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 827196300 183 PGPPQNLAVKEVKKDSVILVWEPPIIDGGaKVKSYVIDKRESTRKAYANVSSK-CNKTSFKVENLTEGAIYYFRVMAENE 261
Cdd:cd00063    1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGG-PITGYVVEYREKGSGDWKEVEVTpGSETSYTLTGLKPGTEYEFRVRAVNG 79

                         90
                 ....*....|...
gi 827196300 262 FGVGVPVETVDAV 274
Cdd:cd00063   80 GGESPPSESVTVT 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
                 ....*....|....*....|....*....|....*....|....*
gi 827196300 280 PSPPGKVTLTDVSQTSASLMWEKPEYDGGsRILGYVVEMQSKGTE 324
Cdd:cd00063    1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGG-PITGYVVEYREKGSG 44

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 827196300 183 PGPPQNLAVKEVKKDSVILVWEPPIIDGGaKVKSYVIDKRESTRKAYANVSSK-CNKTSFKVENLTEGAIYYFRVMAENE 261
Cdd:cd00063    1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGG-PITGYVVEYREKGSGDWKEVEVTpGSETSYTLTGLKPGTEYEFRVRAVNG 79

                         90
                 ....*....|...
gi 827196300 262 FGVGVPVETVDAV 274
Cdd:cd00063   80 GGESPPSESVTVT 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 827196300   1 NSITVAWGKPIYDGGsEILGYVVELCKADEEEWQIVTPPTGlKATRFEIAKLTEHQEYKIRVCALNKVGLGEPTP 75
Cdd:cd00063   15 TSVTLSWTPPEDDGG-PITGYVVEYREKGSGDWKEVEVTPG-SETSYTLTGLKPGTEYEFRVRAVNGGGESPPSE 87

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 827196300    99 KGIVVRAGGSARIHIPFKGRPTPEITWSREEGEFA---DKVQIEKGLNYTQLSIDNCDRNDAGKYILKLENSSGSKSAFV 175
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLaesGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGT 81

                   ....
gi 827196300   176 TVKV 179
Cdd:smart00410  82 TLTV 85

Fibronectin type III domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 827196300    1 NSITVAWgKPIYDGGSEILGYVVELCKADEEE---WQIVTPPTglkaTRFEIAKLTEHQEYKIRVCALNKVGLGEPT 74
Cdd:pfam00041  14 TSLTVSW-TPPPDGNGPITGYEVEYRPKNSGEpwnEITVPGTT----TSVTLTGLKPGTEYEVRVQAVNGGGEGPPS 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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 827196300     1 NSITVAWGKPIYDGG-SEILGYVVELCKADEEEWQIVTPPTglkATRFEIAKLTEHQEYKIRVCALNKVGLG 71
Cdd:smart00060  15 TSVTLSWEPPPDDGItGYIVGYRVEYREEGSEWKEVNVTPS---STSYTLTGLKPGTEYEFRVRAVNGAGEG 83

Fibronectin type 3 domain [General function prediction only];

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 827196300 243 VENLTEGAIYYFRVMAENEFGVGVPVETVDAVKAAEPPSPPGKVTLTDVSQTSASLMWEKPEydgGSRILGYVVE 317
Cdd:COG3401  196 GGDIEPGTTYYYRVAATDTGGESAPSNEVSVTTPTTPPSAPTGLTATADTPGSVTLSWDPVT---ESDATGYRVY 267

Fibronectin type III domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 827196300  281 SPPGKVTLTDVSQTSASLMWEKPEyDGGSRILGYVVEMQSKGTE 324
Cdd:pfam00041   1 SAPSNLTVTDVTSTSLTVSWTPPP-DGNGPITGYEVEYRPKNSG 43

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 827196300 183 PGPPQNLAVKEVKKDSVILVWEPPIIDGGaKVKSYVIDKRESTRKAYANVSSK-CNKTSFKVENLTEGAIYYFRVMAENE 261
Cdd:cd00063    1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGG-PITGYVVEYREKGSGDWKEVEVTpGSETSYTLTGLKPGTEYEFRVRAVNG 79

                         90
                 ....*....|...
gi 827196300 262 FGVGVPVETVDAV 274
Cdd:cd00063   80 GGESPPSESVTVT 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 827196300   1 NSITVAWGKPIYDGGsEILGYVVELCKADEEEWQIVTPPTGlKATRFEIAKLTEHQEYKIRVCALNKVGLGEPTP 75
Cdd:cd00063   15 TSVTLSWTPPEDDGG-PITGYVVEYREKGSGDWKEVEVTPG-SETSYTLTGLKPGTEYEFRVRAVNGGGESPPSE 87

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 827196300    99 KGIVVRAGGSARIHIPFKGRPTPEITWSREEGEFA---DKVQIEKGLNYTQLSIDNCDRNDAGKYILKLENSSGSKSAFV 175
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLaesGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGT 81

