Leucine rich repeat;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 229089140   76 LRRLYLHNNSLRALEAGAFRAQPRLLELALTSNRLRGLRSGAFVGLAQLRVLYLAGNQL 134
Cdd:pfam13855   3 LRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

polycystin cation channel protein; The Polycystin Cation Channel (PCC) Family (TC 1.A.5) Polycystin is a huge protein of 4303aas. Its repeated leucine-rich (LRR) segment is found in many proteins. It contains 16 polycystic kidney disease (PKD) domains, one LDL-receptor class A domain, one C-type lectin family domain, and 16-18 putative TMSs in positions between residues 2200 and 4100. Polycystin-L has been shown to be a cation (Na+, K+ and Ca2+) channel that is activated by Ca2+. Two members of the PCC family (polycystin 1 and 2) are mutated in autosomal dominant polycystic kidney disease, and polycystin-L is deleted in mice with renal and retinal defects. Note: this model is restricted to the amino half.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 229089140   180 NQLGTISREALQPLASLQVLRLTENPWRCDCALHWLGAWIKEGGQRLLtsRDRKIMCAEPPRLALQSLLDVSHSSLIC 257
Cdd:TIGR00864    5 NKISTIEEGICANLCNLSEIDLSGNPFECDCGLARLPRWAEEKGVKVR--QPEAALCAGPGALAGQPLLGIPLLDSGC 80

Leucine rich repeat;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 229089140   76 LRRLYLHNNSLRALEAGAFRAQPRLLELALTSNRLRGLRSGAFVGLAQLRVLYLAGNQL 134
Cdd:pfam13855   3 LRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229089140  53 QTLFLQDNNIARLePGALAPLAALRRLYLHNNSLRALEAgAFRAQPRLLELALTSNRLRGLRSgaFVGLAQLRVLYLAGN 132
Cdd:COG4886  185 KELDLSNNQITDL-PEPLGNLTNLEELDLSGNQLTDLPE-PLANLTNLETLDLSNNQLTDLPE--LGNLTNLEELDLSNN 260

                         90       100       110
                 ....*....|....*....|....*....|
gi 229089140 133 QLARLldFTFLHLPRLQELHLQENSIELLE 162
Cdd:COG4886  261 QLTDL--PPLANLTNLKTLDLSNNQLTDLK 288

protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 (PPP1R42), also known as leucine-rich repeat-containing protein 67 (lrrc67) or testis leucine-rich repeat (TLRR) protein, plays a role in centrosome separation. PPP1R42 has been shown to interact with the well-conserved signaling protein phosphatase-1 (PP1) and thereby increasing PP1's activity, which counters centrosome separation. Inhibition of PPP1R42 expression increases the number of centrosomes per cell while its depletion reduces the activity of PP1 leading to activation of NEK2, the kinase responsible for phosphorylation of centrosomal linker proteins promoting centrosome separation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229089140  55 LFLQDNNIARLEpgALAPLAALRRLYLHNNSLRALEagAFRAQPRLLELALTSNRLRGLRSgaFVGLAQLRVLYLAGNQL 134
Cdd:cd21340    7 LYLNDKNITKID--NLSLCKNLKVLYLYDNKITKIE--NLEFLTNLTHLYLQNNQIEKIEN--LENLVNLKKLYLGGNRI 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 229089140 135 ARL--LDftflHLPRLQELHLQENSI----ELLEDQALAGLSSLALLD--LSRNQLGTIsrEALQPLASLQVLRLTEN 204
Cdd:cd21340   81 SVVegLE----NLTNLEELHIENQRLppgeKLTFDPRSLAALSNSLRVlnISGNNIDSL--EPLAPLRNLEQLDASNN 152

polycystin cation channel protein; The Polycystin Cation Channel (PCC) Family (TC 1.A.5) Polycystin is a huge protein of 4303aas. Its repeated leucine-rich (LRR) segment is found in many proteins. It contains 16 polycystic kidney disease (PKD) domains, one LDL-receptor class A domain, one C-type lectin family domain, and 16-18 putative TMSs in positions between residues 2200 and 4100. Polycystin-L has been shown to be a cation (Na+, K+ and Ca2+) channel that is activated by Ca2+. Two members of the PCC family (polycystin 1 and 2) are mutated in autosomal dominant polycystic kidney disease, and polycystin-L is deleted in mice with renal and retinal defects. Note: this model is restricted to the amino half.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 229089140   180 NQLGTISREALQPLASLQVLRLTENPWRCDCALHWLGAWIKEGGQRLLtsRDRKIMCAEPPRLALQSLLDVSHSSLIC 257
Cdd:TIGR00864    5 NKISTIEEGICANLCNLSEIDLSGNPFECDCGLARLPRWAEEKGVKVR--QPEAALCAGPGALAGQPLLGIPLLDSGC 80

