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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61806620 240 TYQPNIEktELYEGYMVMLYCETKGTPKPEVTWEIFagNQLITFplpaivEKSDIpingpptntrFLVFQNG--TLIVPR 317
Cdd:cd05744   4 LQAPGDL--EVQEGRLCRFDCKVSGLPTPDLFWQLN--GKPVRP------DSAHK----------MLVRENGrhSLIIEP 63

                        90       100
                ....*....|....*....|....*...
gi 61806620 318 MSKKEEGNYTCSAVNDIGKAESSVRLVV 345
Cdd:cd05744  64 VTKRDAGIYTCIARNRAGENSFNAELVV 91

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61806620 240 TYQPNIEktELYEGYMVMLYCETKGTPKPEVTWEIFagNQLITFplpaivEKSDIpingpptntrFLVFQNG--TLIVPR 317
Cdd:cd05744   4 LQAPGDL--EVQEGRLCRFDCKVSGLPTPDLFWQLN--GKPVRP------DSAHK----------MLVRENGrhSLIIEP 63

                        90       100
                ....*....|....*....|....*...
gi 61806620 318 MSKKEEGNYTCSAVNDIGKAESSVRLVV 345
Cdd:cd05744  64 VTKRDAGIYTCIARNRAGENSFNAELVV 91

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61806620    252 EGYMVMLYCETKGTPKPEVTWeIFAGNQLITFPlpaiveksdipingpptnTRFLVFQNG---TLIVPRMSKKEEGNYTC 328
Cdd:smart00410   8 EGESVTLSCEASGSPPPEVTW-YKQGGKLLAES------------------GRFSVSRSGstsTLTISNVTPEDSGTYTC 68

                           90
                   ....*....|....*..
gi 61806620    329 SAVNDIGKAESSVRLVV 345
Cdd:smart00410  69 AATNSSGSASSGTTLTV 85

Leucine rich repeat C-terminal domain;

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 61806620    183 NPFICSCNLEWLRDWiLKSSISIPEQNNIACDAPSHLKG 221
Cdd:smart00082   1 NPFICDCELRWLLRW-LQANEHLQDPVDLRCASPSSLRG 38

leucine-rich repeat receptor-like protein kinase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61806620   50 GLP-----SNASTLSLSANKIKVLKSKTFVNVTQVTSLWLAHNEIITVERDTLAPLIQLKNLDISNNKIV-HFPwEDLAN 123
Cdd:PLN00113 467 GLPdsfgsKRLENLDLSRNQFSGAVPRKLGSLSELMQLKLSENKLSGEIPDELSSCKKLVSLDLSHNQLSgQIP-ASFSE 545

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 61806620  124 LGALQLLKMNNNEMV-SIPKNaFSNLKDLRSIRINNNKF 161
Cdd:PLN00113 546 MPVLSQLDLSQNQLSgEIPKN-LGNVESLVQVNISHNHL 583

Leucine-rich repeat (LRR) protein [Transcription];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61806620  57 TLSLSANKIKVLkSKTFVNVTQVTSLWLAHNEIITVErDTLAPLIQLKNLDISNNKIVHFPWedLANLGALQLLKMNNNE 136
Cdd:COG4886 186 ELDLSNNQITDL-PEPLGNLTNLEELDLSGNQLTDLP-EPLANLTNLETLDLSNNQLTDLPE--LGNLTNLEELDLSNNQ 261

                        90       100
                ....*....|....*....|....*...
gi 61806620 137 MVSIPKNAfsNLKDLRSIRINNNKFTTI 164
Cdd:COG4886 262 LTDLPPLA--NLTNLKTLDLSNNQLTDL 287

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61806620   238 SITYQPNieKTELYEGYMVMLYCETKGTPKPEVTWEifagnqlitfplpaiveKSDIPINGPPTNTRFLVFQNGTLIVPR 317
Cdd:pfam13927   3 VITVSPS--SVTVREGETVTLTCEATGSPPPTITWY-----------------KNGEPISSGSTRSRSLSGSNSTLTISN 63

