NCBI Conserved Domain Search

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.

Pssm-ID: 409460 [Multi-domain] Cd Length: 83 Bit Score: 171.25 E-value: 4.91e-50

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  242 SSSRLVALQGQSLILECIAEGFPTPTIKWLHPSDPMPTDRVIYQNHNKTLQLLNVGEEDDGEYTCLAENSLGSARHAYYV 321
Cdd:cd05876     1 SSSSLVALRGQSLVLECIAEGLPTPTVKWLRPSGPLPPDRVKYQNHNKTLQLLNVGESDDGEYVCLAENSLGSARHAYYV 80


                  ...
gi 569009785  322 TVE 324
Cdd:cd05876    81 TVE 83

Immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains NrCAM [Ng(neuronglia)CAM-related cell adhesion molecule], which is primarily expressed in the nervous system, and human neurofascin. 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 lacks a C" strand.

Pssm-ID: 409396 [Multi-domain] Cd Length: 94 Bit Score: 170.66 E-value: 9.50e-50

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785   30 PVITEQSPRRLVVFPTDDISLKCEARGRPQVEFRWTKDGIHFKPKEELGVVVHEApySGSFTIEGNNSFAQRFQGIYRCY 109
Cdd:cd05733     1 PTITEQSPKDYIVDPRDNITIKCEAKGNPQPTFRWTKDGKFFDPAKDPRVSMRRR--SGTLVIDNHNGGPEDYQGEYQCY 78

                          90
                  ....*....|....*.
gi 569009785  110 ASNKLGTAMSHEIQLV 125
Cdd:cd05733    79 ASNELGTAISNEIRLV 94

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.

Pssm-ID: 409453 [Multi-domain] Cd Length: 89 Bit Score: 164.68 E-value: 1.04e-47

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  328 YWLQKPQSHLYGPGETARLDCQVQGRPQPEITWRINGMSMETVNKDQKYRIEQGSLILSNVQPSDTMVTQCEARNQHGLL 407
Cdd:cd05867     1 YWTRRPQSHLYGPGETARLDCQVEGIPTPNITWSINGAPIEGTDPDPRRHVSSGALILTDVQPSDTAVYQCEARNRHGNL 80


                  ....*....
gi 569009785  408 LANAYIYVV 416
Cdd:cd05867    81 LANAHVHVV 89

Second immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), 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 of the L1 cell adhesion molecule (CAM) and similar proteins. 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 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.

Pssm-ID: 409432 Cd Length: 91 Bit Score: 164.59 E-value: 1.22e-47

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  134 KETVKPVEVEEGESVVLPCNPPPSAAPLRIYWMNSKILHIKQDERVSMGQNGDLYFANVLTSDNHSDYICNAHFPGTRTI 213
Cdd:cd05845     1 KEKIDPVEVEEGDPVVLPCNPPKGAPPPRIYWMNSSLEHITQDERVSMGQNGDLYFSNVMEQDSHPDYICHAHFPGTRTI 80

                          90
                  ....*....|.
gi 569009785  214 IQKEPIDLRVK 224
Cdd:cd05845    81 VQKEPITLKVL 91

Bravo-like intracellular region; This is the very C-terminal intracellular region of neural adhesion molecule L1 proteins that are also known as Bravo or NrCAM. It lies upstream of the IG and Fn3 domains and has the highly conserved motif FIGEY. The function is not known.

Pssm-ID: 464016 Cd Length: 88 Bit Score: 142.46 E-value: 6.27e-40

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  1141 KRSKGGKYSVKDKEDTQVDSEARPMKDETFGEYrsleSDNEEKAFGSSQPSLNGDIKPLGSD--DSLADYGGSVDVQFNE 1218
Cdd:pfam13882    1 KRNKGGKYSVKEKEDAHGDPEDQPMDEDAFGEY----SDLDEKPLKSSQPSLSSDSKLVDSDstDSLDDYGDGDGGQFNE 76

                           90
                   ....*....|..
gi 569009785  1219 DGSFIGQYSGKK 1230
Cdd:pfam13882   77 DGSFIGQYGGKK 88

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.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 116.78 E-value: 6.26e-31

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  328 YWLQKPQSHLYGPGETARLDCQVQGRPQPEITWRINGMSMETVNKDQKYRIEQGSLILSNVQPSDTMVTQCEARNQHGLL 407
Cdd:cd04978     1 YWIIEPPSLVLSPGETGELICEAEGNPQPTITWRLNGVPIEPAPEDMRRTVDGRTLIFSNLQPNDTAVYQCNASNVHGYL 80


                  ....*....
gi 569009785  408 LANAYIYVV 416
Cdd:cd04978    81 LANAFLHVL 89

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 112.12 E-value: 2.27e-29

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  242 SSSRLVALQGQSLILECIAEGFPTPTIKWLHPSDPMPTDRVIYQNHNKTLQLLNVGEEDDGEYTCLAENSLGSARHAYYV 321
Cdd:cd05731     1 SESSTMVLRGGVLLLECIAEGLPTPDIRWIKLGGELPKGRTKFENFNKTLKIENVSEADSGEYQCTASNTMGSARHTISV 80


                  ...
gi 569009785  322 TVE 324
Cdd:cd05731    81 TVE 83

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.

Pssm-ID: 409454 Cd Length: 89 Bit Score: 91.97 E-value: 3.43e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  328 YWLQKPQSHLYGPGETARLDCQVQGRPQPEITWRINGMSMETVNKDQKYRIEQGSLILSNVQPSDTMVTQCEARNQHGLL 407
Cdd:cd05868     1 YWITAPTNLVLSPGEDGTLICRANGNPKPSISWLTNGVPIEIAPTDPSRKVDGDTIIFSKVQERSSAVYQCNASNEYGYL 80


                  ....*....
gi 569009785  408 LANAYIYVV 416
Cdd:cd05868    81 LANAFVNVL 89

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

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 81.77 E-value: 1.32e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  422 ILTKDNQTYMAVEGSTAYLLCKAFGAPVPSVQWLDEEGTTVLQDERFFPYANGTLSIRDLQANDTGRYFCQAANDQNNVT 501
Cdd:cd20952     1 IILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTLENGSLQIKGAEKSDTGEYTCVALNLSGEAT 80


                  ....*..
gi 569009785  502 ILANLQV 508
Cdd:cd20952    81 WSAVLDV 87

Immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-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.

