24653061 135 PVISDNSTQSVVASEGSE--VQMECYASGYPTPTITWRRENNAI-LPTDSATYVGNTLRIKSV-KKEDRGTYYCVADN 208
Cdd:cd05849   2 PVFEEQPIDTIYPEESTEgkVSVNCRARANPFPIYKWRKNNLDIdLTNDRYSMVGGNLVINNPdKYKDAGRYVCIVSN 79

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

Pssm-ID: 409395 [Multi-domain] Cd Length: 96 Bit Score: 49.45 E-value: 9.30e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 143 QSVVASEGSEVQMECYASGYPTPTITWRRENNAILPTDS---------ATYVGNTLRIKSVKKEDRGTYYCVADNGVSkG 213
Cdd:cd05732   9 ENQTAVELEQITLTCEAEGDPIPEITWRRATRGISFEEGdldgrivvrGHARVSSLTLKDVQLTDAGRYDCEASNRIG-G 87


                ....*....
gi 24653061 214 DRRNINVEV 222
Cdd:cd05732  88 DQQSMYLEV 96

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; 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. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 49.13 E-value: 9.50e-08

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24653061 253 PPPAIVWTKDDIQLANNQHYSIShfaTADEYTdsTLRVITVEKRQYGDYVCKATNRFGEAEARVNL 318
Cdd:cd05748  20 PTPTVTWSKDGQPLKETGRVQIE---TTASST--SLVIKNAKRSDSGKYTLTLKNSAGEKSATINV 80

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

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 49.00 E-value: 1.04e-07

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24653061 242 DMDLECHIEAYPPPAIVWTKDDIQLANNQHYSIshfatadeYTDSTLRVITVEKRQYGDYVCKATNRFGEAE 313
Cdd:cd04969  19 DVIIECKPKASPKPTISWSKGTELLTNSSRICI--------LPDGSLKIKNVTKSDEGKYTCFAVNFFGKAN 82

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

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 49.04 E-value: 1.37e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 226 PVITVPRPRLGQALQY--DMDLECHIEAYPPPAIVWTKDDIQL-ANNQHYSISHFATadeytdsTLRVITVEKRQYGDYV 302
Cdd:cd20970   1 PVISTPQPSFTVTAREgeNATFMCRAEGSPEPEISWTRNGNLIiEFNTRYIVRENGT-------TLTIRNIRRSDMGIYL 73

                        90
                ....*....|....*..
gi 24653061 303 CKATNR-FGEAEARVNL 318
Cdd:cd20970  74 CIASNGvPGSVEKRITL 90

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

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 48.77 E-value: 1.83e-07

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24653061 245 LECHIEAYPPPAIVWTKDDIQLAN-NQHYSIShfatadeYTDSTLRVITVEKRQYGDYVCKATNRFGEAEARVNL 318
Cdd:cd05730  23 LACDADGFPEPTMTWTKDGEPIESgEEKYSFN-------EDGSEMTILDVDKLDEAEYTCIAENKAGEQEAEIHL 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.

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 47.63 E-value: 2.14e-07

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 24653061 149 EGSEVQMECYASGYPTPTITWRRENNAiLPTDSATYV--GNTLRIKSVKKEDRGTYYCVADNGV 210
Cdd:cd05745   1 EGQTVDFLCEAQGYPQPVIAWTKGGSQ-LSVDRRHLVlsSGTLRISRVALHDQGQYECQAVNIV 63

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.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 47.24 E-value: 4.82e-07

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24653061 147 ASEGSEVQMECYASGYPTPTITWRReNNAILPTDSATYVGNT----LRIKSVKKEDRGTYYCVADNGV 210
Cdd:cd20976  13 AVEGQDFVAQCSARGKPVPRITWIR-NAQPLQYAADRSTCEAgvgeLHIQDVLPEDHGTYTCLAKNAA 79

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.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 46.80 E-value: 5.94e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061   141 STQSVVASEGSEVQMECYAS-GYPTPTITWRRENNAIL-----PTDSATYVGNTLRIKSVKKEDRGTYYCVADNGVSKGD 214
Cdd:pfam00047   2 APPTVTVLEGDSATLTCSAStGSPGPDVTWSKEGGTLIeslkvKHDNGRTTQSSLLISNVTKEDAGTYTCVVNNPGGSAT 81


                  ..
gi 24653061   215 RR 216
Cdd:pfam00047  82 LS 83

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

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 47.10 E-value: 5.97e-07

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 150 GSEVQMECYASGYPTPTITWRRENNAILPTDSATYVGN---------TLRIKSVKKEDRGTYYCVADNGV 210
Cdd:cd05734  16 GKAVVLNCSADGYPPPTIVWKHSKGSGVPQFQHIVPLNgriqllsngSLLIKHVLEEDSGYYLCKVSNDV 85

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 46.80 E-value: 6.37e-07

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24653061 236 GQALQYDmdleCHIEAYPPPAIVWTKDDIQLANNQHYSISHfataDEYTDSTLRVITVEKRQYGDYVCKATNRFGEA 312
Cdd:cd20973  12 GSAARFD----CKVEGYPDPEVKWMKDDNPIVESRRFQIDQ----DEDGLCSLIISDVCGDDSGKYTCKAVNSLGEA 80

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. 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.

Pssm-ID: 409473 Cd Length: 92 Bit Score: 47.07 E-value: 6.54e-07

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24653061 142 TQSVVASEGSEVQMECYASGYPTPTITWRRENNAI--------LPTDSATYVgnTLRIKSVKKEDRGTYYCVADNG 209
Cdd:cd05892   7 PQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLqyntdrisLYQDNCGRI--CLLIQNANKKDAGWYTVSAVNE 80

Second 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 second immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. 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.

Pssm-ID: 409545 Cd Length: 95 Bit Score: 46.77 E-value: 8.15e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 133 RPPVISDNSTQSVVASEGSEVQMECYASGYPTPTITWRR------ENNAILPTDSATYVGNTLRIKSVKKEDRGTYYCVA 206
Cdd:cd20953   1 APKIPGLSKSQPLTVSSASSIALLCPAQGYPAPSFRWYKfiegttRKQAVVLNDRVKQVSGTLIIKDAVVEDSGKYLCVV 80


                ....
gi 24653061 207 DNGV 210
Cdd:cd20953  81 NNSV 84

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains.

Pssm-ID: 409400 [Multi-domain] Cd Length: 91 Bit Score: 46.54 E-value: 8.22e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 137 ISDNSTQSVVASEGSEVQMECYASGYPTPTITWRREnnaILPTDSATYVG-------NTLRIKSVKKEDRGTYYCVADNg 209
Cdd:cd05738   1 IIDMGPQLKVVEKARTATMLCAASGNPDPEISWFKD---FLPVDTATSNGrikqlrsGALQIENSEESDQGKYECVATN- 76


                ....*.
gi 24653061 210 vSKGDR 215
Cdd:cd05738  77 -SAGTR 81

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.

Pssm-ID: 409421 [Multi-domain] Cd Length: 88 Bit Score: 46.31 E-value: 1.15e-06

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24653061 135 PVISDNSTQSVVAsEGSEVQMECYASGYPTPTITWRRENNAILPTDSAT--YVGNTLRIKSVKKEDRGTYYCVADN 208
Cdd:cd05764   1 PLITRHTHELRVL-EGQRATLRCKARGDPEPAIHWISPEGKLISNSSRTlvYDNGTLDILITTVKDTGAFTCIASN 75

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.