                          90
                  ....*....|....*
gi 61806620   318 MSKKEEGNYTCSAVN 332
Cdd:pfam13927  64 VTRSDAGTYTCVASN 78

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61806620   252 EGYMVMLYCETKGTPKPEVTWEifagnqlitfplpaiveKSDIPINgppTNTRFLVFQNG---TLIVPRMSKKEEGNYTC 328
Cdd:pfam07679  14 EGESARFTCTVTGTPDPEVSWF-----------------KDGQPLR---SSDRFKVTYEGgtyTLTISNVQPDDSGKYTC 73

                          90
                  ....*....|....*..
gi 61806620   329 SAVNDIGKAESSVRLVV 345
Cdd:pfam07679  74 VATNSAGEAEASAELTV 90

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61806620 252 EGYMVMLYCETKGTPKPEVTWEIfAGNQLitfplpaiveksdipingpPTNTRFLVFQNGTLIVPRMSKKEEGNYTCSAV 331
Cdd:cd05745   1 EGQTVDFLCEAQGYPQPVIAWTK-GGSQL-------------------SVDRRHLVLSSGTLRISRVALHDQGQYECQAV 60

                        90
                ....*....|....
gi 61806620 332 NDIGKAESSVRLVV 345
Cdd:cd05745  61 NIVGSQRTVAQLTV 74

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61806620    252 EGYMVMLYCETKGTPKPEVTWeIFAGNQLITFPlpaiveksdipingpptnTRFLVFQNG---TLIVPRMSKKEEGNYTC 328
Cdd:smart00410   8 EGESVTLSCEASGSPPPEVTW-YKQGGKLLAES------------------GRFSVSRSGstsTLTISNVTPEDSGTYTC 68

                           90
                   ....*....|....*..
gi 61806620    329 SAVNDIGKAESSVRLVV 345
Cdd:smart00410  69 AATNSSGSASSGTTLTV 85

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61806620 256 VMLYCETKGTPKPEVTWEifagnqlitfplpaiveKSDIPINGPPTNTRFLVFQNGTLIVPRMSKKEEGNYTCSAVNDIG 335
Cdd:cd00096   1 VTLTCSASGNPPPTITWY-----------------KNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAG 63

                ....*
gi 61806620 336 KAESS 340
Cdd:cd00096  64 GSASA 68

Leucine rich repeat C-terminal domain;

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 61806620    183 NPFICSCNLEWLRDWiLKSSISIPEQNNIACDAPSHLKG 221
Cdd:smart00082   1 NPFICDCELRWLLRW-LQANEHLQDPVDLRCASPSSLRG 38

Leucine rich repeat;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 61806620    53 SNASTLSLSANKIKVLKSKTFVNVTQVTSLWLAHNEIITVERDTLAPLIQLKNLDISNNKI 113
Cdd:pfam13855   1 PNLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61806620 241 YQPNIEKTELYEGYMVMLYCETKGTPKPEVTWEifAGNQLItfplpaiveksdipINgpptNTRFLVFQNGTLIVPRMSK 320
Cdd:cd05852   5 FNPMKKKILAAKGGRVIIECKPKAAPKPKFSWS--KGTELL--------------VN----NSRISIWDDGSLEILNITK 64

                        90       100
                ....*....|....*....|....*
gi 61806620 321 KEEGNYTCSAVNDIGKAESSVRLVV 345
Cdd:cd05852  65 LDEGSYTCFAENNRGKANSTGVLSV 89

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61806620 256 VMLYCETKGTPKPEVTWEIfAGNQLitfplpaiveksdipingpPTNTRFLVFQNGTLIVPRMSKKE-EGNYTCSAVNDI 334
Cdd:cd20958  18 LRLHCPVAGYPISSITWEK-DGRRL-------------------PLNHRQRVFPNGTLVIENVQRSSdEGEYTCTARNQQ 77

                        90
                ....*....|..
gi 61806620 335 G-KAESSVRLVV 345
Cdd:cd20958  78 GqSASRSVFVKV 89

