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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 213972562  69 ELRLTDNFIAAVRRrDFANMTSLVHLTLSRNTIGQVAAgAFADLRALRALHLDSNRLAEVrGDQLRGLGNLRHLILGNNQ 148
Cdd:COG4886  140 ELDLSNNQLTDLPE-PLGNLTNLKSLDLSNNQLTDLPE-ELGNLTNLKELDLSNNQITDL-PEPLGNLTNLEELDLSGNQ 216

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 213972562 149 IRKVeSAAFdAFLSTVEDLDLSYNNLEALPWeaVGQMVNLNTLTLDHNLIDHIAEGTfvQLHKLVRLDMTSNRLHKLPPD 228
Cdd:COG4886  217 LTDL-PEPL-ANLTNLETLDLSNNQLTDLPE--LGNLTNLEELDLSNNQLTDLPPLA--NLTNLKTLDLSNNQLTDLKLK 290

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 213972562 229 GLFLrsQGGGPKPPTPLTVSFGGNPLHCNCELLWLRRLTREDDLETCATPEHLTDRYFWSIPEEEFLCEPPLITRQAGGR 308
Cdd:COG4886  291 ELEL--LLGLNSLLLLLLLLNLLELLILLLLLTTLLLLLLLLKGLLVTLTTLALSLSLLALLTLLLLLNLLSLLLTLLLT 368

                        250
                 ....*....|....*...
gi 213972562 309 ALVVEGQAVSLRCRAVGD 326
Cdd:COG4886  369 LGLLGLLEATLLTLALLL 386

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 213972562  69 ELRLTDNFIAAVRRrDFANMTSLVHLTLSRNTIGQVAAgAFADLRALRALHLDSNRLAEVrGDQLRGLGNLRHLILGNNQ 148
Cdd:COG4886  140 ELDLSNNQLTDLPE-PLGNLTNLKSLDLSNNQLTDLPE-ELGNLTNLKELDLSNNQITDL-PEPLGNLTNLEELDLSGNQ 216

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 213972562 149 IRKVeSAAFdAFLSTVEDLDLSYNNLEALPWeaVGQMVNLNTLTLDHNLIDHIAEGTfvQLHKLVRLDMTSNRLHKLPPD 228
Cdd:COG4886  217 LTDL-PEPL-ANLTNLETLDLSNNQLTDLPE--LGNLTNLEELDLSNNQLTDLPPLA--NLTNLKTLDLSNNQLTDLKLK 290

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 213972562 229 GLFLrsQGGGPKPPTPLTVSFGGNPLHCNCELLWLRRLTREDDLETCATPEHLTDRYFWSIPEEEFLCEPPLITRQAGGR 308
Cdd:COG4886  291 ELEL--LLGLNSLLLLLLLLNLLELLILLLLLTTLLLLLLLLKGLLVTLTTLALSLSLLALLTLLLLLNLLSLLLTLLLT 368

                        250
                 ....*....|....*...
gi 213972562 309 ALVVEGQAVSLRCRAVGD 326
Cdd:COG4886  369 LGLLGLLEATLLTLALLL 386

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 213972562   310 LVVEGQAVSLRCRAVGDPEPVVHWVAPDGRLLGNSSRTRVRGDG-TLDVTIT--TLRDSGTFTCIASNAAGEATAPVEV 385
Cdd:smart00410   5 TVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGsTSTLTISnvTPEDSGTYTCAATNSSGSASSGTTL 83

Leucine rich repeat;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 213972562   65 RRVVELRLTDNFIAAVRRRDFANMTSLVHLTLSRNTIGQVAAGAFADLRALRALHLDSNRL 125
Cdd:pfam13855   1 PNLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

Leucine rich repeat C-terminal domain;

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 213972562   252 NPLHCNCELLWLRRLTREDDLE------TCATPEHLTDR 284
Cdd:smart00082   1 NPFICDCELRWLLRWLQANEHLqdpvdlRCASPSSLRGP 39