Pssm-ID: 409458 Cd Length: 95 Bit Score: 80.03 E-value: 6.21e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785   30 PVITEQSPRRLVVFPTDDISLKCEARGRPQVEFRWTKDGIHFKPKEELGVVVheAPYSGSFTIE-GNNSFAQRFQGIYRC 108
Cdd:cd05874     1 PTITHQSPKDYIVDPRENIVIQCEAKGKPPPSFSWTRNGTHFDIDKDPKVTM--KPNTGTLVINiMNGEKAEAYEGVYQC 78

                          90
                  ....*....|....
gi 569009785  109 YASNKLGTAMSHEI 122
Cdd:cd05874    79 TARNERGAAVSNNI 92

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 79.85 E-value: 6.58e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  606 PGPVPHLELSDrhlLKQSQVHLSWSPAEDHNSPIEKYDIEFedKEMAPEKWFSLGKVPGNQTSTTLK-LSPYVHYTFRVT 684
Cdd:cd00063     1 PSPPTNLRVTD---VTSTSVTLSWTPPEDDGGPITGYVVEY--REKGSGDWKEVEVTPGSETSYTLTgLKPGTEYEFRVR 75

                          90
                  ....*....|....*....
gi 569009785  685 AINKYGPGEPSPvSETVVT 703
Cdd:cd00063    76 AVNGGGESPPSE-SVTVTT 93

Immunoglobulin (Ig)-like domain of human neurofascin (NF); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of human neurofascin (NF). NF 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 a cytoplasmic domain. NF has many alternatively spliced isoforms having different temporal expression patterns during development. NF participates in axon subcellular targeting and synapse formation, however little is known of the functions of the different isoforms. 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 lacks a C" strand.

Pssm-ID: 409459 Cd Length: 95 Bit Score: 72.70 E-value: 2.32e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785   30 PVITEQSPRRLVVFPTDDISLKCEARGRPQVEFRWTKDGIHFKPKEELGVVVHEApySGSFTIEGNNS-FAQRFQGIYRC 108
Cdd:cd05875     1 PTITKQSAKDYIVDPRDNILIECEAKGNPVPTFHWTRNGKFFNVAKDPRVSMRRR--SGTLVIDFRGGgRPEDYEGEYQC 78

                          90
                  ....*....|....*.
gi 569009785  109 YASNKLGTAMSHEIQL 124
Cdd:cd05875    79 FARNKFGTALSNKIRL 94

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.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 71.68 E-value: 4.99e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  327 PYWLQKPQSHLYGPGETARLDCQVQGRPQPEITWRINGMSMETVNKDQKYRIE--QG--SLILSNVQPSDTMVTQCEARN 402
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSIPGKYKIEseYGvhVLHIRRVTVEDSAVYSAVAKN 80

                          90
                  ....*....|...
gi 569009785  403 QHGLLLANAYIYV 415
Cdd:cd20951    81 IHGEASSSASVVV 93

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 70.67 E-value: 8.00e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785   233 KPRLlfpTNSSSRLVALQGQSLILECIAEGFPTPTIKWLHPSDPMPTDRVIYQNHNK---TLQLLNVGEEDDGEYTCLAE 309
Cdd:pfam13927    1 KPVI---TVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGsnsTLTISNVTRSDAGTYTCVAS 77


                   .
gi 569009785   310 N 310
Cdd:pfam13927   78 N 78

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 70.61 E-value: 8.44e-15

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785    243 SSRLVALQGQSLILECIAEGFPTPTIKWLHPSDPMPTD----RVIYQNHNKTLQLLNVGEEDDGEYTCLAENSLGSARHA 318
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAEsgrfSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSG 80


                    ....*
gi 569009785    319 YYVTV 323
Cdd:smart00410   81 TTLTV 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.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 70.11 E-value: 1.51e-14

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569009785  246 LVALQGQSLILECIAEGFPTPTIKWLHPSDPMPTDRVIYQNHNKTLQLLNVGEEDDGEYTCLAENSLGSARHAYYVTV 323
Cdd:cd20978    11 VVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATVEDGTLTIINVQPEDTGYYGCVATNEIGDIYTETLLHV 88

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 69.84 E-value: 1.70e-14

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785    428 QTYMAVEGSTAYLLCKAFGAPVPSVQWLDEEGTTVLQDERF---FPYANGTLSIRDLQANDTGRYFCQAANDQNNVTILA 504
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFsvsRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGT 81


                    ....
gi 569009785    505 NLQV 508
Cdd:smart00410   82 TLTV 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.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 69.34 E-value: 2.66e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  327 PYWLQKPQSHL-YGPGETARLDCQVQGRPQPEITWRINGMSMETVNkdQKYRIEQGSLILSNVQPSDTMVTQCEARNQHG 405
Cdd:cd20978     1 PKFIQKPEKNVvVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPM--ERATVEDGTLTIINVQPEDTGYYGCVATNEIG 78

                          90
                  ....*....|
gi 569009785  406 LLLANAYIYV 415
Cdd:cd20978    79 DIYTETLLHV 88

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 69.45 E-value: 3.27e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  327 PYWLQKPQSHLYGPGETARLDCQVQGRPQPEITWRINGMSMETVNKDQKYRIEQG--SLILSNVQPSDTMVTQCEARNQH 404
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENGrhSLIIEPVTKRDAGIYTCIARNRA 80

                          90
                  ....*....|.
gi 569009785  405 GLLLANAYIYV 415
Cdd:cd05744    81 GENSFNAELVV 91

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 69.06 E-value: 4.33e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  912 PGHPEALHLECQSDTSLLLHWQPPLSHNGVLTGYLLSYHPVEGESKEQLffNLSDPELRTHNLTNLNPDLQYRFQLQATT 991
Cdd:cd00063     1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGSGDWKEV--EVTPGSETSYTLTGLKPGTEYEFRVRAVN 78


                  ....*.
gi 569009785  992 QQGPGE 997
Cdd:cd00063    79 GGGESP 84

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 68.60 E-value: 5.45e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785   915 PEALHLECQSDTSLLLHWQPPLSHNGVLTGYLLSYHPVEGESKEQLFFNlsDPELRTHNLTNLNPDLQYRFQLQATTQQG 994
Cdd:pfam00041    3 PSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNSGEPWNEITV--PGTTTSVTLTGLKPGTEYEVRVQAVNGGG 80


                   ...
gi 569009785   995 PGE 997
Cdd:pfam00041   81 EGP 83

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 68.60 E-value: 5.67e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785   819 NSSTVLVRWRPVDlaQVKGHLKGYNVTYWWKGSQRkhskrhiHKSHIVVPANTTSAILSGLRPYSSYHVEVQAFNGRGLG 898
Cdd:pfam00041   12 TSTSLTVSWTPPP--DGNGPITGYEVEYRPKNSGE-------PWNEITVPGTTTSVTLTGLKPGTEYEVRVQAVNGGGEG 82


