Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1023300939 429 DSFPNRLNVDIGTTVFLDCRAMAEPEPEIYWVTPiGNKITVetlSDKYKLSSEG---TLEISNIQIEDSGRYTCVAQNVQ 505
Cdd:pfam07679   4 TQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKD-GQPLRS---SDRFKVTYEGgtyTLTISNVQPDDSGKYTCVATNSA 79

                          90
                  ....*....|.
gi 1023300939 506 GADTRVATIKV 516
Cdd:pfam07679  80 GEAEASAELTV 90

Leucine rich repeat N-terminal domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 1023300939   32 CPQLCVCeirpwftpqstyrEATTVDCNDLRLTRIPSNLSSDTQ 75
Cdd:smart00013   2 CPAPCNC-------------SGTAVDCSGRGLTEVPLDLPPDTT 32

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 1023300939  77 LLLQSNNIaKTVDELQQLFNLTELDFSQNNFTNIKevGLANLTQLTTLHLEENQITEMTDycLQDLSNLQELYINHNQIS 156
Cdd:cd21340     7 LYLNDKNI-TKIDNLSLCKNLKVLYLYDNKITKIE--NLEFLTNLTHLYLQNNQIEKIEN--LENLVNLKKLYLGGNRIS 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1023300939 157 TISahAFAGLKNLLRLHLNSNKLkvidsrwfdstPNLEILMIGENPVIGILDmnfkplaNLRSLVLAGMYLTDIpgNALV 236
Cdd:cd21340    82 VVE--GLENLTNLEELHIENQRL-----------PPGEKLTFDPRSLAALSN-------SLRVLNISGNNIDSL--EPLA 139

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 1023300939 237 GLDSLESLSFYDNKLVKVPQLA--LQKVPNLKFLDLNKNPIHKIQ 279
Cdd:cd21340   140 PLRNLEQLDASNNQISDLEELLdlLSSWPSLRELDLTGNPVCKKP 184

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 1023300939 424 PMISHDSFPNRLNVDIGTTVFLDCRAMAEPEPEIYWVTpigNKITVETLSDKYKLSSEGT-LEISNIQIEDSGRYTCVAQ 502
Cdd:cd20970     1 PVISTPQPSFTVTAREGENATFMCRAEGSPEPEISWTR---NGNLIIEFNTRYIVRENGTtLTIRNIRRSDMGIYLCIAS 77

                          90
                  ....*....|....*
gi 1023300939 503 N-VQGADTRVATIKV 516
Cdd:cd20970    78 NgVPGSVEKRITLQV 92

Leucine rich repeat;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1023300939 119 TQLTTLHLEENQITEMTDYCLQDLSNLQELYINHNQISTISAHAFAGLKNLLRLHLNSNKL 179
Cdd:pfam13855   1 PNLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

Leucine rich repeat C-terminal domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1023300939  371 NPLRCDCVIHWINSN-KTNIRFMEPLSMFCAMPPEYKGhQVKEVLIQDSS 419
Cdd:smart00082   1 NPFICDCELRWLLRWlQANEHLQDPVDLRCASPSSLRG-PLLELLHSEFK 49

Leucine rich repeat N-terminal domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 1023300939   32 CPQLCVCeirpwftpqstyrEATTVDCNDLRLTRIPSNLSSDTQ 75
Cdd:smart00013   2 CPAPCNC-------------SGTAVDCSGRGLTEVPLDLPPDTT 32

Fibronectin type III domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1023300939 531 VKQTESHSILVSWK----VNSNVMTSNLKWSsatmKIDNPHITYTARVPVDVHEYNLTHLQPSTDYEVCLTVSNIHQQTQ 606
Cdd:pfam00041   8 VTDVTSTSLTVSWTpppdGNGPITGYEVEYR----PKNSGEPWNEITVPGTTTSVTLTGLKPGTEYEVRVQAVNGGGEGP 83

                  ..
gi 1023300939 607 KS 608
Cdd:pfam00041  84 PS 85

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1023300939 531 VKQTESHSILVSWKV----NSNVMTSNLKWSSAtmkiDNPHITYTARVPVDVHEYNLTHLQPSTDYEVCLTVSNIHQQTQ 606
Cdd:cd00063     9 VTDVTSTSVTLSWTPpeddGGPITGYVVEYREK----GSGDWKEVEVTPGSETSYTLTGLKPGTEYEFRVRAVNGGGESP 84

                  ....*....
gi 1023300939 607 KS-CVNVTT 614
Cdd:cd00063    85 PSeSVTVTT 93

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1023300939  48 STYREATTVDCNDLRLTRIPSNLSSDTQVLLLQSNNIAKTVDELQQLFNLTELDFSQNNftnikevGLANLTQLTTLHLE 127
Cdd:COG4886    49 LTLLLSLLLRDLLLSSLLLLLSLLLLLLLSLLLLSLLLLGLTDLGDLTNLTELDLSGNE-------ELSNLTNLESLDLS 121

