MAEBL; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568923878   28 KGDVKDKFEAMQRAREERN--------QRRSRDEKQRRKEQYIREREWNRRKQEIKEMlASDDEEESSPKIEKAYVPKLT 99
Cdd:PTZ00121 1273 KAEEARKADELKKAEEKKKadeakkaeEKKKADEAKKKAEEAKKADEAKKKAEEAKKK-ADAAKKKAEEAKKAAEAAKAE 1351

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568923878  100 GTVKGKFDEMEKHRQEEQRKRTEEERKRRIE-QDLLEKRKIQRELAKRAEQEGDDSLLITVVPAKSYKTPGKTKDPEDLD 178
Cdd:PTZ00121 1352 AEAAADEAEAAEEKAEAAEKKKEEAKKKADAaKKKAEEKKKADEAKKKAEEDKKKADELKKAAAAKKKADEAKKKAEEKK 1431

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568923878  179 REEGNGRTNHEEDKM----RYEEECRVLKEAKCLSLVMDDETEAKKESHFPGK---LKSTFEELERQRQENRKKQAEEEA 251
Cdd:PTZ00121 1432 KADEAKKKAEEAKKAdeakKKAEEAKKAEEAKKKAEEAKKADEAKKKAEEAKKadeAKKKAEEAKKKADEAKKAAEAKKK 1511

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568923878  252 RRRLEEERRSFEEARRHMVNEE---DENQDRETVFKEYRPGKLKLSFEEIERQRREDEKRKAEEEARRRIEEEKAAFAEA 328
Cdd:PTZ00121 1512 ADEAKKAEEAKKADEAKKAEEAkkaDEAKKAEEKKKADELKKAEELKKAEEKKKAEEAKKAEEDKNMALRKAEEAKKAEE 1591

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568923878  329 RRSMVLDDDSPEIYKTVSQESLTPGKLEINFEQLlrqKMEEERRRTEEERRHKLEMEKQEFEQLRQE-----MGKEEEEN 403
Cdd:PTZ00121 1592 ARIEEVMKLYEEEKKMKAEEAKKAEEAKIKAEEL---KKAEEEKKKVEQLKKKEAEEKKKAEELKKAeeenkIKAAEEAK 1668

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568923878  404 ESFGLSREYEELIKLKRSGSIQAKNLKSKFE---KIGQLSEKEVQKKIEEERAKRRAIDLEIKEREAENFHEDDDVDVRP 480
Cdd:PTZ00121 1669 KAEEDKKKAEEAKKAEEDEKKAAEALKKEAEeakKAEELKKKEAEEKKKAEELKKAEEENKIKAEEAKKEAEEDKKKAEE 1748

                  ....*
gi 568923878  481 AKKSE 485
Cdd:PTZ00121 1749 AKKDE 1753

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 568923878 563 PWFKKPLRNTSVVDSEPVRFTVKVTGEPKPEITWWFEGEILQ---DGEDYQYIERGETYCLYLPETFPEDGGEYMCKAVN 639
Cdd:cd20951    1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDpssIPGKYKIESEYGVHVLHIRRVTVEDSAVYSAVAKN 80

                         90
                 ....*....|....
gi 568923878 640 NKGSAASTCILTIE 653
Cdd:cd20951   81 IHGEASSSASVVVE 94

MAEBL; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568923878   28 KGDVKDKFEAMQRAREERN--------QRRSRDEKQRRKEQYIREREWNRRKQEIKEMlASDDEEESSPKIEKAYVPKLT 99
Cdd:PTZ00121 1273 KAEEARKADELKKAEEKKKadeakkaeEKKKADEAKKKAEEAKKADEAKKKAEEAKKK-ADAAKKKAEEAKKAAEAAKAE 1351

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568923878  100 GTVKGKFDEMEKHRQEEQRKRTEEERKRRIE-QDLLEKRKIQRELAKRAEQEGDDSLLITVVPAKSYKTPGKTKDPEDLD 178
Cdd:PTZ00121 1352 AEAAADEAEAAEEKAEAAEKKKEEAKKKADAaKKKAEEKKKADEAKKKAEEDKKKADELKKAAAAKKKADEAKKKAEEKK 1431

