Mucin-2 protein WxxW repeating region; This family is repeating region found on mucins 2 and 5. The function is not known, but the repeat can be present in up to 32 copies, as in Swiss:C3Y5K5, from Branchiostoma floridae. The region carries a highly conserved WxxW sequence motif and also has at least six well conserved cysteine residues.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564388576    59 WTSWFNVDHPGGDG--DFESLAAIRFYYgpaRVCPRPLALEAR--TTDWALPAAIGERVHANPERGFWCLNREQPRGrRC 134
Cdd:pfam13330    1 WTPWFDVDNPSGSGggDFETLENLRAYG---KFCENPTDIECRaePPTGVPASETGQVVTCDVTTGLVCRNADQQPD-GC 76

                   ....*....
gi 564388576   135 SNYHVRFRC 143
Cdd:pfam13330   77 LDYEVRFLC 85

Carboxypeptidase regulatory-like domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 564388576   213 GSVVTPSGRPLSGARVSLRTRPGTV---ATSDTHGTFRVPGVCAGSkANVSARMNGFSTGTAQAHANTSNSAV-VTIVL 287
Cdd:pfam13620    4 GTVTDPSGAPVPGATVTVTNTDTGTvrtTTTDADGRYRFPGLPPGT-YTVTVSAPGFKTATRTGVTVTAGQTTtLDVTL 81

Mucin-2 protein WxxW repeating region; This family is repeating region found on mucins 2 and 5. The function is not known, but the repeat can be present in up to 32 copies, as in Swiss:C3Y5K5, from Branchiostoma floridae. The region carries a highly conserved WxxW sequence motif and also has at least six well conserved cysteine residues.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564388576    59 WTSWFNVDHPGGDG--DFESLAAIRFYYgpaRVCPRPLALEAR--TTDWALPAAIGERVHANPERGFWCLNREQPRGrRC 134
Cdd:pfam13330    1 WTPWFDVDNPSGSGggDFETLENLRAYG---KFCENPTDIECRaePPTGVPASETGQVVTCDVTTGLVCRNADQQPD-GC 76

                   ....*....
gi 564388576   135 SNYHVRFRC 143
Cdd:pfam13330   77 LDYEVRFLC 85

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564388576  293 PYLVKHPESRV-REAGQNVTFCCKASGTPMPKkYSWFHNGTLLDRR------QQGSgphLELQGLREEQAGEYHCKAWNE 365
Cdd:cd20978     1 PKFIQKPEKNVvVKGGQDVTLPCQVTGVPQPK-ITWLHNGKPLQGPmeratvEDGT---LTIINVQPEDTGYYGCVATNE 76

                  ....*....
gi 564388576  366 AGTVRSRAA 374
Cdd:cd20978    77 IGDIYTETL 85

Carboxypeptidase regulatory-like domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 564388576   213 GSVVTPSGRPLSGARVSLRTRPGTV---ATSDTHGTFRVPGVCAGSkANVSARMNGFSTGTAQAHANTSNSAV-VTIVL 287
Cdd:pfam13620    4 GTVTDPSGAPVPGATVTVTNTDTGTvrtTTTDADGRYRFPGLPPGT-YTVTVSAPGFKTATRTGVTVTAGQTTtLDVTL 81

Thrombospondin type 1 domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 564388576   158 CSKSCGPGRRLRRRSCQSSS--GDTCPGSPQEAQKCVRSRC 196
Cdd:pfam00090    9 CSVTCGKGIQVRQRTCKSPFpgGEPCTGDDIETQACKMDKC 49

Mucin-2 protein WxxW repeating region; This family is repeating region found on mucins 2 and 5. The function is not known, but the repeat can be present in up to 32 copies, as in Swiss:C3Y5K5, from Branchiostoma floridae. The region carries a highly conserved WxxW sequence motif and also has at least six well conserved cysteine residues.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564388576    59 WTSWFNVDHPGGDG--DFESLAAIRFYYgpaRVCPRPLALEAR--TTDWALPAAIGERVHANPERGFWCLNREQPRGrRC 134
Cdd:pfam13330    1 WTPWFDVDNPSGSGggDFETLENLRAYG---KFCENPTDIECRaePPTGVPASETGQVVTCDVTTGLVCRNADQQPD-GC 76