Pssm-ID: 409355 [Multi-domain] Cd Length: 111 Bit Score: 46.56 E-value: 1.18e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 141 STQSVVASEGSEVQMECYASG-YPTPTITWRREN---------------NAILPTDSATYVGN-------TLRIKSVKKE 197
Cdd:cd00099   4 SPRSLSVQEGESVTLSCEVSSsFSSTYIYWYRQKpgqgpefliylssskGKTKGGVPGRFSGSrdgtssfSLTISNLQPE 83

                        90
                ....*....|..
gi 24653061 198 DRGTYYCVADNG 209
Cdd:cd00099  84 DSGTYYCAVSES 95

Immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan, also known as HSPG2, and similar proteins. Perlecan consists of five domains: domain I has three putative heparan sulfate attachment sites, domain II has four LDL receptor-like repeats, and one Ig-like repeat, domain III resembles the short arm of laminin chains, domain IV has multiple Ig-like repeats (21 repeats in human perlecan), and domain V resembles the globular G domain of the laminin A chain and internal repeats of EGF. Perlecan may participate in a variety of biological functions including cell binding, LDL-metabolism, basement membrane assembly and selective permeability, calcium binding, and growth- and neurite-promoting activities.

Pssm-ID: 143220 Cd Length: 78 Bit Score: 45.17 E-value: 2.20e-06

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24653061 150 GSEVQMECYASGYPTPTITWRR------ENNAILPTDSATYvgNTLRIKSVKKEDRGTYYCVADN 208
Cdd:cd05743   1 GETVEFTCVATGVPTPIINWRLnwghvpDSARVSITSEGGY--GTLTIRDVKESDQGAYTCEAIN 63

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 45.33 E-value: 2.30e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061    42 IGGTVEFDCSVQYAKEYNVLFLKTDSDpvflstgstlVIKDSRFSLRYDPNSSTykLQIKDIQETDAGTYTCQVVIStVH 121
Cdd:pfam07679  14 EGESARFTCTVTGTPDPEVSWFKDGQP----------LRSSDRFKVTYEGGTYT--LTISNVQPDDSGKYTCVATNS-AG 80

                          90
                  ....*....|
gi 24653061   122 KVSAEVKLSV 131
Cdd:pfam07679  81 EAEASAELTV 90

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth 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.

Pssm-ID: 143223 Cd Length: 69 Bit Score: 44.87 E-value: 2.31e-06

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 24653061 153 VQMECYASGYPTPTITWRRENNAIlpTDSATY---VGNTLRIKSVKKEDRGTYYCVADN 208
Cdd:cd05746   1 VQIPCSAQGDPEPTITWNKDGVQV--TESGKFhisPEGYLAIRDVGVADQGRYECVARN 57

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

Pssm-ID: 409356 [Multi-domain] Cd Length: 96 Bit Score: 44.93 E-value: 3.23e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 135 PVISDNSTQSVVASEGSE--VQMECYASGYPTPTITWRRENNAILPTDSATY--VGNTLRIKS-VKKEDRGTYYCVADNG 209
Cdd:cd04967   2 PVFEEQPDDTIFPEDSDEkkVALNCRARANPVPSYRWLMNGTEIDLESDYRYslVDGTLVISNpSKAKDAGHYQCLATNT 81


                .
gi 24653061 210 V 210
Cdd:cd04967  82 V 82

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup 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. 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. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin 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. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 44.92 E-value: 3.32e-06

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 150 GSEVQMECYASGYPTPTITWRRENNA-----------ILPTDSATYVGNtlriksVKKEDRGTYYCVADN 208
Cdd:cd05763  14 GSTARLECAATGHPTPQIAWQKDGGTdfpaarerrmhVMPEDDVFFIVD------VKIEDTGVYSCTAQN 77

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; 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. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 44.50 E-value: 3.38e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 145 VVASEGSEVQMECYASGYPTPTITWRRENNAILP--------TDSATyvgnTLRIKSVKKEDRGTYYCVADNGVSKgDRR 216
Cdd:cd05748   2 IVVRAGESLRLDIPIKGRPTPTVTWSKDGQPLKEtgrvqietTASST----SLVIKNAKRSDSGKYTLTLKNSAGE-KSA 76


                ....*.
gi 24653061 217 NINVEV 222
Cdd:cd05748  77 TINVKV 82

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.

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 44.16 E-value: 3.59e-06

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24653061 243 MDLECHIEAYPPPAIVWTKDDIQLA-NNQHYSIShfatadeytDSTLRVITVEKRQYGDYVCKATNRFGEAEARVNL 318
Cdd:cd05745   5 VDFLCEAQGYPQPVIAWTKGGSQLSvDRRHLVLS---------SGTLRISRVALHDQGQYECQAVNIVGSQRTVAQL 72

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 44.88 E-value: 3.98e-06

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24653061 143 QSVVASEGSEVQMECYASGYPTPTITWRRENNAILPTDSATYVGN----TLRIKSVKKEDRGTYYCVADNGV 210
Cdd:cd20972   9 RSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQEgdlhSLIIAEAFEEDTGRYSCLATNSV 80

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.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 44.86 E-value: 4.01e-06

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24653061 253 PPPAIVWTKDDIQLANNQHYSISHFATADEYTDSTLRVITVEKRQYGDYVCKATNRFGEA--EARVN 317
Cdd:cd20956  29 PLPQITWTLDGFPIPESPRFRVGDYVTSDGDVVSYVNISSVRVEDGGEYTCTATNDVGSVshSARIN 95

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.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 44.31 E-value: 4.33e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 232 RPRLGQALQYDMD-LECHI-EAYPPPAIVWTKDDIQLA-NNQHYSISHfatadeytDSTLRVITVEKRQYGDYVCKATNR 308
Cdd:cd05724   3 EPSDTQVAVGEMAvLECSPpRGHPEPTVSWRKDGQPLNlDNERVRIVD--------DGNLLIAEARKSDEGTYKCVATNM 74


                ....*...
gi 24653061 309 FGEAEARV 316
Cdd:cd05724  75 VGERESRA 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

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 44.02 E-value: 5.59e-06

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24653061 245 LECHIEAYPPPAIVWTKDDIQLA-NNQHYSISHfatadeytDSTLRVITVEKRQYGDYVCKATNRFGEAEARVNL 318
Cdd:cd20952  19 LNCQATGEPVPTISWLKDGVPLLgKDERITTLE--------NGSLQIKGAEKSDTGEYTCVALNLSGEATWSAVL 85

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 44.46 E-value: 6.48e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 144 SVVASEGSEVQMECYASGYPTPTITW-------------RRENNAILPTDSATYvgntLRIKSVKK--EDRGTYYCVADN 208
Cdd:cd07693   9 DLIVSKGDPATLNCKAEGRPTPTIQWlkngqpletdkddPRSHRIVLPSGSLFF----LRVVHGRKgrSDEGVYVCVAHN 84

                        90
                ....*....|....
gi 24653061 209 GVSKGDRRNINVEV 222
Cdd:cd07693  85 SLGEAVSRNASLEV 98

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 2 (NCAM-2); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule NCAM-2 (also known as OCAM/mamFas II and RNCAM). NCAM-2 is organized similarly to NCAM, including five N-terminal Ig-like domains and two fibronectin type III domains. NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE), and may function like NCAM, as an adhesion molecule. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143278 [Multi-domain] Cd Length: 98 Bit Score: 44.20 E-value: 7.31e-06

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24653061 143 QSVVASEGSEVQMECYASGYPTPTITWRRENNAILPTDS-----------ATYVGNTLRIKSVKKEDRGTYYCVA 206
Cdd:cd05870   9 KNETTVENGAATLSCKAEGEPIPEITWKRASDGHTFSEGdkspdgrievkGQHGESSLHIKDVKLSDSGRYDCEA 83

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.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 43.94 E-value: 7.38e-06

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 145 VVASEGSEVQMECYASGYPTPTITWRRENNAILPtDSATYV------GNTLRIKSVKKEDRGTYYCVADN 208
Cdd:cd20990  10 LTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRP-DSAHKMlvrengVHSLIIEPVTSRDAGIYTCIATN 78