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568923878  179 REEGNGRTNHEEDKM----RYEEECRVLKEAKCLSLVMDDETEAKKESHFPGK---LKSTFEELERQRQENRKKQAEEEA 251
Cdd:PTZ00121 1432 KADEAKKKAEEAKKAdeakKKAEEAKKAEEAKKKAEEAKKADEAKKKAEEAKKadeAKKKAEEAKKKADEAKKAAEAKKK 1511

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568923878  252 RRRLEEERRSFEEARRHMVNEE---DENQDRETVFKEYRPGKLKLSFEEIERQRREDEKRKAEEEARRRIEEEKAAFAEA 328
Cdd:PTZ00121 1512 ADEAKKAEEAKKADEAKKAEEAkkaDEAKKAEEKKKADELKKAEELKKAEEKKKAEEAKKAEEDKNMALRKAEEAKKAEE 1591

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568923878  329 RRSMVLDDDSPEIYKTVSQESLTPGKLEINFEQLlrqKMEEERRRTEEERRHKLEMEKQEFEQLRQE-----MGKEEEEN 403
Cdd:PTZ00121 1592 ARIEEVMKLYEEEKKMKAEEAKKAEEAKIKAEEL---KKAEEEKKKVEQLKKKEAEEKKKAEELKKAeeenkIKAAEEAK 1668

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568923878  404 ESFGLSREYEELIKLKRSGSIQAKNLKSKFE---KIGQLSEKEVQKKIEEERAKRRAIDLEIKEREAENFHEDDDVDVRP 480
Cdd:PTZ00121 1669 KAEEDKKKAEEAKKAEEDEKKAAEALKKEAEeakKAEELKKKEAEEKKKAEELKKAEEENKIKAEEAKKEAEEDKKKAEE 1748

                  ....*
gi 568923878  481 AKKSE 485
Cdd:PTZ00121 1749 AKKDE 1753

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 568923878 563 PWFKKPLRNTSVVDSEPVRFTVKVTGEPKPEITWWFEGEILQ---DGEDYQYIERGETYCLYLPETFPEDGGEYMCKAVN 639
Cdd:cd20951    1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDpssIPGKYKIESEYGVHVLHIRRVTVEDSAVYSAVAKN 80

                         90
                 ....*....|....
gi 568923878 640 NKGSAASTCILTIE 653
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 568923878 567 KPLRNTSVVDSEPVRFTVKVTGEPKPEITWWFEGEILQDGEDYQYIERGETYC-LYLPETFPEDGGEYMCKAVNNKGSAA 645
Cdd:cd20973    2 QTLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEDGLCsLIISDVCGDDSGKYTCKAVNSLGEAT 81

                 ....*..
gi 568923878 646 STCILTI 652
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 568923878 564 WFKKPLRNTSVVDSEPVRFTVKVTGEPKPEITWWFEGEILQDGEDYQYIERGEtycLYLPETFPEDGGEYMCKAVNNKG 642
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 568923878   570 RNTSVVDSEPVRFTVKVTGEPKPEITWWFEG-EILQDGEDYQYIERGETYCLYLPETFPEDGGEYMCKAVNNKGSAASTC 648
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGT 81

                   ....
gi 568923878   649 ILTI 652
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 568923878 568 PLRNTSVVDSEPVRFTVKVTGEPKPEITWWFEGEILQDG-EDYQYIERGETycLYLPETFPEDGGEYMCKAVNNKGSAAS 646
Cdd:cd20970    8 PSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFnTRYIVRENGTT--LTIRNIRRSDMGIYLCIASNGVPGSVE 85

                 ...
gi 568923878 647 TCI 649
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 568923878 562 APWFKKPLRNTSVVDSEPVRFTVKVTGEPKPEITWWFEGEILQDGEDYQYIERGeTYCLYLPETFPEDGGEYMCKAVNNK 641
Cdd:cd20976    1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAADRSTCEAG-VGELHIQDVLPEDHGTYTCLAKNAA 79