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 213972562   426 RRLVAAELTSSSVLIRW-PAQRPVPG--IRMYQVQYNSSADDSLVYRMIPSTSqTFLVNDLAAGRAYDLCVLAVYDDG 500
Cdd:smart00060   5 SNLRVTDVTSTSVTLSWePPPDDGITgyIVGYRVEYREEGSEWKEVNVTPSST-SYTLTGLKPGTEYEFRVRAVNGAG 81

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 213972562  69 ELRLTDNFIAAVRRrDFANMTSLVHLTLSRNTIGQVAAgAFADLRALRALHLDSNRLAEVrGDQLRGLGNLRHLILGNNQ 148
Cdd:COG4886  140 ELDLSNNQLTDLPE-PLGNLTNLKSLDLSNNQLTDLPE-ELGNLTNLKELDLSNNQITDL-PEPLGNLTNLEELDLSGNQ 216

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 213972562 149 IRKVeSAAFdAFLSTVEDLDLSYNNLEALPWeaVGQMVNLNTLTLDHNLIDHIAEGTfvQLHKLVRLDMTSNRLHKLPPD 228
Cdd:COG4886  217 LTDL-PEPL-ANLTNLETLDLSNNQLTDLPE--LGNLTNLEELDLSNNQLTDLPPLA--NLTNLKTLDLSNNQLTDLKLK 290

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 213972562 229 GLFLrsQGGGPKPPTPLTVSFGGNPLHCNCELLWLRRLTREDDLETCATPEHLTDRYFWSIPEEEFLCEPPLITRQAGGR 308
Cdd:COG4886  291 ELEL--LLGLNSLLLLLLLLNLLELLILLLLLTTLLLLLLLLKGLLVTLTTLALSLSLLALLTLLLLLNLLSLLLTLLLT 368

                        250
                 ....*....|....*...
gi 213972562 309 ALVVEGQAVSLRCRAVGD 326
Cdd:COG4886  369 LGLLGLLEATLLTLALLL 386

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 213972562  311 VVEGQAVSLRCRAVGDPEPVVHWVApDGRLLGNSSRTRVR---GDGTLdvTIT--TLRDSGTFTCIASNAAGEATAPVEV 385
Cdd:pfam07679  12 VQEGESARFTCTVTGTPDPEVSWFK-DGQPLRSSDRFKVTyegGTYTL--TISnvQPDDSGKYTCVATNSAGEAEASAEL 88

                  ..
gi 213972562  386 CV 387
Cdd:pfam07679  89 TV 90

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 213972562  45 PTLTML-CAKTGLLFVPPAIDR--RVVELRLTDNFIAAVRRrDFANMTSLVHLTLSRNTIGQVAAgAFADLRALRALHLD 121
Cdd:COG4886  159 TNLKSLdLSNNQLTDLPEELGNltNLKELDLSNNQITDLPE-PLGNLTNLEELDLSGNQLTDLPE-PLANLTNLETLDLS 236

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 213972562 122 SNRLAEVrgDQLRGLGNLRHLILGNNQIRKVESAAFdafLSTVEDLDLSYNNLEALPWEAVGQMVNLNTLTLDHNLIDHI 201
Cdd:COG4886  237 NNQLTDL--PELGNLTNLEELDLSNNQLTDLPPLAN---LTNLKTLDLSNNQLTDLKLKELELLLGLNSLLLLLLLLNLL 311

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 213972562 202 AEgtFVQLHKLVRLDMTSNRLHKLPPDGLFLRSQGGGPKPPTPLT 246
Cdd:COG4886  312 EL--LILLLLLTTLLLLLLLLKGLLVTLTTLALSLSLLALLTLLL 354

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 213972562 313 EGQAVSLRCRAVGDPEPVVHWVAPDGRLLGNSS--RTRVRGDGTLDVTITTLRDSGTFTCIASNAAGEATAPVEVCV 387
Cdd:cd20969   16 EGHTVQFVCRADGDPPPAILWLSPRKHLVSAKSngRLTVFPDGTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHLHV 92

