MAEBL; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755504357   25 KLGKGDVKDKFEAMQRAREERNQRRSRDEKQRRKEQYIREREWNRRKQEIKEMLASDDEEESSPKIEKAYVPKLTGtvKG 104
Cdd:PTZ00121 1192 ELRKAEDARKAEAARKAEEERKAEEARKAEDAKKAEAVKKAEEAKKDAEEAKKAEEERNNEEIRKFEEARMAHFAR--RQ 1269

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755504357  105 KFDEMEKHRQEEQRKRTEEERKRRIEQDLLEKRKIQrELAKRAEQIEDINNTGTESASEEGDDSLLITVVPAKSYKTPGK 184
Cdd:PTZ00121 1270 AAIKAEEARKADELKKAEEKKKADEAKKAEEKKKAD-EAKKKAEEAKKADEAKKKAEEAKKKADAAKKKAEEAKKAAEAA 1348

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755504357  185 TKDPEDLDREEGNGRTNHEEDKMRYEEECRVLKEAKCLSLVMDDETEAKKEShfpgklkstfEELERQRQENRKKQAEEE 264
Cdd:PTZ00121 1349 KAEAEAAADEAEAAEEKAEAAEKKKEEAKKKADAAKKKAEEKKKADEAKKKA----------EEDKKKADELKKAAAAKK 1418

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755504357  265 ARRRLEEERRSFEEARRHMVNEEDENQDRETVFKEYRPGKLKLSFEEIERQRREDEKRKAEEEARRRIEEEKAAFAEARR 344
Cdd:PTZ00121 1419 KADEAKKKAEEKKKADEAKKKAEEAKKADEAKKKAEEAKKAEEAKKKAEEAKKADEAKKKAEEAKKADEAKKKAEEAKKK 1498

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755504357  345 SmvldddspEIYKTVSQESLTPGKLEINFEQLLRQKMEEERRRTEEERRHKLEmEKQEFEQLR--QEMGKEEEENESFGL 422
Cdd:PTZ00121 1499 A--------DEAKKAAEAKKKADEAKKAEEAKKADEAKKAEEAKKADEAKKAE-EKKKADELKkaEELKKAEEKKKAEEA 1569

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755504357  423 SREYEELIKLKRSGSIQAKNLKSKFEKIGQLSEKEVQKKIEE----ERAKRRAIDLEIKEREAENFHEDDDVDVRPAKKS 498
Cdd:PTZ00121 1570 KKAEEDKNMALRKAEEAKKAEEARIEEVMKLYEEEKKMKAEEakkaEEAKIKAEELKKAEEEKKKVEQLKKKEAEEKKKA 1649

                         490       500       510       520       530
                  ....*....|....*....|....*....|....*....|....*....|.
gi 755504357  499 ESPFTHKVNMKARFEQMAKAREEEEQRRIEEQKllrMQFEQKEIDAALQKK 549
Cdd:PTZ00121 1650 EELKKAEEENKIKAAEEAKKAEEDKKKAEEAKK---AEEDEKKAAEALKKE 1697

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band 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. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. 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 I1 domain of the titin I-band 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, 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 755504357 577 PWFKKPLRNTSVVDSEPVRFTVKVTGEPKPEITWWFEGEILQ---DGEDYQYIERGETYCLYLPETFPEDGGEYMCKAVN 653
Cdd:cd20951    1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDpssIPGKYKIESEYGVHVLHIRRVTVEDSAVYSAVAKN 80

                         90
                 ....*....|....
gi 755504357 654 NKGSAASTCILTIE 667
Cdd:cd20951   81 IHGEASSSASVVVE 94

MAEBL; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755504357   25 KLGKGDVKDKFEAMQRAREERNQRRSRDEKQRRKEQYIREREWNRRKQEIKEMLASDDEEESSPKIEKAYVPKLTGtvKG 104
Cdd:PTZ00121 1192 ELRKAEDARKAEAARKAEEERKAEEARKAEDAKKAEAVKKAEEAKKDAEEAKKAEEERNNEEIRKFEEARMAHFAR--RQ 1269

