RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The SMC (structural maintenance of chromosomes) superfamily proteins have ATP-binding domains at the N- and C-termini, and two extended coiled-coil domains separated by a hinge in the middle. The eukaryotic SMC proteins form two kind of heterodimers: the SMC1/SMC3 and the SMC2/SMC4 types. These heterodimers constitute an essential part of higher order complexes, which are involved in chromatin and DNA dynamics. This family also includes the RecF and RecN proteins that are involved in DNA metabolism and recombination.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907141631  282 DLGGSLQSTSDLRRRWIAMKPQLQQLHEDVQQITKEWEVLSSQGAPLKEKAEQLKDLVHLHRRQRE----RIQEYE-EIL 356
Cdd:TIGR02169  689 ELSSLQSELRRIENRLDELSQELSDASRKIGEIEKEIEQLEQEEEKLKERLEELEEDLSSLEQEIEnvksELKELEaRIE 768

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907141631  357 YKTVQFHQVKEELVHL---IKPRELELLAQPMElASSEEVQMQLGRSQERRAHVDHLHQLALTLGVDIISSVQQPNCSNI 433
Cdd:TIGR02169  769 ELEEDLHKLEEALNDLearLSHSRIPEIQAELS-KLEEEVSRIEARLREIEQKLNRLTLEKEYLEKEIQELQEQRIDLKE 847

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907141631  434 SAKNLQQQLEALELESRSWSAQAKEHE-RVLSCSLEYCTARDEISELKESFKDIKKKFNNLKFNYSKKNEKSRNLK-TLQ 511
Cdd:TIGR02169  848 QIKSIEKEIENLNGKKEELEEELEELEaALRDLESRLGDLKKERDELEAQLRELERKIEELEAQIEKKRKRLSELKaKLE 927

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907141631  512 YQIQQVDTY----------------AEKIQALRKKMEK-------VNNKTSDSF------LSYPSNKANMLSEAMEDLKK 562
Cdd:TIGR02169  928 ALEEELSEIedpkgedeeipeeelsLEDVQAELQRVEEeiralepVNMLAIQEYeevlkrLDELKEKRAKLEEERKAILE 1007

                   ....*..
gi 1907141631  563 NVDDFDK 569
Cdd:TIGR02169 1008 RIEEYEK 1014

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

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907141631   987 SNVTVMEGSPVTLEVEVTGFPEPTLTWFKKGQK-LCADGHLQVLHKDTKHSVFIPKVCEADAGLYVAQAQNSSGTLSSKA 1065
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKlLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGT 81

                    ....
gi 1907141631  1066 ILHV 1069
Cdd:smart00410   82 TLTV 85

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907141631  282 DLGGSLQSTSDLRRRWIAMKPQLQQLHEDVQQITKEWEVLSSQGAPLKEKAEQLKDLVHLHRRQRE----RIQEYE-EIL 356
Cdd:TIGR02169  689 ELSSLQSELRRIENRLDELSQELSDASRKIGEIEKEIEQLEQEEEKLKERLEELEEDLSSLEQEIEnvksELKELEaRIE 768

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907141631  357 YKTVQFHQVKEELVHL---IKPRELELLAQPMElASSEEVQMQLGRSQERRAHVDHLHQLALTLGVDIISSVQQPNCSNI 433
Cdd:TIGR02169  769 ELEEDLHKLEEALNDLearLSHSRIPEIQAELS-KLEEEVSRIEARLREIEQKLNRLTLEKEYLEKEIQELQEQRIDLKE 847

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907141631  434 SAKNLQQQLEALELESRSWSAQAKEHE-RVLSCSLEYCTARDEISELKESFKDIKKKFNNLKFNYSKKNEKSRNLK-TLQ 511
Cdd:TIGR02169  848 QIKSIEKEIENLNGKKEELEEELEELEaALRDLESRLGDLKKERDELEAQLRELERKIEELEAQIEKKRKRLSELKaKLE 927

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907141631  512 YQIQQVDTY----------------AEKIQALRKKMEK-------VNNKTSDSF------LSYPSNKANMLSEAMEDLKK 562
Cdd:TIGR02169  928 ALEEELSEIedpkgedeeipeeelsLEDVQAELQRVEEeiralepVNMLAIQEYeevlkrLDELKEKRAKLEEERKAILE 1007

                   ....*..
gi 1907141631  563 NVDDFDK 569
Cdd:TIGR02169 1008 RIEEYEK 1014

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

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907141631   987 SNVTVMEGSPVTLEVEVTGFPEPTLTWFKKGQK-LCADGHLQVLHKDTKHSVFIPKVCEADAGLYVAQAQNSSGTLSSKA 1065
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKlLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGT 81