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1023300939 128 ENQITEMTDyCLQDLSNLQELYINHNQISTISAhAFAGLKNLLRLHLNSNKLKVIDSrWFDSTPNLEILMIGENPvIGIL 207
Cdd:COG4886   122 GNQLTDLPE-ELANLTNLKELDLSNNQLTDLPE-PLGNLTNLKSLDLSNNQLTDLPE-ELGNLTNLKELDLSNNQ-ITDL 197

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1023300939 208 DMNFKPLANLRSLVLAGMYLTDIPgNALVGLDSLESLSFYDNKLVKVPQLAlqKVPNLKFLDLNKNPIHKIqeGDFKNML 287
Cdd:COG4886   198 PEPLGNLTNLEELDLSGNQLTDLP-EPLANLTNLETLDLSNNQLTDLPELG--NLTNLEELDLSNNQLTDL--PPLANLT 272

                  ....*....
gi 1023300939 288 RLKELGINN 296
Cdd:COG4886   273 NLKTLDLSN 281

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 1023300939  77 LLLQSNNIaKTVDELQQLFNLTELDFSQNNFTNIKevGLANLTQLTTLHLEENQITEMTDycLQDLSNLQELYINHNQIS 156
Cdd:cd21340     7 LYLNDKNI-TKIDNLSLCKNLKVLYLYDNKITKIE--NLEFLTNLTHLYLQNNQIEKIEN--LENLVNLKKLYLGGNRIS 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1023300939 157 TISahAFAGLKNLLRLHLNSNKLkvidsrwfdstPNLEILMIGENPVIGILDmnfkplaNLRSLVLAGMYLTDIpgNALV 236
Cdd:cd21340    82 VVE--GLENLTNLEELHIENQRL-----------PPGEKLTFDPRSLAALSN-------SLRVLNISGNNIDSL--EPLA 139

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 1023300939 237 GLDSLESLSFYDNKLVKVPQLA--LQKVPNLKFLDLNKNPIHKIQ 279
Cdd:cd21340   140 PLRNLEQLDASNNQISDLEELLdlLSSWPSLRELDLTGNPVCKKP 184

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 1023300939 424 PMISHDSFPNRLNVDIGTTVFLDCRAMAEPEPEIYWVTpigNKITVETLSDKYKLSSEGT-LEISNIQIEDSGRYTCVAQ 502
Cdd:cd20970     1 PVISTPQPSFTVTAREGENATFMCRAEGSPEPEISWTR---NGNLIIEFNTRYIVRENGTtLTIRNIRRSDMGIYLCIAS 77

                          90
                  ....*....|....*
gi 1023300939 503 N-VQGADTRVATIKV 516
Cdd:cd20970    78 NgVPGSVEKRITLQV 92

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1023300939 431 FPNRLNVDIGTTVFLDCRAMAEPEPEIYWVTPIGNKItvetlSDKYKLSSEGTLEISNIQIEDSGRYTCVAQNVQGADTR 510
Cdd:cd04968     7 FPADTYALKGQTVTLECFALGNPVPQIKWRKVDGSPS-----SQWEITTSEPVLEIPNVQFEDEGTYECEAENSRGKDTV 81

                  ....*.
gi 1023300939 511 VATIKV 516
Cdd:cd04968    82 QGRIIV 87

Leucine rich repeat;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1023300939 119 TQLTTLHLEENQITEMTDYCLQDLSNLQELYINHNQISTISAHAFAGLKNLLRLHLNSNKL 179
Cdd:pfam13855   1 PNLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1023300939 437 VDIGTTVFLDCRAMAEPEPEIYWVTPiGNKITVETLSDKYKLSSEGTLEISNIQIEDSGRYTCVAQNVQGADTRVATIKV 516
Cdd:cd20969    14 VDEGHTVQFVCRADGDPPPAILWLSP-RKHLVSAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHLHV 92

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (IgSF) domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1023300939 424 PMISHDSfpNRLNVDIGTTVFLDCRAMAEPEPEIYWVTPIGNKITVETLSDKYKlssEGTLEISNIQIEDSGRYTCVAQN 503
Cdd:cd05764     1 PLITRHT--HELRVLEGQRATLRCKARGDPEPAIHWISPEGKLISNSSRTLVYD---NGTLDILITTVKDTGAFTCIASN 75

                          90
                  ....*....|...
gi 1023300939 504 VQGADTRVATIKV 516
Cdd:cd05764    76 PAGEATARVELHI 88

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 1023300939 429 DSFPNRLNVDIGTTVFLDCRAMAEPEPEIYWvtpIGNKITVETLSDKYKLSsEGTLEISNIQIEDSGRYTCVAQNVQGAD 508
Cdd:cd20978     5 QKPEKNVVVKGGQDVTLPCQVTGVPQPKITW---LHNGKPLQGPMERATVE-DGTLTIINVQPEDTGYYGCVATNEIGDI 80