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 213972562 299 PLIT-RQAGGRALVVEGQAVSLRCRAVGDPEPVVHWVAPDGRLLGNSSRTRVRGDGTlDVTITTLR--DSGTFTCIASNA 375
Cdd:cd20970    1 PVIStPQPSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRYIVRENGT-TLTIRNIRrsDMGIYLCIASNG 79

                 ..
gi 213972562 376 AG 377
Cdd:cd20970   80 VP 81

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 213972562 311 VVEGQAVSLRCRAVGDPEPVVHWVAPDGRLlgNSSRTRVRGDGTLDVTITTLRDSGTFTCIASNAAGEATA 381
Cdd:cd05725    9 VLVDDSAEFQCEVGGDPVPTVRWRKEDGEL--PKGRYEILDDHSLKIRKVTAGDMGSYTCVAENMVGKIEA 77

Leucine rich repeat;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 213972562  113 RALRALHLDSNRLAEVRGDQLRGLGNLRHLILGNNQIRKVESAAFDaFLSTVEDLDLSYNNL 174
Cdd:pfam13855   1 PNLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFS-GLPSLRYLDLSGNRL 61

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 213972562 317 VSLRCRAVGDPEPVVHWVaPDGRLLGNSSRTRVR---GDGTLDVTITTLRDSGTFTCIASNAAGEATA 381
Cdd:cd00096    1 VTLTCSASGNPPPTITWY-KNGKPLPPSSRDSRRselGNGTLTISNVTLEDSGTYTCVASNSAGGSAS 67

Leucine rich repeat;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 213972562  138 NLRHLILGNNQIRKVESAAFdAFLSTVEDLDLSYNNLEALPWEAVGQMVNLNTLTLDHNLI 198
Cdd:pfam13855   2 NLRSLDLSNNRLTSLDDGAF-KGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

Fourth 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 fourth 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 213972562 314 GQAVSLRCRAVGDPEPVVHWVApDGRLLGNSSRTRV------RGDGTLDVTITTLR--DSGTFTCIASNAAGEAT 380
Cdd:cd20956   16 GPSVSLKCVASGNPLPQITWTL-DGFPIPESPRFRVgdyvtsDGDVVSYVNISSVRveDGGEYTCTATNDVGSVS 89

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 213972562 299 PLITRQAGGRALVVE---GQAVSLRCRAVGDPEPVVHWVAPDGRLLGNSSRTRVRGDGTLDVTITTLRDSGTFTCIASNA 375
Cdd:cd05856    1 PRFTQPAKMRRRVIArpvGSSVRLKCVASGNPRPDITWLKDNKPLTPPEIGENKKKKWTLSLKNLKPEDSGKYTCHVSNR 80

                         90
                 ....*....|..
gi 213972562 376 AGE--ATAPVEV 385
Cdd:cd05856   81 AGEinATYKVDV 92

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 213972562 311 VVEGQAVSLRCRAVGDPEPVVHWVApDGRLLGNSSRTRVRGDGTLDVTITT---LRDSGTFTCIASNAAGEATAPVEVCV 387
Cdd:cd20972   13 VAEGSKVRLECRVTGNPTPVVRWFC-EGKELQNSPDIQIHQEGDLHSLIIAeafEEDTGRYSCLATNSVGSDTTSAEIFV 91

Ran GTPase-activating protein (RanGAP) involved in mRNA processing and transport [Translation, ribosomal structure and biogenesis];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 213972562  67 VVELRLTDNFIAAVRRRDFANM----TSLVHLTLSRNTIGQVAAGAFADL----RALRALHLDSNRL----AEVRGDQLR 134
Cdd:COG5238  210 VTTLWLKRNPIGDEGAEILAEAlkgnKSLTTLDLSNNQIGDEGVIALAEAlknnTTVETLYLSGNQIgaegAIALAKALQ 289