                   ....*....
gi 564388576   135 SNYHVRFRC 143
Cdd:pfam13330   77 LDYEVRFLC 85

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564388576  293 PYLVKHPESRV-REAGQNVTFCCKASGTPMPKkYSWFHNGTLLDRR------QQGSgphLELQGLREEQAGEYHCKAWNE 365
Cdd:cd20978     1 PKFIQKPEKNVvVKGGQDVTLPCQVTGVPQPK-ITWLHNGKPLQGPmeratvEDGT---LTIINVQPEDTGYYGCVATNE 76

                  ....*....
gi 564388576  366 AGTVRSRAA 374
Cdd:cd20978    77 IGDIYTETL 85

Immunoglobulin I-set domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564388576   293 PYLVKHPESRVREAGQNVTFCCKASGTPMPKkYSWFHNGTLL--DRR----QQGSGPHLELQGLREEQAGEYHCKAWNEA 366
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPE-VSWFKDGQPLrsSDRfkvtYEGGTYTLTISNVQPDDSGKYTCVATNSA 79

                           90
                   ....*....|..
gi 564388576   367 GTVRSRaAHLTV 378
Cdd:pfam07679   80 GEAEAS-AELTV 90

Carboxypeptidase regulatory-like domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 564388576   213 GSVVTPSGRPLSGARVSLRTRPGTV---ATSDTHGTFRVPGVCAGSkANVSARMNGFSTGTAQAHANTSNSAV-VTIVL 287
Cdd:pfam13620    4 GTVTDPSGAPVPGATVTVTNTDTGTvrtTTTDADGRYRFPGLPPGT-YTVTVSAPGFKTATRTGVTVTAGQTTtLDVTL 81

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564388576  293 PYLVKHPESRVREAGQNVTFCCKASGTPMPkKYSWFHNGTLLDRRQQGSGPH-----------LELQGLREEQ--AGEYH 359
Cdd:cd07693     1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTP-TIQWLKNGQPLETDKDDPRSHrivlpsgslffLRVVHGRKGRsdEGVYV 79

                          90
                  ....*....|....*....
gi 564388576  360 CKAWNEAGTVRSRAAHLTV 378
Cdd:cd07693    80 CVAHNSLGEAVSRNASLEV 98

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564388576  293 PYLVKHPESRVREAGQNVTFCCKASGTPMPKkYSWFHNGTLLDRRQ------QGSGPHLELQGLREEQAGEYHCKAWNEA 366
Cdd:cd05736     1 PVIRVYPEFQAKEPGVEASLRCHAEGIPLPR-VQWLKNGMDINPKLskqltlIANGSELHISNVRYEDTGAYTCIAKNEG 79

                  ....
gi 564388576  367 GTVR 370
Cdd:cd05736    80 GVDE 83

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 564388576  303 VREaGQNVTFCCKASGTPMPkKYSWFHNGTLLDRRQQG-----SGPHLELQGLREEQAGEYHCKAWNEA-GTVRSRAA 374
Cdd:cd20970    14 ARE-GENATFMCRAEGSPEP-EISWTRNGNLIIEFNTRyivreNGTTLTIRNIRRSDMGIYLCIASNGVpGSVEKRIT 89

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 564388576  307 GQNVTFCCKASGTPMPKkYSWFHNGTLL----DRRQQGSG-PHLELQGLREEQAGEYHCKAWNEAGTVrSRAAHLTV 378
Cdd:cd20976    16 GQDFVAQCSARGKPVPR-ITWIRNAQPLqyaaDRSTCEAGvGELHIQDVLPEDHGTYTCLAKNAAGQV-SCSAWVTV 90

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 564388576  307 GQNVTFCCKASGTPMPKkYSWFHNGTLL--DRRQQGSGPHLELQGLREEQAGEYHCKAWNEAGTVRSrAAHLTV 378
Cdd:cd05728    14 GSSLRWECKASGNPRPA-YRWLKNGQPLasENRIEVEAGDLRITKLSLSDSGMYQCVAENKHGTIYA-SAELAV 85

Fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains; member of the C2-set IgSF domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains. 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. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), also known as CD66e (Cluster of Differentiation 66e), is a cell surface glycoprotein that plays a role in cell adhesion, intracellular signaling and tumor progression. Diseases associated with CEACAM5 include lung cancer and rectum cancer. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564388576  299 PESRVREAGQNVTFCCKASGTPmPKKYSWFHNGTLldrrqQGSGPHLELQGLREEQAGEYHCKAWNEAGT 368
Cdd:cd20948     2 PSDTYYLSGENLNLSCHAASNP-PAQYSWTINGTF-----QTSSQELFLPAITENNEGTYTCSAHNSLTG 65