                   ...
gi 569009785   899 PAS 901
Cdd:pfam00041   83 PPS 85

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 68.44 E-value: 6.23e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785   243 SSRLVALQGQSLILECIAEGFPTPTIKWLHPSDPMPTD---RVIYQNHNKTLQLLNVGEEDDGEYTCLAENSLGSARHAY 319
Cdd:pfam07679    7 PKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSdrfKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAGEAEASA 86


                   ....
gi 569009785   320 YVTV 323
Cdd:pfam07679   87 ELTV 90

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

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 67.14 E-value: 1.58e-13

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 569009785  250 QGQSLILECIAEGFPTPTIKWLHPSDPMPT-DRVIYQNHNKTLQLLNVGEEDDGEYTCLAENSLGSARHAYYVTV 323
Cdd:cd20952    13 VGGTVVLNCQATGEPVPTISWLKDGVPLLGkDERITTLENGSLQIKGAEKSDTGEYTCVALNLSGEATWSAVLDV 87

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 66.67 E-value: 2.01e-13

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 569009785   623 SQVHLSWSPAEDHNSPIEKYDIEFEDK-EMAPEKWFSlgkVPGNQTSTTLK-LSPYVHYTFRVTAINKYGPGEPS 695
Cdd:pfam00041   14 TSLTVSWTPPPDGNGPITGYEVEYRPKnSGEPWNEIT---VPGTTTSVTLTgLKPGTEYEVRVQAVNGGGEGPPS 85

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 143259 Cd Length: 88 Bit Score: 66.20 E-value: 3.81e-13

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 569009785  248 ALQGQSLILECIAEGFPTPTIKWLHPSDPMPTDRVIYQNhNKTLQLLNVGEEDDGEYTCLAENSLGSARHAYYVTVE 324
Cdd:cd05851    13 ALKGQNVTLECFALGNPVPVIRWRKILEPMPATAEISMS-GAVLKIFNIQPEDEGTYECEAENIKGKDKHQARVYVQ 88

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.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 65.88 E-value: 4.09e-13

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 569009785  244 SRLVALQGQSLILECIAEGFPTPTIKWLHPSDPMPTDRViYQNHNKTLQLLNVGEEDDGEYTCLAENSLGSA 315
Cdd:cd05725     5 QNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPKGRY-EILDDHSLKIRKVTAGDMGSYTCVAENMVGKI 75

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

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 65.43 E-value: 4.27e-13

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569009785  254 LILECIAEGFPTPTIKWLHPSDPMPTD---RVIYQNHNKTLQLLNVGEEDDGEYTCLAENSLGSARHA 318
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSsrdSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASA 68

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 65.99 E-value: 4.59e-13

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785    333 PQSHLYGPGETARLDCQVQGRPQPEITWRINGmsMETVNKDQKYRIE----QGSLILSNVQPSDTMVTQCEARNQHGLLL 408
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQG--GKLLAESGRFSVSrsgsTSTLTISNVTPEDSGTYTCAATNSSGSAS 78


                    ....*..
gi 569009785    409 ANAYIYV 415
Cdd:smart00410   79 SGTTLTV 85

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.

Pssm-ID: 409359 Cd Length: 102 Bit Score: 66.03 E-value: 5.59e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  510 EATQITQGPRSAIEKKGARVTFTCQASFDPSLQASITWRGDGR--DLQERGDSDK--YFIED-GKLVIQSLDYSDQGNYS 584
Cdd:cd04970     1 DATRITLAPSNADITVGENATLQCHASHDPTLDLTFTWSFNGVpiDLEKIEGHYRrrYGKDSnGDLEIVNAQLKHAGRYT 80

                          90       100
                  ....*....|....*....|..
gi 569009785  585 CVASTELDEVESRAQLLVVGSP 606
Cdd:cd04970    81 CTAQTVVDSDSASATLVVRGPP 102

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.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 65.11 E-value: 7.82e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  514 ITQGPRSAIEKKGA-RVTFTCQASFDPslQASITWRGDGRDLQerGDSDKYFIEDGKLVIQSLDYSDQGNYSCVASTELD 592
Cdd:cd20978     3 FIQKPEKNVVVKGGqDVTLPCQVTGVP--QPKITWLHNGKPLQ--GPMERATVEDGTLTIINVQPEDTGYYGCVATNEIG 78

                          90
                  ....*....|
gi 569009785  593 EVESRAQLLV 602
Cdd:cd20978    79 DIYTETLLHV 88

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 64.89 E-value: 9.43e-13

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 569009785   332 KPQSHLYGPGETARLDCQVQGRPQPEITWRINGMSMETVNKDQKYR-IEQGSLILSNVQPSDTMVTQCEARN 402
Cdd:pfam13927    7 SPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLsGSNSTLTISNVTRSDAGTYTCVASN 78

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third 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. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 64.88 E-value: 1.05e-12

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 569009785  248 ALQGQSLILECIAEGFPTPTIKWlHPSDPMPTDRVIYQNHNKTLQLLNVGEEDDGEYTCLAENSLGSARHAYYVTV 323
Cdd:cd04968    13 ALKGQTVTLECFALGNPVPQIKW-RKVDGSPSSQWEITTSEPVLEIPNVQFEDEGTYECEAENSRGKDTVQGRIIV 87

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 64.17 E-value: 1.90e-12

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785    912 PGHPEALHLECQSDTSLLLHWQPPLSHNGvlTGYLLSYHPVEGESKEQLFFNLSDPELRTHNLTNLNPDLQYRFQLQATT 991
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGI--TGYIVGYRVEYREEGSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVN 78


                    ....*
gi 569009785    992 QQGPG 996
Cdd:smart00060   79 GAGEG 83

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 64.20 E-value: 2.25e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785   327 PYWLQKPQSHLYGPGETARLDCQVQGRPQPEITWRINGmsmETVNKDQKYRIEQ----GSLILSNVQPSDTMVTQCEARN 402
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDG---QPLRSSDRFKVTYeggtYTLTISNVQPDDSGKYTCVATN 77


                   ...
gi 569009785   403 QHG 405
Cdd:pfam07679   78 SAG 80

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 64.16 E-value: 2.51e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  234 PRLLFPTNSSSRLVAL-QGQSLILECIAEGFPTPTIKWLHPSDP-MPTDRV-IYQNHNK--TLQLLNVGEEDDGEYTCLA 308
Cdd:cd05729     1 PRFTDTEKMEEREHALpAANKVRLECGAGGNPMPNITWLKDGKEfKKEHRIgGTKVEEKgwSLIIERAIPRDKGKYTCIV 80

                          90
                  ....*....|....*
gi 569009785  309 ENSLGSARHAYYVTV 323
Cdd:cd05729    81 ENEYGSINHTYDVDV 95

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. 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 Lingo-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.

