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 1958783014 287 PLITRHTHEMRVLEGQRATLRCKARGDPEPAIHWISPEGKLISNATRSLVYDNGTLDILITTVKDTGAFTCIASNPAGEA 366
Cdd:cd05764     1 PLITRHTHELRVLEGQRATLRCKARGDPEPAIHWISPEGKLISNSSRTLVYDNGTLDILITTVKDTGAFTCIASNPAGEA 80

                  ....*...
gi 1958783014 367 TQTMDLHI 374
Cdd:cd05764    81 TARVELHI 88

Leucine rich repeat C-terminal domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1958783014  240 NPLHCNCELLWLRR-------LSREDDLeTCASPALLTGR 272
Cdd:smart00082   1 NPFICDCELRWLLRwlqanehLQDPVDL-RCASPSSLRGP 39

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958783014 421 IVVAEASSSTALLKFN--FQRNIPgIRMFQIQYNGTYD-DTLVYRMIPPTSKTFLVNNLASGTMYDLCVLAIYDDGI 494
Cdd:pfam00041   6 LTVTDVTSTSLTVSWTppPDGNGP-ITGYEVEYRPKNSgEPWNEITVPGTTTSVTLTGLKPGTEYEVRVQAVNGGGE 81

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 1958783014 287 PLITRHTHEMRVLEGQRATLRCKARGDPEPAIHWISPEGKLISNATRSLVYDNGTLDILITTVKDTGAFTCIASNPAGEA 366
Cdd:cd05764     1 PLITRHTHELRVLEGQRATLRCKARGDPEPAIHWISPEGKLISNSSRTLVYDNGTLDILITTVKDTGAFTCIASNPAGEA 80

                  ....*...
gi 1958783014 367 TQTMDLHI 374
Cdd:cd05764    81 TARVELHI 88

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958783014 286 PPLITRHTHEMRVLEGQRATLRCKARGDPEPAIHWISPEGKLISNATR--SLVYDNGTLDILITTVKDTGAFTCIASN 361
Cdd:pfam13927   1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRsrSLSGSNSTLTISNVTRSDAGTYTCVASN 78

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958783014  296 MRVLEGQRATLRCKARGDPEPAIHWISPEGKLISNATR-SLVYDNGTLDILIT--TVKDTGAFTCIASNPAGEATQTMDL 372
Cdd:smart00410   4 VTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRfSVSRSGSTSTLTISnvTPEDSGTYTCAATNSSGSASSGTTL 83

                   ..
gi 1958783014  373 HI 374
Cdd:smart00410  84 TV 85

leucine-rich repeat receptor-like protein kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958783014  70 DFANMTSLVDLTLSRNTISFITPHAFADLRNLRALHLNSNRLTKITNDMFSGLSNLHHLILNNNQLTLISSTAFDDVFAL 149
Cdd:PLN00113  470 DSFGSKRLENLDLSRNQFSGAVPRKLGSLSELMQLKLSENKLSGEIPDELSSCKKLVSLDLSHNQLSGQIPASFSEMPVL 549

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1958783014 150 EELDLSYNNLE-TIPWDaVEKMVSLHTLSLDHNMI 183
Cdd:PLN00113  550 SQLDLSQNQLSgEIPKN-LGNVESLVQVNISHNHL 583

Metaviral_G glycoprotein; This is a viral attachment glycoprotein from region G of metaviruses. It is high in serine and threonine suggesting it is highly glycosylated.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958783014 631 PTWTSSAPVSQKQKRKTGTKPSAEPQSEAVTNVESQNTNRNNSTALQLASCPPDSVTEGPtsQRAHTKPKAGVHIKSTTS 710
Cdd:pfam09595  78 PSESEDAPDIDPNNQHPSQDRSEAPPLEPAAKTKPSEHEPANPPDASNRLSPPDASTAAI--REARTFRKPSTGKRNNPS 155

