Leucine rich repeat;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 37674275    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 37674275    188 NQLGTISKEALQPLSSLQVLRLTENPWRCDCALHWLGSWIKEGGRRLLssRDKKITCAEPPRLALQSLLEVS 259
Cdd:TIGR00864    5 NKISTIEEGICANLCNLSEIDLSGNPFECDCGLARLPRWAEEKGVKVR--QPEAALCAGPGALAGQPLLGIP 74

Leucine rich repeat;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 37674275    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 37674275  63 LFLQDNSIAHLEqgSLAPLAALRHLYLHNNTLRALESgaFRAQPRLLELALTGNRLRGLRGgaFVGLVQLRVLYLAGNQL 142
Cdd:cd21340   7 LYLNDKNITKID--NLSLCKNLKVLYLYDNKITKIEN--LEFLTNLTHLYLQNNQIEKIEN--LENLVNLKKLYLGGNRI 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 37674275 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 37674275 267 PPSVNVEPPEFTANLGEDLQVACQASGYPQPLVVWRKVP--QPRDGKPQAQAQleggapglgghGTRDTGSGMLFLTNIT 344
Cdd:cd20954   1 PPRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWKKATgsTPGEYKDLLYDP-----------NVRILPNGTLVFGHVQ 69

                        90
                ....*....|....*.
gi 37674275 345 LAHAGKYECEAANAGG 360
Cdd:cd20954  70 KENEGHYLCEAKNGIG 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 37674275    188 NQLGTISKEALQPLSSLQVLRLTENPWRCDCALHWLGSWIKEGGRRLLssRDKKITCAEPPRLALQSLLEVS 259
Cdd:TIGR00864    5 NKISTIEEGICANLCNLSEIDLSGNPFECDCGLARLPRWAEEKGVKVR--QPEAALCAGPGALAGQPLLGIP 74

Leucine rich repeat;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37674275   131 QLRVLYLAGNQLAKLLDFTFLHLPRLQELHLqensielledqalaglsslalldlSRNQLGTISKEALQPLSSLQVLRLT 210
Cdd:pfam13855   2 NLRSLDLSNNRLTSLDDGAFKGLSNLKVLDL------------------------SNNLLTTLSPGAFSGLPSLRYLDLS 57

                  ...
gi 37674275   211 ENP 213
Cdd:pfam13855  58 GNR 60

Leucine-rich repeats, outliers;

                           10        20
                   ....*....|....*....|...
gi 37674275     81 LAALRHLYLHNNTLRALESGAFR 103
Cdd:smart00370   1 LPNLRELDLSNNQLSSLPPGAFQ 23

Leucine rich repeat;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 37674275    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 37674275  63 LFLQDNSIAHLEqgSLAPLAALRHLYLHNNTLRALESgaFRAQPRLLELALTGNRLRGLRGgaFVGLVQLRVLYLAGNQL 142
Cdd:cd21340   7 LYLNDKNITKID--NLSLCKNLKVLYLYDNKITKIEN--LEFLTNLTHLYLQNNQIEKIEN--LENLVNLKKLYLGGNRI 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 37674275 143 AKL--LDftflHLPRLQELHLQENSI----ELLEDQALAGLSSLALLD--LSRNQLGTIskEALQPLSSLQVLRLTEN 212
Cdd:cd21340  81 SVVegLE----NLTNLEELHIENQRLppgeKLTFDPRSLAALSNSLRVlnISGNNIDSL--EPLAPLRNLEQLDASNN 152

Leucine rich repeat;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 37674275   106 PRLLELALTGNRLRGLRGGAFVGLVQLRVLYLAGNQLAKLLDFTFLHLPRLQELHLQENSI 166
Cdd:pfam13855   1 PNLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

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 37674275 267 PPSVNVEPPEFTANLGEDLQVACQASGYPQPLVVWRKVP--QPRDGKPQAQAQleggapglgghGTRDTGSGMLFLTNIT 344
Cdd:cd20954   1 PPRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWKKATgsTPGEYKDLLYDP-----------NVRILPNGTLVFGHVQ 69

                        90
                ....*....|....*.
gi 37674275 345 LAHAGKYECEAANAGG 360
Cdd:cd20954  70 KENEGHYLCEAKNGIG 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 37674275  63 LFLQDNSIAHLEqgSLAPLAALRHLYLHNNTLRALESgaFRAQPRLLEL------------------------------A 112
Cdd:cd21340  51 LYLQNNQIEKIE--NLENLVNLKKLYLGGNRISVVEG--LENLTNLEELhienqrlppgekltfdprslaalsnslrvlN 126