                         90
                 ....*....|.
gi 568923878 642 GSAASTCILTI 652
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 568923878 562 APWFKKPLRNTSVVDSEPVRFTVKVTGEPKPEITWWFEGEILQDGEDYQYIER--GETYCLYLPETFPEDGGEYMCKAVN 639
Cdd:cd20971    1 APHFKEELRNLNVRYQSNATLVCKVTGHPKPIVKWYRQGKEIIADGLKYRIQEfkGGYHQLIIASVTDDDATVYQVRATN 80

                 ....*..
gi 568923878 640 NKGSAAS 646
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 568923878  567 KPLRNTSVVDSEPVRFTVKV-TGEPKPEITWWFEGEILQDGEDYQYIERGET-YCLYLPETFPEDGGEYMCKAVNNKGSA 644
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSAsTGSPGPDVTWSKEGGTLIESLKVKHDNGRTTqSSLLISNVTKEDAGTYTCVVNNPGGSA 80

                  ...
gi 568923878  645 AST 647
Cdd:pfam00047  81 TLS 83

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 568923878 563 PWFKK-PLRNTS-VVDSEPVRFTVKVTGEPKPEITWWFEGEILQDGEDYQYIERGEtycLYLPETFPEDGGEYMCKAVNN 640
Cdd:cd04969    1 PDFELnPVKKKIlAAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICILPDGS---LKIKNVTKSDEGKYTCFAVNF 77

                         90
                 ....*....|..
gi 568923878 641 KGSAASTCILTI 652
Cdd:cd04969   78 FGKANSTGSLSV 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 568923878 563 PWFKKPLRNTSVVDSEP----VRFTVKVTGEPKPEITWWFEGEILQDGEDYQyiERGETYCLYLPETFPEDGGEYMCKAV 638
Cdd:cd05856    1 PRFTQPAKMRRRVIARPvgssVRLKCVASGNPRPDITWLKDNKPLTPPEIGE--NKKKKWTLSLKNLKPEDSGKYTCHVS 78

                 ....*....
gi 568923878 639 NNKGSAAST 647
Cdd:cd05856   79 NRAGEINAT 87

Fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568923878 564 WFKKPlRNTSVVDSEPVRFTVKVTGEPKPEITWWFEG-EILQDGEDYQYIERGETycLYLPETFPEDGGEYMCKAVNNKG 642
Cdd:cd05867    2 WTRRP-QSHLYGPGETARLDCQVEGIPTPNITWSINGaPIEGTDPDPRRHVSSGA--LILTDVQPSDTAVYQCEARNRHG 78

MAEBL; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568923878   25 KLGKGDVKDKFEAMQRAREER---NQRRSRDEKQ----RRKEQYIREREWNRRKQEIKEMLASDDEEESSPKIEKAYVPK 97
Cdd:PTZ00121 1192 ELRKAEDARKAEAARKAEEERkaeEARKAEDAKKaeavKKAEEAKKDAEEAKKAEEERNNEEIRKFEEARMAHFARRQAA 1271

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568923878   98 LTGTVKGKFDEM---EKHRQEEQRKRTEEERKRRIEQDLLEKRKIQRELAKRAEQEGDDS-LLITVVPAKSYKTPGKTKD 173
Cdd:PTZ00121 1272 IKAEEARKADELkkaEEKKKADEAKKAEEKKKADEAKKKAEEAKKADEAKKKAEEAKKKAdAAKKKAEEAKKAAEAAKAE 1351

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568923878  174 PEDLDREEGNGRTNHEEDKMRYEEECRVLKEAKCLSLVMDDETEAKKEShfpgklkstfEELERQRQENRKKQAEEEARR 253
Cdd:PTZ00121 1352 AEAAADEAEAAEEKAEAAEKKKEEAKKKADAAKKKAEEKKKADEAKKKA----------EEDKKKADELKKAAAAKKKAD 1421

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568923878  254 RLEEERRSFEEARRHMVNEEDENQDRETVFKEYRPGKLKLSFEEIERQRREDEKRKAEEEARRRIEEEKAAFAEARRSmv 333
Cdd:PTZ00121 1422 EAKKKAEEKKKADEAKKKAEEAKKADEAKKKAEEAKKAEEAKKKAEEAKKADEAKKKAEEAKKADEAKKKAEEAKKKA-- 1499