Leucine rich repeat;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229089140  123 QLRVLYLAGNQLARLLDFTFLHLPRLQELHLqensielledqalaglsslalldlSRNQLGTISREALQPLASLQVLRLT 202
Cdd:pfam13855   2 NLRSLDLSNNRLTSLDDGAFKGLSNLKVLDL------------------------SNNLLTTLSPGAFSGLPSLRYLDLS 57

                  ...
gi 229089140  203 ENP 205
Cdd:pfam13855  58 GNR 60

Leucine-rich repeats, outliers;

                           10        20
                   ....*....|....*....|...
gi 229089140    73 LAALRRLYLHNNSLRALEAGAFR 95
Cdd:smart00370   1 LPNLRELDLSNNQLSSLPPGAFQ 23

Leucine rich repeat;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 229089140   76 LRRLYLHNNSLRALEAGAFRAQPRLLELALTSNRLRGLRSGAFVGLAQLRVLYLAGNQL 134
Cdd:pfam13855   3 LRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229089140  53 QTLFLQDNNIARLePGALAPLAALRRLYLHNNSLRALEAgAFRAQPRLLELALTSNRLRGLrSGAFVGLAQLRVLYLAGN 132
Cdd:COG4886  162 KSLDLSNNQLTDL-PEELGNLTNLKELDLSNNQITDLPE-PLGNLTNLEELDLSGNQLTDL-PEPLANLTNLETLDLSNN 238

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 229089140 133 QLARLLDFTflHLPRLQELHLQENsielledqalaglsslalldlsrnQLGTISreALQPLASLQVLRLTENP 205
Cdd:COG4886  239 QLTDLPELG--NLTNLEELDLSNN------------------------QLTDLP--PLANLTNLKTLDLSNNQ 283

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229089140   266 PLELTANLGEDLRVACQASGYPQPLVTWRKV-PQPREGRPRAQAQleggllglgghsaSDTGSGMLFLSNITLAHAGKYE 344
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQgGKLLAESGRFSVS-------------RSGSTSTLTISNVTPEDSGTYT 67

                           90
                   ....*....|....*...
gi 229089140   345 CEASNAGGAARVPFRLLV 362
Cdd:smart00410  68 CAATNSSGSASSGTTLTV 85

protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 (PPP1R42), also known as leucine-rich repeat-containing protein 67 (lrrc67) or testis leucine-rich repeat (TLRR) protein, plays a role in centrosome separation. PPP1R42 has been shown to interact with the well-conserved signaling protein phosphatase-1 (PP1) and thereby increasing PP1's activity, which counters centrosome separation. Inhibition of PPP1R42 expression increases the number of centrosomes per cell while its depletion reduces the activity of PP1 leading to activation of NEK2, the kinase responsible for phosphorylation of centrosomal linker proteins promoting centrosome separation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229089140  55 LFLQDNNIARLEpgALAPLAALRRLYLHNNSLRALEagAFRAQPRLLELALTSNRLRGLRSgaFVGLAQLRVLYLAGNQL 134
Cdd:cd21340    7 LYLNDKNITKID--NLSLCKNLKVLYLYDNKITKIE--NLEFLTNLTHLYLQNNQIEKIEN--LENLVNLKKLYLGGNRI 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 229089140 135 ARL--LDftflHLPRLQELHLQENSI----ELLEDQALAGLSSLALLD--LSRNQLGTIsrEALQPLASLQVLRLTEN 204
Cdd:cd21340   81 SVVegLE----NLTNLEELHIENQRLppgeKLTFDPRSLAALSNSLRVlnISGNNIDSL--EPLAPLRNLEQLDASNN 152

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229089140 259 PPSVHVQPLELTANLGEDLRVACQASGYPQPLVTWRKVPQPREG-----RPRAQAQLEggllglgghsasdtGSGMLFLS 333
Cdd:cd20954    1 PPRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWKKATGSTPGeykdlLYDPNVRIL--------------PNGTLVFG 66

