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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153792227 421 PLIAPESfpSNLNVEAGSYVSFHCRATAEPQPEIYWITPSGqKLLPNTltDKFYVHSEGTLDINGVTPKEGGLYTCIATN 500
Cdd:cd05764    1 PLITRHT--HELRVLEGQRATLRCKARGDPEPAIHWISPEG-KLISNS--SRTLVYDNGTLDILITTVKDTGAFTCIASN 75

                         90
                 ....*....|...
gi 153792227 501 LVGADLKSVMIKV 513
Cdd:cd05764   76 PAGEATARVELHI 88

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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153792227   341 LNSNALSALYHGTIESLPNLKEISIHSNPIRCDCVIRWMN--MNKTNIRFMEPDSLFCVDPPEFQGQNVRQVHFRDMM-- 416
Cdd:TIGR00864    2 ISNNKISTIEEGICANLCNLSEIDLSGNPFECDCGLARLPrwAEEKGVKVRQPEAALCAGPGALAGQPLLGIPLLDSGcd 81

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 153792227   417 ---EICLP-------------LIAPESFPSNLNVEAGSYVSF 442
Cdd:TIGR00864   82 eeyVACLKdnssgggaarselVIFSAAHEGLFQPEACNAFCF 123

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 153792227 421 PLIAPESfpSNLNVEAGSYVSFHCRATAEPQPEIYWITPSGqKLLPNTltDKFYVHSEGTLDINGVTPKEGGLYTCIATN 500
Cdd:cd05764    1 PLITRHT--HELRVLEGQRATLRCKARGDPEPAIHWISPEG-KLISNS--SRTLVYDNGTLDILITTVKDTGAFTCIASN 75

                         90
                 ....*....|...
gi 153792227 501 LVGADLKSVMIKV 513
Cdd:cd05764   76 PAGEATARVELHI 88

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153792227   429 PSNLNVEAGSYVSFHCRATAEPQPEIYWITPSGQKLLPNtltDKFYVHSEG---TLDINGVTPKEGGLYTCIATNLVGAD 505
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAES---GRFSVSRSGstsTLTISNVTPEDSGTYTCAATNSSGSA 77

                   ....*...
gi 153792227   506 LKSVMIKV 513
Cdd:smart00410  78 SSGTTLTV 85

type III secretion system effector E3 ubiquitin transferase SlrP;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153792227  43 PRSIYMEASTVDCNDLGLLTFPARLPANTQILLLQTNNIakIEYSTDFPVNLTGLDLSQNNLSSVTNiNVKKMPQLLSVY 122
Cdd:PRK15370 215 PENLQGNIKTLYANSNQLTSIPATLPDTIQEMELSINRI--TELPERLPSALQSLDLFHNKISCLPE-NLPEELRYLSVY 291

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153792227 123 leENKLTELPEKCLSELSnlqELYINHNLLS----TISPGAFIglhnllrLHLNSNRLQMINSKwfdALPNLEILMIGEN 198
Cdd:PRK15370 292 --DNSIRTLPAHLPSGIT---HLNVQSNSLTalpeTLPPGLKT-------LEAGENALTSLPAS---LPPELQVLDVSKN 356

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 153792227 199 PIIRIKDmNFKPliNLRSLVIAGINLTEIPDNALVGLENLESISfydNRLIKVP 252
Cdd:PRK15370 357 QITVLPE-TLPP--TITTLDVSRNALTNLPENLPAALQIMQASR---NNLVRLP 404

Fibronectin type III domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 153792227  526 NIKIRDIQANSVLVSWKA----SSKILKSSVKWtafVKTENSHAAQSARIPSDVKVYNLTHLNPSTEYKICI 593
Cdd:pfam00041   5 NLTVTDVTSTSLTVSWTPppdgNGPITGYEVEY---RPKNSGEPWNEITVPGTTTSVTLTGLKPGTEYEVRV 73

