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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907122802 770 ARVLGGLPDVVTIQEGKALNLTCNVWGDPPPEVSWLKNEKPLTSDDHCSLKFEAGKTAFFTISGVSTADSGKYGLVVKNK 849
Cdd:cd05737     1 ARVLGGLPDVVTIMEGKTLNLTCNVWGDPPPEVSWLKNDQALAFLDHCNLKVEAGRTVYFTINGVSSEDSGKYGLVVKNK 80

                          90
                  ....*....|..
gi 1907122802 850 YGSETSDFTVSV 861
Cdd:cd05737    81 YGSETSDVTVSV 92

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907122802 132 PSAPYDITCLESFRDSMVLGWKQPDTTGGaEITGYYVNYREVVGevpGKWREANIKAVSDAAYKISNLKENTLYQFQVSA 211
Cdd:cd00063     1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGG-PITGYVVEYREKGS---GDWKEVEVTPGSETSYTLTGLKPGTEYEFRVRA 76

                          90
                  ....*....|....*
gi 1907122802 212 MNIAGLGAPSTVSEC 226
Cdd:cd00063    77 VNGGGESPPSESVTV 91

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 1907122802 576 CKVANIKKETHIVWYKDEREISVDEKHD--FKDGICTLLITEFSKKDAGFYEVILKDDRGKDKSRLKL 641
Cdd:cd20927    21 CKIENYDQSTQVTWYFGVRQLENSEKYEitYEDGVAILYVKDITKFDDGTYRCKVVNDYGEDSSYAEL 88

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 1907122802 770 ARVLGGLPDVVTIQEGKALNLTCNVWGDPPPEVSWLKNEKPLTSDDHCSLKFEAGKTAFFTISGVSTADSGKYGLVVKNK 849
Cdd:cd05737     1 ARVLGGLPDVVTIMEGKTLNLTCNVWGDPPPEVSWLKNDQALAFLDHCNLKVEAGRTVYFTINGVSSEDSGKYGLVVKNK 80

                          90
                  ....*....|..
gi 1907122802 850 YGSETSDFTVSV 861
Cdd:cd05737    81 YGSETSDVTVSV 92

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907122802 237 PGPPHSVKLSEVRKNSLVLQWKPPVYSGRtPVTGYFVDLKEASakDDQWRGLNEAAIVNKYLRVQGLKEGTSYVFRVRAV 316
Cdd:cd00063     1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGG-PITGYVVEYREKG--SGDWKEVEVTPGSETSYTLTGLKPGTEYEFRVRAV 77

                          90
                  ....*....|
gi 1907122802 317 NQAGVGKPSD 326
Cdd:cd00063    78 NGGGESPPSE 87

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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907122802  237 PGPPHSVKLSEVRKNSLVLQWKPPVYSGRT-PVTGYFVDLKEasaKDDQWRGLNEAAIVNKYlRVQGLKEGTSYVFRVRA 315
Cdd:smart00060   1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGITgYIVGYRVEYRE---EGSEWKEVNVTPSSTSY-TLTGLKPGTEYEFRVRA 76

                   ....*..
gi 1907122802  316 VNQAGVG 322
Cdd:smart00060  77 VNGAGEG 83

Fibronectin type III domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907122802 238 GPPHSVKLSEVRKNSLVLQWKPPVySGRTPVTGYFVDLKEASaKDDQWRGLNEAAIVNKYLrVQGLKEGTSYVFRVRAVN 317
Cdd:pfam00041   1 SAPSNLTVTDVTSTSLTVSWTPPP-DGNGPITGYEVEYRPKN-SGEPWNEITVPGTTTSVT-LTGLKPGTEYEVRVQAVN 77

                  ....*...
gi 1907122802 318 QAGVGKPS 325
Cdd:pfam00041  78 GGGEGPPS 85

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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907122802  132 PSAPYDITCLESFRDSMVLGWKQPDTTGGaeiTGYYVNYREVVGEVPGKWREANIKaVSDAAYKISNLKENTLYQFQVSA 211
Cdd:smart00060   1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGI---TGYIVGYRVEYREEGSEWKEVNVT-PSSTSYTLTGLKPGTEYEFRVRA 76