                  ....*...
gi 1958783014 711 LSPENSCP 718
Cdd:pfam09595 156 SAQSDQSP 163

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 1958783014 287 PLITRHTHEMRVLEGQRATLRCKARGDPEPAIHWISPEGKLISNATRSLVYDNGTLDILITTVKDTGAFTCIASNPAGEA 366
Cdd:cd05764     1 PLITRHTHELRVLEGQRATLRCKARGDPEPAIHWISPEGKLISNSSRTLVYDNGTLDILITTVKDTGAFTCIASNPAGEA 80

                  ....*...
gi 1958783014 367 TQTMDLHI 374
Cdd:cd05764    81 TARVELHI 88

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958783014  55 ELRLADNFVTNIKrKDFANMTSLVDLTLSRNTISFItPHAFADLRNLRALHLNSNRLTKITNDmFSGLSNLHHLILNNNQ 134
Cdd:COG4886   163 SLDLSNNQLTDLP-EELGNLTNLKELDLSNNQITDL-PEPLGNLTNLEELDLSGNQLTDLPEP-LANLTNLETLDLSNNQ 239

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958783014 135 LTLISStaFDDVFALEELDLSYNNLETIPwdAVEKMVSLHTLSLDHNMIDNIPKGTFSHLHKMTRLDVTSNKLQKLPPDP 214
Cdd:COG4886   240 LTDLPE--LGNLTNLEELDLSNNQLTDLP--PLANLTNLKTLDLSNNQLTDLKLKELELLLGLNSLLLLLLLLNLLELLI 315

                         170
                  ....*....|....*
gi 1958783014 215 LFQRAQVLATSGIIS 229
Cdd:COG4886   316 LLLLLTTLLLLLLLL 330

Leucine rich repeat;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958783014  99 RNLRALHLNSNRLTKITNDMFSGLSNLHHLILNNNQLTLISSTAFDDVFALEELDLSYNNL 159
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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958783014 300 EGQRATLRCKARGDPEPAIHWISPEGKLISNAT--RSLVYDNGTLDILITTVKDTGAFTCIASNPAGEATQTMDLHI 374
Cdd:cd20969    16 EGHTVQFVCRADGDPPPAILWLSPRKHLVSAKSngRLTVFPDGTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHLHV 92

Leucine rich repeat;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958783014  51 RRTVELRLADNFVTNIKRKDFANMTSLVDLTLSRNTISFITPHAFADLRNLRALHLNSNRL 111
Cdd:pfam13855   1 PNLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 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 1958783014 286 PPLITRHTHEMRVLEGQRATLRCKARGDPEPAIHWISpEGKLISNATRSLVYDNGTLDILITT---VKDTGAFTCIASNP 362
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFC-EGKELQNSPDIQIHQEGDLHSLIIAeafEEDTGRYSCLATNS 79

                          90
                  ....*....|..
gi 1958783014 363 AGEATQTMDLHI 374
Cdd:cd20972    80 VGSDTTSAEIFV 91

Leucine rich repeat;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958783014 123 SNLHHLILNNNQLTLISSTAFDDVFALEELDLSYNNLETIPWDAVEKMVSLHTLSLDHNMI 183
Cdd:pfam13855   1 PNLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958783014 289 ITRHTHEMRVLEGQRATLRCKARGDPEPAIHWISPEGKLISNAtRSLVYDNGTLDILITTVKDTGAFTCIASNPAGEA 366
Cdd:cd20968     2 ITRPPTNVTIIEGLKAVLPCTTMGNPKPSVSWIKGDDLIKENN-RIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGIA 78

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 1958783014 288 LITRHTHEMRVLEGQRATLRCKARGDPEPAIHWISPEGKLISNATRSLVYDNGTLDILITTVKDTGAFTCIASNPAGEAT 367
Cdd:cd20952     1 IILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTLENGSLQIKGAEKSDTGEYTCVALNLSGEAT 80

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 1958783014 287 PLITRHTHEMRVLEGQRATLRCKARGDPEPAIHWiSPEGKLISNATRS--LVYDNGTLDILITTV--KDTGAFTCIASNP 362
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFW-QLNGKPVRPDSAHkmLVRENGRHSLIIEPVtkRDAGIYTCIARNR 79

