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 1391723571 281 PLIARHTQRLWVLEGQRATLRCRALGDPAPTMHWVGPDDRLVGNSSRARAFPNGTLEIGVTGAGDAGGYTCIATNPAGEA 360
Cdd:cd05764     1 PLITRHTHELRVLEGQRATLRCKARGDPEPAIHWISPEGKLISNSSRTLVYDNGTLDILITTVKDTGAFTCIASNPAGEA 80

                  ....*...
gi 1391723571 361 TARVELRV 368
Cdd:cd05764    81 TARVELHI 88

Fibronectin type III domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1391723571 409 VQVTEVTATSGLVSWGPGRPAD-PVWMFQIQY-NSSEDETLIYRIVPASSHHFLLKHLVPGADYDLCLLALS 478
Cdd:pfam00041   6 LTVTDVTSTSLTVSWTPPPDGNgPITGYEVEYrPKNSGEPWNEITVPGTTTSVTLTGLKPGTEYEVRVQAVN 77

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 1391723571 281 PLIARHTQRLWVLEGQRATLRCRALGDPAPTMHWVGPDDRLVGNSSRARAFPNGTLEIGVTGAGDAGGYTCIATNPAGEA 360
Cdd:cd05764     1 PLITRHTHELRVLEGQRATLRCKARGDPEPAIHWISPEGKLISNSSRTLVYDNGTLDILITTVKDTGAFTCIASNPAGEA 80

                  ....*...
gi 1391723571 361 TARVELRV 368
Cdd:cd05764    81 TARVELHI 88

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 1391723571  53 LRLADNFIQALgpPDFRNMTGLVDLTLSRNAITRIgarafGDLESLRSL---HLDGNRL--VElgtgSLRGPVNLQHLIL 127
Cdd:cd21340    29 LYLYDNKITKI--ENLEFLTNLTHLYLQNNQIEKI-----ENLENLVNLkklYLGGNRIsvVE----GLENLTNLEELHI 97

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1391723571 128 SgNQlgRIAPG---AFDDF-----LESLEDLDLSYNNLRQVpwAGIGAMPALHTLNLDHNLIDALPP--GAFAQLGQLSR 197
Cdd:cd21340    98 E-NQ--RLPPGeklTFDPRslaalSNSLRVLNISGNNIDSL--EPLAPLRNLEQLDASNNQISDLEEllDLLSSWPSLRE 172

                         170
                  ....*....|..
gi 1391723571 198 LDLTSNRLATLA 209
Cdd:cd21340   173 LDLTGNPVCKKP 184

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1391723571 281 PLIARHTQRLWVLEGQRATLRCRALGDPAPTMHWVgPDDRLVGNSSRARAFPNG---TLEI-GVTGAgDAGGYTCIATNP 356
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWF-KDGQPLRSSDRFKVTYEGgtyTLTIsNVQPD-DSGKYTCVATNS 78

                          90
                  ....*....|..
gi 1391723571 357 AGEATARVELRV 368
Cdd:pfam07679  79 AGEAEASAELTV 90

leucine-rich repeat receptor-like protein kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1391723571  53 LRLADNFIQALGPPDFRNMTGLVDLTLSRNAIT-RIGARAFgDLESLRSLHLDGNRLVElGTGSLRGPVNLQHLILSGNQ 131
Cdd:PLN00113  409 VRLQDNSFSGELPSEFTKLPLVYFLDISNNNLQgRINSRKW-DMPSLQMLSLARNKFFG-GLPDSFGSKRLENLDLSRNQ 486

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1391723571 132 LGRIAPGAFDDFLEsLEDLDLSYNNLRQVPWAGIGAMPALHTLNLDHNLIDALPPGAFAQLGQLSRLDLTSNRLATLAPD 211
Cdd:PLN00113  487 FSGAVPRKLGSLSE-LMQLKLSENKLSGEIPDELSSCKKLVSLDLSHNQLSGQIPASFSEMPVLSQLDLSQNQLSGEIPK 565