                   ....
gi 827196300   176 TVKV 179
Cdd:smart00410  82 TLTV 85

Fibronectin type III domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 827196300    1 NSITVAWgKPIYDGGSEILGYVVELCKADEEE---WQIVTPPTglkaTRFEIAKLTEHQEYKIRVCALNKVGLGEPT 74
Cdd:pfam00041  14 TSLTVSW-TPPPDGNGPITGYEVEYRPKNSGEpwnEITVPGTT----TSVTLTGLKPGTEYEVRVQAVNGGGEGPPS 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 827196300  99 KGIVVRAGGSARIHIPFKGRPTPEITWSREeGEFAD-----KVQIEKGLNYTQLSIDNCDRNDAGKYILKLENSSGSKSA 173
Cdd:cd20974    8 QSVVVLEGSTATFEAHVSGKPVPEVSWFRD-GQVIStstlpGVQISFSDGRAKLSIPAVTKANSGRYSLTATNGSGQATS 86

                 ....*..
gi 827196300 174 FVTVKVL 180
Cdd:cd20974   87 TAELLVL 93

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 827196300     1 NSITVAWGKPIYDGG-SEILGYVVELCKADEEEWQIVTPPTglkATRFEIAKLTEHQEYKIRVCALNKVGLG 71
Cdd:smart00060  15 TSVTLSWEPPPDDGItGYIVGYRVEYREEGSEWKEVNVTPS---STSYTLTGLKPGTEYEFRVRAVNGAGEG 83

Fibronectin type 3 domain [General function prediction only];

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 827196300 243 VENLTEGAIYYFRVMAENEFGVGVPVETVDAVKAAEPPSPPGKVTLTDVSQTSASLMWEKPEydgGSRILGYVVE 317
Cdd:COG3401  196 GGDIEPGTTYYYRVAATDTGGESAPSNEVSVTTPTTPPSAPTGLTATADTPGSVTLSWDPVT---ESDATGYRVY 267

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 827196300 102 VVRAGGSARIHIPFKGRPTPEITWSREEGEFAD-KVQIekgLNYTQLSIDNCDRNDAGKYILKLENSSGSKSAFVTVKV 179
Cdd:cd05725    8 VVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPKgRYEI---LDDHSLKIRKVTAGDMGSYTCVAENMVGKIEASATLTV 83

Eighth immunoglobulin (Ig)-like domain of human myosin light-chain kinase (MLCK) and similar protein; member of the I-set of IgSF domains; The members here are composed of the eighth immunoglobulin (Ig)-like domain of human myosin light-chain kinase (MLCK) and similar proteins. Myosin light-chain kinase (MLCK) is a key regulator of different forms of cell motility involving actin and myosin II. Agonist stimulation of smooth muscle cells increases cytosolic Ca2+ which binds calmodulin. This Ca2+-calmodulin complex in turn binds to and activates MLCK. Activated MLCK leads to the phosphorylation of the 20 kDa myosin regulatory light chain (RLC) of myosin II and the stimulation of actin-activated myosin MgATPase activity. MLCK is widely present in vertebrate tissues; it phosphorylates the 20 kDa RLC of both smooth and nonmuscle myosin II. Phosphorylation leads to the activation of the myosin motor domain and altered structural properties of myosin II. In smooth muscle MLCK it is involved in initiating contraction. In nonmuscle cells, MLCK may participate in cell division and cell motility; it has been suggested MLCK plays a role in cardiomyocyte differentiation and contraction through regulation of nonmuscle myosin II.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 827196300 103 VRAGGSARIHIPFKGRPTPEITWSR-----EEGEFadkVQIEKGLNYTQLSIDNCDRNDAGKYILKLENSSGSKSAFVTV 177
Cdd:cd05762   13 VRAGESVELFCKVTGTQPITCTWMKfrkqiQEGEG---IKIENTENSSKLTITEGQQEHCGCYTLEVENKLGSRQAQVNL 89

                 ....*....
gi 827196300 178 KVLDTPGPP 186
Cdd:cd05762   90 TVVDKPDPP 98

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 827196300  101 IVVRAGGSARIHIPFKGRPTPEITWSREEGEFADKVQIEKGL--NYTQLSIDNCDRNDAGKYILKLEN 166
Cdd:pfam13927  11 VTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLsgSNSTLTISNVTRSDAGTYTCVASN 78

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 827196300 102 VVRAGGSARIHIPFKGRPTPEITWSREEGEFADKVQIEKGLNYTQLSIDNCDRNDAGKYILKLENSSGSKSAFVTVKV 179
Cdd:cd20952   10 TVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTLENGSLQIKGAEKSDTGEYTCVALNLSGEATWSAVLDV 87

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; 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. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). 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 827196300  98 RKGIVVRAGGSARIHIPFKGRPTPEITWSREEGEFADKVQIEKGLNYTQ---LSIDNCDRNDAGKYILKLENSSGSKSAF 174
Cdd:cd05729   11 EREHALPAANKVRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEEKgwsLIIERAIPRDKGKYTCIVENEYGSINHT 90