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568923878  334 ldddspEIYKTVSQESLTPGKLEINFEQLLRQKMEEERRRTEEERRHKLEmEKQEFEQLR--QEMGKEEEENESFGLSRE 411
Cdd:PTZ00121 1500 ------DEAKKAAEAKKKADEAKKAEEAKKADEAKKAEEAKKADEAKKAE-EKKKADELKkaEELKKAEEKKKAEEAKKA 1572

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568923878  412 YEELIKLKRSGSIQAKNLKSKFEKIGQLSEKEVQKKIEE----ERAKRRAIDLEIKEREAENFHEDDDVDVRPAKKSESP 487
Cdd:PTZ00121 1573 EEDKNMALRKAEEAKKAEEARIEEVMKLYEEEKKMKAEEakkaEEAKIKAEELKKAEEEKKKVEQLKKKEAEEKKKAEEL 1652

                         490       500       510       520
                  ....*....|....*....|....*....|....*....|....*...
gi 568923878  488 FTHKVNMKARFEQMAKAREEEEQRRIEEQKllrMQFEQKEIDAALQKK 535
Cdd:PTZ00121 1653 KKAEEENKIKAAEEAKKAEEDKKKAEEAKK---AEEDEKKAAEALKKE 1697

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 568923878 562 APWFKKPLRNTSVVDSEpVRFTVKVTGEPKPEITWWFEG----EI---LQDGEDYQYIERGETY------CLYLPETFPE 628
Cdd:cd20940    1 AGFIKSPLSQQRLVGDS-VELHCEAVGSPIPEIQWWFEGqepnEIcsqLWDGARLDRVHINATYhqhatsTISIDNLTEE 79

                         90
                 ....*....|..
gi 568923878 629 DGGEYMCKAVNN 640
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 568923878 567 KPLRNTSVVDSEPVRFTVKVTGEPKPEITWWFEGEILQDGEDYQYIERGetycLYLPETFPEDGGEYMCKAVNNKGSAAS 646
Cdd:cd05725    2 KRPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPKGRYEILDDHS----LKIRKVTAGDMGSYTCVAENMVGKIEA 77

                 ....*.
gi 568923878 647 TCILTI 652
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 568923878 587 TGEPKPEITWWFEGEILQDGEDYQY----IERGET--YcLYLPETFPEDGGEYMCKAVNNKGSA 644
Cdd:cd20956   26 SGNPLPQITWTLDGFPIPESPRFRVgdyvTSDGDVvsY-VNISSVRVEDGGEYTCTATNDVGSV 88

Second immunoglobulin (Ig)-like domain of protein tyrosine kinase (PTK) 7; The members here are composed of the second immunoglobulin (Ig)-like domain in protein tyrosine kinase (PTK) 7, also known as CCK4. PTK7 is a subfamily of the receptor protein tyrosine kinase family, and is referred to as an RPTK-like molecule. RPTKs transduce extracellular signals across the cell membrane and play important roles in regulating cell proliferation, migration, and differentiation. PTK7 is organized as an extracellular portion having seven Ig-like domains, a single transmembrane region, and a cytoplasmic tyrosine kinase-like domain. PTK7 is considered a pseudokinase as it has several unusual residues in some of the highly conserved tyrosine kinase (TK) motifs; it is predicted to lack TK activity. PTK7 may function as a cell-adhesion molecule. PTK7 mRNA is expressed at high levels in placenta, melanocytes, liver, lung, pancreas, and kidney. PTK7 is overexpressed in several cancers, including melanoma and colon cancer lines.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568923878 566 KKPLRNTSVVDSEPVRFTVKVTGEPKPEITWWFEGEILQDGEDYQYIERGETyCLYLPETFPEDGGEYMCKAVNNKGSAA 645
Cdd:cd05760    5 KHPASAAEIQPSSRVTLRCHIDGHPRPTYQWFRDGTPLSDGQGNYSVSSKER-TLTLRSAGPDDSGLYYCCAHNAFGSVC 83

                         90
                 ....*....|.
gi 568923878 646 STCILTIEMDD 656
Cdd:cd05760   84 SSQNFTLSIID 94