Pssm-ID: 409561 Cd Length: 92 Bit Score: 63.56 E-value: 4.23e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  419 PARILTKDNQTYMAVEGSTAYLLCKAFGAPVPSVQWLD--EEGTTVLQDERFFPYANGTLSIRDLQANDTGRYFCQAAND 496
Cdd:cd20969     1 RAAIRDRKAQQVFVDEGHTVQFVCRADGDPPPAILWLSprKHLVSAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAANA 80

                          90
                  ....*....|..
gi 569009785  497 QNNVTILANLQV 508
Cdd:cd20969    81 GGNDSMPAHLHV 92

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 62.43 E-value: 6.23e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785   712 PVDVRGEGNETNNMVITWKPLRwmDWNAPQIQYRVQWRPQGKQETWREQTVSDP--FLVVSNTSTFVPYEIKVQAVNNQG 789
Cdd:pfam00041    3 PSNLTVTDVTSTSLTVSWTPPP--DGNGPITGYEVEYRPKNSGEPWNEITVPGTttSVTLTGLKPGTEYEVRVQAVNGGG 80


                   ....
gi 569009785   790 KGPE 793
Cdd:pfam00041   81 EGPP 84

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 61.81 E-value: 9.44e-12

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 569009785   423 LTKDNQTYMAVEGSTAYLLCKAFGAPVPSVQWL--DEEGTTVLQDERFFPYANGTLSIRDLQANDTGRYFCQAAN 495
Cdd:pfam13927    4 ITVSPSSVTVREGETVTLTCEATGSPPPTITWYknGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

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.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 61.85 E-value: 1.05e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  329 WLQKPQSHLYGPGETARLDCQVQGRPQPEITWRINGmsmETVNKDQKYRIEQGSLILSNVQPSDTMVTQCEARNQHGLLL 408
Cdd:cd05728     2 WLKVISDTEADIGSSLRWECKASGNPRPAYRWLKNG---QPLASENRIEVEAGDLRITKLSLSDSGMYQCVAENKHGTIY 78


                  ....*..
gi 569009785  409 ANAYIYV 415
Cdd:cd05728    79 ASAELAV 85

Sixth immunoglobulin (Ig) domain of contactin-2; The members here are composed of the sixth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. 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. 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-2 is also expressed in retinal amacrine cells (AC) in the developing chick retina, corresponding to the period of formation and maturation of AC processes.

Pssm-ID: 409440 Cd Length: 102 Bit Score: 61.98 E-value: 1.59e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  510 EATQITQGPRSAIEKKGARVTFTCQASFDPSLQASITWRGDG--RDLQE-----RGDSDKYFIedGKLVIQSLDYSDQGN 582
Cdd:cd05854     1 DATKITLAPSSADINQGENLTLQCHASHDPTMDLTFTWSLDDfpIDLDKpnghyRRMEVKETI--GDLVIVNAQLSHAGT 78

                          90       100
                  ....*....|....*....|....
gi 569009785  583 YSCVASTELDEVESRAQLLVVGSP 606
Cdd:cd05854    79 YTCTAQTVVDSASASATLVVRGPP 102

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 61.36 E-value: 2.39e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  815 ITIFNSSTVLVRWRPVDLAQvkGHLKGYNVTYWWKGSQRkhskrhiHKSHIVVPANTTSAILSGLRPYSSYHVEVQAFNG 894
Cdd:cd00063     9 VTDVTSTSVTLSWTPPEDDG--GPITGYVVEYREKGSGD-------WKEVEVTPGSETSYTLTGLKPGTEYEFRVRAVNG 79

                          90
                  ....*....|....
gi 569009785  895 RGLGPASEW-TFST 907
Cdd:cd00063    80 GGESPPSESvTVTT 93

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 67.72 E-value: 3.08e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  623 SQVHLSWSPAEdhNSPIEKYDIefEDKEMAPEKWFSLGKVPGNQ-TSTTLKLSpyVHYTFRVTAINKYgpGEPSPVSETV 701
Cdd:COG3401   247 GSVTLSWDPVT--ESDATGYRV--YRSNSGDGPFTKVATVTTTSyTDTGLTNG--TTYYYRVTAVDAA--GNESAPSNVV 318

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  702 -VTPEAAPEKNPVDVRGEGNETNNMVITWKPLrwMDWNApqIQYRVqWRPQGKQETWRE--QTVSDPFLVVSNTSTFVPY 778
Cdd:COG3401   319 sVTTDLTPPAAPSGLTATAVGSSSITLSWTAS--SDADV--TGYNV-YRSTSGGGTYTKiaETVTTTSYTDTGLTPGTTY 393

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 569009785  779 EIKVQAVNNQGKGPEP-QVTIGYSGEDYPQVSPELEDITIFNSSTVLVRWRPVD 831
Cdd:COG3401   394 YYKVTAVDAAGNESAPsEEVSATTASAASGESLTASVDAVPLTDVAGATAAASA 447

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.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 60.60 E-value: 3.44e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  242 SSSRLVALQGQSLILECIAEGFPTPTIKWLHPSDPMPT--DRVIYQNHNKTLQLLNVGEEDDGEYTCLAENSL-GSARHA 318
Cdd:cd20970     8 PSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEfnTRYIVRENGTTLTIRNIRRSDMGIYLCIASNGVpGSVEKR 87


                  ....*
gi 569009785  319 YYVTV 323
Cdd:cd20970    88 ITLQV 92

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 60.73 E-value: 3.58e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785   513 QITQGPRSAIEKKGARVTFTCQASFDPSLQasITWRGDGRDLQErgdSDKYFI----EDGKLVIQSLDYSDQGNYSCVAS 588
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTGTPDPE--VSWFKDGQPLRS---SDRFKVtyegGTYTLTISNVQPDDSGKYTCVAT 76

                           90
                   ....*....|....
gi 569009785   589 TELDEVESRAQLLV 602
Cdd:pfam07679   77 NSAGEAEASAELTV 90