                   ....*..
gi 1907122802  212 MNIAGLG 218
Cdd:smart00060  77 VNGAGEG 83

Immunoglobulin I-set domain;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907122802 353 SLNFECD-QMTPKSEFVWSKDYVPTEDSPRLEVENKGDKTKMTFKDLGTDDLGTYSCDVTDTDGIASS 419
Cdd:pfam07679  17 SARFTCTvTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAGEAEA 84

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907122802 572 VLLKCKVANiKKETHIVWYKDEREISVDEKH--DFKDGICTLLITEFSKKDAGFYEVILKDDRGKDKSRLKL 641
Cdd:pfam07679  18 ARFTCTVTG-TPDPEVSWFKDGQPLRSSDRFkvTYEGGTYTLTISNVQPDDSGKYTCVATNSAGEAEASAEL 88

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 1907122802 360 QMTPKSEFVWSKDYVPTEDSPRLEVENKGdktKMTFKDLGTDDLGTYSCDVTDTDGIASS 419
Cdd:cd05746     8 QGDPEPTITWNKDGVQVTESGKFHISPEG---YLAIRDVGVADQGRYECVARNTIGYASV 64

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 1907122802 770 ARVLGGLPDVVTIQEGKALNLTCNVWGDPPPEVSWLKNEKPLTSDDHCSLKFEAGKTAFFTISGVSTADSGKYGLVVKNK 849
Cdd:cd05737     1 ARVLGGLPDVVTIMEGKTLNLTCNVWGDPPPEVSWLKNDQALAFLDHCNLKVEAGRTVYFTINGVSSEDSGKYGLVVKNK 80

                          90
                  ....*....|..
gi 1907122802 850 YGSETSDFTVSV 861
Cdd:cd05737    81 YGSETSDVTVSV 92

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907122802 777 PDVVTIQEGKALNLTCNVWGDPPPEVSWLKNEKPLTSDDHCSLKFEaGKTAFFTISGVSTADSGKYGLVVKNKYGSETSD 856
Cdd:pfam07679   7 PKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYE-GGTYTLTISNVQPDDSGKYTCVATNSAGEAEAS 85

                  ....*
gi 1907122802 857 FTVSV 861
Cdd:pfam07679  86 AELTV 90

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907122802 132 PSAPYDITCLESFRDSMVLGWKQPDTTGGaEITGYYVNYREVVGevpGKWREANIKAVSDAAYKISNLKENTLYQFQVSA 211
Cdd:cd00063     1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGG-PITGYVVEYREKGS---GDWKEVEVTPGSETSYTLTGLKPGTEYEFRVRA 76

                          90
                  ....*....|....*
gi 1907122802 212 MNIAGLGAPSTVSEC 226
Cdd:cd00063    77 VNGGGESPPSESVTV 91

Fibronectin type 3 domain [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907122802 128 PVAVPSAPYDITCLESFRDSMVLGWkQPDTTGGAeiTGYYVnYREVVGEvpGKWREanIKAVSDAAYKISNLKENTLYQF 207
Cdd:COG3401   229 PTTPPSAPTGLTATADTPGSVTLSW-DPVTESDA--TGYRV-YRSNSGD--GPFTK--VATVTTTSYTDTGLTNGTTYYY 300

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907122802 208 QVSAMNIAGL-GAPSTVSECFKCeewtIAVPGPPHSVKLSEVRKNSLVLQWKPPVYSGrtpVTGYFVdlKEASAKDDQWR 286
Cdd:COG3401   301 RVTAVDAAGNeSAPSNVVSVTTD----LTPPAAPSGLTATAVGSSSITLSWTASSDAD---VTGYNV--YRSTSGGGTYT 371

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 1907122802 287 GLNEAAIVNKYlRVQGLKEGTSYVFRVRAVNQAGVGkpSDLAGPVVAET 335
Cdd:COG3401   372 KIAETVTTTSY-TDTGLTPGTTYYYKVTAVDAAGNE--SAPSEEVSATT 417

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907122802  777 PDVVTIQEGKALNLTCNVWGDPPPEVSWLKN-EKPLTSDDHCSLKFEaGKTAFFTISGVSTADSGKYGLVVKNKYGSETS 855
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQgGKLLAESGRFSVSRS-GSTSTLTISNVTPEDSGTYTCAATNSSGSASS 79