                    ....
gi 1907141631  1066 ILHV 1069
Cdd:smart00410   82 TLTV 85

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first 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 1907141631  980 PHFSRLLSNVTVMEGSPVTLEVEVTGFPEPTLTWFKKGQ--KLCADGHLQVLHKDTKHSVFIPKVCEADAGLYVAQAQNS 1057
Cdd:cd20974      1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQviSTSTLPGVQISFSDGRAKLSIPAVTKANSGRYSLTATNG 80

                           90
                   ....*....|...
gi 1907141631 1058 SGTLSSKAILHVT 1070
Cdd:cd20974     81 SGQATSTAELLVL 93

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907141631  989 VTVMEGSPVTLEVEVTGFPEPTLTWFKKGQKLCADGHLQVLHKDTKHSVFIPKVCEADAGLYVAQAQNSSGTlsSKAILH 1068
Cdd:cd05748      2 IVVRAGESLRLDIPIKGRPTPTVTWSKDGQPLKETGRVQIETTASSTSLVIKNAKRSDSGKYTLTLKNSAGE--KSATIN 79

                   .
gi 1907141631 1069 V 1069
Cdd:cd05748     80 V 80

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907141631  997 VTLEVEVTGFPEPTLTWFKKGQKLCADGHLQVLHKDTKHSVFIPKVCEADAGLYVAQAQNSSGTLSSKAI 1066
Cdd:cd00096      1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907141631  980 PHF-SRLLSNVTVMEGSPVTLEVEVTGFPEPTLTWFKKGQKLCAD-GHLQVlhkdTKHSVFIPKVCEADAGLYVAQAQNS 1057
Cdd:cd20978      1 PKFiQKPEKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPmERATV----EDGTLTIINVQPEDTGYYGCVATNE 76

                           90
                   ....*....|..
gi 1907141631 1058 SGTLSSKAILHV 1069
Cdd:cd20978     77 IGDIYTETLLHV 88

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 1907141631  987 SNVTVMEGSPVTLEVEVTGFPEPTLTWFKKGQKLCADghlqVLHKDTKH------SVFIPKVC-----EADAGLYVAQAQ 1055
Cdd:cd07693      8 SDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLETD----KDDPRSHRivlpsgSLFFLRVVhgrkgRSDEGVYVCVAH 83

                           90
                   ....*....|....*
gi 1907141631 1056 NSSGTLSSK-AILHV 1069
Cdd:cd07693     84 NSLGEAVSRnASLEV 98

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 1907141631  980 PHFSRLLSNVTVMEGSPVTLEVEVTGFPEPTLTWFKKGQKLCAD-GHLQVLHKDTKHSVFIPKVCEADAGLYVAQAQNSS 1058
Cdd:cd20990      1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDsAHKMLVRENGVHSLIIEPVTSRDAGIYTCIATNRA 80

                   .
gi 1907141631 1059 G 1059
Cdd:cd20990     81 G 81

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. 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 1907141631  988 NVTVMEGSPVTLEVEVTGFPEPTLTWFKKGQKLCADGHLQVLHKDTKHSVFIPKVCEADAGLYVAQAQNSSG 1059
Cdd:cd05747     12 SLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQITSTEYKSTFEISKVQMSDEGNYTVVVENSEG 83

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup 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. 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. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin 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. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907141631  982 FSRLLSNVTVMEGSPVTLEVEVTGFPEPTLTWFKKGQKLCADGHLQVLHKDTKHSVF-IPKVCEADAGLYVAQAQNSSGT 1060
Cdd:cd05763      2 FTKTPHDITIRAGSTARLECAATGHPTPQIAWQKDGGTDFPAARERRMHVMPEDDVFfIVDVKIEDTGVYSCTAQNSAGS 81

                   ....*....
gi 1907141631 1061 LSSKAILHV 1069
Cdd:cd05763     82 ISANATLTV 90

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907141631  282 DLGGSLQSTSDLRRRWIAMKPQLQQLHEDVQQITKEWEVLSSQGAPLKEKAEQLKDLVHLHRRQRE----RIQEYE-EIL 356
Cdd:TIGR02169  689 ELSSLQSELRRIENRLDELSQELSDASRKIGEIEKEIEQLEQEEEKLKERLEELEEDLSSLEQEIEnvksELKELEaRIE 768