Leucine rich repeat C-terminal domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 153792227   368 NPIRCDCVIRWM-NMNKTNIRFMEPDSLFCVDPPEFQGqnvRQVHFRDMMEIC 419
Cdd:smart00082   1 NPFICDCELRWLlRWLQANEHLQDPVDLRCASPSSLRG---PLLELLHSEFKC 50

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 153792227 526 NIKIRDIQANSVLVSWKASSKILKSSVKWTAFVKTENSHAAQSARI-PSDVKVYNLTHLNPSTEYKICI 593
Cdd:cd00063    6 NLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGSGDWKEVEVtPGSETSYTLTGLKPGTEYEFRV 74

Leucine rich repeat N-terminal domain; Leucine Rich Repeats pfam00560 are short sequence motifs present in a number of proteins with diverse functions and cellular locations. Leucine Rich Repeats are often flanked by cysteine rich domains. This domain is often found at the N-terminus of tandem leucine rich repeats.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 153792227   28 DCPRLCTCeirpwftprsiymEASTVDCNDLGLLTFPARLP 68
Cdd:pfam01462   1 ACPVPCHC-------------SATVVNCSDRGLTAVPRDLP 28

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153792227  76 LQTNNIAKIEYSTDFPVNLTGLDLSQNNLSSVTNINVKKMPQLLSVYLEENKLTELPEKCLSELSNLQELYINHNLLSTI 155
Cdd:COG4886    1 LLLLLLSLTLKLLLLLLLELLTTLILLLLLLLLLLALLLLSLLSLLLLLTLLLSLLLRDLLLSSLLLLLSLLLLLLLSLL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153792227 156 SPGAFIGLHNLLRLHLNSNRLQMINSKWFDALPNLEILMIGENPIIRIKDmNFKPLINLRSLVIAGINLTEIPDnALVGL 235
Cdd:COG4886   81 LLSLLLLGLTDLGDLTNLTELDLSGNEELSNLTNLESLDLSGNQLTDLPE-ELANLTNLKELDLSNNQLTDLPE-PLGNL 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153792227 236 ENLESISFYDNRLIKVPHvALQKVVNLKFLDLNKNPINRIrRGDFSNMLHLKELGINNMpELISIdSLAVDNLPDLRKIE 315
Cdd:COG4886  159 TNLKSLDLSNNQLTDLPE-ELGNLTNLKELDLSNNQITDL-PEPLGNLTNLEELDLSGN-QLTDL-PEPLANLTNLETLD 234

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 153792227 316 ATNNpRLSYIhpNAFFRLPKLESLMLNSNALSALyhGTIESLPNLKEISIHSNPI 370
Cdd:COG4886  235 LSNN-QLTDL--PELGNLTNLEELDLSNNQLTDL--PPLANLTNLKTLDLSNNQL 284

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 153792227 421 PLIAPESfpSNLNVEAGSYVSFHCRATAEPQPEIYWITPSGqKLLPNTltDKFYVHSEGTLDINGVTPKEGGLYTCIATN 500
Cdd:cd05764    1 PLITRHT--HELRVLEGQRATLRCKARGDPEPAIHWISPEG-KLISNS--SRTLVYDNGTLDILITTVKDTGAFTCIASN 75

                         90
                 ....*....|...
gi 153792227 501 LVGADLKSVMIKV 513
Cdd:cd05764   76 PAGEATARVELHI 88

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153792227  93 NLTGLDLSQNNLSSVTNINVKKMPQLLSVYLEENKLTELPEKCLSELSNLQELYINHNLLSTISPGAFIGLHNLLRLHLN 172
Cdd:COG4886    1 LLLLLLSLTLKLLLLLLLELLTTLILLLLLLLLLLALLLLSLLSLLLLLTLLLSLLLRDLLLSSLLLLLSLLLLLLLSLL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153792227 173 SNRLQMINSKWFDALPNLEILMIGENPIIrikdmnfKPLINLRSLVIAGINLTEIPDnALVGLENLESISFYDNRLIKVP 252
Cdd:COG4886   81 LLSLLLLGLTDLGDLTNLTELDLSGNEEL-------SNLTNLESLDLSGNQLTDLPE-ELANLTNLKELDLSNNQLTDLP 152