                         90       100
                 ....*....|....*....|
gi 229089140 334 NITLAHAGKYECEASNAGGA 353
Cdd:cd20954   67 HVQKENEGHYLCEAKNGIGS 86

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229089140 260 PSVHVQ-PLELTANLGEDLRVACQASGYPQPLVTWRKVpqprEGRPRAQAQLEggllglgghsasdTGSGMLFLSNITLA 338
Cdd:cd04968    1 PSIKVRfPADTYALKGQTVTLECFALGNPVPQIKWRKV----DGSPSSQWEIT-------------TSEPVLEIPNVQFE 63

                         90       100
                 ....*....|....*....|....
gi 229089140 339 HAGKYECEASNAGGAARVPFRLLV 362
Cdd:cd04968   64 DEGTYECEAENSRGKDTVQGRIIV 87

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 229089140 281 CQASGYPQPLVTWRKVPQPREGRPRaqaqleggllglgGHSASDTGSGMLFLSNITLAHAGKYECEASNAGG 352
Cdd:cd00096    5 CSASGNPPPTITWYKNGKPLPPSSR-------------DSRRSELGNGTLTISNVTLEDSGTYTCVASNSAG 63

polycystin cation channel protein; The Polycystin Cation Channel (PCC) Family (TC 1.A.5) Polycystin is a huge protein of 4303aas. Its repeated leucine-rich (LRR) segment is found in many proteins. It contains 16 polycystic kidney disease (PKD) domains, one LDL-receptor class A domain, one C-type lectin family domain, and 16-18 putative TMSs in positions between residues 2200 and 4100. Polycystin-L has been shown to be a cation (Na+, K+ and Ca2+) channel that is activated by Ca2+. Two members of the PCC family (polycystin 1 and 2) are mutated in autosomal dominant polycystic kidney disease, and polycystin-L is deleted in mice with renal and retinal defects. Note: this model is restricted to the amino half.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 229089140   180 NQLGTISREALQPLASLQVLRLTENPWRCDCALHWLGAWIKEGGQRLLtsRDRKIMCAEPPRLALQSLLDVSHSSLIC 257
Cdd:TIGR00864    5 NKISTIEEGICANLCNLSEIDLSGNPFECDCGLARLPRWAEEKGVKVR--QPEAALCAGPGALAGQPLLGIPLLDSGC 80

Leucine rich repeat C-terminal domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 229089140   204 NPWRCDCALHWLGAWIkEGGQRLLTSRDrkIMCAEPPRLALQsLLDVSHSSLIC 257
Cdd:smart00082   1 NPFICDCELRWLLRWL-QANEHLQDPVD--LRCASPSSLRGP-LLELLHSEFKC 50

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 229089140  274 GEDLRVACQASGYPQPLVTWRKVPQPREGRPRaqaqleggllglgghsasdtgsgmLFLSNITLAHAGKYECEASNAGG 352
Cdd:pfam13895  14 GEPVTLTCSAPGNPPPSYTWYKDGSAISSSPN------------------------FFTLSVSAEDSGTYTCVARNGRG 68

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229089140 259 PPSVHVQPLELTANLGEDLRVACQASGYPQPLVTWRKVPQPregrpraqaqleggLLGLGGHSASDTGSGMLFLSNITLA 338
Cdd:cd20976    1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQP--------------LQYAADRSTCEAGVGELHIQDVLPE 66

                         90       100
                 ....*....|....*....|....
gi 229089140 339 HAGKYECEASNAGGAARVPFRLLV 362
Cdd:cd20976   67 DHGTYTCLAKNAAGQVSCSAWVTV 90

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 229089140 261 SVHVQPLELTANLGEDLRVACQASGYPQPLVTWRkvpqpREG-RPRAQAQleggllglgGHSASDTGSgMLFLSNITLAH 339
Cdd:cd20970    4 STPQPSFTVTAREGENATFMCRAEGSPEPEISWT-----RNGnLIIEFNT---------RYIVRENGT-TLTIRNIRRSD 68