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 37674275 113 LTGNRLRGLRGgaFVGLVQLRVLYLAGNQLAKLLDFTFL--HLPRLQELHLQENSI 166
Cdd:cd21340 127 ISGNNIDSLEP--LAPLRNLEQLDASNNQISDLEELLDLlsSWPSLRELDLTGNPV 180

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 37674275  61 QTLFLQDNSIAHLEQgsLAPLAALRHLYLHNNTLRALESgaFRAQPRLLELALTGNRLR---GLRGgafvgLVQLRVLYL 137
Cdd:cd21340  27 KVLYLYDNKITKIEN--LEFLTNLTHLYLQNNQIEKIEN--LENLVNLKKLYLGGNRISvveGLEN-----LTNLEELHI 97

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37674275 138 AGNQLAKLLDFTF------LHLPRLQELHLQENSIELLEDqaLAGLSSLALLDLSRNQLGTIS--KEALQPLSSLQVLRL 209
Cdd:cd21340  98 ENQRLPPGEKLTFdprslaALSNSLRVLNISGNNIDSLEP--LAPLRNLEQLDASNNQISDLEelLDLLSSWPSLRELDL 175

                ....
gi 37674275 210 TENP 213
Cdd:cd21340 176 TGNP 179

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 37674275 289 CQASGYPQPLVVWRKvpqprDGKPQAQAQLEGGapglgghgTRDTGSGMLFLTNITLAHAGKYECEAANAGGKAR 363
Cdd:cd00096   5 CSASGNPPPTITWYK-----NGKPLPPSSRDSR--------RSELGNGTLTISNVTLEDSGTYTCVASNSAGGSA 66

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37674275 267 PPSVNVEPPEFTANLGEDLQVACQASGYPQPLVVWRKVPQPRdgkpQAQAQLEggapglgghgtrdTGSGMLFLTNITLA 346
Cdd:cd05851   1 PADINVKFKDTYALKGQNVTLECFALGNPVPVIRWRKILEPM----PATAEIS-------------MSGAVLKIFNIQPE 63

                        90
                ....*....|....*
gi 37674275 347 HAGKYECEAANAGGK 361
Cdd:cd05851  64 DEGTYECEAENIKGK 78

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37674275 273 EPPEFTANLGEDLQVACQASGYPQPLVVWRKvpqprDGKPqaqaqLEGGAPGLGGHGTRDTgsgmLFLTNITLAHAGKYE 352
Cdd:cd04978   5 EPPSLVLSPGETGELICEAEGNPQPTITWRL-----NGVP-----IEPAPEDMRRTVDGRT----LIFSNLQPNDTAVYQ 70

                        90       100
                ....*....|....*....|
gi 37674275 353 CEAANAGGkarvpfHLLVNA 372
Cdd:cd04978  71 CNASNVHG------YLLANA 84

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 37674275 276 EFTANLGEDLQVACQASGYPQPLVVWRKVPQPrdgKPQAQAQLEGGAPGlgghgtrdtGSGMLFLTNITL-AHAGKYECE 354
Cdd:cd20971  10 NLNVRYQSNATLVCKVTGHPKPIVKWYRQGKE---IIADGLKYRIQEFK---------GGYHQLIIASVTdDDATVYQVR 77

                ....*...
gi 37674275 355 AANAGGKA 362
Cdd:cd20971  78 ATNQGGSV 85

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37674275   268 PSVNVEPPEFTAnlGEDLQVACQASGYPQPLVVWRKvpqprDGKPQAQaqleggapglgghgtrdtgSGMLFLTNITLAH 347
Cdd:pfam13895   2 PVLTPSPTVVTE--GEPVTLTCSAPGNPPPSYTWYK-----DGSAISS-------------------SPNFFTLSVSAED 55

                          90       100
                  ....*....|....*....|....
gi 37674275   348 AGKYECEAAN-AGGKARVPFHLLV 370
Cdd:pfam13895  56 SGTYTCVARNgRGGKVSNPVELTV 79