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 44.02 E-value: 7.61e-06

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 24653061 245 LECHIEAYPPPAIVWTKDDIQLANNQhysiSHFATADEYTDSTLRVITVEKRQYGDYVCKATNRFGEAEARVNL 318
Cdd:cd05744  20 FDCKVSGLPTPDLFWQLNGKPVRPDS----AHKMLVRENGRHSLIIEPVTKRDAGIYTCIARNRAGENSFNAEL 89

IL-beta-binding protein; Provisional

Pssm-ID: 165149 [Multi-domain] Cd Length: 326 Bit Score: 47.32 E-value: 8.00e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061   98 LQIKDIQETDAGTYTC---QVVISTVHKVSAEVKLSVRR---PPVIsdNSTQSVVASEGSEVQMECYASGYPTPT---IT 168
Cdd:PHA02785 179 ITIEDVRKNDAGYYTCvlkYIYGDKTYNVTRIVKLEVRDriiPPTM--QLPEGVVTSIGSNLTIACRVSLRPPTTdadVF 256

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 24653061  169 WRREN-----------------NAILPTDSATYVGNTLRIKSVKKEDRGTYYCVA 206
Cdd:PHA02785 257 WISNGmyyeeddedgdgrisvaNKIYTTDKRRVITSRLNINPVKEEDATTFTCMA 311

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

Pssm-ID: 409561 Cd Length: 92 Bit Score: 43.53 E-value: 1.02e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 232 RPRLGQALQYD----MDLECHIEAYPPPAIVWTKDDIQL----ANNQHYSIShfatadeytDSTLRVITVEKRQYGDYVC 303
Cdd:cd20969   5 RDRKAQQVFVDeghtVQFVCRADGDPPPAILWLSPRKHLvsakSNGRLTVFP---------DGTLEVRYAQVQDNGTYLC 75

                        90
                ....*....|....*
gi 24653061 304 KATNRFGEAEARVNL 318
Cdd:cd20969  76 IAANAGGNDSMPAHL 90

Fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule); The members here are composed of the fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule). NrCAM 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. NrCAM is primarily expressed in the nervous system.

Pssm-ID: 409454 Cd Length: 89 Bit Score: 43.43 E-value: 1.13e-05

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24653061 143 QSVVASEGSEVQMECYASGYPTPTITWRRENN--AILPTDSATYV-GNTLRIKSVKKEDRGTYYCVADN 208
Cdd:cd05868   7 TNLVLSPGEDGTLICRANGNPKPSISWLTNGVpiEIAPTDPSRKVdGDTIIFSKVQERSSAVYQCNASN 75

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

Pssm-ID: 409417 Cd Length: 95 Bit Score: 43.38 E-value: 1.16e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 134 PPVISDNSTQSVVASEgSEVQMECYASGYPTPTITWRRENNAILPTDSATYVGN---TLRIKSVKKEDRGTYYCVADNGV 210
Cdd:cd05760   1 PVVLKHPASAAEIQPS-SRVTLRCHIDGHPRPTYQWFRDGTPLSDGQGNYSVSSkerTLTLRSAGPDDSGLYYCCAHNAF 79

Immunoglobulin (Ig)-like domain in the polymeric Ig receptor (pIgR) and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain in the polymeric Ig receptor (pIgR) and similar proteins. pIgR delivers dimeric IgA and pentameric IgM to mucosal secretions. Polymeric immunoglobulin (pIgs) are the first defense against pathogens and toxins. IgA and IgM can form polymers via an 18-residue extension at their C-termini referred to as the tailpiece. pIgR transports pIgs across mucosal epithelia into mucosal secretions. Human pIgR is a glycosylated type I transmembrane protein, comprised of a 620-residue extracellular region, a 23-residue transmembrane region, and a 103-residue cytoplasmic tail. The extracellular region contains five domains that share sequence similarity with Ig variable (v) regions. This group also contains the Ig-like extracellular domains of other receptors such as NK cell receptor Nkp44 and myeloid receptors, among others.

Pssm-ID: 409381 Cd Length: 100 Bit Score: 43.16 E-value: 1.56e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061  35 TQEQIKDIGGTVEFDCSVQYAKEYNVLFL----KTDSDPVFLSTGstlVIKDSRFSLRYDPNSSTYKLQIKDIQETDAGT 110
Cdd:cd05716   4 PEVVTGVEGGSVTIQCPYPPKYASSRKYWckwgSEGCQTLVSSEG---VVPGGRISLTDDPDNGVFTVTLNQLRKEDAGW 80

                        90       100
                ....*....|....*....|
gi 24653061 111 YTCQVVISTVHKVSAEVKLS 130
Cdd:cd05716  81 YWCGVGDDGDRGLTVQVKLV 100

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.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 42.77 E-value: 1.62e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061  36 QEQIKDIGGTVEFDCSVQYAKEYNVLFLKTDSDpvflstgstlvIKDSRFSLRYDpNSstykLQIKDIQETDAGTYTCQV 115
Cdd:cd05725   5 QNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGE-----------LPKGRYEILDD-HS----LKIRKVTAGDMGSYTCVA 68

                        90
                ....*....|....*.
gi 24653061 116 ViSTVHKVSAEVKLSV 131
Cdd:cd05725  69 E-NMVGKIEASATLTV 83

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 43.11 E-value: 1.77e-05

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24653061 139 DNSTQSVVASEGSEVQMECYASGYPTPTITWRRENNAILPTDS-----ATYVGNT-LRIKSVKKEDRGTYYCVADNG 209
Cdd:cd20974   4 TQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVISTSTLpgvqiSFSDGRAkLSIPAVTKANSGRYSLTATNG 80

Fifth 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 fifth 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.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 42.55 E-value: 2.38e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 242 DMDLECHIEAYPPPAIVWTKDDIQLANNQHYSIshfatadeYTDSTLRVITVEKRQ-YGDYVCKATNRFGEAeARVNLFE 320
Cdd:cd20958  17 TLRLHCPVAGYPISSITWEKDGRRLPLNHRQRV--------FPNGTLVIENVQRSSdEGEYTCTARNQQGQS-ASRSVFV 87


                ..
gi 24653061 321 TI 322
Cdd:cd20958  88 KV 89

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.

Pssm-ID: 409421 [Multi-domain] Cd Length: 88 Bit Score: 42.46 E-value: 2.40e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 226 PVIT--VPRPRL--GQALQydmdLECHIEAYPPPAIVWTKDDIQLANNQHYSIShfatadeYTDSTLRVITVEKRQYGDY 301
Cdd:cd05764   1 PLITrhTHELRVleGQRAT----LRCKARGDPEPAIHWISPEGKLISNSSRTLV-------YDNGTLDILITTVKDTGAF 69

                        90
                ....*....|....*..
gi 24653061 302 VCKATNRFGEAEARVNL 318
Cdd:cd05764  70 TCIASNPAGEATARVEL 86

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.