                   ....*.
gi 1907122802  856 DFTVSV 861
Cdd:smart00410  80 GTTLTV 85

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907122802 770 ARVLGGlPDVVTIQEGKALNLTCNVWGDPPPEVSWLKNEKPLTSddhcSLKFEAGKTAF---FTISGVSTADSGKYGLVV 846
Cdd:cd05747     4 ATILTK-PRSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVS----SQRHQITSTEYkstFEISKVQMSDEGNYTVVV 78

                          90
                  ....*....|....
gi 1907122802 847 KNKYGSETSDFTVS 860
Cdd:cd05747    79 ENSEGKQEAQFTLT 92

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907122802 777 PDVVTIQEGKALNLTCNVWGDPPPEVSWLKNEKPLTSDDHcSLKFEAGKTAFFTISGVSTADSGKYGLVVKN 848
Cdd:pfam13927   8 PSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGST-RSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

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 1907122802 779 VVTIQEGKALNLTCNVWGDPPPEVSWLKNEKPLTSDDHcsLKFEAGKT-AFFTISGVSTADSGKYGLVVKNKYGSETSDF 857
Cdd:cd05748     1 TIVVRAGESLRLDIPIKGRPTPTVTWSKDGQPLKETGR--VQIETTASsTSLVIKNAKRSDSGKYTLTLKNSAGEKSATI 78

                  ....
gi 1907122802 858 TVSV 861
Cdd:cd05748    79 NVKV 82

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907122802 777 PDVVTIQEGKALNLTCNVWGDPPPEVSWLKNEKPLTSDDHCSLKFEAGKTAFFTISGVSTADSGKYGLVVKNKYG 851
Cdd:cd05744     7 PGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENGRHSLIIEPVTKRDAGIYTCIARNRAG 81

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. 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 telokin Ig domain 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 1907122802 781 TIQEGKALNLTCNVWGDPPPEVSWLKNEKPLTSDDHCSLKFEAGKTAFFTISGVSTADSGKYGLVVKNKYGSETSDFTVS 860
Cdd:cd20973     8 EVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEDGLCSLIISDVCGDDSGKYTCKAVNSLGEATCSAELT 87

                  .
gi 1907122802 861 V 861
Cdd:cd20973    88 V 88

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. 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. The Ig-like domain of the Twitchin is a member of the I-set 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. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907122802 777 PDVVTIQEGKALNLTCNVWGDPPPEVSWLKNEKPLTSDDHCSLKFEaGKTAFFTISGVSTADSGKYGLVVKNKYG--SET 854
Cdd:cd20949     6 AYVTTVKEGQSATILCEVKGEPQPNVTWHFNGQPISASVADMSKYR-ILADGLLINKVTQDDTGEYTCRAYQVNSiaSDM 84

                  ....*
gi 1907122802 855 SDFTV 859
Cdd:cd20949    85 QERTV 89

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 1907122802 780 VTIQEGKALNLTCNVWGDPPPEVSWLKNEKPLTSDDHCSLKFeaGKTafFTISGVSTADSGKYGLVVKNKYGSETSDFTV 859
Cdd:cd05731     5 TMVLRGGVLLLECIAEGLPTPDIRWIKLGGELPKGRTKFENF--NKT--LKIENVSEADSGEYQCTASNTMGSARHTISV 80

                  ..
gi 1907122802 860 SV 861
Cdd:cd05731    81 TV 82

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907122802 785 GKALNLTCNVWGDPPPEVSWLKNEKPLTSDDHcsLKFEAGKtafFTISGVSTADSGKYGLVVKNKYGS 852
Cdd:cd05728    14 GSSLRWECKASGNPRPAYRWLKNGQPLASENR--IEVEAGD---LRITKLSLSDSGMYQCVAENKHGT 76

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 1907122802 790 LTCNVWGDPPPEVSWLKNEKPLTSddhcSLKFEAGKTAFFTISGVSTADSGKYGLVVKNKYGSETSDFTVS 860
Cdd:cd05746     3 IPCSAQGDPEPTITWNKDGVQVTE----SGKFHISPEGYLAIRDVGVADQGRYECVARNTIGYASVSMVLS 69

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907122802 777 PDVVTIQEGKALNLTCNVWGDPPPEVSWLKNEKPLTSDDHCSLKFEAGKTAFFTISGVSTADSGKYGLVVKNKYGSET 854
Cdd:cd20990     7 PGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMLVRENGVHSLIIEPVTSRDAGIYTCIATNRAGQNS 84

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.