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 564388576  293 PYLVKHPESRVREAGQNVTFCCKASGTPMPkKYSWFHNGTLLDRRQQGS--------GPH-LELQGLREEQAGEYHCKAW 363
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDP-EVKWYKNGVPIDPSSIPGkykieseyGVHvLHIRRVTVEDSAVYSAVAK 79

                          90
                  ....*....|.
gi 564388576  364 NEAGTVRSRAA 374
Cdd:cd20951    80 NIHGEASSSAS 90

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 564388576  299 PESRVREAGQNVTFCCKASGTPMpKKYSWFHNGTLL---DRRQQGSGPHLELQGLREEQAGEYHCKAWNEAGTVRSRA 373
Cdd:cd20957     8 PPVQTVDFGRTAVFNCSVTGNPI-HTVLWMKDGKPLghsSRVQILSEDVLVIPSVKREDKGMYQCFVRNDGDSAQATA 84

Thrombospondin type 1 domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 564388576   158 CSKSCGPGRRLRRRSCQSSS--GDTCPGSPQEAQKCVRSRC 196
Cdd:pfam00090    9 CSVTCGKGIQVRQRTCKSPFpgGEPCTGDDIETQACKMDKC 49

Second immunoglobulin (Ig)-like domain of Axl/Tyro3 family receptor tyrosine kinases (RTKs); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in the Axl/Tyro3 family of receptor tyrosine kinases (RTKs). This family includes Axl (also known as Ark, Ufo, and Tyro7), Tyro3 (also known as Sky, Rse, Brt, Dtk, and Tif), and Mer (also known as Nyk, c-Eyk, and Tyro12). Axl/Tyro3 family receptors have an extracellular portion with two Ig-like domains followed by two fibronectin-types III (FNIII) domains, a membrane-spanning single helix, and a cytoplasmic tyrosine kinase domain. Axl, Tyro3, and Mer are widely expressed in adult tissues, though they show higher expression in the brain, lymphatic and vascular systems, and testis. Axl, Tyro3, and Mer bind the vitamin K dependent protein Gas6 with high affinity, and in doing so activate their tyrosine kinase activity. Axl/Gas6 signaling may play a part in cell adhesion processes, prevention of apoptosis, and cell proliferation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564388576  294 YLVKHPESRVREAGQNVTFCCKASGTPMPKKYSWFHNGTLLDRRQQGSGPHLELQGLREEQAgeYHCKAWNEAGTVRSRA 373
Cdd:cd05749     1 HFTVEPEDLAVTANTPFNLTCQAVGPPEPVEILWWQGGSPLGGPPAPSPSVLNVPGLNETTK--FSCEAHNAKGLTSSRT 78

                  ....
gi 564388576  374 AHLT 377
Cdd:cd05749    79 ATVT 82

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564388576  306 AGQNVTFCCKASGTPMpKKYSWFHNGTLL--DRRQQ----GSgphLELQGL-REEQAGEYHCKAWNEAGTVRSRAAHLTV 378
Cdd:cd20958    14 AGQTLRLHCPVAGYPI-SSITWEKDGRRLplNHRQRvfpnGT---LVIENVqRSSDEGEYTCTARNQQGQSASRSVFVKV 89

Fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule); The members here are composed of the fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule). NrCAM belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six IG-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. NrCAM is primarily expressed in the nervous system.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564388576  294 YLVKHPESRVREAGQNVTFCCKASGTPMPkKYSWFHNGTLL-----DRRQQGSGPHLELQGLREEQAGEYHCKAWNEAGT 368
Cdd:cd05868     1 YWITAPTNLVLSPGEDGTLICRANGNPKP-SISWLTNGVPIeiaptDPSRKVDGDTIIFSKVQERSSAVYQCNASNEYGY 79

                  ....*
gi 564388576  369 VRSRA 373
Cdd:cd05868    80 LLANA 84

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564388576  299 PESRVREAGQNVTFCCKASGTPMPKkYSWFHN------GTLLDRRQQGSGPHLELQGLREEQAGEYHCKAWNEAGTVRSR 372
Cdd:cd05738     6 PQLKVVEKARTATMLCAASGNPDPE-ISWFKDflpvdtATSNGRIKQLRSGALQIENSEESDQGKYECVATNSAGTRYSA 84