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 41.91 E-value: 3.79e-05

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24653061 241 YDMDLECHIEAYPPPAIVWTK-------DDIQLANNQHYSIshfatadeYTDSTLRVITVEKRQYGDYVCKATNRFG 310
Cdd:cd20954  17 QDVMLHCQADGFPTPTVTWKKatgstpgEYKDLLYDPNVRI--------LPNGTLVFGHVQKENEGHYLCEAKNGIG 85

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.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 41.61 E-value: 4.02e-05

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24653061 242 DMDLECHIEAYPPPAIVWTKddiqlaNNQHYSISHFATadEYTDSTLRVITVEKRQYGDYVCKATNRFGEAEARVNL 318
Cdd:cd20978  18 DVTLPCQVTGVPQPKITWLH------NGKPLQGPMERA--TVEDGTLTIINVQPEDTGYYGCVATNEIGDIYTETLL 86

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 41.79 E-value: 4.26e-05

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24653061 146 VASEGSEVQMECYASGYPTPTITWRRENNAILPTDSATYV----GN-TLRIKSVKKEDRGTYYCVADN 208
Cdd:cd20973   8 EVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDqdedGLcSLIISDVCGDDSGKYTCKAVN 75

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 41.40 E-value: 4.66e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061    29 PTISYITQEQIKDIGGTVEFDCSVQYAKEYNVLFLKTDSdpvflstgstlvIKDSRFSLRYDPNSSTYKLQIKDIQETDA 108
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGE------------PISSGSTRSRSLSGSNSTLTISNVTRSDA 69


                  ....*..
gi 24653061   109 GTYTCQV 115
Cdd:pfam13927  70 GTYTCVA 76

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.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 41.23 E-value: 5.08e-05

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24653061 244 DLECHIEAYPPPAIVWTKDDIQLANNQhYSISHfatadeytDSTLRVITVEKRQYGDYVCKATNRFGEAEARVNL 318
Cdd:cd05725  16 EFQCEVGGDPVPTVRWRKEDGELPKGR-YEILD--------DHSLKIRKVTAGDMGSYTCVAENMVGKIEASATL 81

Fifth immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3 (also known as Neph2). This protein has five Ig-like domains, one transmembrane domain, and a cytoplasmic tail. Included in this group is mammalian Kirrel (also known as Neph1), Kirrel2 (also known as Neph3), and Drosophila RST (also known as irregular chiasm C-roughest) protein. These proteins contain multiple Ig domains, have properties of cell adhesion molecules, and are important in organ development.

Pssm-ID: 319310 Cd Length: 98 Bit Score: 41.75 E-value: 5.33e-05

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24653061 245 LECHIEAYPPP-AIVWTKDDIQLANNQ--HYSISHFATaDEYTDSTLRVITVEKRQYG-DYVCKATNRFGEAEARVNL 318
Cdd:cd05758  21 LECLVFSSPPPdRIVWSWDEGFLESGSsgRFSVETFPT-EPGVISVLHISGTQRSDFQtSFNCSAWNRFGEGTAIVSL 97

C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C); The members here are composed of the C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C). MyBP-C consists of repeated domains, Ig and fibronectin type 3, and various linkers. Three isoforms of MYBP-C exist: slow-skeletal (ssMyBP-C), fast-skeletal (fsMyBP-C), and cardiac (cMyBP-C). cMYBP-C has insertions between and inside domains and an additional cardiac-specific Ig domain at the N-terminus. For cMYBP_C an interaction has been demonstrated between this C5 domain and the Ig C8 domain.

Pssm-ID: 409475 Cd Length: 86 Bit Score: 41.36 E-value: 5.74e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 138 SDNsTQSVVAseGSEVQMECYASGYPTPTITWRRENNAILPTDSATYVGN-----TLRIKSVKKEDRGTYYCVADNGVSK 212
Cdd:cd05894   1 AEN-TIVVVA--GNKLRLDVPISGEPAPTVTWSRGDKAFTATEGRVRVESykdlsSFVIEGAEREDEGVYTITVTNPVGE 77

                        90
                ....*....|
gi 24653061 213 gDRRNINVEV 222
Cdd:cd05894  78 -DHASLFVKV 86

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 3 (VEGFR-3); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 3 (VEGFR-3). The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. VEGFRs bind VEGFs with high affinity at the Ig-like domains. VEGFR-3 (Flt-4) binds two members of the VEGF family (VEGF-C and VEGF-D) and is involved in tumor angiogenesis and growth. 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.

Pssm-ID: 409449 Cd Length: 88 Bit Score: 41.46 E-value: 6.01e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 127 VKLSVRRPPVISdnstqsvvASEGSE-VQMECYASGYPTPTITWRRENNAILPTDSAtyvgNTLRIKSVKKEDRGTYYCV 205
Cdd:cd05863   3 ISVEWRKGPVIE--------ATAGDElVKLPVKVAAYPPPEFQWYKDGKLISGKHSP----HSLQIKDVTEASAGTYTLV 70

                        90
                ....*....|....*..
gi 24653061 206 ADNGVSkGDRRNINVEV 222
Cdd:cd05863  71 LWNSAA-GLEKRISLEL 86

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

Pssm-ID: 143277 [Multi-domain] Cd Length: 97 Bit Score: 41.12 E-value: 7.48e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 152 EVQMECYASGYPTPTITWRRENNAIlPTDSATYVGN----------TLRIKSVKKEDRGTYYCVADNGVSKgDRRNINVE 221
Cdd:cd05869  19 QITLTCEASGDPIPSITWRTSTRNI-SSEEKTLDGHivvrsharvsSLTLKYIQYTDAGEYLCTASNTIGQ-DSQSMYLE 96


                .
gi 24653061 222 V 222
Cdd:cd05869  97 V 97

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

Pssm-ID: 409398 Cd Length: 101 Bit Score: 41.32 E-value: 7.99e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 140 NSTqsvVASEGSEVQMECYASGYPTPTITWRRENNAILPTDSATY----------VGNTLRIKSVKKEDRGTYYCVADNg 209
Cdd:cd05735  11 NTT---LATKGQKKEMSCTAHGEKPIIVRWEKEDTIINPSEMSRYlvttkevgdeVISTLQILPTVREDSGFFSCHAIN- 86


                ....*....
gi 24653061 210 vSKGDRRNI 218
Cdd:cd05735  87 -SYGEDRGI 94

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 40.87 E-value: 8.02e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 143 QSVVASEGSEVQMECYASGYPTPTITWRRENNAILP-TDSATYV----GN--TLRIKSVKKEDRGTYYCVADN--GVSKG 213
Cdd:cd20951   8 QSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPsSIPGKYKieseYGvhVLHIRRVTVEDSAVYSAVAKNihGEASS 87

                        90
                ....*....|
gi 24653061 214 drrNINVEVE 223
Cdd:cd20951  88 ---SASVVVE 94

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.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 40.64 E-value: 8.62e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24653061   245 LECHI-EAYPPPAIVWTKDDIQLANNQHysisHFATADEYTDSTLRVITVEKRQYGDYVCKATNRFGEAEARVNL 318
Cdd:pfam00047  16 LTCSAsTGSPGPDVTWSKEGGTLIESLK----VKHDNGRTTQSSLLISNVTKEDAGTYTCVVNNPGGSATLSTSL 86

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.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 40.39 E-value: 8.91e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061  46 VEFDCSVQYAKEYNVLFLKTDSDpvflstgstlVIKDSRFSLRYDPNSSTykLQIKDIQETDAGTYTCQVVISTVHKVSA 125
Cdd:cd00096   1 VTLTCSASGNPPPTITWYKNGKP----------LPPSSRDSRRSELGNGT--LTISNVTLEDSGTYTCVASNSAGGSASA 68


                ..
gi 24653061 126 EV 127
Cdd:cd00096  69 SV 70

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

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 40.56 E-value: 9.72e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061  36 QEQIKDIGGTVEFDCSVQyakeynvlflktdSDPV----FLSTGSTLVIKDSRFSLRydPNSStykLQIKDIQETDAGTY 111
Cdd:cd20952   7 QNQTVAVGGTVVLNCQAT-------------GEPVptisWLKDGVPLLGKDERITTL--ENGS---LQIKGAEKSDTGEY 68

                        90       100
                ....*....|....*....|
gi 24653061 112 TCqVVISTVHKVSAEVKLSV 131
Cdd:cd20952  69 TC-VALNLSGEATWSAVLDV 87

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 40.71 E-value: 1.19e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 226 PVITVPRPRLGQALQYDMDLECHIEAYPPPAIVWTKDDIQLANNQHYSISHFATADEytdstLRVITVEKRQYGDYVCKA 305
Cdd:cd05736   1 PVIRVYPEFQAKEPGVEASLRCHAEGIPLPRVQWLKNGMDINPKLSKQLTLIANGSE-----LHISNVRYEDTGAYTCIA 75

                        90
                ....*....|....
gi 24653061 306 TNRFGEAEARVNLF 319
Cdd:cd05736  76 KNEGGVDEDISSLF 89

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 2 (VEGFR-2); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 2 (VEGFR-2). The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. VEGFRs bind VEGFs with high affinity at the Ig-like domains. VEGFR-2 (KDR/Flk-1) is a major mediator of the mitogenic, angiogenic and microvascular permeability-enhancing effects of VEGF-A; VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGF-A also interacts with VEGFR-1, which it binds more strongly than VEGFR-2. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. 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.