                  ..
gi 1391723571 212 PL 213
Cdd:PLN00113  566 NL 567

Leucine rich repeat C-terminal domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1391723571  234 NPLHCNCELLWLRRLAR-------PDDLeTCASPPGLAGRYFwAVPEGEFSC 278
Cdd:smart00082   1 NPFICDCELRWLLRWLQanehlqdPVDL-RCASPSSLRGPLL-ELLHSEFKC 50

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 1391723571 281 PLIARHTQRLWVLEGQRATLRCRALGDPAPTMHWVGPDDRLVGNSSRARAFPNGTLEIGVTGAGDAGGYTCIATNPAGEA 360
Cdd:cd05764     1 PLITRHTHELRVLEGQRATLRCKARGDPEPAIHWISPEGKLISNSSRTLVYDNGTLDILITTVKDTGAFTCIASNPAGEA 80

                  ....*...
gi 1391723571 361 TARVELRV 368
Cdd:cd05764    81 TARVELHI 88

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1391723571  52 ELRLADNFIQALgPPDFRNMTGLVDLTLSRNAITRIGArAFGDLESLRSLHLDGNRLVELGtgSLRGPVNLQHLILSGNQ 131
Cdd:COG4886   186 ELDLSNNQITDL-PEPLGNLTNLEELDLSGNQLTDLPE-PLANLTNLETLDLSNNQLTDLP--ELGNLTNLEELDLSNNQ 261

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1391723571 132 LGRIAPGAFddfLESLEDLDLSYNNLRQVPWAGIGAMPALHTLNLDHNLIDALPPGAFAQLGQLSRLDLTSNRLATLAPD 211
Cdd:COG4886   262 LTDLPPLAN---LTNLKTLDLSNNQLTDLKLKELELLLGLNSLLLLLLLLNLLELLILLLLLTTLLLLLLLLKGLLVTLT 338

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 1391723571 212 PLFSRGRDAEASPAPLVLSFSGNPLHCNCELLWLRRLARPDD 253
Cdd:COG4886   339 TLALSLSLLALLTLLLLLNLLSLLLTLLLTLGLLGLLEATLL 380

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1391723571  288 QRLWVLEGQRATLRCRALGDPAPTMHWVGPDDRLVGNSSRARAFPNG---TLEI-GVTgAGDAGGYTCIATNPAGEATAR 363
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGstsTLTIsNVT-PEDSGTYTCAATNSSGSASSG 80

                   ....*
gi 1391723571  364 VELRV 368
Cdd:smart00410  81 TTLTV 85

Fifth 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 fifth 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 1391723571 280 PPLIaRHTQRLWVLEGQRATLRCRALGDPAPTMHWVgPDDRLVGNSSRARAFPNGTLEI-GVTGAGDAGGYTCIATNPAG 358
Cdd:cd20958     1 PPFI-RPMGNLTAVAGQTLRLHCPVAGYPISSITWE-KDGRRLPLNHRQRVFPNGTLVIeNVQRSSDEGEYTCTARNQQG 78

                          90
                  ....*....|.
gi 1391723571 359 E-ATARVELRV 368
Cdd:cd20958    79 QsASRSVFVKV 89

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1391723571 280 PPLIARHTQRLWVLEGQRATLRCRALGDPAPTMHWVGPDDRLVGNSSRARAF--PNGTLEIGVTGAGDAGGYTCIATN 355
Cdd:pfam13927   1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLsgSNSTLTISNVTRSDAGTYTCVASN 78

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 1391723571 292 VLEGQRATLRCRALGDPAPTMHWVGPDDRLvgNSSRARAFPNGTLEIGVTGAGDAGGYTCIATNPAGEATARVELRV 368
Cdd:cd05725     9 VLVDDSAEFQCEVGGDPVPTVRWRKEDGEL--PKGRYEILDDHSLKIRKVTAGDMGSYTCVAENMVGKIEASATLTV 83