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 213972562 135 GLGNLRHLILGNNQIRKVESAAFDAFL---STVEDLDLSYNNLEALPWEAVGQMV----NLNTLTLDHNLI-DHIAEG-- 204
Cdd:COG5238  290 GNTTLTSLDLSVNRIGDEGAIALAEGLqgnKTLHTLNLAYNGIGAQGAIALAKALqentTLHSLDLSDNQIgDEGAIAla 369

                        170       180
                 ....*....|....*....|..
gi 213972562 205 TFVQLHKLVR-LDMTSNRLHKL 225
Cdd:COG5238  370 KYLEGNTTLReLNLGKNNIGKQ 391

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 213972562 299 PLITRQAGGRAlVVEGQAVSLRCRAVGDPEPVVHWVApDGRLLGNSSRTR--VRGDG--TLDVTITTLRDSGTFTCIASN 374
Cdd:cd05744    1 PHFLQAPGDLE-VQEGRLCRFDCKVSGLPTPDLFWQL-NGKPVRPDSAHKmlVRENGrhSLIIEPVTKRDAGIYTCIARN 78

                         90
                 ....*....|...
gi 213972562 375 AAGEATAPVEVCV 387
Cdd:cd05744   79 RAGENSFNAELVV 91

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

                         10        20        30        40        50        60        70        80
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gi 213972562 298 PPLI-TRQAGGRALVVEGQAVSLRCRAVGDPEPVVHWVApDGRLLGNSSRTRVRGDGTLDVTI--TTLRDSGTFTCIASN 374
Cdd:cd05730    1 PPTIrARQSEVNATANLGQSVTLACDADGFPEPTMTWTK-DGEPIESGEEKYSFNEDGSEMTIldVDKLDEAEYTCIAEN 79

                         90
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gi 213972562 375 AAGEATAPVEVCV 387
Cdd:cd05730   80 KAGEQEAEIHLKV 92

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

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gi 213972562 318 SLR--CRAVGDPEPVVHWVApDGRLLGNSSRTRVRGdGTLDVTITTLRDSGTFTCIASNAAGEATAPVEVCV 387
Cdd:cd05728   16 SLRweCKASGNPRPAYRWLK-NGQPLASENRIEVEA-GDLRITKLSLSDSGMYQCVAENKHGTIYASAELAV 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.

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gi 213972562 298 PPLItRQAGGRAlVVEGQAVSLRCRAVGDPEPVVHWVApDGRLLGNSSRTRVRGDGTLDV-TITTLRDSGTFTCIASNAA 376
Cdd:cd20958    1 PPFI-RPMGNLT-AVAGQTLRLHCPVAGYPISSITWEK-DGRRLPLNHRQRVFPNGTLVIeNVQRSSDEGEYTCTARNQQ 77

                         90
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gi 213972562 377 GE-ATAPVEVCV 387
Cdd:cd20958   78 GQsASRSVFVKV 89

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.

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gi 213972562 310 LVVEGQAVSLRCRAVGDPEPVVHWVAPDGrLLGNSSRTRVRGDGTLDVTITTLRDSGTFTCIASNAAGEA 379
Cdd:cd04969   13 LAAKGGDVIIECKPKASPKPTISWSKGTE-LLTNSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGKA 81

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.

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gi 213972562 317 VSLRCRAVGDPEPVVHWVApDGRLLGNSSRTRVRGDGTLDVTITTLRDSGTFTCIASNAAGEATAPVEV 385
Cdd:cd05746    1 VQIPCSAQGDPEPTITWNK-DGVQVTESGKFHISPEGYLAIRDVGVADQGRYECVARNTIGYASVSMVL 68

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.

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gi 213972562 301 ITRQAGGRALVVEGQAVsLRCRAVGDPEPVVHWVAPDGRLLGNsSRTRVRGDGTLDVTITTLRDSGTFTCIASNAAGEA- 379
Cdd:cd20968    2 ITRPPTNVTIIEGLKAV-LPCTTMGNPKPSVSWIKGDDLIKEN-NRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGIAy 79

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gi 213972562 380 TAPVEVCV 387
Cdd:cd20968   80 SKPVTIEV 87