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907141631  357 YKTVQFHQVKEELVHL---IKPRELELLAQPMElASSEEVQMQLGRSQERRAHVDHLHQLALTLGVDIISSVQQPNCSNI 433
Cdd:TIGR02169  769 ELEEDLHKLEEALNDLearLSHSRIPEIQAELS-KLEEEVSRIEARLREIEQKLNRLTLEKEYLEKEIQELQEQRIDLKE 847

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907141631  434 SAKNLQQQLEALELESRSWSAQAKEHE-RVLSCSLEYCTARDEISELKESFKDIKKKFNNLKFNYSKKNEKSRNLK-TLQ 511
Cdd:TIGR02169  848 QIKSIEKEIENLNGKKEELEEELEELEaALRDLESRLGDLKKERDELEAQLRELERKIEELEAQIEKKRKRLSELKaKLE 927

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907141631  512 YQIQQVDTY----------------AEKIQALRKKMEK-------VNNKTSDSF------LSYPSNKANMLSEAMEDLKK 562
Cdd:TIGR02169  928 ALEEELSEIedpkgedeeipeeelsLEDVQAELQRVEEeiralepVNMLAIQEYeevlkrLDELKEKRAKLEEERKAILE 1007

                   ....*..
gi 1907141631  563 NVDDFDK 569
Cdd:TIGR02169 1008 RIEEYEK 1014

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907141631  987 SNVTVMEGSPVTLEVEV-TGFPEPTLTWFKKGQKLCADG-HLQVLHKDtkhSVFIPKVCEADAGLYVAQAQNSSGTLSSK 1064
Cdd:cd05724      5 SDTQVAVGEMAVLECSPpRGHPEPTVSWRKDGQPLNLDNeRVRIVDDG---NLLIAEARKSDEGTYKCVATNMVGERESR 81

                   .
gi 1907141631 1065 A 1065
Cdd:cd05724     82 A 82

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 1907141631  980 PHFSRLLSNVTVMEGSPVTLEVEVTGFPEPTLTWFKKGQKLcADGHLQVLHKD---TKHSVFIpkvcEADAGLYVAQAQN 1056
Cdd:cd20958      1 PPFIRPMGNLTAVAGQTLRLHCPVAGYPISSITWEKDGRRL-PLNHRQRVFPNgtlVIENVQR----SSDEGEYTCTARN 75

                           90
                   ....*....|....
gi 1907141631 1057 SSGtLSSKAILHVT 1070
Cdd:cd20958     76 QQG-QSASRSVFVK 88

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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907141631  980 PHFSR--LLSNVTVMEGSPVTLEVEVTGFPEPTLTWFKKGQKLCADGHLQVLhkdTKHSVFIPKVCEADAGLYVAQAQNS 1057
Cdd:cd04969      1 PDFELnpVKKKILAAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICIL---PDGSLKIKNVTKSDEGKYTCFAVNF 77

                           90
                   ....*....|..
gi 1907141631 1058 SGTLSSKAILHV 1069
Cdd:cd04969     78 FGKANSTGSLSV 89

First 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 1907141631  980 PHFSRLLSNVTVMEGSPVTLEVEVTGFPEPTLTWFKKGQKLCADGHLQVLHKDTKHSVFIPKVCEA--DAGLYVAQAQNS 1057
Cdd:cd05893      1 PFFEMKLKHYKIFEGMPVTFTCRVAGNPKPKIYWFKDGKQISPKSDHYTIQRDLDGTCSLHTTASTldDDGNYTIMAANP 80

                           90
                   ....*....|..
gi 1907141631 1058 SGTLSSKAILHV 1069
Cdd:cd05893     81 QGRISCTGRLMV 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.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907141631  994 GSPVTLEVEVTGFPEPTLTWFKKGQKLCADGHLQVLHKDTKhsvfIPKVCEADAGLYVAQAQNSSGTLSSKAILHV 1069
Cdd:cd05728     14 GSSLRWECKASGNPRPAYRWLKNGQPLASENRIEVEAGDLR----ITKLSLSDSGMYQCVAENKHGTIYASAELAV 85

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907141631  993 EGSPVTLEVEVTGFPEPTLTWFKKGQKLCADGHLQVLHKDTkhsVFIPKVCEADAGLYVAQAQNSSGTLSSKAILHV 1069
Cdd:cd05745      1 EGQTVDFLCEAQGYPQPVIAWTKGGSQLSVDRRHLVLSSGT---LRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third 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. 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. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907141631  990 TVMEGSPVTLEVEVTGFPEPTLTWFKKGQKLCADGHLQVLHKDTKHsvfIPKVCEADAGLYVAQAQNSSGTLSSKAIL 1067
Cdd:cd20957     12 TVDFGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILSEDVLV---IPSVKREDKGMYQCFVRNDGDSAQATAEL 86