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61806620 252 EGYMVMLYCETKGTPKPEVTWeIFAGNQLITfplpaiveksdipingPPTNTRFLVFQNGTLIVPRMSKKEEGNYTCSAV 331
Cdd:cd20969  16 EGHTVQFVCRADGDPPPAILW-LSPRKHLVS----------------AKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAA 78

                        90
                ....*....|....
gi 61806620 332 NDIGKAESSVRLVV 345
Cdd:cd20969  79 NAGGNDSMPAHLHV 92

Leucine-rich repeat (LRR) protein [Transcription];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61806620  58 LSLSANKIKVLKSKTFVNVTQVTSLWLAHNEIITVERDTLAPLIQLKNLDISNNkivhfpwEDLANLGALQLLKMNNNEM 137
Cdd:COG4886  53 LSLLLRDLLLSSLLLLLSLLLLLLLSLLLLSLLLLGLTDLGDLTNLTELDLSGN-------EELSNLTNLESLDLSGNQL 125

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 61806620 138 VSIPKnAFSNLKDLRSIRINNNKFTTIVqgtfDSLAAMSHLQ 179
Cdd:COG4886 126 TDLPE-ELANLTNLKELDLSNNQLTDLP----EPLGNLTNLK 162

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61806620 252 EGYMVMLYCETKGTPKPEVTWEiFAGNQLITFplpaiveksdipingpptNTRFLVFQNGT-LIVPRMSKKEEGNYTCSA 330
Cdd:cd20970  16 EGENATFMCRAEGSPEPEISWT-RNGNLIIEF------------------NTRYIVRENGTtLTIRNIRRSDMGIYLCIA 76

                        90
                ....*....|....*.
gi 61806620 331 VNDI-GKAESSVRLVV 345
Cdd:cd20970  77 SNGVpGSVEKRITLQV 92

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61806620 240 TYQPNIEKTELYEGYMVMLYCETKGTPKPEVTWeifagnqlitfplpaivEKSDIPIN-GPPTNTRFLVFQNGtLIVPRM 318
Cdd:cd20949   1 TFTENAYVTTVKEGQSATILCEVKGEPQPNVTW-----------------HFNGQPISaSVADMSKYRILADG-LLINKV 62

                        90       100
                ....*....|....*....|....*..
gi 61806620 319 SKKEEGNYTCSAVNDIGKAESSVRLVV 345
Cdd:cd20949  63 TQDDTGEYTCRAYQVNSIASDMQERTV 89

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61806620 252 EGYMVMLYCETKGTPKPEVTWeifagnqlitfplpaivEKSDIPINGPPTNTRFLVFQNG---TLIVPRMSKKEEGNYTC 328
Cdd:cd20951  14 EKSDAKLRVEVQGKPDPEVKW-----------------YKNGVPIDPSSIPGKYKIESEYgvhVLHIRRVTVEDSAVYSA 76

                        90
                ....*....|....*..
gi 61806620 329 SAVNDIGKAESSVRLVV 345
Cdd:cd20951  77 VAKNIHGEASSSASVVV 93

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61806620 252 EGYMVMLYCETKGTPKPEVTWEIfagnqlitfplpaivekSDIPINgPPTNTRFLVFQNG--TLIVPRMSKKEEGNYTCS 329
Cdd:cd20990  14 EGKLCRMDCKVSGLPTPDLSWQL-----------------DGKPIR-PDSAHKMLVRENGvhSLIIEPVTSRDAGIYTCI 75

                        90
                ....*....|....*.
gi 61806620 330 AVNDIGKAESSVRLVV 345
Cdd:cd20990  76 ATNRAGQNSFNLELVV 91

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61806620 248 TELYEGYMVMLYCETKGTPKPEVTWEifAGNQLITFplpaiveksdipingpptNT-RFLVFQNGT----LIVPRMSKKE 322
Cdd:cd05892  10 KKVLEGDPVRLECQISAIPPPQIFWK--KNNEMLQY------------------NTdRISLYQDNCgricLLIQNANKKD 69