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755504357  105 KFDEMEKHRQEEQRKRTEEERKRRIEQDLLEKRKIQrELAKRAEQIEDINNTGTESASEEGDDSLLITVVPAKSYKTPGK 184
Cdd:PTZ00121 1270 AAIKAEEARKADELKKAEEKKKADEAKKAEEKKKAD-EAKKKAEEAKKADEAKKKAEEAKKKADAAKKKAEEAKKAAEAA 1348

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755504357  185 TKDPEDLDREEGNGRTNHEEDKMRYEEECRVLKEAKCLSLVMDDETEAKKEShfpgklkstfEELERQRQENRKKQAEEE 264
Cdd:PTZ00121 1349 KAEAEAAADEAEAAEEKAEAAEKKKEEAKKKADAAKKKAEEKKKADEAKKKA----------EEDKKKADELKKAAAAKK 1418

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755504357  265 ARRRLEEERRSFEEARRHMVNEEDENQDRETVFKEYRPGKLKLSFEEIERQRREDEKRKAEEEARRRIEEEKAAFAEARR 344
Cdd:PTZ00121 1419 KADEAKKKAEEKKKADEAKKKAEEAKKADEAKKKAEEAKKAEEAKKKAEEAKKADEAKKKAEEAKKADEAKKKAEEAKKK 1498

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755504357  345 SmvldddspEIYKTVSQESLTPGKLEINFEQLLRQKMEEERRRTEEERRHKLEmEKQEFEQLR--QEMGKEEEENESFGL 422
Cdd:PTZ00121 1499 A--------DEAKKAAEAKKKADEAKKAEEAKKADEAKKAEEAKKADEAKKAE-EKKKADELKkaEELKKAEEKKKAEEA 1569

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755504357  423 SREYEELIKLKRSGSIQAKNLKSKFEKIGQLSEKEVQKKIEE----ERAKRRAIDLEIKEREAENFHEDDDVDVRPAKKS 498
Cdd:PTZ00121 1570 KKAEEDKNMALRKAEEAKKAEEARIEEVMKLYEEEKKMKAEEakkaEEAKIKAEELKKAEEEKKKVEQLKKKEAEEKKKA 1649

                         490       500       510       520       530
                  ....*....|....*....|....*....|....*....|....*....|.
gi 755504357  499 ESPFTHKVNMKARFEQMAKAREEEEQRRIEEQKllrMQFEQKEIDAALQKK 549
Cdd:PTZ00121 1650 EELKKAEEENKIKAAEEAKKAEEDKKKAEEAKK---AEEDEKKAAEALKKE 1697

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band 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. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. 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 I1 domain of the titin I-band 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, 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 755504357 577 PWFKKPLRNTSVVDSEPVRFTVKVTGEPKPEITWWFEGEILQ---DGEDYQYIERGETYCLYLPETFPEDGGEYMCKAVN 653
Cdd:cd20951    1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDpssIPGKYKIESEYGVHVLHIRRVTVEDSAVYSAVAKN 80

                         90
                 ....*....|....
gi 755504357 654 NKGSAASTCILTIE 667
Cdd:cd20951   81 IHGEASSSASVVVE 94

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 755504357 581 KPLRNTSVVDSEPVRFTVKVTGEPKPEITWWFEGEILQDGEDYQYIERGETYC-LYLPETFPEDGGEYMCKAVNNKGSAA 659
Cdd:cd20973    2 QTLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEDGLCsLIISDVCGDDSGKYTCKAVNSLGEAT 81

                 ....*..
gi 755504357 660 STCILTI 666
Cdd:cd20973   82 CSAELTV 88

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 755504357 578 WFKKPLRNTSVVDSEPVRFTVKVTGEPKPEITWWFEGEILQDGEDYQYIERGEtycLYLPETFPEDGGEYMCKAVNNKG 656
Cdd:cd20978    3 FIQKPEKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATVEDGT---LTIINVQPEDTGYYGCVATNEIG 78

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755504357   584 RNTSVVDSEPVRFTVKVTGEPKPEITWWFEG-EILQDGEDYQYIERGETYCLYLPETFPEDGGEYMCKAVNNKGSAASTC 662
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGT 81