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153792227 253 hVALQKVVNLKFLDLNKNPINRIrrgdfsnmlhlkelginnmPELISidslavdNLPDLRKIEATNNpRLSYIhPNAFFR 332
Cdd:COG4886  153 -EPLGNLTNLKSLDLSNNQLTDL-------------------PEELG-------NLTNLKELDLSNN-QITDL-PEPLGN 203

                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 153792227 333 LPKLESLMLNSNALSALyHGTIESLPNLKEISIHSNPIR 371
Cdd:COG4886  204 LTNLEELDLSGNQLTDL-PEPLANLTNLETLDLSNNQLT 241

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153792227   429 PSNLNVEAGSYVSFHCRATAEPQPEIYWITPSGQKLLPNtltDKFYVHSEG---TLDINGVTPKEGGLYTCIATNLVGAD 505
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAES---GRFSVSRSGstsTLTISNVTPEDSGTYTCAATNSSGSA 77

                   ....*...
gi 153792227   506 LKSVMIKV 513
Cdd:smart00410  78 SSGTTLTV 85

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 153792227 421 PLIAPESFPSNLNVEAGSYVSFHCRATAEPQPEIYWITPSGQKLLPNTltdKFYVHSEGT-LDINGVTPKEGGLYTCIAT 499
Cdd:cd20970    1 PVISTPQPSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNT---RYIVRENGTtLTIRNIRRSDMGIYLCIAS 77

                         90
                 ....*....|....*
gi 153792227 500 NLV-GADLKSVMIKV 513
Cdd:cd20970   78 NGVpGSVEKRITLQV 92

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 153792227 426 ESFPSNLNVEAGSYVSFHCRATAEPQPEIYWiTPSGQKLLPNTLTDKFyvhSEGTLDINGVTPKEGGLYTCIATNLVGAD 505
Cdd:cd20978    5 QKPEKNVVVKGGQDVTLPCQVTGVPQPKITW-LHNGKPLQGPMERATV---EDGTLTIINVQPEDTGYYGCVATNEIGDI 80

                 ....*...
gi 153792227 506 LKSVMIKV 513
Cdd:cd20978   81 YTETLLHV 88

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 153792227 429 PSNLNVEAGSYVSFHCRATAEPQPEIYWITPSGQK----LLPNTLTDKFYVHSEGTLDINGVTPKEGGLYTCIATNLVG 503
Cdd:cd05765    7 PTHQTVKVGETASFHCDVTGRPQPEITWEKQVPGKenliMRPNHVRGNVVVTNIGQLVIYNAQPQDAGLYTCTARNSGG 85

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 153792227 429 PSNLNVEAGSYVSFHCRATAEPQPEIYWITPSGQklLPNTltdKFYVHSEGTLDINGVTPKEGGLYTCIATNLVGA 504
Cdd:cd05725    4 PQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGE--LPKG---RYEILDDHSLKIRKVTAGDMGSYTCVAENMVGK 74

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 153792227  74 LLLQTNNIAKIEySTDFPVNLTGLDLSQNNLSSVTNINvkKMPQLLSVYLEENKLTELPEkcLSELSNLQELYINHNLLS 153
Cdd:cd21340    7 LYLNDKNITKID-NLSLCKNLKVLYLYDNKITKIENLE--FLTNLTHLYLQNNQIEKIEN--LENLVNLKKLYLGGNRIS 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153792227 154 TISpGafiglhnllrlhlnsnrlqminskwFDALPNLEILMIG------ENPIIrikdmnFKPLI------NLRSLVIAG 221
Cdd:cd21340   82 VVE-G-------------------------LENLTNLEELHIEnqrlppGEKLT------FDPRSlaalsnSLRVLNISG 129

