Leucine rich repeat;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1958790501  84 LRHLYLHNNTLRALESGAFRAQPRLLELALTGNRLRGLRGGAFVGLVQLRVLYLAGNQL 142
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 1958790501  188 NQLGTISKEALQPLSSLQVLRLTENPWRCDCALHWLGSWIKEGGRRLLssRDKKITCAEPPRLALQSLLEVS 259
Cdd:TIGR00864    5 NKISTIEEGICANLCNLSEIDLSGNPFECDCGLARLPRWAEEKGVKVR--QPEAALCAGPGALAGQPLLGIP 74

Leucine rich repeat;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1958790501  84 LRHLYLHNNTLRALESGAFRAQPRLLELALTGNRLRGLRGGAFVGLVQLRVLYLAGNQL 142
Cdd:pfam13855   3 LRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

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 1958790501  63 LFLQDNSIAHLEqgALAPLAALRHLYLHNNTLRALESgaFRAQPRLLELALTGNRLRGLRGgaFVGLVQLRVLYLAGNQL 142
Cdd:cd21340     7 LYLNDKNITKID--NLSLCKNLKVLYLYDNKITKIEN--LEFLTNLTHLYLQNNQIEKIEN--LENLVNLKKLYLGGNRI 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958790501 143 AKL--LDftflHLPRLQELHLQENSI----ELLEDQALAGLSSLALLD--LSRNQLGTIskEALQPLSSLQVLRLTEN 212
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 1958790501 267 PPSVNAEPPELTANLGEDLQVACQASGYPQPLVVWRKMLqprdgkpqaqvqleGGAPG-----LGGHATRDTGSGMLFLT 341
Cdd:cd20954     1 PPRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWKKAT--------------GSTPGeykdlLYDPNVRILPNGTLVFG 66

                          90
                  ....*....|....*....
gi 1958790501 342 NITLAHAGKYECEATNAGG 360
Cdd:cd20954    67 HVQKENEGHYLCEAKNGIG 85

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 1958790501  188 NQLGTISKEALQPLSSLQVLRLTENPWRCDCALHWLGSWIKEGGRRLLssRDKKITCAEPPRLALQSLLEVS 259
Cdd:TIGR00864    5 NKISTIEEGICANLCNLSEIDLSGNPFECDCGLARLPRWAEEKGVKVR--QPEAALCAGPGALAGQPLLGIP 74

Leucine rich repeat;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958790501 131 QLRVLYLAGNQLAKLLDFTFLHLPRLQELHLqensielledqalaglsslalldlSRNQLGTISKEALQPLSSLQVLRLT 210
Cdd:pfam13855   2 NLRSLDLSNNRLTSLDDGAFKGLSNLKVLDL------------------------SNNLLTTLSPGAFSGLPSLRYLDLS 57

                  ...
gi 1958790501 211 ENP 213
Cdd:pfam13855  58 GNR 60

Leucine rich repeat;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1958790501  84 LRHLYLHNNTLRALESGAFRAQPRLLELALTGNRLRGLRGGAFVGLVQLRVLYLAGNQL 142
Cdd:pfam13855   3 LRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

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 1958790501  63 LFLQDNSIAHLEqgALAPLAALRHLYLHNNTLRALESgaFRAQPRLLELALTGNRLRGLRGgaFVGLVQLRVLYLAGNQL 142
Cdd:cd21340     7 LYLNDKNITKID--NLSLCKNLKVLYLYDNKITKIEN--LEFLTNLTHLYLQNNQIEKIEN--LENLVNLKKLYLGGNRI 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958790501 143 AKL--LDftflHLPRLQELHLQENSI----ELLEDQALAGLSSLALLD--LSRNQLGTIskEALQPLSSLQVLRLTEN 212
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 1958790501 267 PPSVNAEPPELTANLGEDLQVACQASGYPQPLVVWRKMLqprdgkpqaqvqleGGAPG-----LGGHATRDTGSGMLFLT 341
Cdd:cd20954     1 PPRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWKKAT--------------GSTPGeykdlLYDPNVRILPNGTLVFG 66

                          90
                  ....*....|....*....
gi 1958790501 342 NITLAHAGKYECEATNAGG 360
Cdd:cd20954    67 HVQKENEGHYLCEAKNGIG 85