                   ....
gi 755504357   663 ILTI 666
Cdd:smart00410  82 TLTV 85

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755504357 582 PLRNTSVVDSEPVRFTVKVTGEPKPEITWWFEGEILQDG-EDYQYIERGETycLYLPETFPEDGGEYMCKAVNNKGSAAS 660
Cdd:cd20970    8 PSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFnTRYIVRENGTT--LTIRNIRRSDMGIYLCIASNGVPGSVE 85

                 ...
gi 755504357 661 TCI 663
Cdd:cd20970   86 KRI 88

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. 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 this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus 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 755504357 576 APWFKKPLRNTSVVDSEPVRFTVKVTGEPKPEITWWFEGEILQDGEDYQYIERGeTYCLYLPETFPEDGGEYMCKAVNNK 655
Cdd:cd20976    1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAADRSTCEAG-VGELHIQDVLPEDHGTYTCLAKNAA 79

                         90
                 ....*....|.
gi 755504357 656 GSAASTCILTI 666
Cdd:cd20976   80 GQVSCSAWVTV 90

First immunoglobulin-like domains A168 within the A-band segment of human cardiac titin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domain A168 within the A-band segment of human cardiac titin. 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 structures of the titin-A168169 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 755504357 576 APWFKKPLRNTSVVDSEPVRFTVKVTGEPKPEITWWFEGEILQDGEDYQYIER--GETYCLYLPETFPEDGGEYMCKAVN 653
Cdd:cd20971    1 APHFKEELRNLNVRYQSNATLVCKVTGHPKPIVKWYRQGKEIIADGLKYRIQEfkGGYHQLIIASVTDDDATVYQVRATN 80

                 ....*..
gi 755504357 654 NKGSAAS 660
Cdd:cd20971   81 QGGSVSG 87

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755504357  581 KPLRNTSVVDSEPVRFTVKV-TGEPKPEITWWFEGEILQDGEDYQYIERGET-YCLYLPETFPEDGGEYMCKAVNNKGSA 658
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSAsTGSPGPDVTWSKEGGTLIESLKVKHDNGRTTqSSLLISNVTKEDAGTYTCVVNNPGGSA 80

                  ...
gi 755504357  659 AST 661
Cdd:pfam00047  81 TLS 83

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 755504357 586 TSVVDSEPVRFTVKVTGEPKPEITWWFEGEILQDGEDYQYIERGETYCLYLPETFPEDGGEYMCKAVNNKGSAASTCILT 665
Cdd:cd20949    9 TTVKEGQSATILCEVKGEPQPNVTWHFNGQPISASVADMSKYRILADGLLINKVTQDDTGEYTCRAYQVNSIASDMQERT 88

                 .
gi 755504357 666 I 666
Cdd:cd20949   89 V 89

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755504357 577 PWFKKPLRNTSVVDSEP----VRFTVKVTGEPKPEITWWFEGEILQDGEDYQyiERGETYCLYLPETFPEDGGEYMCKAV 652
Cdd:cd05856    1 PRFTQPAKMRRRVIARPvgssVRLKCVASGNPRPDITWLKDNKPLTPPEIGE--NKKKKWTLSLKNLKPEDSGKYTCHVS 78

                 ....*....
gi 755504357 653 NNKGSAAST 661
Cdd:cd05856   79 NRAGEINAT 87

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 755504357 581 KPlRNTSVVDSEPVRFTVKVTGEPKPEITWWFEGEILQDGEDYQYIERGETYCLYLPETFPEDGGEYMCKAVNNKGSAAS 660
Cdd:cd05747    9 KP-RSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQITSTEYKSTFEISKVQMSDEGNYTVVVENSEGKQEA 87

                 ....*
gi 755504357 661 TCILT 665
Cdd:cd05747   88 QFTLT 92

Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor 2 (FGFR2); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain of human fibroblast growth factor receptor 2 (FGFR2). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for FGFs. FGFR2 is required for male sex determination. 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 755504357 585 NTSVVDSEPVRFTVKVTGEPKPEITWWFEGEI-----LQDGEDYQYIERG--------ETYCLYLPETFPEDGGEYMCKA 651
Cdd:cd05858   10 NTSVVVGTDAEFVCKVYSDAQPHIQWLKHVEKngskyGPDGLPYVEVLKTagvnttdkEIEVLYLRNVTFEDAGEYTCLA 89