                  ....*.
gi 564388576  373 AAHLTV 378
Cdd:cd05738    85 PANLYV 90

Sixth immunoglobulin (Ig) domain of contactin; The members here are composed of the sixth 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564388576  298 HPESRVREAGQNVTFCCKASGTP-MPKKYSWFHNGTLLD--------RRQQG--SGPHLELQGLREEQAGEYHCKAWNEA 366
Cdd:cd04970     8 APSNADITVGENATLQCHASHDPtLDLTFTWSFNGVPIDlekieghyRRRYGkdSNGDLEIVNAQLKHAGRYTCTAQTVV 87

                          90
                  ....*....|....*
gi 564388576  367 GTVRSrAAHLTVLAP 381
Cdd:cd04970    88 DSDSA-SATLVVRGP 101

First 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 first 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564388576  294 YLVKHPESRVREAGQNVTFCCKASGTPmPKKYSWFHNGTLL-----DRRQQGSGPHLELQGLREEQA-----GEYHCKAW 363
Cdd:cd05722     3 YFLSEPSDIVAMRGGPVVLNCSAESDP-PPKIEWKKDGVLLnlvsdERRQQLPNGSLLITSVVHSKHnkpdeGFYQCVAQ 81

                          90
                  ....*....|....*.
gi 564388576  364 NEA-GTVRSRAAHLTV 378
Cdd:cd05722    82 NESlGSIVSRTARVTV 97

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564388576  295 LVKHPESRVREAGQNVTFCCKASGTPMPKKYSWFH------------NGTLLDRRQ------QGSGPHLELQGLREEQAG 356
Cdd:cd20940     3 FIKSPLSQQRLVGDSVELHCEAVGSPIPEIQWWFEgqepneicsqlwDGARLDRVHinatyhQHATSTISIDNLTEEDTG 82

                  ....*....
gi 564388576  357 EYHCKAWNE 365
Cdd:cd20940    83 TYECRASND 91

First immunoglobulin (Ig) domain of contactin-5; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-5. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains, anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. In rats, a lack of contactin-5 (NB-2) results in an impairment of the neuronal activity in the auditory system. Contactin-5 is expressed specifically in the postnatal nervous system, peaking at about 3 weeks postnatal. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala; lower levels of expression have been detected in the corpus callosum, caudate nucleus, and spinal cord. This group belongs to the I-set of IgSF domains.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 564388576  308 QNVTFCCKASGTPMPKkYSWFHNGTLLD-----RRQQGSGPHLELQGLREEQAGEYHCKAWNEAGTVRSRAAHL 376
Cdd:cd05848    20 KKVILNCEARGNPVPT-YRWLRNGTEIDtesdyRYSLIDGNLIISNPSEVKDSGRYQCLATNSIGSILSREALL 92

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564388576  292 KPYLVKHPESRVREAGQNVTFCCKASGTPMPKkYSWFHNGTLL---DRRQQGSGP--------HLELQGLREEQAGEYHC 360
Cdd:cd20956     1 APVLLETFSEQTLQPGPSVSLKCVASGNPLPQ-ITWTLDGFPIpesPRFRVGDYVtsdgdvvsYVNISSVRVEDGGEYTC 79

                          90
                  ....*....|....*...
gi 564388576  361 KAWNEAGTVrSRAAHLTV 378
Cdd:cd20956    80 TATNDVGSV-SHSARINV 96

Immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan, also known as HSPG2, and similar proteins. Perlecan consists of five domains: domain I has three putative heparan sulfate attachment sites, domain II has four LDL receptor-like repeats, and one Ig-like repeat, domain III resembles the short arm of laminin chains, domain IV has multiple Ig-like repeats (21 repeats in human perlecan), and domain V resembles the globular G domain of the laminin A chain and internal repeats of EGF. Perlecan may participate in a variety of biological functions including cell binding, LDL-metabolism, basement membrane assembly and selective permeability, calcium binding, and growth- and neurite-promoting activities.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 564388576  307 GQNVTFCCKASGTPMPkKYSWFHN-GTLLDRRQ-----QGSGPHLELQGLREEQAGEYHCKAWNEAGTV 369
Cdd:cd05743     1 GETVEFTCVATGVPTP-IINWRLNwGHVPDSARvsitsEGGYGTLTIRDVKESDQGAYTCEAINTRGMV 68