Leucine rich repeat;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958790501 106 PRLLELALTGNRLRGLRGGAFVGLVQLRVLYLAGNQLAKLLDFTFLHLPRLQELHLQENSI 166
Cdd:pfam13855   1 PNLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958790501 267 PPSVNAEPPEL--TANLGEDLQVACQASGYPQPLVVWRKmlqprDGKPQAQvqleggapGLGGHATRDTGSGMLFLtNIT 344
Cdd:cd05730     1 PPTIRARQSEVnaTANLGQSVTLACDADGFPEPTMTWTK-----DGEPIES--------GEEKYSFNEDGSEMTIL-DVD 66

                          90       100
                  ....*....|....*....|....*...
gi 1958790501 345 LAHAGKYECEATNAGGKARVLFHLLVNA 372
Cdd:cd05730    67 KLDEAEYTCIAENKAGEQEAEIHLKVFA 94

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 1958790501  63 LFLQDNSIAHLEQgaLAPLAALRHLYLHNNTLRALESgaFRAQPRLLEL------------------------------A 112
Cdd:cd21340    51 LYLQNNQIEKIEN--LENLVNLKKLYLGGNRISVVEG--LENLTNLEELhienqrlppgekltfdprslaalsnslrvlN 126

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1958790501 113 LTGNRLRGLRGgaFVGLVQLRVLYLAGNQLAKLLDFTFL--HLPRLQELHLQENSI 166
Cdd:cd21340   127 ISGNNIDSLEP--LAPLRNLEQLDASNNQISDLEELLDLlsSWPSLRELDLTGNPV 180

First immunoglobulin-like domains A168 within the A-band segment of human cardiac titin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domain A168 within the A-band segment of human cardiac titin. 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 structures of the titin-A168169 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 1958790501 279 ANLGEDLQVACQASGYPQPLVVWRKMLQPrdgkpqaqvqleggAPGLGGHATRDT--GSGMLFLTNITL-AHAGKYECEA 355
Cdd:cd20971    13 VRYQSNATLVCKVTGHPKPIVKWYRQGKE--------------IIADGLKYRIQEfkGGYHQLIIASVTdDDATVYQVRA 78

                          90
                  ....*....|....*
gi 1958790501 356 TNAGGKARVLFHLLV 370
Cdd:cd20971    79 TNQGGSVSGTASLEV 93

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 1958790501  188 NQLGTISKEALQPLSSLQVLRLTENPWRCDCALHWLGSWIKEGGRRLLssRDKKITCAEPPRLALQSLLEVS 259
Cdd:TIGR00864    5 NKISTIEEGICANLCNLSEIDLSGNPFECDCGLARLPRWAEEKGVKVR--QPEAALCAGPGALAGQPLLGIP 74

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 1958790501 289 CQASGYPQPLVVWRKmlqprDGKPQAQVQLEGGapglgghaTRDTGSGMLFLTNITLAHAGKYECEATNAGGKAR 363
Cdd:cd00096     5 CSASGNPPPTITWYK-----NGKPLPPSSRDSR--------RSELGNGTLTISNVTLEDSGTYTCVASNSAGGSA 66

Leucine rich repeat C-terminal domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1958790501  212 NPWRCDCALHWLGSWIKEGGRRLLSSRdkkITCAEPPRLALQsLLEVSGGSLIC 265
Cdd:smart00082   1 NPFICDCELRWLLRWLQANEHLQDPVD---LRCASPSSLRGP-LLELLHSEFKC 50

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 1958790501 282 GEDLQVACQASGYPQPLVVWRKmlqprdgkpqaqvqleGGAPGLGGHATRDTGSGMLFLTNITLAHAGKYECEATNAGGK 361
Cdd:cd05745     2 GQTVDFLCEAQGYPQPVIAWTK----------------GGSQLSVDRRHLVLSSGTLRISRVALHDQGQYECQAVNIVGS 65

                  ....*....
gi 1958790501 362 ARVLFHLLV 370
Cdd:cd05745    66 QRTVAQLTV 74

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 1958790501 273 EPPELTANLGEDLQVACQAS-GYPQPLVVWRKMLQprdgkpqaqvQLEGGApgLGGHATRDTGSGMLFLTNITLAHAGKY 351
Cdd:pfam00047   2 APPTVTVLEGDSATLTCSAStGSPGPDVTWSKEGG----------TLIESL--KVKHDNGRTTQSSLLISNVTKEDAGTY 69

                          90
                  ....*....|.
gi 1958790501 352 ECEATNAGGKA 362
Cdd:pfam00047  70 TCVVNNPGGSA 80