                         90
                 ....*....|....*
gi 755504357 652 VNNKGSAASTCILTI 666
Cdd:cd05858   90 GNSIGISHHSAWLTV 104

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 755504357 576 APWFKKPLRNTSVVDSEpVRFTVKVTGEPKPEITWWFEG----EI---LQDGEDYQYIERGETY------CLYLPETFPE 642
Cdd:cd20940    1 AGFIKSPLSQQRLVGDS-VELHCEAVGSPIPEIQWWFEGqepnEIcsqLWDGARLDRVHINATYhqhatsTISIDNLTEE 79

                         90
                 ....*....|..
gi 755504357 643 DGGEYMCKAVNN 654
Cdd:cd20940   80 DTGTYECRASND 91

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755504357 581 KPLRNTSVVDSEPVRFTVKVTGEPKPEITWWFEGEILQDGEDYQYIERGetycLYLPETFPEDGGEYMCKAVNNKGSAAS 660
Cdd:cd05725    2 KRPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPKGRYEILDDHS----LKIRKVTAGDMGSYTCVAENMVGKIEA 77

                 ....*.
gi 755504357 661 TCILTI 666
Cdd:cd05725   78 SATLTV 83

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 755504357 601 TGEPKPEITWWFEGEILQDGEDYQY----IERGET--YcLYLPETFPEDGGEYMCKAVNNKGSA 658
Cdd:cd20956   26 SGNPLPQITWTLDGFPIPESPRFRVgdyvTSDGDVvsY-VNISSVRVEDGGEYTCTATNDVGSV 88

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755504357 578 WFKKPlRNTSVVDSEPVRFTVKVTGEPKPEITWWFEGEILQDgEDYQYIERGEtycLYLPETFPEDGGEYMCKAVNNKGS 657
Cdd:cd05728    2 WLKVI-SDTEADIGSSLRWECKASGNPRPAYRWLKNGQPLAS-ENRIEVEAGD---LRITKLSLSDSGMYQCVAENKHGT 76

                 ....*....
gi 755504357 658 AASTCILTI 666
Cdd:cd05728   77 IYASAELAV 85

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; 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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 755504357 594 VRFTVKVTGEPKPEITWWFEG-EILQDGEDYQYIERGETYCLYLPETFPEDGGEYMCKAVNNKGSAAST 661
Cdd:cd05857   22 VKFRCPAAGNPTPTMRWLKNGkEFKQEHRIGGYKVRNQHWSLIMESVVPSDKGNYTCVVENEYGSINHT 90

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); 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, 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, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 755504357 602 GEPKPEITWW-FEGEILQDGEDYQYIERgetyCLYLPETFPEDGGEYMCKAVNNKGSAASTCILTIE 667
Cdd:cd05876   21 GLPTPTVKWLrPSGPLPPDRVKYQNHNK----TLQLLNVGESDDGEYVCLAENSLGSARHAYYVTVE 83

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as 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. 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 755504357 587 SVVDSEPVRFTVKVTGEPKPEITW--WFEGE---ILQDGEDYQYIERGETYCLYLPETFPEDGGEYMCKAVNNKGS 657
Cdd:cd05765   11 TVKVGETASFHCDVTGRPQPEITWekQVPGKenlIMRPNHVRGNVVVTNIGQLVIYNAQPQDAGLYTCTARNSGGL 86

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 755504357 577 PWFKKPLRNTSVVDSEPVRFTVKVTGEPKPEITWWFEGE-ILQDGEDYQYIERGETYCLYLPETFPEDGGEYMCKAVNNK 655
Cdd:cd20990    1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKpIRPDSAHKMLVRENGVHSLIIEPVTSRDAGIYTCIATNRA 80

                         90
                 ....*....|.
gi 755504357 656 GSAASTCILTI 666
Cdd:cd20990   81 GQNSFNLELVV 91

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755504357 578 WFKKPlRNTSVVDSEPVRFTVKVTGEPKPEITWWFEGEILQD-GEDYQYIERGETycLYLPETFPEDGGEYMCKAVNNKG 656
Cdd:cd04978    2 WIIEP-PSLVLSPGETGELICEAEGNPQPTITWRLNGVPIEPaPEDMRRTVDGRT--LIFSNLQPNDTAVYQCNASNVHG 78

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. 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.