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 37674275 272 VEPPEFTANLGEDLQVACQASGYPQPLVVWRKVPQPRDGKPQAQAQLEggapglgghgtrdtgSGMLFLTNITLAHAGKY 351
Cdd:cd20952   4 QGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTLE---------------NGSLQIKGAEKSDTGEY 68

                        90
                ....*....|...
gi 37674275 352 ECEAANAGGKARV 364
Cdd:cd20952  69 TCVALNLSGEATW 81

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 37674275 268 PSVNVEPPEFTANLGEDLQVACQASGYPQPLVVWRKVPQPRDGKPQAQAQLEGGAPGlgghgtrdTGSGMLFLTNITLAH 347
Cdd:cd05765   1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWEKQVPGKENLIMRPNHVRGNVVV--------TNIGQLVIYNAQPQD 72

                        90       100
                ....*....|....*....|...
gi 37674275 348 AGKYECEAANAGGKARVPFHLLV 370
Cdd:cd05765  73 AGLYTCTARNSGGLLRANFPLSV 95

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37674275 282 GEDLQVACQASGYPQPLVVWR----KVPQPRdgkpqaqaqleggapglGGHGTRDTGSGMLFLTNITLAHAGKYECEAAN 357
Cdd:cd05743   1 GETVEFTCVATGVPTPIINWRlnwgHVPDSA-----------------RVSITSEGGYGTLTIRDVKESDQGAYTCEAIN 63

                ...
gi 37674275 358 AGG 360
Cdd:cd05743  64 TRG 66

Leucine rich repeat;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 37674275    48 RLRVVPPGI---PPGTQTLFLQDNSIAHLEQGSLAPLAALRHLYLHNN 92
Cdd:pfam13855  12 RLTSLDDGAfkgLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGN 59

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37674275 289 CQASGYPQPLVVWRKVPQPRDgkpqaqaqleggaPGLGGHGTRDTGSGMLFLTNITLAHAGKYECEAAN-AGGKARVPFH 367
Cdd:cd05738  21 CAASGNPDPEISWFKDFLPVD-------------TATSNGRIKQLRSGALQIENSEESDQGKYECVATNsAGTRYSAPAN 87

                ...
gi 37674275 368 LLV 370
Cdd:cd05738  88 LYV 90

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 37674275 267 PPSVNVEPPEFTANLGEDLQVACQASGYPQPLVVWRKVPQPrdgkpqaqaqleggAPGLGGHGTRDTGSGMLFLTNITLA 346
Cdd:cd20976   1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQP--------------LQYAADRSTCEAGVGELHIQDVLPE 66

                        90
                ....*....|....*.
gi 37674275 347 HAGKYECEAANAGGKA 362
Cdd:cd20976  67 DHGTYTCLAKNAAGQV 82

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37674275 267 PPSVNVEPPEFTANLGEDLQVACQASGYPQPLVVWRKvpqprDGKPQAQAQleggapgLGGHGTRDTgsgmLFLTNITLA 346
Cdd:cd20957   1 PLSATIDPPVQTVDFGRTAVFNCSVTGNPIHTVLWMK-----DGKPLGHSS-------RVQILSEDV----LVIPSVKRE 64

                        90
                ....*....|...
gi 37674275 347 HAGKYECEAANAG 359
Cdd:cd20957  65 DKGMYQCFVRNDG 77

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 37674275 268 PSVnVEPPE--FTANLGEDLQVACQASGYPQPLVVWRKVPQPRDGKPqaqaqleggapglgghGTRDTGSGMLFLTNITL 345
Cdd:cd20978   1 PKF-IQKPEknVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPM----------------ERATVEDGTLTIINVQP 63

                        90       100
                ....*....|....*....|....*
gi 37674275 346 AHAGKYECEAANAGGKARVPFHLLV 370
Cdd:cd20978  64 EDTGYYGCVATNEIGDIYTETLLHV 88

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37674275 272 VEPPEFTANLGEDLQVACQASGYPQPLVVWRKvpqprDGkpqAQAQLEGGAPGLGGHGTRDTGSGMLFLTNITLAHAGKY 351
Cdd:cd05726   4 VKPRDQVVALGRTVTFQCETKGNPQPAIFWQK-----EG---SQNLLFPYQPPQPSSRFSVSPTGDLTITNVQRSDVGYY 75

                ....*....
gi 37674275 352 ECEAANAGG 360
Cdd:cd05726  76 ICQALNVAG 84