Pssm-ID: 409450 Cd Length: 89 Bit Score: 40.30 E-value: 1.23e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 137 ISDNSTQSVVASEGSEVQMECYASGYPTPTITWRReNNAILPTDSATYVGNTLRIKSVKKEDRGTYYCVADNGVSKGDRR 216
Cdd:cd05864   4 LGSGMESLVEAKVGERVRIPVKYLGYPPPEIKWYK-NGIPIESNHTIKAGHVLTIMEVTEKDAGNYTVVLTNPISKEKQR 82


                ..
gi 24653061 217 NI 218
Cdd:cd05864  83 HT 84

Fourth immunoglobulin (Ig)-like domain of platelet-derived growth factor receptor (PDGFR); The members here are composed of the fourth immunoglobulin (Ig)-like domain of platelet-derived growth factor receptor (PDGFR; also known as cluster of differentiation (CD) 140a) alpha and beta. PDGF is a potent mitogen for connective tissue cells. PDGF-stimulated processes are mediated by three different PDGFs (PDGF-A,PDGF-B, and PDGF-C). PDGFR alpha binds to all three PDGFs, whereas the PDGFR beta binds only to PDGF-B. PDGF alpha is organized as an extracellular component having five Ig-like domains, a transmembrane segment, and a cytoplasmic portion having protein tyrosine kinase activity. In mice, PDGFR alpha and PDGFR beta are essential for normal development.

Pssm-ID: 409445 Cd Length: 101 Bit Score: 40.62 E-value: 1.40e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 218 INVEVEFAPVITVprprlgqALQYDMDLECHIEAYPPPAIVWTKDDIQLANNQHYSISHFATADE--YTdSTLRVITVEK 295
Cdd:cd05859   3 IALKPTFGQLEFA-------NLHEVKEFVVEVEAYPPPQIRWLKDNRTLIENLTEITTSTRNVQEtrYV-SKLKLIRAKE 74

                        90
                ....*....|..
gi 24653061 296 RQYGDYVCKATN 307
Cdd:cd05859  75 EDSGLYTALAQN 86

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

Pssm-ID: 409553 Cd Length: 87 Bit Score: 40.12 E-value: 1.45e-04

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24653061 145 VVASEGSEVQMECYASGYPTPTITWRRENNAI-------LPTDSATYVGnTLRIKSVKKEDRGTYYCVADNG 209
Cdd:cd20961   3 LTVSQGQPVKLNCSVEGMEEPDIQWVKDGAVVqnldqlyIPVSEQHWIG-FLSLKSVERSDAGRYWCQVEDG 73

Fifth immunoglobulin (Ig) domain of contactin-1; The members here are composed of the fifth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409438 Cd Length: 89 Bit Score: 39.60 E-value: 2.16e-04

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 245 LECHIEAYPPPAIVWTKDDIQLANNQHYSIshfatadeYTDSTLRVITVEKRQYGDYVCKATNRFGEAEA 314
Cdd:cd05852  22 IECKPKAAPKPKFSWSKGTELLVNNSRISI--------WDDGSLEILNITKLDEGSYTCFAENNRGKANS 83

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

Pssm-ID: 409402 [Multi-domain] Cd Length: 89 Bit Score: 39.30 E-value: 2.60e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 135 PVISDNSTQSVVasEGSEVQMECYASGyPTPTITWRRENNAILPTDSATYVGN--TLRIKSVKKEDRGTYYCVADNGVSK 212
Cdd:cd05740   2 PFISSNNSNPVE--DKDAVTLTCEPET-QNTSYLWWFNGQSLPVTPRLTLSNGnrTLTLLNVTREDAGAYQCEISNPVSA 78

IL-1 receptor-like protein; Provisional

Pssm-ID: 165173 [Multi-domain] Cd Length: 227 Bit Score: 41.82 E-value: 2.62e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061   57 EYNVLFLKTDSDPVFLSTGSTLVIKdsrfSLRYDPNSS-TYKLQIKDIQETDAGTYTCQVVISTVHKVSAeVKLSVrrpp 135
Cdd:PHA02826  62 SYNVTWSKTDSLAFVRDSGARTKIK----KITHNEIGDrSENLWIGNVINIDEGIYICTISSGNICEEST-IRLTF---- 132

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061  136 visDNSTQSVVASEGSEVQMECY-----ASGYPTPTITWRRENNAILPTDSATYVGN--TLRIKSVKKEDRGTYYC---V 205
Cdd:PHA02826 133 ---DSGTINYQFNSGKDSKLHCYgtdgiSSTFKDYTLTWYKNGNIVLYTDRIQLRNNnsTLVIKSATHDDSGIYTCnlrF 209

                        170
                 ....*....|....*..
gi 24653061  206 ADNGVSKGDRRNINVEV 222
Cdd:PHA02826 210 NKNSNNYNITKEYKVTI 226

C-terminal immunoglobulin (Ig)-like domain of M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of M-protein (also known as myomesin-2). M-protein is a structural protein localized to the M-band, a transverse structure in the center of the sarcomere, and is a candidate for M-band bridges. M-protein is modular consisting mainly of repetitive IG-like and fibronectin type III (FnIII) domains and has a muscle-type specific expression pattern. M-protein is present in fast fibers.

Pssm-ID: 143299 Cd Length: 92 Bit Score: 39.12 E-value: 3.53e-04

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24653061 243 MDLECHIEAYPPPAIVWTKDDIQLANNQHYSIShfATADEYTDSTLRVITVEKRqyGDYVCKATNRFG 310
Cdd:cd05891  19 LNLTCTVFGNPDPEVIWFKNDQDIELSEHYSVK--LEQGKYASLTIKGVTSEDS--GKYSINVKNKYG 82

First Ig-like domain of Junctional adhesion molecule-1 (JAM1)and similar domains; a member of the V-set of IgSF domains; The members here are composed of the first Ig-like domain of Junctional Adhesion Molecule-1 (JAM1)and similar domains. JAM1 is an immunoglobulin superfamily (IgSF) protein with two Ig-like domains in its extracellular region; it plays a role in the formation of endothelial and epithelial tight junction and acts as a receptor for mammalian reovirus sigma-1. The IgSF is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The first Ig-like domain of JAM1 is a member of the V-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C'-C" in the other.

Pssm-ID: 409538 Cd Length: 102 Bit Score: 39.44 E-value: 3.57e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 141 STQSVVASEGSEVQMECYASGYPT-PTITWRR----------ENNAILPT--DSATYVGNTLRIKSVKKEDRGTYYCVAd 207
Cdd:cd20946   5 SQQVVTVVENQEVILSCKTPKKTSsPRVEWKKlqrdvtfvvfQNNKIQGDykGRAEILGTNITIKNVTRSDSGKYRCEV- 83

                        90
                ....*....|.
gi 24653061 208 ngVSKGDRRNI 218
Cdd:cd20946  84 --SARSDGQNL 92

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; 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. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three IG-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans.