                          90
                  ....*....|..
gi 1958783014 363 AGEATQTMDLHI 374
Cdd:cd05744    80 AGENSFNAELVV 91

Leucine rich repeat;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1958783014 149 LEELDLSYNNLETIPWDAVEKMVSLHTLSLDHNMIDNIPKGTFSHLHKMTRLDVTSNKL 207
Cdd:pfam13855   3 LRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 (PPP1R42), also known as leucine-rich repeat-containing protein 67 (lrrc67) or testis leucine-rich repeat (TLRR) protein, plays a role in centrosome separation. PPP1R42 has been shown to interact with the well-conserved signaling protein phosphatase-1 (PP1) and thereby increasing PP1's activity, which counters centrosome separation. Inhibition of PPP1R42 expression increases the number of centrosomes per cell while its depletion reduces the activity of PP1 leading to activation of NEK2, the kinase responsible for phosphorylation of centrosomal linker proteins promoting centrosome separation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958783014  74 MTSLVDLTLSRNTISFItpHAFADLRNLRALHLNSNRLTKITNdmFSGLSNLHHLILNNNQLTLI--------------- 138
Cdd:cd21340     1 LKRITHLYLNDKNITKI--DNLSLCKNLKVLYLYDNKITKIEN--LEFLTNLTHLYLQNNQIEKIenlenlvnlkklylg 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958783014 139 -----------------------------SSTAFDD--VFA----LEELDLSYNNLETIpwDAVEKMVSLHTLSLDHNMI 183
Cdd:cd21340    77 gnrisvveglenltnleelhienqrlppgEKLTFDPrsLAAlsnsLRVLNISGNNIDSL--EPLAPLRNLEQLDASNNQI 154

                         170       180       190
                  ....*....|....*....|....*....|
gi 1958783014 184 DNIP--KGTFSHLHKMTRLDVTSNKLQKLP 211
Cdd:cd21340   155 SDLEelLDLLSSWPSLRELDLTGNPVCKKP 184

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958783014 298 VLEGQRATLRCKARGDPEPAIHWISPEGKLISNATRSLVYDNGtldILITTVK--DTGAFTCIASNPAGE 365
Cdd:cd20978    13 VKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATVEDGT---LTIINVQpeDTGYYGCVATNEIGD 79

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958783014 298 VLEGQRATLRCKARGDPEPAIHWiSPEGKLISNATRSLVYDNGTLDILITTVKDTGAFTCIASNPAGEATQT 369
Cdd:cd04969    14 AAKGGDVIIECKPKASPKPTISW-SKGTELLTNSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGKANST 84

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 1958783014 306 LRCKARGDPEPAIHWISpEGKLISNATRSLVYDNGTLDILITTVKDTGAFTCIASNPAGEATQTMDL 372
Cdd:cd05746     3 IPCSAQGDPEPTITWNK-DGVQVTESGKFHISPEGYLAIRDVGVADQGRYECVARNTIGYASVSMVL 68

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) 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, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), 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 Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958783014 287 PLITRHTHEMRVLEGQRATLRCKARGDPEPAIHWISPEGKLISNA----TRSLVYDNGTLDILIT-----TVKDTGAFTC 357
Cdd:cd07693     1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLETDKddprSHRIVLPSGSLFFLRVvhgrkGRSDEGVYVC 80

                          90
                  ....*....|
gi 1958783014 358 IASNPAGEAT 367
Cdd:cd07693    81 VAHNSLGEAV 90

BspA type Leucine rich repeat region (6 copies); This family includes a number of leucine rich repeats. This family contains a large number of BSPA-like surface antigens from Trichomonas vaginalis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958783014  64 TNIKRKDFANmTSLVDLTLSrNTISFITPHAFADLRNLRALHLNSNrLTKITNDMFSGlSNLHHLILNNNqLTLISSTAF 143
Cdd:pfam13306   1 TSIGSYAFYN-CSLTSITIP-SSLTSIGEYAFSNCTSLKSITLPSS-LTSIGSYAFYN-CSLTSITIPSS-LTSIGEYAF 75