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 60.27 E-value: 3.60e-11

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 569009785   513 QITQGPRSAIEKKGARVTFTCQASFDPslQASITWRGDGRDLQERGDSDKYFIED-GKLVIQSLDYSDQGNYSCVAS 588
Cdd:pfam13927    3 VITVSPSSVTVREGETVTLTCEATGSP--PPTITWYKNGEPISSGSTRSRSLSGSnSTLTISNVTRSDAGTYTCVAS 77

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 60.33 E-value: 4.93e-11

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 569009785  251 GQSLILECIAEGFPTPTIKWLHPSDPMPT--DRVIYQNHNKTLQLLNVGEEDDGEYTCLAENSLGSA 315
Cdd:cd05730    18 GQSVTLACDADGFPEPTMTWTKDGEPIESgeEKYSFNEDGSEMTILDVDKLDEAEYTCIAENKAGEQ 84

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 66.56 E-value: 6.89e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  658 SLGKVPGNQTSTTLKLSPYVHYTFRVTAINKYGPGEPSPVSEtVVTPEAAPEKnPVDVRGEGNETNNMVITWKPLRWMDW 737
Cdd:COG3401   184 SLTVTSTTLVDGGGDIEPGTTYYYRVAATDTGGESAPSNEVS-VTTPTTPPSA-PTGLTATADTPGSVTLSWDPVTESDA 261

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  738 NApqiqYRVQWRPQGkQETWREqtvsdpfLVVSNTSTFV--------PYEIKVQAVNNQGKGPEPQVTIGYSGEDYPQVS 809
Cdd:COG3401   262 TG----YRVYRSNSG-DGPFTK-------VATVTTTSYTdtgltngtTYYYRVTAVDAAGNESAPSNVVSVTTDLTPPAA 329

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  810 PELEDITIFNSSTVLVRWRPVDLAQVkghlKGYNVtYWWKGSQRKHSKrhihkshIVVPANTTSAILSGLRPYSSYHVEV 889
Cdd:COG3401   330 PSGLTATAVGSSSITLSWTASSDADV----TGYNV-YRSTSGGGTYTK-------IAETVTTTSYTDTGLTPGTTYYYKV 397

                         250       260
                  ....*....|....*....|....*..
gi 569009785  890 QAFNGRGL-GPASEWTFSTPEGVPGHP 915
Cdd:COG3401   398 TAVDAAGNeSAPSEEVSATTASAASGE 424

Seventh 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 seventh 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.

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 59.63 E-value: 1.04e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  234 PR-LLFPTNSSsrlvALQGQSLILECIAEGFPTPTIKW--LHPSDPMPTDRVIYQNH-----NKTLQLLNVGEEDDGEYT 305
Cdd:cd20954     2 PRwIVEPVDAN----VAAGQDVMLHCQADGFPTPTVTWkkATGSTPGEYKDLLYDPNvrilpNGTLVFGHVQKENEGHYL 77


                  ....*....
gi 569009785  306 CLAENSLGS 314
Cdd:cd20954    78 CEAKNGIGS 86

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (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.

Pssm-ID: 409421 [Multi-domain] Cd Length: 88 Bit Score: 58.64 E-value: 1.77e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569009785  422 ILTKDNQTYMAVEGSTAYLLCKAFGAPVPSVQWLDEEGTTVLQDERFFPYANGTLSIRDLQANDTGRYFCQAAN 495
Cdd:cd05764     2 LITRHTHELRVLEGQRATLRCKARGDPEPAIHWISPEGKLISNSSRTLVYDNGTLDILITTVKDTGAFTCIASN 75

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 58.42 E-value: 1.86e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785   432 AVEGSTAYLLCKAFGAPVPSVQWLdEEGTTVLQDERF---FPYANGTLSIRDLQANDTGRYFCQAANDQNNVTILANLQV 508
Cdd:pfam07679   12 VQEGESARFTCTVTGTPDPEVSWF-KDGQPLRSSDRFkvtYEGGTYTLTISNVQPDDSGKYTCVATNSAGEAEASAELTV 90

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.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 58.81 E-value: 1.97e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 569009785  333 PQSHLYGPGETARLDCQVQGRPQPEITWRINGMSMETVNKDQKYRIEQGS-LILSNVQPSDTMVTQCEARNQHGL 406
Cdd:cd05736     7 PEFQAKEPGVEASLRCHAEGIPLPRVQWLKNGMDINPKLSKQLTLIANGSeLHISNVRYEDTGAYTCIAKNEGGV 81

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 57.96 E-value: 2.05e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785    29 PPVITeQSPRRLVVFPTDDISLKCEARGRPQVEFRWTKDGIHFKPKEELGVVVHEapYSGSFTIegnNSFAQRFQGIYRC 108
Cdd:pfam13927    1 KPVIT-VSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSG--SNSTLTI---SNVTRSDAGTYTC 74


                   ....
gi 569009785   109 YASN 112
Cdd:pfam13927   75 VASN 78

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 57.62 E-value: 2.98e-10

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785    606 PGPVPHLELSDRHllkQSQVHLSWSPAEDHN--SPIEKYDIEFEDKEmapEKWFSLgKVPGNQTSTTLK-LSPYVHYTFR 682
Cdd:smart00060    1 PSPPSNLRVTDVT---STSVTLSWEPPPDDGitGYIVGYRVEYREEG---SEWKEV-NVTPSSTSYTLTgLKPGTEYEFR 73

                            90
                    ....*....|
gi 569009785    683 VTAINKYGPG 692
Cdd:smart00060   74 VRAVNGAGEG 83

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.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 58.03 E-value: 3.10e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  238 FPTNsssrLVALQGQSLILECIAEGFPTPTIKWLHPSDPM--PTDRVIYQNHNKTLQLLNVGEEDDGEYTCLAENSLGSA 315
Cdd:cd20976     7 VPKD----LEAVEGQDFVAQCSARGKPVPRITWIRNAQPLqyAADRSTCEAGVGELHIQDVLPEDHGTYTCLAKNAAGQV 82


                  ....*...
gi 569009785  316 RHAYYVTV 323
Cdd:cd20976    83 SCSAWVTV 90

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.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 57.95 E-value: 4.02e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  234 PRLlfpTNSSSRLVALQGQSLILECIAEGFPTPTIKWLHPSDPMPTDRVIYQNH-----NKTLQLLNV-----GEEDDGE 303
Cdd:cd07693     1 PRI---VEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLETDKDDPRSHrivlpSGSLFFLRVvhgrkGRSDEGV 77

                          90
                  ....*....|...
gi 569009785  304 YTCLAENSLGSAR 316
Cdd:cd07693    78 YVCVAHNSLGEAV 90

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (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.