                  ....*...
gi 1023300939 509 TRVATIKV 516
Cdd:cd20978    81 YTETLLHV 88

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1023300939 440 GTTVFLDCRAMAEPEPEIYWVTpigNKITVET-LSDKYKLSSEGT-LEISNIQIEDSGRYTCVAQNVQGADTRVATIKV 516
Cdd:cd05736    15 GVEASLRCHAEGIPLPRVQWLK---NGMDINPkLSKQLTLIANGSeLHISNVRYEDTGAYTCIAKNEGGVDEDISSLFV 90

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1023300939 432 PNRLNVDIGTTVFLDCRAMAEPEPEIYWVTPIGN--KITVETLSDKyklssegTLEISNIQIEDSGRYTCVAQNVQGADT 509
Cdd:cd05725     4 PQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGElpKGRYEILDDH-------SLKIRKVTAGDMGSYTCVAENMVGKIE 76

                  ....*..
gi 1023300939 510 RVATIKV 516
Cdd:cd05725    77 ASATLTV 83

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1023300939 440 GTTVFLDCRAMAEPEPEIYWvtpigNKITVETLSDKYKLSSEG-TLEISNIQIEDSGRYTCVAQNVQGADTRVATIKV 516
Cdd:cd05731    10 GGVLLLECIAEGLPTPDIRW-----IKLGGELPKGRTKFENFNkTLKIENVSEADSGEYQCTASNTMGSARHTISVTV 82

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1023300939 437 VDIGTTVFLDCRAMAEPEPEIYWVT-----PIGNKITVETlsdkyklsseGTLEISNIQIEDSGRYTCVAQNVQGADTRV 511
Cdd:cd05728    11 ADIGSSLRWECKASGNPRPAYRWLKngqplASENRIEVEA----------GDLRITKLSLSDSGMYQCVAENKHGTIYAS 80

                  ....*
gi 1023300939 512 ATIKV 516
Cdd:cd05728    81 AELAV 85

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1023300939 432 PNRLNVDIGTTVFLDCRA-MAEPEPEIYWvtpIGNKITVETLSDKYKLSSEGTLEISNIQIEDSGRYTCVAQNVQGA-DT 509
Cdd:cd05724     4 PSDTQVAVGEMAVLECSPpRGHPEPTVSW---RKDGQPLNLDNERVRIVDDGNLLIAEARKSDEGTYKCVATNMVGErES 80

                  ....*..
gi 1023300939 510 RVATIKV 516
Cdd:cd05724    81 RAARLSV 87

leucine-rich repeat receptor-like protein kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1023300939  79 LQSNNIAKTV-DELQQLFNLTELDFSQNNFTNIKEVGLANLTQLTTLHLEENQITEMTDYCLQDLSNLQELYINHNQIST 157
Cdd:PLN00113  219 LGYNNLSGEIpYEIGGLTSLNHLDLVYNNLTGPIPSSLGNLKNLQYLFLYQNKLSGPIPPSIFSLQKLISLDLSDNSLSG 298

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1023300939 158 ISAHAFAGLKNLLRLHLNSNKLKVIDSRWFDSTPNLEILMIGENPVIGILDMNFKPLANLRSLVLAGMYLT-DIP----- 231
Cdd:PLN00113  299 EIPELVIQLQNLEILHLFSNNFTGKIPVALTSLPRLQVLQLWSNKFSGEIPKNLGKHNNLTVLDLSTNNLTgEIPeglcs 378

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1023300939 232 ----------GNALVG--------LDSLESLSFYDNKLVKVPQLALQKVPNLKFLDLNKNPIHKIQEGDFKNM--LRLKE 291
Cdd:PLN00113  379 sgnlfklilfSNSLEGeipkslgaCRSLRRVRLQDNSFSGELPSEFTKLPLVYFLDISNNNLQGRINSRKWDMpsLQMLS 458

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1023300939 292 LGINN-MGELvsVDRYALDNlpeLTKLEATNNpKLSYIHRLAFRSVPALESLMLNNNALNAIYQKTVESLPNLREISIHS 370
Cdd:PLN00113  459 LARNKfFGGL--PDSFGSKR---LENLDLSRN-QFSGAVPRKLGSLSELMQLKLSENKLSGEIPDELSSCKKLVSLDLSH 532

                  ...
gi 1023300939 371 NPL 373
Cdd:PLN00113  533 NQL 535

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1023300939 432 PNRLNVDIGTTVFLDCRAMAEPEPEIYWVTPI-GNKITVETLSDKYK----LSSEGTLEISNIQIEDSGRYTCVAQNVQG 506
Cdd:cd04970     9 PSNADITVGENATLQCHASHDPTLDLTFTWSFnGVPIDLEKIEGHYRrrygKDSNGDLEIVNAQLKHAGRYTCTAQTVVD 88

                          90
                  ....*....|..
gi 1023300939 507 ADTRVATIKVNG 518
Cdd:cd04970    89 SDSASATLVVRG 100