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 1391723571 285 RHTQRLWVLEGQRATLRCRALGDPAPTMHWVGPDDRLVGNSS--RARAFPNGTLEIGVTGAGDAGGYTCIATNPAGEATA 362
Cdd:cd20969     7 RKAQQVFVDEGHTVQFVCRADGDPPPAILWLSPRKHLVSAKSngRLTVFPDGTLEVRYAQVQDNGTYLCIAANAGGNDSM 86

                  ....*.
gi 1391723571 363 RVELRV 368
Cdd:cd20969    87 PAHLHV 92

Leucine rich repeat;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1391723571  72 TGLVDLTLSRNAITRIGARAFGDLESLRSLHLDGNRLVELGTGSLRGPVNLQHLILSGNQL 132
Cdd:pfam13855   1 PNLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

Leucine rich repeat;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1391723571 146 SLEDLDLSYNNLRQVPWAGIGAMPALHTLNLDHNLIDALPPGAFAQLGQLSRLDLTSNRL 205
Cdd:pfam13855   2 NLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1391723571 292 VLEGQRATLRCRALGDPAPTMHWVGPDDRLVGNSSRARaFPNGTLEIGVTGAGDAGGYTCIATNPAGE 359
Cdd:cd20978    13 VKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERAT-VEDGTLTIINVQPEDTGYYGCVATNEIGD 79

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 1391723571 280 PPLIARHTQRLWVLEGQRATLRCRALGDPAPTMHWVGPDDRLVGNSSRARAfpNGTLEIGVTGAGDAGGYTCIATNPAGE 359
Cdd:cd04968     1 PSIKVRFPADTYALKGQTVTLECFALGNPVPQIKWRKVDGSPSSQWEITTS--EPVLEIPNVQFEDEGTYECEAENSRGK 78

                  ....*....
gi 1391723571 360 ATARVELRV 368
Cdd:cd04968    79 DTVQGRIIV 87

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). 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 1391723571 281 PLIARHTQRLWVLEGQRATLRCRALGDPAPTMHWVGPDDRLVGNSSRARAFPNG---TLEIGVTGAGDAGGYTCIATNPA 357
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENgrhSLIIEPVTKRDAGIYTCIARNRA 80

                          90
                  ....*....|.
gi 1391723571 358 GEATARVELRV 368
Cdd:cd05744    81 GENSFNAELVV 91

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1391723571 292 VLEGQRATLRCRA-LGDPAPTMHWVGPDDRLVGNSSRARAFP---NGTLEIGVTGAGDAGGYTCIATNPAGEATARVEL 366
Cdd:pfam00047   8 VLEGDSATLTCSAsTGSPGPDVTWSKEGGTLIESLKVKHDNGrttQSSLLISNVTKEDAGTYTCVVNNPGGSATLSTSL 86

leucine-rich repeat receptor-like protein kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1391723571  53 LRLADNFIQALGPPDFRNMTGLVDLTLSRNAIT-RIGARAFgDLESLRSLHLDGNRLVElGTGSLRGPVNLQHLILSGNQ 131
Cdd:PLN00113  409 VRLQDNSFSGELPSEFTKLPLVYFLDISNNNLQgRINSRKW-DMPSLQMLSLARNKFFG-GLPDSFGSKRLENLDLSRNQ 486

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1391723571 132 LGRIAPGAFDDFLEsLEDLDLSYNNLRQVPWAGIGAMPALHTLNLDHNLIDALPPGAFAQLGQLSRLDLTSNRLATLAPD 211
Cdd:PLN00113  487 FSGAVPRKLGSLSE-LMQLKLSENKLSGEIPDELSSCKKLVSLDLSHNQLSGQIPASFSEMPVLSQLDLSQNQLSGEIPK 565