Pssm-ID: 409421 [Multi-domain] Cd Length: 88 Bit Score: 56.72 E-value: 8.69e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569009785  240 TNSSSRLVALQGQSLILECIAEGFPTPTIKWLHPSDPM--PTDRVIYQNhNKTLQLLNVGEEDDGEYTCLAENSLGSA 315
Cdd:cd05764     4 TRHTHELRVLEGQRATLRCKARGDPEPAIHWISPEGKLisNSSRTLVYD-NGTLDILITTVKDTGAFTCIASNPAGEA 80

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

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 55.80 E-value: 1.06e-09

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 569009785  438 AYLLCKAFGAPVPSVQWL--DEEGTTVLQDERFFPYANGTLSIRDLQANDTGRYFCQAAND 496
Cdd:cd00096     1 VTLTCSASGNPPPTITWYknGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNS 61

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.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 56.41 E-value: 1.10e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 569009785  251 GQSLILECIAEGFPTPTIKWLHPSDPMP-TDRVIY----QNHNKTLQLLNVGE---EDDGEYTCLAENSLGSARHA 318
Cdd:cd20956    16 GPSVSLKCVASGNPLPQITWTLDGFPIPeSPRFRVgdyvTSDGDVVSYVNISSvrvEDGGEYTCTATNDVGSVSHS 91

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 55.71 E-value: 1.42e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569009785  250 QGQSLILECIAEGFPTPTIKWLHPSDPMPTDRVIYQNHNKTLQLLNVGEEDDGEYTCLAENSLGSARHAYYVTV 323
Cdd:cd05745     1 EGQTVDFLCEAQGYPQPVIAWTKGGSQLSVDRRHLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

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

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 55.41 E-value: 1.42e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  529 VTFTCQASFDPslQASITWRGDGRDLQERGDSDKYFIE-DGKLVIQSLDYSDQGNYSCVASTELDEVESR 597
Cdd:cd00096     1 VTLTCSASGNP--PPTITWYKNGKPLPPSSRDSRRSELgNGTLTISNVTLEDSGTYTCVASNSAGGSASA 68

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 55.59 E-value: 1.77e-09

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785    518 PRSAIEKKGARVTFTCQASFDPSLQasITWRGDGrdLQERGDSDKYFIE----DGKLVIQSLDYSDQGNYSCVASTELDE 593
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPE--VTWYKQG--GKLLAESGRFSVSrsgsTSTLTISNVTPEDSGTYTCAATNSSGS 76


                    ....*....
gi 569009785    594 VESRAQLLV 602
Cdd:smart00410   77 ASSGTTLTV 85

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 55.31 E-value: 2.38e-09

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785    819 NSSTVLVRWRPVDLAQVKGHLKGYNVTYWWKGSQRKHskrhihkshIVVPANTTSAILSGLRPYSSYHVEVQAFNGRGLG 898
Cdd:smart00060   13 TSTSVTLSWEPPPDDGITGYIVGYRVEYREEGSEWKE---------VNVTPSSTSYTLTGLKPGTEYEFRVRAVNGAGEG 83

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 55.58 E-value: 2.60e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  711 NPVDVRGEGNETNNMVITWKPLRwmDWNAPQIQYRVQWRPQGKQE--TWREQTVSDPFLVVSNTSTFVPYEIKVQAVNNQ 788
Cdd:cd00063     3 PPTNLRVTDVTSTSVTLSWTPPE--DDGGPITGYVVEYREKGSGDwkEVEVTPGSETSYTLTGLKPGTEYEFRVRAVNGG 80


                  ....
gi 569009785  789 GKGP 792
Cdd:cd00063    81 GESP 84

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

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 55.20 E-value: 2.85e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  330 LQKPQSHLYGPGETARLDCQVQGRPQPEITWRINGMSMETvnKDQKYRI-EQGSLILSNVQPSDTMVTQCEARNQHGLLL 408
Cdd:cd20952     3 LQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLG--KDERITTlENGSLQIKGAEKSDTGEYTCVALNLSGEAT 80


                  ....*..
gi 569009785  409 ANAYIYV 415
Cdd:cd20952    81 WSAVLDV 87

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.

Pssm-ID: 409443 [Multi-domain] Cd Length: 95 Bit Score: 55.24 E-value: 2.98e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  234 PRLLFPTNSSSRLVAL-QGQSLILECIAEGFPTPTIKWLHPSDPMPTDRVI----YQNHNKTLQLLNVGEEDDGEYTCLA 308
Cdd:cd05857     1 PYWTNPEKMEKKLHAVpAANTVKFRCPAAGNPTPTMRWLKNGKEFKQEHRIggykVRNQHWSLIMESVVPSDKGNYTCVV 80

                          90
                  ....*....|....*
gi 569009785  309 ENSLGSARHAYYVTV 323
Cdd:cd05857    81 ENEYGSINHTYHLDV 95

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.

Pssm-ID: 409442 Cd Length: 92 Bit Score: 55.25 E-value: 2.99e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  234 PRLLFPTNSSSRLVALQ-GQSLILECIAEGFPTPTIKWLHPSDPMpTDRVIYQNHNK--TLQLLNVGEEDDGEYTCLAEN 310
Cdd:cd05856     1 PRFTQPAKMRRRVIARPvGSSVRLKCVASGNPRPDITWLKDNKPL-TPPEIGENKKKkwTLSLKNLKPEDSGKYTCHVSN 79

                          90
                  ....*....|...
gi 569009785  311 SLGSARHAYYVTV 323
Cdd:cd05856    80 RAGEINATYKVDV 92

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 54.96 E-value: 3.06e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785    30 PVITeQSPRRLVVFPTDDISLKCEARGRPQVEFRWTKDGIHFKPKEElgVVVHEAPYSGSFTIEGnnsfAQRFQ-GIYRC 108
Cdd:pfam07679    1 PKFT-QKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDR--FKVTYEGGTYTLTISN----VQPDDsGKYTC 73

                           90
                   ....*....|....*.
gi 569009785   109 YASNKLGTAmSHEIQL 124
Cdd:pfam07679   74 VATNSAGEA-EASAEL 88

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.