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 153792227 222 INLTEIpdNALVGLENLESISFYDNRLIKVPHVA--LQKVVNLKFLDLNKNPINRIRR 277
Cdd:cd21340  130 NNIDSL--EPLAPLRNLEQLDASNNQISDLEELLdlLSSWPSLRELDLTGNPVCKKPK 185

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 153792227 429 PSNLNVEAGSYVSFHCRATAEPQPEIYWITPSGQKLLPNtltDKFYVHSEGTLDINGVTPKEGGLYTCIATNLVGADLKS 508
Cdd:cd20952    6 PQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKD---ERITTLENGSLQIKGAEKSDTGEYTCVALNLSGEATWS 82

                 ....*
gi 153792227 509 VMIKV 513
Cdd:cd20952   83 AVLDV 87

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 153792227 437 GSYVSFHCRATAEPQPEIYWiTPSGQKLlpnTLTDKFYVHSEGTLDINGVTPKEGGLYTCIATNLVGADLKSVMIKV 513
Cdd:cd05745    2 GQTVDFLCEAQGYPQPVIAW-TKGGSQL---SVDRRHLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 153792227 434 VEAGSYVSFHCRATAEPQPEIYWITpSGQKLLPNTLTDKFYVHSEG---TLDINGVTPKEGGLYTCIATNLVG 503
Cdd:cd20951   12 VWEKSDAKLRVEVQGKPDPEVKWYK-NGVPIDPSSIPGKYKIESEYgvhVLHIRRVTVEDSAVYSAVAKNIHG 83

Leucine rich repeat;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 153792227   93 NLTGLDLSQNNLSSVTNINVKKMPQLLSVYLEENKLTELPEKCLSELSNLQELYINHNLL 152
Cdd:pfam13855   2 NLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153792227 429 PSNLNVEAGSYVSFHCRATAEPQPEIYWITPSgqKLLPNTLtdKFYVHSEG---TLDINGVTPKEGGLYTCIATNLVGAD 505
Cdd:cd20972    8 LRSQEVAEGSKVRLECRVTGNPTPVVRWFCEG--KELQNSP--DIQIHQEGdlhSLIIAEAFEEDTGRYSCLATNSVGSD 83

                 ....*...
gi 153792227 506 LKSVMIKV 513
Cdd:cd20972   84 TTSAEIFV 91

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153792227 429 PSNLNVEAGSYVSFHCRATAEPQPEIYWiTPSGQKLLPNTlTDKFYVHSEG--TLDINGVTPKEGGLYTCIATNLVGADL 506
Cdd:cd20990    7 PGDLTVQEGKLCRMDCKVSGLPTPDLSW-QLDGKPIRPDS-AHKMLVRENGvhSLIIEPVTSRDAGIYTCIATNRAGQNS 84

                 ....*..
gi 153792227 507 KSVMIKV 513
Cdd:cd20990   85 FNLELVV 91

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153792227 423 IAPESFPSNLNVEAgsyvSFHCRATAEPQPEIYWITpSGQKLLPNtLTDKFYVHSEGT-LDINGVTPKEGGLYTCIATNL 501
Cdd:cd05736    5 VYPEFQAKEPGVEA----SLRCHAEGIPLPRVQWLK-NGMDINPK-LSKQLTLIANGSeLHISNVRYEDTGAYTCIAKNE 78

                 ....
gi 153792227 502 VGAD 505
Cdd:cd05736   79 GGVD 82

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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153792227   341 LNSNALSALYHGTIESLPNLKEISIHSNPIRCDCVIRWMN--MNKTNIRFMEPDSLFCVDPPEFQGQNVRQVHFRDMM-- 416
Cdd:TIGR00864    2 ISNNKISTIEEGICANLCNLSEIDLSGNPFECDCGLARLPrwAEEKGVKVRQPEAALCAGPGALAGQPLLGIPLLDSGcd 81