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gi 1907122802 781 TIQEGKALNLTCNVWGD-PPPEVSWLKNEKPLTSDDHCSLKFEAG-KTAFFTISGVSTADSGKYGLVVKNKYGSETSDFT 858
Cdd:cd05750    10 TVQEGSKLVLKCEATSEnPSPRYRWFKDGKELNRKRPKNIKIRNKkKNSELQINKAKLEDSGEYTCVVENILGKDTVTGN 89

                  ...
gi 1907122802 859 VSV 861
Cdd:cd05750    90 VTV 92

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 2 (VEGFR-2); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 2 (VEGFR-2). The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. VEGFRs bind VEGFs with high affinity at the Ig-like domains. VEGFR-2 (KDR/Flk-1) is a major mediator of the mitogenic, angiogenic and microvascular permeability-enhancing effects of VEGF-A; VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGF-A also interacts with VEGFR-1, which it binds more strongly than VEGFR-2. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. 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.

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gi 1907122802 775 GLPDVVTIQEGKALNLTCNVWGDPPPEVSWLKNEKPLTSDdhcsLKFEAGKTafFTISGVSTADSGKYGLVVKNKYGSET 854
Cdd:cd05864     7 GMESLVEAKVGERVRIPVKYLGYPPPEIKWYKNGIPIESN----HTIKAGHV--LTIMEVTEKDAGNYTVVLTNPISKEK 80

                  ....*....
gi 1907122802 855 SDFTVSVFI 863
Cdd:cd05864    81 QRHTFSLVV 89

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 1907122802 777 PDVVTIQEGKALNLTCNVWGDPPPEVSWLKNEKPLTSDDHCSLkFEAGKtafFTISGVSTADSGKYGLVVKNKYGSETS 855
Cdd:cd20968     6 PTNVTIIEGLKAVLPCTTMGNPKPSVSWIKGDDLIKENNRIAV-LESGS---LRIHNVQKEDAGQYRCVAKNSLGIAYS 80

Fifth domain (immunoglobulin-like) of Trk receptors TrkA, TrkB, and TrkC; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth domain of Trk receptors TrkA, TrkB, and TrkC, an immunoglobulin (Ig)-like domain which binds to neurotrophin. The Trk family of receptors are tyrosine kinase receptors. They are activated by dimerization, leading to autophosphorylation of intracellular tyrosine residues, and triggering the signal transduction pathway. TrkA, TrkB, and TrkC share significant sequence homology and domain organization. The first three domains are leucine-rich domains while the fourth and fifth domains are Ig-like domains playing a part in ligand binding. TrkA, TrkB, and TrkC mediate the trophic effects of the neurotrophin Nerve Growth Factor (NGF) family. TrkA is recognized by NGF. TrkB is recognized by brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-4. TrkC is recognized by NT-3. NT-3 is promiscuous as in some cell systems it activates TrkA and TrkB receptors. TrkA is a receptor found in all major NGF targets, including the sympathetic, trigeminal, and dorsal root ganglia, cholinergic neurons of the basal forebrain, and the striatum. TrKB transcripts are found throughout multiple structures of the central and peripheral nervous systems. The TrkC gene is expressed throughout the mammalian nervous system. This group belongs to the I-set of IgSF domains.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907122802 777 PDVVTIQEGKALNLTC---NVWGDPPPEVSWLKNEKPLTSDDHCSLKFEAGKTAFFTISGV------STADSGKYGLVVK 847
Cdd:cd04971     2 PVIVRLEEPELRHHWCipfTVRGNPKPTLTWYHNGAVLNESDYIRTEIHYEAATPTEYHGClkfdnpTHVNNGNYTLVAS 81

                  ....*..
gi 1907122802 848 NKYGSET 854
Cdd:cd04971    82 NEYGQDS 88

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907122802 778 DVVTIQeGKALNLTCNV-WGDPPPEVSWLKNEKPLTSDDHCSLKFEAGKTAfftISGVSTADSGKYGLVVKNKYGSETS 855
Cdd:cd05724     6 DTQVAV-GEMAVLECSPpRGHPEPTVSWRKDGQPLNLDNERVRIVDDGNLL---IAEARKSDEGTYKCVATNMVGERES 80