Immunoglobulin (Ig)-like domain of human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) domains 2, 4, and 6, and similar domains; The members here are composed of the second, fourth, and sixth immunoglobulin (Ig)-like domains in human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) protein subfamily. The CEA family is a group of anchored or secreted glycoproteins expressed by epithelial cells, leukocytes, endothelial cells, and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. This group represents the CEACAM subfamily. CEACAM1 has many important cellular functions; it is a cell adhesion molecule and a signaling molecule that regulates the growth of tumor cells, an angiogenic factor, and a receptor for bacterial and viral pathogens, including mouse hepatitis virus (MHV). In mice, four isoforms of CEACAM1 generated by alternative splicing have either two [D1, D4] or four [D1-D4] Ig-like domains on the cell surface.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568923878 571 NTSVVDSEPVRFTVKVTGePKPEITWWFEGEILQDGEDYQYIERGETycLYLPETFPEDGGEYMCKAVN 639
Cdd:cd05740    9 SNPVEDKDAVTLTCEPET-QNTSYLWWFNGQSLPVTPRLTLSNGNRT--LTLLNVTREDAGAYQCEISN 74

MAEBL; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568923878   23 VPKLGKGDVKDKFEAMQRAREERNQ----RRSRDEKQRRKEQYIREREWNRRKQEIKEmlasddeEESSPKIEKAYVPKL 98
Cdd:PTZ00121 1597 VMKLYEEEKKMKAEEAKKAEEAKIKaeelKKAEEEKKKVEQLKKKEAEEKKKAEELKK-------AEEENKIKAAEEAKK 1669

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568923878   99 TGTVKGKFDEMEKHRQEEQRKRTEEERKRRIEQDLLEKRKIQRELAKRAEQ--EGDDSLLITVVPAKSYKTPGKTKdPED 176
Cdd:PTZ00121 1670 AEEDKKKAEEAKKAEEDEKKAAEALKKEAEEAKKAEELKKKEAEEKKKAEElkKAEEENKIKAEEAKKEAEEDKKK-AEE 1748

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568923878  177 LDREEGNGRTNHEEDKMRYEEECRVLKEAKCLSLVMDDETEAKKESHFPGKLKSTFEELERQRQENRKKQAEEEARRRLE 256
Cdd:PTZ00121 1749 AKKDEEEKKKIAHLKKEEEKKAEEIRKEKEAVIEEELDEEDEKRRMEVDKKIKDIFDNFANIIEGGKEGNLVINDSKEME 1828

                         250       260       270
                  ....*....|....*....|....*....|....
gi 568923878  257 EERRSFEEARRHMVNEEDENQDRETVFKEYRPGK 290
Cdd:PTZ00121 1829 DSAIKEVADSKNMQLEEADAFEKHKFNKNNENGE 1862

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 568923878 573 SVVDSEPVRFTVKVTGEPKPEITW--WFEGE---ILQDGEDYQYIERGETYCLYLPETFPEDGGEYMCKAVNNKGS 643
Cdd:cd05765   11 TVKVGETASFHCDVTGRPQPEITWekQVPGKenlIMRPNHVRGNVVVTNIGQLVIYNAQPQDAGLYTCTARNSGGL 86

Immunoglobulin-like domain of human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin I-set (IgI) domain of the Human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins. APEG-1 is a novel specific smooth muscle differentiation marker predicted to play a role in the growth and differentiation of arterial smooth muscle cells (SMCs). 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 human APEG-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568923878 563 PWFKKPLRNTSVVDSEPVRFTVKVTGEPKPEITWWFEGEILQDGEDYQYIERGETYC-LYLPETFPEDGGEYMCKAVNNK 641
Cdd:cd20975    1 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCrLRILAAERGDAGFYTCKAVNEY 80

                 ..
gi 568923878 642 GS 643
Cdd:cd20975   81 GA 82

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 568923878 564 WFKKPlRNTSVVDSEPVRFTVKVTGEPKPEITWWFEGEILQD-GEDYQYIERGETycLYLPETFPEDGGEYMCKAVNNKG 642
Cdd:cd04978    2 WIIEP-PSLVLSPGETGELICEAEGNPQPTITWRLNGVPIEPaPEDMRRTVDGRT--LIFSNLQPNDTAVYQCNASNVHG 78