Pssm-ID: 409443 [Multi-domain] Cd Length: 95 Bit Score: 39.07 E-value: 3.65e-04

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 24653061 150 GSEVQMECYASGYPTPTITWRRENNAILPTD-----SATYVGNTLRIKSVKKEDRGTYYCVADN 208
Cdd:cd05857  19 ANTVKFRCPAAGNPTPTMRWLKNGKEFKQEHriggyKVRNQHWSLIMESVVPSDKGNYTCVVEN 82

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 39.15 E-value: 3.94e-04

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 24653061 245 LECHIEAYPPPAIVWTKDDIQLANNQHYSIshfatadeYTDSTLRVITVEKRQYGDYVCKATNRFGEAEAR 315
Cdd:cd20968  19 LPCTTMGNPKPSVSWIKGDDLIKENNRIAV--------LESGSLRIHNVQKEDAGQYRCVAKNSLGIAYSK 81

Immunoglobulin-like domain of human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin I-set (IgI) domain of the Human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins. APEG-1 is a novel specific smooth muscle differentiation marker predicted to play a role in the growth and differentiation of arterial smooth muscle cells (SMCs). The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the human APEG-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409567 Cd Length: 91 Bit Score: 38.99 E-value: 4.00e-04

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24653061 242 DMDLECHIEAYPPPAIVWTKDDIQLANNQHysisHFATADEYTDSTLRVITVEKRQYGDYVCKATNRFG--EAEARVNL 318
Cdd:cd20975  17 DVIMSIRVQGEPKPVVSWLRNRQPVRPDQR----RFAEEAEGGLCRLRILAAERGDAGFYTCKAVNEYGarQCEARLEV 91

Second 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 second 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. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of this group show that the second Ig domain lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules, including vascular (VCAM), intercellular (ICAM), neural (NCAM) and mucosal addressin (MADCAM) cell adhesion molecules, as well as junction adhesion molecules (JAM).

Pssm-ID: 409557 Cd Length: 101 Bit Score: 39.15 E-value: 4.78e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 136 VISDNSTQSVVASEGSEVQMEC-YASGYPTPTITWRRENNAILPTDSATYVG-------NTLRIKSVKKEDRGT---YYC 204
Cdd:cd20965   3 LDPQVKTKEKKPVEGKPFKLDCnVPPGYPKPTIEWKKQLVSDSSKADTILDRritispnGDLYFTNVTKEDVSTdykYVC 82

                        90
                ....*....|
gi 24653061 205 VADNGVSKGD 214
Cdd:cd20965  83 VAKTPAVDGE 92

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth 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.

Pssm-ID: 143223 Cd Length: 69 Bit Score: 37.93 E-value: 5.22e-04

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 24653061 245 LECHIEAYPPPAIVWTKDDIQLANNQHYSISHfatadeytDSTLRVITVEKRQYGDYVCKATNRFGEAEARVNL 318
Cdd:cd05746   3 IPCSAQGDPEPTITWNKDGVQVTESGKFHISP--------EGYLAIRDVGVADQGRYECVARNTIGYASVSMVL 68

Fifth immunoglobulin (Ig) domain of contactin-1; The members here are composed of the fifth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409438 Cd Length: 89 Bit Score: 38.44 E-value: 5.75e-04

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 24653061 143 QSVVASEGSEVQMECYASGYPTPTITWRReNNAILPTDSATYVGN--TLRIKSVKKEDRGTYYCVADNGVSKGD 214
Cdd:cd05852  10 KKILAAKGGRVIIECKPKAAPKPKFSWSK-GTELLVNNSRISIWDdgSLEILNITKLDEGSYTCFAENNRGKAN 82

Immunoglobulin (Ig)-like domain of human neurofascin (NF); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of human neurofascin (NF). NF 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 a cytoplasmic domain. NF has many alternatively spliced isoforms having different temporal expression patterns during development. NF participates in axon subcellular targeting and synapse formation, however little is known of the functions of the different isoforms. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lacks a C" strand.

Pssm-ID: 409459 Cd Length: 95 Bit Score: 38.42 E-value: 7.05e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 135 PVISDNSTQSVVASEGSEVQMECYASGYPTPTITWRRE----NNAILPTDSATYVGNTLRIKSVKK---ED-RGTYYCVA 206
Cdd:cd05875   1 PTITKQSAKDYIVDPRDNILIECEAKGNPVPTFHWTRNgkffNVAKDPRVSMRRRSGTLVIDFRGGgrpEDyEGEYQCFA 80


                ..
gi 24653061 207 DN 208
Cdd:cd05875  81 RN 82

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 38.30 E-value: 9.24e-04

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 24653061 245 LECHIEAYPPPAIVWTKDDIQLANNQHYSISHFATADEYTDSTLRVITVEKRQY--GDYVCKATNRFGEAEAR 315
Cdd:cd07693  20 LNCKAEGRPTPTIQWLKNGQPLETDKDDPRSHRIVLPSGSLFFLRVVHGRKGRSdeGVYVCVAHNSLGEAVSR 92

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.

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 37.77 E-value: 9.32e-04

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24653061 236 GQALQydmdLECHIEAYPPPAIVWTKDDIQLANNQhysishfATADEYtDSTLRVITVEKRQYGDYVCKATNRFGEA 312
Cdd:cd05731  10 GGVLL----LECIAEGLPTPDIRWIKLGGELPKGR-------TKFENF-NKTLKIENVSEADSGEYQCTASNTMGSA 74

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third 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. 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 C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 37.51 E-value: 1.33e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061  30 TISYITQEQIKDIGGTVEFDCSVQYAKEYNVLFLKtDSDPvflstgstlVIKDSRFSLRYDPnsstyKLQIKDIQETDAG 109
Cdd:cd20957   3 SATIDPPVQTVDFGRTAVFNCSVTGNPIHTVLWMK-DGKP---------LGHSSRVQILSED-----VLVIPSVKREDKG 67


                ....*.
gi 24653061 110 TYTCQV 115
Cdd:cd20957  68 MYQCFV 73

Fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409453 [Multi-domain] Cd Length: 89 Bit Score: 37.57 E-value: 1.35e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 131 VRRPpvisdnstQSVVASEGSEVQMECYASGYPTPTITWRRENNAILPTDSAT---YVGNTLRIKSVKKEDRGTYYCVAD 207
Cdd:cd05867   3 TRRP--------QSHLYGPGETARLDCQVEGIPTPNITWSINGAPIEGTDPDPrrhVSSGALILTDVQPSDTAVYQCEAR 74


                .
gi 24653061 208 N 208
Cdd:cd05867  75 N 75

Second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 - Necl-4; member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 (also known as cell adhesion molecule 3 or CADM3), Necl-2 (also known as CADM1), Necl-3 (also known as CADM2) and Necl-4 (also known as CADM4). These nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1 and Necl-2 have Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue and is important to the formation of synapses, axon bundles, and myelinated axons. Necl-2 is expressed in a wide variety of tissues, and is a putative tumour suppressor gene, which is downregulated in aggressive neuroblastoma. Necl-3 has been shown to accumulate in tissues of the central and peripheral nervous system, where it is expressed in ependymal cells and myelinated axons. It is observed at the interface between the axon shaft and the myelin sheath. Necl-4 is expressed on Schwann cells, and plays a key part in initiating peripheral nervous system (PNS) myelination. Necl-4 participates in cell-cell adhesion and is proposed to play a role in tumor suppression.

Pssm-ID: 409418 Cd Length: 102 Bit Score: 37.41 E-value: 1.56e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 129 LSVRRPPVIsDNSTQSVVasEGSEVQMECYASG-YPTPTITWRRENNAI-----LPTDSA--TY-VGNTLRIKSVKKEDR 199
Cdd:cd05761   1 LGVPEKPVI-TGFTSPVV--EGDEITLTCTTSGsKPAADIRWFKNDKELkgvkeVQESGAgkTFtVTSTLRFRVDRDDDG 77


                ....*....
gi 24653061 200 GTYYCVADN 208
Cdd:cd05761  78 VAVICRVDH 86

First immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. 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.