                 ....*
gi 827196300 175 VTVKV 179
Cdd:cd05729   91 YDVDV 95

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 827196300  99 KGIVVRAGGSARIHIPFKGRPTPEITWSReEGEF---ADKVQIEKGLNYTQLSIDNCDRNDAGKYILKLENSSGSKSAFV 175
Cdd:cd05747   11 RSLTVSEGESARFSCDVDGEPAPTVTWMR-EGQIivsSQRHQITSTEYKSTFEISKVQMSDEGNYTVVVENSEGKQEAQF 89

                 ..
gi 827196300 176 TV 177
Cdd:cd05747   90 TL 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 827196300 114 PFKGRPTPEITWSREEGE--FADKVQIEKGLNYTQLSIDNCDRNDAGKYILKLENSSGSKSA 173
Cdd:cd00096    6 SASGNPPPTITWYKNGKPlpPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSAS 67

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 827196300 117 GRPTPEITWSREEGEFAD----KVQIEKGlNYTQLSIDNCDRNDAGKYILKLENSSGSKSAFVTVKV 179
Cdd:cd05737   27 GDPPPEVSWLKNDQALAFldhcNLKVEAG-RTVYFTINGVSSEDSGKYGLVVKNKYGSETSDVTVSV 92

Immunoglobulin-like Ig0 domain of basigin-1 (BSG1) and similar proteins; The members here are composed of the immunoglobulin (Ig) domain of the collagenase stimulatory factor, basigin-1 (BSG1; also known as Cluster of Differentiation 147 (CD147) and Extracellular Matrix Metalloproteinase Inducer (EMMPRIN)) and similar proteins. CD147 is a transmembrane glycoprotein that belongs to the immunoglobulin superfamily. It is expressed in nearly all cells including platelets and fibroblasts and is involved in inflammatory diseases, and cancer progression. CD147 is highly expressed in several cancers and used as a prognostic marker. The two primary isoforms of CD147 that are related to cancer progression have been identified: CD147 Ig1-Ig2 (also called Basigin-2) that is ubiquitously expressed in most tissues and CD147 Ig0-Ig1-Ig2 (also called Basigin-1) that is retinal specific and implicated in retinoblastoma. Studies showed that CD147 Ig0 domain is a potent stimulator of interleukin-6 and suggest that the CD147 Ig0 dimer is the functional unit required for activity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 827196300 106 GGSARIHIPFKGRPTPEITWSREEGE------------FADKVQIEKGLN---YTQLSIDNCDRNDAGKYILKLENSSGS 170
Cdd:cd20940   15 GDSVELHCEAVGSPIPEIQWWFEGQEpneicsqlwdgaRLDRVHINATYHqhaTSTISIDNLTEEDTGTYECRASNDPDR 94

                         90       100       110
                 ....*....|....*....|....*....|....
gi 827196300 171 KsafvtvkvlDTPGPPQnlaVKEVKKDSVILVWE 204
Cdd:cd20940   95 N---------HLTRAPK---VKWIRSQANVLVLE 116

C-terminal immunoglobulin (Ig)-like domain of 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 M-protein (also known as myomesin-2). M-protein is a structural protein localized to the M-band, a transverse structure in the center of the sarcomere, and is a candidate for M-band bridges. M-protein is modular consisting mainly of repetitive IG-like and fibronectin type III (FnIII) domains and has a muscle-type specific expression pattern. M-protein is present in fast fibers.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 827196300 117 GRPTPEITWSR--EEGEFADK--VQIEKGlNYTQLSIDNCDRNDAGKYILKLENSSGSKSAFVTVKV 179
Cdd:cd05891   27 GNPDPEVIWFKndQDIELSEHysVKLEQG-KYASLTIKGVTSEDSGKYSINVKNKYGGETVDVTVSV 92

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 827196300  89 PELDLDSELRKGIVVR-AGGSARIHIPFKGRPTPEITWSREEGEFADKVQIEKGLNYTQLSIDNCDRNDAGKYILKLENS 167
Cdd:cd05856    1 PRFTQPAKMRRRVIARpVGSSVRLKCVASGNPRPDITWLKDNKPLTPPEIGENKKKKWTLSLKNLKPEDSGKYTCHVSNR 80

                         90
                 ....*....|..
gi 827196300 168 SGSKSAFVTVKV 179
Cdd:cd05856   81 AGEINATYKVDV 92

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 827196300 117 GRPTPEITWSREeGEFADKVQIEKGLNY--TQLSIDNCDRNDAGKYILKLENSSGSKSAFVTVKV 179
Cdd:cd05730   29 GFPEPTMTWTKD-GEPIESGEEKYSFNEdgSEMTILDVDKLDEAEYTCIAENKAGEQEAEIHLKV 92

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 827196300  89 PELDLDsELRKGIVVRAGGSARIHIPFKGRPTPEITWSREEGEFADKVQIEKGLNYTqLSIDNCDRNDAGKYILKLENSS 168
Cdd:cd04969    1 PDFELN-PVKKKILAAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICILPDGS-LKIKNVTKSDEGKYTCFAVNFF 78

                 ....
gi 827196300 169 GSKS 172
Cdd:cd04969   79 GKAN 82