                         90
                 ....*....|....*.
gi 229089140 340 AGKYECEASN-AGGAA 354
Cdd:cd20970   69 MGIYLCIASNgVPGSV 84

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229089140 273 LGEDLRVACQASGYPQPLVTWRKVPQP----REGRPRAQaqleggllglgghsasdtgSGMLFLSNITLAHAGKYECEAS 348
Cdd:cd05856   18 VGSSVRLKCVASGNPRPDITWLKDNKPltppEIGENKKK-------------------KWTLSLKNLKPEDSGKYTCHVS 78

                 ....*
gi 229089140 349 NAGGA 353
Cdd:cd05856   79 NRAGE 83

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229089140 260 PSVhVQPLE--LTANLGEDLRVACQASGYPQPLVTWRKVPQPREGrPRAQAQLEggllglgghsasdtgSGMLFLSNITL 337
Cdd:cd20978    1 PKF-IQKPEknVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQG-PMERATVE---------------DGTLTIINVQP 63

                         90       100
                 ....*....|....*....|....*
gi 229089140 338 AHAGKYECEASNAGGAARVPFRLLV 362
Cdd:cd20978   64 EDTGYYGCVATNEIGDIYTETLLHV 88

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229089140 261 SVHVQPLELTANLGEDLRVACQASGYPQPLVTWRK-----VPQPREGRPRAQAQLEggllglgghsasdtgsgMLFLSNI 335
Cdd:cd05763    1 SFTKTPHDITIRAGSTARLECAATGHPTPQIAWQKdggtdFPAARERRMHVMPEDD-----------------VFFIVDV 63

                         90
                 ....*....|....*..
gi 229089140 336 TLAHAGKYECEASNAGG 352
Cdd:cd05763   64 KIEDTGVYSCTAQNSAG 80

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229089140  268 ELTANLGEDLRVACQAS-GYPQPLVTWRK-VPQPREGRpraqaqleggllgLGGHSASDTGSGMLFLSNITLAHAGKYEC 345
Cdd:pfam00047   5 TVTVLEGDSATLTCSAStGSPGPDVTWSKeGGTLIESL-------------KVKHDNGRTTQSSLLISNVTKEDAGTYTC 71

                  ....*..
gi 229089140  346 EASNAGG 352
Cdd:pfam00047  72 VVNNPGG 78

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 229089140  49 PPGTQTLFLQDNNIARLEPG------ALAPLAALRRLYLHNNSLRALEAGAFRA---QPRLLELALTSNRLrGLRSGAFV 119
Cdd:cd00116   50 QPSLKELCLSLNETGRIPRGlqsllqGLTKGCGLQELDLSDNALGPDGCGVLESllrSSSLQELKLNNNGL-GDRGLRLL 128

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 229089140 120 GLA------QLRVLYLAGNQL----ARLLDFTFLHLPRLQELHLQENSI 158
Cdd:cd00116  129 AKGlkdlppALEKLVLGRNRLegasCEALAKALRANRDLKELNLANNGI 177

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229089140 270 TANLGEDLRVACQASGYPQPLVTWR---KVPQPREGRPRAQAQLEggllglgghsaSDTGSGMLFLSNITLAHAGKYECE 346
Cdd:cd05732   12 TAVELEQITLTCEAEGDPIPEITWRratRGISFEEGDLDGRIVVR-----------GHARVSSLTLKDVQLTDAGRYDCE 80

                 ....*.
gi 229089140 347 ASNAGG 352
Cdd:cd05732   81 ASNRIG 86

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229089140 260 PSVHVQPLELTANLGEDLRVACQASGYPQPLVTWRKVPQP---REGRPRAQaqleggllglggHSASDTGSgMLFLSNI- 335
Cdd:cd07693    1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPletDKDDPRSH------------RIVLPSGS-LFFLRVVh 67

                         90       100
                 ....*....|....*....|...
gi 229089140 336 ---TLAHAGKYECEASNAGGAAR 355
Cdd:cd07693   68 grkGRSDEGVYVCVAHNSLGEAV 90

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229089140 274 GEDLRVACQASGYPQPLVTWRKVPQPREG---RPRAQAQleggllglgghsasdtgSGMLFLSNITLAHAGKYECEASNA 350
Cdd:cd05867   14 GETARLDCQVEGIPTPNITWSINGAPIEGtdpDPRRHVS-----------------SGALILTDVQPSDTAVYQCEARNR 76

                         90
                 ....*....|....
gi 229089140 351 GGAarvpfrLLVNA 364
Cdd:cd05867   77 HGN------LLANA 84