Pssm-ID: 409387 Cd Length: 97 Bit Score: 37.46 E-value: 1.72e-03

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24653061 145 VVASEGSEVQMECYASGYPTPTITWRR----------ENNAILPtDSATYVGNTLRIKSvKKEDRGTYYCVADNG 209
Cdd:cd05722  11 IVAMRGGPVVLNCSAESDPPPKIEWKKdgvllnlvsdERRQQLP-NGSLLITSVVHSKH-NKPDEGFYQCVAQNE 83

T-cell surface glycoprotein CD3 delta chain; This is an immunoglobulin-like domain. It is found on the T-cell surface glycoprotein CD3 delta chain. CD3delta and CD3epsilon complex together as part of the T-cell receptor complex.

Pssm-ID: 465231 Cd Length: 63 Bit Score: 36.07 E-value: 2.11e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 24653061   164 TPTITWRRENNAILPTDsatyvGNTLRIKSVKKEDRGTYYCVADNGVSK 212
Cdd:pfam16680  12 SKSITWLKDGKGIKSTN-----TKTLDLGKFSEDPRGLYQCQGEKKKSS 55

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.

Pssm-ID: 409355 [Multi-domain] Cd Length: 111 Bit Score: 37.31 E-value: 2.53e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061  34 ITQEQ---IKDIGGTVEFDCSVQYAKEYNVLF---LKTDSDPVFL-----STGSTLVIKDSRFSLRYDPNSStYKLQIKD 102
Cdd:cd00099   1 VTQSPrslSVQEGESVTLSCEVSSSFSSTYIYwyrQKPGQGPEFLiylssSKGKTKGGVPGRFSGSRDGTSS-FSLTISN 79

                        90
                ....*....|....*.
gi 24653061 103 IQETDAGTYTCQVVIS 118
Cdd:cd00099  80 LQPEDSGTYYCAVSES 95

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); 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, five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409460 [Multi-domain] Cd Length: 83 Bit Score: 36.43 E-value: 2.64e-03

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24653061 245 LECHIEAYPPPAIVWTKDDIQLANNQhysishfaTADEYTDSTLRVITVEKRQYGDYVCKATNRFGEA 312
Cdd:cd05876  15 LECIAEGLPTPTVKWLRPSGPLPPDR--------VKYQNHNKTLQLLNVGESDDGEYVCLAENSLGSA 74

Sixth immunoglobulin (Ig) domain of contactin; The members here are composed of the sixth 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.

Pssm-ID: 409359 Cd Length: 102 Bit Score: 36.76 E-value: 2.78e-03

                        10        20        30
                ....*....|....*....|....*....|....*...
gi 24653061  98 LQIKDIQETDAGTYTCqVVISTVHKVSAEVKLSVRRPP 135
Cdd:cd04970  66 LEIVNAQLKHAGRYTC-TAQTVVDSDSASATLVVRGPP 102

Second immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R), and similar domains; The members here are composed of the second immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R; also known as cluster of differentiation (CD) 121). IL-1 alpha and IL-1 beta are cytokines which participate in the regulation of inflammation, immune responses, and hematopoiesis. These cytokines bind to the IL-1 receptor type 1 (IL1R1), which is activated on additional association with interleukin-1 receptor accessory protein (IL1RAP). IL-1 also binds a second receptor designated type II (IL1R2). Mature IL1R1 consists of three IG-like domains, a transmembrane domain, and a large cytoplasmic domain. Mature IL1R2 is organized similarly except that it has a short cytoplasmic domain. The latter does not initiate signal transduction. A naturally occurring cytokine IL-1RA (IL-1 receptor antagonist) is widely expressed and binds to IL-1 receptors, inhibiting the binding of IL-1 alpha and IL-1 beta. This group also contains ILIR-like 1 (IL1R1L) which maps to the same chromosomal location as IL1R1 and IL1R2.

Pssm-ID: 409415 Cd Length: 92 Bit Score: 36.53 E-value: 3.14e-03

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 24653061 164 TPTITWRRENNAILPTDSATYVGNTLRIKSVKKEDRGTYYCV---ADNGVSKGDRRNINVEVE 223
Cdd:cd05757  29 LPPIQWYKDCKPLQGDKRFIPKGSKLLIQNVTEEDAGNYTCKftyTHNGKQYNVTRTISLTVT 91

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

Pssm-ID: 409417 Cd Length: 95 Bit Score: 36.44 E-value: 3.15e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 245 LECHIEAYPPPAIVWTKDDIQLANNQ-HYSISHfatadeyTDSTLRVITVEKRQYGDYVCKATNRFGEAEARVNLFETII 323
Cdd:cd05760  21 LRCHIDGHPRPTYQWFRDGTPLSDGQgNYSVSS-------KERTLTLRSAGPDDSGLYYCCAHNAFGSVCSSQNFTLSII 93

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 36.24 E-value: 3.58e-03

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24653061 242 DMDLECHIEAYPPPAIVWTKDdiQLANNQHYSISHFATADEYTDSTLRVITVEKRQYGDYVCKATNRFGEAEARVNL 318
Cdd:cd20951  17 DAKLRVEVQGKPDPEVKWYKN--GVPIDPSSIPGKYKIESEYGVHVLHIRRVTVEDSAVYSAVAKNIHGEASSSASV 91

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

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 36.32 E-value: 3.58e-03

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24653061 245 LECHIEAYPPPAIVWtKDDIQLANNQHYSISHF-ATADEYTDSTLRVITVEKRQYGDYVCKATNRFG 310
Cdd:cd05734  21 LNCSADGYPPPTIVW-KHSKGSGVPQFQHIVPLnGRIQLLSNGSLLIKHVLEEDSGYYLCKVSNDVG 86

First (N-terminal) immunoglobulin (Ig)-like domain of nectin-like molecule-1 (Necl-1); member of the V-set of Ig superfamily (IgSF) domains; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain of nectin-like molecule-1, Necl-1 (also known as celll adhesion molecule 3 (CADM3), SynCAM2, or IGSF4). Nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 - Necl-5). They all have an extracellular region containing three Ig-like domains, a transmembrane region, and a cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1 has Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue and is important to the formation of synapses, axon bundles, and myelinated axons.

Pssm-ID: 143290 Cd Length: 95 Bit Score: 36.56 E-value: 3.62e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061  34 ITQEQIKDIGGTVEFDCSVQYAKEYNVLFLKTDSDPVFLstGSTLVIKDSRFSL-RYDPNSSTykLQIKDIQETDAGTYT 112
Cdd:cd05882   3 VTQDETVAVGGTVTLKCGVKEHDNSSLQWSNTAQQTLYF--GEKRALRDNRIQLvKSTPTELI--ISISNVQLSDEGEYT 78

                        90
                ....*....|....*
gi 24653061 113 CQVVISTVHKVSAEV 127
Cdd:cd05882  79 CSIFTMPVRTAKATV 93

Immunoglobulin (Ig) variable (V) domain of Cluster of Differentiation (CD) 8 beta chain; The members here are composed of the immunoglobulin (Ig)-like domain in Cluster of Differentiation (CD) 8 beta. The CD8 glycoprotein plays an essential role in the control of T-cell selection, maturation, and the T-cell receptor (TCR)-mediated response to peptide antigen. CD8 is comprised of alpha and beta subunits and is expressed as either an alpha/alpha or alpha/beta dimer. Both dimeric isoforms can serve as a coreceptor for T cell activation and differentiation, however they have distinct physiological roles, different cellular distributions, unique binding partners, etc. Each CD8 subunit is comprised of an extracellular domain containing a V-type Ig-like domain, a single pass transmembrane portion, and a short intracellular domain. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

Pssm-ID: 409497 Cd Length: 116 Bit Score: 36.66 E-value: 3.80e-03

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 24653061 156 ECYASGYPTPTITW----RRENNAILPTDSATYVgnTLRIKSVKKEDRGTYYC 204
Cdd:cd07700  47 EFLASWDPSKGIVYgegvDQEKLIILSDSDSSRY--ILSLMSVKPEDSGTYFC 97

C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein (also known as myomesin-2). Myomesin and M-protein are both structural proteins localized to the M-band, a transverse structure in the center of the sarcomere, and are candidates for M-band bridges. Both proteins are modular, consisting mainly of repetitive Ig-like and fibronectin type III (FnIII) domains. Myomesin is expressed in all types of vertebrate striated muscle; M-protein has a muscle-type specific expression pattern. Myomesin is present in both slow and fast fibers; M-protein is present only in fast fibers. It has been suggested that myomesin acts as a molecular spring with alternative splicing as a means of modifying its elasticity.