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1958783014 144 DDVFALEELDLSyNNLETIPWDAVEKMvSLHTLSLdHNMIDNIPKGTFSHLHKMT 198
Cdd:pfam13306  76 SNCSNLKSITLP-SNLTSIGSYAFSNC-SLKSITI-PSSVTTIGSYAFSNCSNLK 127

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 1958783014 295 EMRVLEGQRATLRCKARGDPEPAIHWiSPEGKLI--SNATRSLVYDNGTLDILI--TTVKDTGAFTCIASNPAGEATQTM 370
Cdd:cd20990     9 DLTVQEGKLCRMDCKVSGLPTPDLSW-QLDGKPIrpDSAHKMLVRENGVHSLIIepVTSRDAGIYTCIATNRAGQNSFNL 87

                  ..
gi 1958783014 371 DL 372
Cdd:cd20990    88 EL 89

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 1958783014 286 PPLITRHTHEMRVLEGQRATLRCKARGDPEPAIHWISPEGKLISNATRSlvYDNGTLDILITTVKDTGAFTCIASNPAGE 365
Cdd:cd04968     1 PSIKVRFPADTYALKGQTVTLECFALGNPVPQIKWRKVDGSPSSQWEIT--TSEPVLEIPNVQFEDEGTYECEAENSRGK 78

                  ..
gi 1958783014 366 AT 367
Cdd:cd04968    79 DT 80

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958783014 296 MRVLEGQRATLRCKA-RGDPEPAIHWISPEGKLISNATRSLVYDNGTLdiLITTVK--DTGAFTCIASNPAGE 365
Cdd:cd05724     7 TQVAVGEMAVLECSPpRGHPEPTVSWRKDGQPLNLDNERVRIVDDGNL--LIAEARksDEGTYKCVATNMVGE 77

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 1958783014 286 PPLItRHTHEMRVLEGQRATLRCKARGDPEPAIHWISpEGKLISNATRSLVYDNGTLdiLITTVK---DTGAFTCIASNP 362
Cdd:cd20958     1 PPFI-RPMGNLTAVAGQTLRLHCPVAGYPISSITWEK-DGRRLPLNHRQRVFPNGTL--VIENVQrssDEGEYTCTARNQ 76

                          90
                  ....*....|...
gi 1958783014 363 AGE-ATQTMDLHI 374
Cdd:cd20958    77 QGQsASRSVFVKV 89

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 1958783014 298 VLEGQRATLRCKAR-GDPEPAIHWISPEGKLISNATRSLV-YDNGTLDILI--TTVKDTGAFTCIASNPAGEAT 367
Cdd:pfam00047   8 VLEGDSATLTCSAStGSPGPDVTWSKEGGTLIESLKVKHDnGRTTQSSLLIsnVTKEDAGTYTCVVNNPGGSAT 81

leucine-rich repeat receptor-like protein kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958783014  56 LRLADNFVTNIKRKDFANMTSLVDLTLSRNTISFITPHAFADLRNLRALHLNSNRLTKITNDMFSGLSNLHHlilnnnql 135
Cdd:PLN00113  169 LDLGGNVLVGKIPNSLTNLTSLEFLTLASNQLVGQIPRELGQMKSLKWIYLGYNNLSGEIPYEIGGLTSLNH-------- 240

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958783014 136 tlisstafddvfaleeLDLSYNNLE-TIPwDAVEKMVSLHTLSLDHNMI-DNIPKGTFShLHKMTRLDVTSNKLQKLPPD 213
Cdd:PLN00113  241 ----------------LDLVYNNLTgPIP-SSLGNLKNLQYLFLYQNKLsGPIPPSIFS-LQKLISLDLSDNSLSGEIPE 302

                  ....
gi 1958783014 214 PLFQ 217
Cdd:PLN00113  303 LVIQ 306