Pssm-ID: 409388 Cd Length: 84 Bit Score: 54.89 E-value: 3.11e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  241 NSSSRLVALQGQSLILECIAEGFPTPTIKWLHPSDP-MPTDRV-IYQNHNktLQLLNVGEEDDGEYTCLAENSLGSARHA 318
Cdd:cd05723     2 KKPSNIYAHESMDIVFECEVTGKPTPTVKWVKNGDVvIPSDYFkIVKEHN--LQVLGLVKSDEGFYQCIAENDVGNAQAS 79

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. 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. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 54.93 E-value: 3.61e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569009785  341 GETARLDCQVQGRPQPEITWRINGMSMETVNKDQKYRI--EQGSLILSNVQPSDTMVTQCEARNQHGLLLANAYIYVV 416
Cdd:cd05763    14 GSTARLECAATGHPTPQIAWQKDGGTDFPAARERRMHVmpEDDVFFIVDVKIEDTGVYSCTAQNSAGSISANATLTVL 91

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.

Pssm-ID: 143220 Cd Length: 78 Bit Score: 54.03 E-value: 5.63e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 569009785  341 GETARLDCQVQGRPQPEITWRIN-GMSMETVNKDQKYRIEQGSLILSNVQPSDTMVTQCEARNQHGLLLAN 410
Cdd:cd05743     1 GETVEFTCVATGVPTPIINWRLNwGHVPDSARVSITSEGGYGTLTIRDVKESDQGAYTCEAINTRGMVFGI 71

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.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 54.00 E-value: 8.11e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 569009785  247 VALQGQSLILECIAEGFPTPTIKWLHPSDPMPTDRVIYQNHNKTLQLLNVGEEDDGEYTCLAENSLGSARHAYYVTV 323
Cdd:cd04969    13 LAAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89

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

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 53.10 E-value: 9.01e-09

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569009785  344 ARLDCQVQGRPQPEITWRINGMSMETVNKDQKYRIE-QGSLILSNVQPSDT-MVTqCEARNQHG 405
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELgNGTLTISNVTLEDSgTYT-CVASNSAG 63

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 53.56 E-value: 1.06e-08

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 569009785  341 GETARLDCQV-QGRPQPEITWRINGMSMETVNKdqKYRI-EQGSLILSNVQPSDTMVTQCEARNQHG 405
Cdd:cd05724    12 GEMAVLECSPpRGHPEPTVSWRKDGQPLNLDNE--RVRIvDDGNLLIAEARKSDEGTYKCVATNMVG 76

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

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 53.27 E-value: 1.44e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  514 ITQGPRSAIEKKGARVTFTCQASFDPSlqASITWRGDGRdlQERGDSDKYFI-EDGKLVIQSLDYSDQGNYSCVASTELD 592
Cdd:cd20952     2 ILQGPQNQTVAVGGTVVLNCQATGEPV--PTISWLKDGV--PLLGKDERITTlENGSLQIKGAEKSDTGEYTCVALNLSG 77

                          90
                  ....*....|
gi 569009785  593 EVESRAQLLV 602
Cdd:cd20952    78 EATWSAVLDV 87

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 53.17 E-value: 1.57e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 569009785  545 ITWRGDGRDLQERgDSDKYFIEDGKLVIQSLDYSDQGNYSCVASTELDEVESRAQLLVV 603
Cdd:cd05724    30 VSWRKDGQPLNLD-NERVRIVDDGNLLIAEARKSDEGTYKCVATNMVGERESRAARLSV 87

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.

Pssm-ID: 409540 Cd Length: 76 Bit Score: 52.50 E-value: 1.62e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 569009785  242 SSSRLVALQGQSLILECIAEGFPTPTIKWlhpsdpmpTDRVIYQNHNKTLQLLNVGEEDDGEYTCLAENSLGS 314
Cdd:cd20948     1 SPSDTYYLSGENLNLSCHAASNPPAQYSW--------TINGTFQTSSQELFLPAITENNEGTYTCSAHNSLTG 65

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 53.00 E-value: 1.68e-08

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785    711 NPVDVRGEGNETNNMVITWKPLRWMDWNAPQIQYRVQWRPQGKQetWREQTV--SDPFLVVSNTSTFVPYEIKVQAVNNQ 788
Cdd:smart00060    3 PPSNLRVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEYREEGSE--WKEVNVtpSSTSYTLTGLKPGTEYEFRVRAVNGA 80


                    ...
gi 569009785    789 GKG 791
Cdd:smart00060   81 GEG 83

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.

Pssm-ID: 409387 Cd Length: 97 Bit Score: 53.25 E-value: 1.76e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  518 PRSAIEKKGARVTFTCQASFDPSlqASITWRGDGRDLQERGDSDKYFIEDGKLVIQSL-----DYSDQGNYSCVASTE-L 591
Cdd:cd05722     8 PSDIVAMRGGPVVLNCSAESDPP--PKIEWKKDGVLLNLVSDERRQQLPNGSLLITSVvhskhNKPDEGFYQCVAQNEsL 85

                          90
                  ....*....|..
gi 569009785  592 DEVESR-AQLLV 602
Cdd:cd05722    86 GSIVSRtARVTV 97

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.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 52.95 E-value: 1.89e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  246 LVALQGQSLILECIAEGFPTPTIKWLHPSDPMPTDRVIYQNHNKTLQLLNV-GEEDDGEYTCLAENSLG-SARHAYYVTV 323
Cdd:cd20958    10 LTAVAGQTLRLHCPVAGYPISSITWEKDGRRLPLNHRQRVFPNGTLVIENVqRSSDEGEYTCTARNQQGqSASRSVFVKV 89

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 53.01 E-value: 1.92e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  239 PTNsssrLVALQGQSLILECIAEGFPTPTIKWLHPSDPMPTDRVIYQNHNKTLQLLNVGEEDDGEYTCLAENSLGSArHA 318
Cdd:cd20968     6 PTN----VTIIEGLKAVLPCTTMGNPKPSVSWIKGDDLIKENNRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGIA-YS 80


                  ....*.
gi 569009785  319 YYVTVE 324
Cdd:cd20968    81 KPVTIE 86

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.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 52.40 E-value: 2.70e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  427 NQTymAVEGSTAYLLCKAFGAPVPSVQWLDEEGTtvLQDERFFPYANGTLSIRDLQANDTGRYFCQAANDQNNVTILANL 506
Cdd:cd05725     6 NQV--VLVDDSAEFQCEVGGDPVPTVRWRKEDGE--LPKGRYEILDDHSLKIRKVTAGDMGSYTCVAENMVGKIEASATL 81


                  ..
gi 569009785  507 QV 508
Cdd:cd05725    82 TV 83

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.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 52.01 E-value: 2.92e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  330 LQKPQSHLYGPGETARLDCQVQGRPQPEITWRINGMSMetvnKDQKYRI-EQGSLILSNVQPSDTMVTQCEARNQHGLLL 408
Cdd:cd05725     1 VKRPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGEL----PKGRYEIlDDHSLKIRKVTAGDMGSYTCVAENMVGKIE 76


                  ....*..
gi 569009785  409 ANAYIYV 415
Cdd:cd05725    77 ASATLTV 83

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.