Pssm-ID: 319300 Cd Length: 92 Bit Score: 36.03 E-value: 4.05e-03

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24653061 145 VVASEGSEVQMECYASGYPTPTITWRRENNAILPTD-------SATYVgnTLRIKSVKKEDRGTYYCVADN--GVSKGD 214
Cdd:cd05737  11 VTIMEGKTLNLTCNVWGDPPPEVSWLKNDQALAFLDhcnlkveAGRTV--YFTINGVSSEDSGKYGLVVKNkyGSETSD 87

Fifth immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3 protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3 protein (also known as Neph2). This protein has five Ig-like domains, one transmembrane domain, and a cytoplasmic tail. Included in this group is mammalian Kirrel (Neph1). These proteins contain multiple Ig domains, have properties of cell adhesion molecules, and are important in organ development. Neph1 and 2 may mediate axonal guidance and synapse formation in certain areas of the CNS. In the kidney they participate in the formation of the slit diaphragm.

Pssm-ID: 409479 Cd Length: 98 Bit Score: 36.08 E-value: 4.45e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 134 PPVISDNSTQSVVASEGSEVqmECYASGYPTP-TITWRRENNAILPTDSATY----------VGNTLRIKSVKKEDRGTY 202
Cdd:cd05898   2 PPIISSEQVQYAVRGERGKV--KCFIGSTPPPdRIAWAWKENVLESGTLERYtvertstgsgVLSTLTINNIMEADFQTH 79

                        90
                ....*....|..
gi 24653061 203 Y-CVADNGVSKG 213
Cdd:cd05898  80 YnCTAWNSFGSG 91

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

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 36.09 E-value: 4.66e-03

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24653061 143 QSVVASEGSEVQMECYASGYPTPTITWRRE--NNAILPTDSATYVG-------NTLRIKSVKKEDRGTYYCVADN 208
Cdd:cd05726   7 RDQVVALGRTVTFQCETKGNPQPAIFWQKEgsQNLLFPYQPPQPSSrfsvsptGDLTITNVQRSDVGYYICQALN 81

C-terminal immunoglobulin (Ig)-like domain of M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of M-protein (also known as myomesin-2). M-protein is a structural protein localized to the M-band, a transverse structure in the center of the sarcomere, and is a candidate for M-band bridges. M-protein is modular consisting mainly of repetitive IG-like and fibronectin type III (FnIII) domains and has a muscle-type specific expression pattern. M-protein is present in fast fibers.

Pssm-ID: 143299 Cd Length: 92 Bit Score: 36.04 E-value: 4.79e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 145 VVASEGSEVQMECYASGYPTPTITWRRENNAILPT-------DSATYVgnTLRIKSVKKEDRGTYYCVADNGVSkGDRRN 217
Cdd:cd05891  11 VTIMEGKTLNLTCTVFGNPDPEVIWFKNDQDIELSehysvklEQGKYA--SLTIKGVTSEDSGKYSINVKNKYG-GETVD 87


                ....*
gi 24653061 218 INVEV 222
Cdd:cd05891  88 VTVSV 92

C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein (also known as myomesin-2). Myomesin and M-protein are both structural proteins localized to the M-band, a transverse structure in the center of the sarcomere, and are candidates for M-band bridges. Both proteins are modular, consisting mainly of repetitive Ig-like and fibronectin type III (FnIII) domains. Myomesin is expressed in all types of vertebrate striated muscle; M-protein has a muscle-type specific expression pattern. Myomesin is present in both slow and fast fibers; M-protein is present only in fast fibers. It has been suggested that myomesin acts as a molecular spring with alternative splicing as a means of modifying its elasticity.

Pssm-ID: 319300 Cd Length: 92 Bit Score: 36.03 E-value: 5.07e-03

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24653061 243 MDLECHIEAYPPPAIVWTKDDIQLANNQHYSIShFATADEYTDSTLRVITVEKRQYGDYVckaTNRFG 310
Cdd:cd05737  19 LNLTCNVWGDPPPEVSWLKNDQALAFLDHCNLK-VEAGRTVYFTINGVSSEDSGKYGLVV---KNKYG 82

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

Pssm-ID: 409396 [Multi-domain] Cd Length: 94 Bit Score: 35.84 E-value: 5.08e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 135 PVISDNSTQSVVASEGSEVQMECYASGYPTPTITWRR---------ENNAILPTDSATYVgntLRIKSVKKED-RGTYYC 204
Cdd:cd05733   1 PTITEQSPKDYIVDPRDNITIKCEAKGNPQPTFRWTKdgkffdpakDPRVSMRRRSGTLV---IDNHNGGPEDyQGEYQC 77


                ....
gi 24653061 205 VADN 208
Cdd:cd05733  78 YASN 81

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.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 35.84 E-value: 5.31e-03

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 24653061  75 GSTLVIKDSRFSLRYDPNsstykLQIKDIQETDAGTYTCQVVISTVHKVSAEVKLSV 131
Cdd:cd05724  36 GQPLNLDNERVRIVDDGN-----LLIAEARKSDEGTYKCVATNMVGERESRAARLSV 87

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 35.38 E-value: 6.39e-03

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 24653061 149 EGSEVQMECYASGYPTPTITWRRENNAILPT--DSATYVGNT--LRIKSVKKEDRGTYYCVADN 208
Cdd:cd20949  13 EGQSATILCEVKGEPQPNVTWHFNGQPISASvaDMSKYRILAdgLLINKVTQDDTGEYTCRAYQ 76

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 35.06 E-value: 7.23e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 24653061    91 PNSSTYKLQIKDIQETDAGTYTCQVVISTVHKVSAEVKLSV 131
Cdd:pfam13895  39 AISSSPNFFTLSVSAEDSGTYTCVARNGRGGKVSNPVELTV 79

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.

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 35.60 E-value: 7.73e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653061 134 PPVISDNSTQSVVAseGSEVQMECYASGYPTPTITWRR----ENNAILPTDSAtyVGNT-------LRIKSVKKEDRGTY 202
Cdd:cd05765   1 PALVNSPTHQTVKV--GETASFHCDVTGRPQPEITWEKqvpgKENLIMRPNHV--RGNVvvtnigqLVIYNAQPQDAGLY 76


                ....*.
gi 24653061 203 YCVADN 208
Cdd:cd05765  77 TCTARN 82

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. 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.

Pssm-ID: 409388 Cd Length: 84 Bit Score: 34.86 E-value: 9.90e-03

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24653061 242 DMDLECHIEAYPPPAIVWTKDDIQLANNQHYSIshfatadeYTDSTLRVITVEKRQYGDYVCKATNRFGEAEARVNL 318
Cdd:cd05723  14 DIVFECEVTGKPTPTVKWVKNGDVVIPSDYFKI--------VKEHNLQVLGLVKSDEGFYQCIAENDVGNAQASAQL 82