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 1907141631  988 NVTVMEGSPVTLEVEVTGFPEPTLTWFKKG-QKLCADGHLQVLHKDtkhSVFIPKVCEADAGLYVAQAQNSSGTLSSKAI 1066
Cdd:cd20952      8 NQTVAVGGTVVLNCQATGEPVPTISWLKDGvPLLGKDERITTLENG---SLQIKGAEKSDTGEYTCVALNLSGEATWSAV 84

                   ...
gi 1907141631 1067 LHV 1069
Cdd:cd20952     85 LDV 87

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907141631  987 SNVTVMEGSPVTLEVEVTGFPEPTLTWFKKGQKLCADghlQVLHKDTKHSVFIPKVCEADAGLYVAQAQNSSGtlSSKAI 1066
Cdd:cd05731      3 SSTMVLRGGVLLLECIAEGLPTPDIRWIKLGGELPKG---RTKFENFNKTLKIENVSEADSGEYQCTASNTMG--SARHT 77

                   ....
gi 1907141631 1067 LHVT 1070
Cdd:cd05731     78 ISVT 81

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth 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. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907141631  980 PHFSRLlSNVTVMEGSPVTLEVEVTGFPEPTLTW--------FKKGQklcADGHLQVLHKDTKHSVFIPKVCEADAGLYV 1051
Cdd:cd05732      3 PKITYL-ENQTAVELEQITLTCEAEGDPIPEITWrratrgisFEEGD---LDGRIVVRGHARVSSLTLKDVQLTDAGRYD 78

                   ....*...
gi 1907141631 1052 AQAQNSSG 1059
Cdd:cd05732     79 CEASNRIG 86

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907141631  988 NVTVMEGSPVTLEVEVTG-FPEPTLTWFKKGQKLCA--DGHLQVLHKDTKHSVFIPKVCEADAGLYVAQAQNSSGTLSSK 1064
Cdd:cd05750      8 SQTVQEGSKLVLKCEATSeNPSPRYRWFKDGKELNRkrPKNIKIRNKKKNSELQINKAKLEDSGEYTCVVENILGKDTVT 87

                   ....*
gi 1907141631 1065 AILHV 1069
Cdd:cd05750     88 GNVTV 92

C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein (also known as myomesin-2). Myomesin and M-protein are both structural proteins localized to the M-band, a transverse structure in the center of the sarcomere, and are candidates for M-band bridges. Both proteins are modular, consisting mainly of repetitive Ig-like and fibronectin type III (FnIII) domains. Myomesin is expressed in all types of vertebrate striated muscle; M-protein has a muscle-type specific expression pattern. Myomesin is present in both slow and fast fibers; M-protein is present only in fast fibers. It has been suggested that myomesin acts as a molecular spring with alternative splicing as a means of modifying its elasticity.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907141631  989 VTVMEGSPVTLEVEVTGFPEPTLTWFKKGQKLCADGHLQVLHKDTKHSVF-IPKVCEADAGLYVAQAQNSSGTLSSKAIL 1067
Cdd:cd05737     11 VTIMEGKTLNLTCNVWGDPPPEVSWLKNDQALAFLDHCNLKVEAGRTVYFtINGVSSEDSGKYGLVVKNKYGSETSDVTV 90

                   ..
gi 1907141631 1068 HV 1069
Cdd:cd05737     91 SV 92

C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C); The members here are composed of the C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C). MyBP-C consists of repeated domains, Ig and fibronectin type 3, and various linkers. Three isoforms of MYBP-C exist: slow-skeletal (ssMyBP-C), fast-skeletal (fsMyBP-C), and cardiac (cMyBP-C). cMYBP-C has insertions between and inside domains and an additional cardiac-specific Ig domain at the N-terminus. For cMYBP_C an interaction has been demonstrated between this C5 domain and the Ig C8 domain.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907141631  989 VTVMEGSPVTLEVEVTGFPEPTLTWfKKGQKLCADGHLQVLHKDTKH-SVFIPKVCE-ADAGLYVAQAQNSSGtlSSKAI 1066
Cdd:cd05894      5 IVVVAGNKLRLDVPISGEPAPTVTW-SRGDKAFTATEGRVRVESYKDlSSFVIEGAErEDEGVYTITVTNPVG--EDHAS 81

                   ...
gi 1907141631 1067 LHV 1069
Cdd:cd05894     82 LFV 84