                        90       100
                ....*....|....*....|...
gi 61806620 323 EGNYTCSAVNDIGKAESSVRLVV 345
Cdd:cd05892  70 AGWYTVSAVNEAGVVSCNARLDV 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61806620 253 GYMVMLYCETKGTPKPEVTWEifagnqlitfplpaiveKSDipinGPPTNTRFLVFQNGTLIVPRMSKKEEGNYTCSAVN 332
Cdd:cd04968  16 GQTVTLECFALGNPVPQIKWR-----------------KVD----GSPSSQWEITTSEPVLEIPNVQFEDEGTYECEAEN 74

                        90
                ....*....|...
gi 61806620 333 DIGKAESSVRLVV 345
Cdd:cd04968  75 SRGKDTVQGRIIV 87

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61806620 263 KGTPKPEVTWEifAGNQLITFPLPAIVEKSDipingppTNTrflvfqngTLIVPRMSKKEEGNYTCSAVNDIGKAESSVR 342
Cdd:cd05748  17 KGRPTPTVTWS--KDGQPLKETGRVQIETTA-------SST--------SLVIKNAKRSDSGKYTLTLKNSAGEKSATIN 79

                ...
gi 61806620 343 LVV 345
Cdd:cd05748  80 VKV 82

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61806620 249 ELYEGYMVMLYCETKGTPKPEVTWeIFAGNQLITFPlpaiveksDIPINgpptntrflvfQNG---TLIVPRMSKKEEGN 325
Cdd:cd20972  12 EVAEGSKVRLECRVTGNPTPVVRW-FCEGKELQNSP--------DIQIH-----------QEGdlhSLIIAEAFEEDTGR 71

                        90       100
                ....*....|....*....|
gi 61806620 326 YTCSAVNDIGKAESSVRLVV 345
Cdd:cd20972  72 YSCLATNSVGSDTTSAEIFV 91

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61806620 253 GYMVMLYCETKGTPKPEVTWEIFAGnqlitfPLPAIVEKSDIPINGpptntrflvfqNGTLIVPRMSKKEEGNYTCSAVN 332
Cdd:cd05743   1 GETVEFTCVATGVPTPIINWRLNWG------HVPDSARVSITSEGG-----------YGTLTIRDVKESDQGAYTCEAIN 63

                ...
gi 61806620 333 DIG 335
Cdd:cd05743  64 TRG 66

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61806620 256 VMLYCETKGTPKPEVTWeIFAGNQLITfplpaiveksdipingppTNTRFLVFQNGTLIVPRMSKKEEGNYTCSAVNDIG 335
Cdd:cd20952  17 VVLNCQATGEPVPTISW-LKDGVPLLG------------------KDERITTLENGSLQIKGAEKSDTGEYTCVALNLSG 77

                        90
                ....*....|
gi 61806620 336 KAESSVRLVV 345
Cdd:cd20952  78 EATWSAVLDV 87

leucine-rich repeat receptor-like protein kinase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61806620   50 GLP-----SNASTLSLSANKIKVLKSKTFVNVTQVTSLWLAHNEIITVERDTLAPLIQLKNLDISNNKIV-HFPwEDLAN 123
Cdd:PLN00113 467 GLPdsfgsKRLENLDLSRNQFSGAVPRKLGSLSELMQLKLSENKLSGEIPDELSSCKKLVSLDLSHNQLSgQIP-ASFSE 545

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 61806620  124 LGALQLLKMNNNEMV-SIPKNaFSNLKDLRSIRINNNKF 161
Cdd:PLN00113 546 MPVLSQLDLSQNQLSgEIPKN-LGNVESLVQVNISHNHL 583

Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond to structural units consisting of a beta strand (LxxLxLxxN/CxL conserved pattern) and an alpha helix. This alignment contains 12 strands corresponding to 11 full repeats, consistent with the extent observed in the subfamily acting as Ran GTPase Activating Proteins (RanGAP1).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61806620  47 VPVGLPSNA--STLSLSANKIKVLKSKTFVNVTQVTSL---WLAHNEiitvERDTLAPLIQ---------LKNLDISNNK 112
Cdd:cd00116  73 LLQGLTKGCglQELDLSDNALGPDGCGVLESLLRSSSLqelKLNNNG----LGDRGLRLLAkglkdlppaLEKLVLGRNR 148