                  ..
gi 1391723571 212 PL 213
Cdd:PLN00113  566 NL 567

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); 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, 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, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1391723571 289 RLWVLEGQRATLRCRALGDPAPTMHWVGPDDRLVGNSSRARAFpNGTLEIGVTGAGDAGGYTCIATNpaGEATAR 363
Cdd:cd05876     4 SLVALRGQSLVLECIAEGLPTPTVKWLRPSGPLPPDRVKYQNH-NKTLQLLNVGESDDGEYVCLAEN--SLGSAR 75

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1391723571 300 LRCRALGDPAPTMHWVgPDDRLVGNSSRARAFPNGTLEIGVTGAGDAGGYTCIATNPAGEATARVEL 366
Cdd:cd05746     3 IPCSAQGDPEPTITWN-KDGVQVTESGKFHISPEGYLAIRDVGVADQGRYECVARNTIGYASVSMVL 68

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 1391723571 280 PPLIARHTQRLWVLEGQRATLRCRALGDPAPTMHWVGpDDRLVGNSSRARAFPNG---TLEIGVTGAGDAGGYTCIATNP 356
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFC-EGKELQNSPDIQIHQEGdlhSLIIAEAFEEDTGRYSCLATNS 79

                          90
                  ....*....|..
gi 1391723571 357 AGEATARVELRV 368
Cdd:cd20972    80 VGSDTTSAEIFV 91

leucine-rich repeat receptor-like protein kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1391723571  53 LRLADNFIQALGPPDFRNMTGLVDLTLSRNAITRIGARAFGDLESLRSLHLDGNRL----------------VELGTGSL 116
Cdd:PLN00113  169 LDLGGNVLVGKIPNSLTNLTSLEFLTLASNQLVGQIPRELGQMKSLKWIYLGYNNLsgeipyeiggltslnhLDLVYNNL 248

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1391723571 117 RGPV--------NLQHLILSGNQL-GRIAPGAFDdfLESLEDLDLSYNNLR-QVPWAgIGAMPALHTLNLDHNLIDALPP 186
Cdd:PLN00113  249 TGPIpsslgnlkNLQYLFLYQNKLsGPIPPSIFS--LQKLISLDLSDNSLSgEIPEL-VIQLQNLEILHLFSNNFTGKIP 325

                         170       180
                  ....*....|....*....|....*..
gi 1391723571 187 GAFAQLGQLSRLDLTSNRLATLAPDPL 213
Cdd:PLN00113  326 VALTSLPRLQVLQLWSNKFSGEIPKNL 352

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1391723571  52 ELRLADNFIQALgpPDFRNMTGLVDLTLSRNAITRIGAraFGDLESLRSLHLDGNRLVELGTGSLRGPVNLQHLILSGNQ 131
Cdd:COG4886   232 TLDLSNNQLTDL--PELGNLTNLEELDLSNNQLTDLPP--LANLTNLKTLDLSNNQLTDLKLKELELLLGLNSLLLLLLL 307

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1391723571 132 LGRIAPGAFDDFLESLEDLDLSYNNLRQVPWAGIGAMPALHTLNLDHNLIDALPPGAFAQLGQLSRLDLTSNRLATLAPD 211
Cdd:COG4886   308 LNLLELLILLLLLTTLLLLLLLLKGLLVTLTTLALSLSLLALLTLLLLLNLLSLLLTLLLTLGLLGLLEATLLTLALLLL 387

                  ..
gi 1391723571 212 PL 213
Cdd:COG4886   388 TL 389

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 1391723571  77 LTLSRNAITRIGarafgDLESLRS---LHLDGNRLVEL-GTGSLRgpvNLQHLILSGNQLGRIapgafDDF--LESLEDL 150
Cdd:cd21340     7 LYLNDKNITKID-----NLSLCKNlkvLYLYDNKITKIeNLEFLT---NLTHLYLQNNQIEKI-----ENLenLVNLKKL 73