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 1958790501  81 LAALRHLYLHNNTLRALEsgAFRAQPRLLELALTGNRLRGLRGgaFVGLVQLRVLYLAGNQLAKLLDFTflHLPRLQELH 160
Cdd:cd21340     1 LKRITHLYLNDKNITKID--NLSLCKNLKVLYLYDNKITKIEN--LEFLTNLTHLYLQNNQIEKIENLE--NLVNLKKLY 74

                          90
                  ....*....|
gi 1958790501 161 LQENSIELLE 170
Cdd:cd21340    75 LGGNRISVVE 84

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958790501 268 PSVNAEPPELTANLGEDLQVACQASGYPQPLVVWRKMLQPRDGKPQAQVQLEGGapglgghaTRDTGSGMLFLTNITLAH 347
Cdd:cd05765     1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWEKQVPGKENLIMRPNHVRGN--------VVVTNIGQLVIYNAQPQD 72

                          90       100
                  ....*....|....*....|...
gi 1958790501 348 AGKYECEATNAGGKARVLFHLLV 370
Cdd:cd05765    73 AGLYTCTARNSGGLLRANFPLSV 95

Leucine rich repeat;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958790501 131 QLRVLYLAGNQLAKLLDFTFLHLPRLQELHLqensielledqalaglsslalldlSRNQLGTISKEALQPLSSLQVLRLT 210
Cdd:pfam13855   2 NLRSLDLSNNRLTSLDDGAFKGLSNLKVLDL------------------------SNNLLTTLSPGAFSGLPSLRYLDLS 57

                  ...
gi 1958790501 211 ENP 213
Cdd:pfam13855  58 GNR 60

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 1958790501 268 PSVNAEPPELT-ANLGEDLQVACQASGYPQPLVVWRkmlqpRDGKPqaqvqLEGGAPglgghaTRDTGSGMLFLTNITLA 346
Cdd:cd20978     1 PKFIQKPEKNVvVKGGQDVTLPCQVTGVPQPKITWL-----HNGKP-----LQGPME------RATVEDGTLTIINVQPE 64

                          90       100
                  ....*....|....*....|....
gi 1958790501 347 HAGKYECEATNAGGKARVLFHLLV 370
Cdd:cd20978    65 DTGYYGCVATNEIGDIYTETLLHV 88

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958790501 282 GEDLQVACQASGYPQPLVVWRKmlqprdgkpqaqvqleggapglGGHATRDTG------SGMLFLTNITLAHAGKYECEA 355
Cdd:cd04969    17 GGDVIIECKPKASPKPTISWSK----------------------GTELLTNSSricilpDGSLKIKNVTKSDEGKYTCFA 74

                  ....*..
gi 1958790501 356 TNAGGKA 362
Cdd:cd04969    75 VNFFGKA 81

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958790501 273 EPPELTANLGEDLQVACQASGYPQPLVVWRKmlqpRDGK-PQAQVQLeggapglgghatRDTGSgmLFLTNITLAHAGKY 351
Cdd:cd05725     3 RPQNQVVLVDDSAEFQCEVGGDPVPTVRWRK----EDGElPKGRYEI------------LDDHS--LKIRKVTAGDMGSY 64

                          90
                  ....*....|.
gi 1958790501 352 ECEATNAGGKA 362
Cdd:cd05725    65 TCVAENMVGKI 75

Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor 2 (FGFR2); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain of human fibroblast growth factor receptor 2 (FGFR2). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for FGFs. FGFR2 is required for male sex determination. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958790501 274 PPELTANLGEDLQVACQASGYPQPLVVWRKMLQPR------DGKPQAQVQLEGGApglgghATRDTGSGMLFLTNITLAH 347
Cdd:cd05858     8 PANTSVVVGTDAEFVCKVYSDAQPHIQWLKHVEKNgskygpDGLPYVEVLKTAGV------NTTDKEIEVLYLRNVTFED 81

                          90
                  ....*....|...
gi 1958790501 348 AGKYECEATNAGG 360
Cdd:cd05858    82 AGEYTCLAGNSIG 94

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958790501 282 GEDLQVACQASGYPQPLVVWRKmlqprDGKPQAqvqleggapGLGGHATRDTGSGMLFLTNITLAHAGKYECEATNAGGk 361
Cdd:cd05867    14 GETARLDCQVEGIPTPNITWSI-----NGAPIE---------GTDPDPRRHVSSGALILTDVQPSDTAVYQCEARNRHG- 78

                          90
                  ....*....|.
gi 1958790501 362 arvlfHLLVNA 372
Cdd:cd05867    79 -----NLLANA 84