Pssm-ID: 409417 Cd Length: 95 Bit Score: 52.62 E-value: 3.14e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  249 LQGQSLI-LECIAEGFPTPTIKWLHPSDPMPTDRVIYQNHNK--TLQLLNVGEEDDGEYTCLAENSLGSA 315
Cdd:cd05760    13 IQPSSRVtLRCHIDGHPRPTYQWFRDGTPLSDGQGNYSVSSKerTLTLRSAGPDDSGLYYCCAHNAFGSV 82

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.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 52.13 E-value: 3.63e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  415 VVQLPARILTKDnqtymAVEGSTAYLLCKAFGAPVPSVQWLDEEGTTVLQDERFFPYANGT-LSIRDLQANDTGRYFCQA 493
Cdd:cd20970     2 VISTPQPSFTVT-----AREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRYIVRENGTtLTIRNIRRSDMGIYLCIA 76


                  ..
gi 569009785  494 AN 495
Cdd:cd20970    77 SN 78

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.

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 52.17 E-value: 3.78e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 569009785  341 GETARLDCQVQGRPQPEITW--RINGMSMETVNKDQKYR----IEQGSLILSNVQPSDTMVTQCEARNQHGLLLAN 410
Cdd:cd05765    15 GETASFHCDVTGRPQPEITWekQVPGKENLIMRPNHVRGnvvvTNIGQLVIYNAQPQDAGLYTCTARNSGGLLRAN 90

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.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 51.42 E-value: 5.29e-08

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 569009785  341 GETARLDCQVQGRPQPEITWRINGMSMETVNKDQKYRIEQG--SLILSNVQPSDTMVTQCEARNQHG 405
Cdd:cd20973    12 GSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEDGlcSLIISDVCGDDSGKYTCKAVNSLG 78

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.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 51.45 E-value: 5.40e-08

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569009785  251 GQSLILECIAEGFPTPTIKWLHPSDPMPTDRVIYQNhNKTLQLLNVGEEDDGEYTCLAENSLGS 314
Cdd:cd05728    14 GSSLRWECKASGNPRPAYRWLKNGQPLASENRIEVE-AGDLRITKLSLSDSGMYQCVAENKHGT 76

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.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 51.18 E-value: 6.60e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 569009785  329 WLQKPQSHLYGPGETARLDCQVQGRPQPEITWRINGMSM-ETVNKDQKYRIEQGSLILSNVQPSDTMVTQCEARNQHGL 406
Cdd:cd20949     2 FTENAYVTTVKEGQSATILCEVKGEPQPNVTWHFNGQPIsASVADMSKYRILADGLLINKVTQDDTGEYTCRAYQVNSI 80

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.

Pssm-ID: 409387 Cd Length: 97 Bit Score: 51.32 E-value: 7.37e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  328 YWLQKPQSHLYGPGETARLDCQVQGRPQPEITWRINGMSMETVNKDQKYRIEQGSLILSNVQPS-----DTMVTQCEARN 402
Cdd:cd05722     3 YFLSEPSDIVAMRGGPVVLNCSAESDPPPKIEWKKDGVLLNLVSDERRQQLPNGSLLITSVVHSkhnkpDEGFYQCVAQN 82

Sixth immunoglobulin (Ig) domain of contactin-4; The members here are composed of the sixth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-4. 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 different contactins show different expression patterns in the central nervous system. Highest expression of contactin-4 is in testes, thyroid, small intestine, uterus, and brain. Contactin-4 plays a role in the response of neuroblastoma cells to differentiating agents, such as retinoids. The contactin 4 gene is associated with cerebellar degeneration in spinocerebellar ataxia type 16.

Pssm-ID: 409439 Cd Length: 102 Bit Score: 51.55 E-value: 9.04e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  510 EATQITQGPRSAIEKKGARVTFTCQASFDPSLQASITWRGDGR--DLQERGDS-DKYFIED--GKLVIQSLDYSDQGNYS 584
Cdd:cd05853     1 DPTRVMVPPSSMDVTVGESIVLPCQVSHDHSLDIVFTWSFNGHliDFQKDGDHfERVGGQDsaGDLMIRSIQLKHAGKYV 80

                          90       100
                  ....*....|....*....|..
gi 569009785  585 CVASTELDEVESRAQLLVVGSP 606
Cdd:cd05853    81 CMVQTSVDKLSAAADLIVRGPP 102

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.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 50.65 E-value: 1.14e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  433 VEGSTAYLLCKAFGAPVPSVQWLdEEGTTVLQDERF-FPY---ANGTLSIRDLQANDTGRYFCQAANDQNNVTILANLQV 508
Cdd:cd20973    10 VEGSAARFDCKVEGYPDPEVKWM-KDDNPIVESRRFqIDQdedGLCSLIISDVCGDDSGKYTCKAVNSLGEATCSAELTV 88

Third immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F (also known as LAR), type IIa; member of the I-set of IgSF domains; The members here are composed of the third 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. Included in this group is Drosophila LAR (DLAR).

Pssm-ID: 409401 Cd Length: 82 Bit Score: 49.90 E-value: 1.53e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  239 PTNSSsrlvALQGQSLILECIAEGFPTPTIKW------LHPSDPMPTDRviyqnhnKTLQLLNVGEEDDgeYTCLAENSL 312
Cdd:cd05739     4 PSNHE----VMPGGSVNLTCVAVGAPMPYVKWmkggeeLTKEDEMPVGR-------NVLELTNIYESAN--YTCVAISSL 70

                          90
                  ....*....|..
gi 569009785  313 GSARHAYYVTVE 324
Cdd:cd05739    71 GMIEATAQVTVK 82

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first 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. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409356 [Multi-domain] Cd Length: 96 Bit Score: 50.32 E-value: 1.56e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785   30 PVITEQSPRrlVVFPTDD----ISLKCEARGRPQVEFRWTKDG--IHFKPKEELGVVvheapySGSFTIegNNSFAQRFQ 103
Cdd:cd04967     2 PVFEEQPDD--TIFPEDSdekkVALNCRARANPVPSYRWLMNGteIDLESDYRYSLV------DGTLVI--SNPSKAKDA 71

                          90       100
                  ....*....|....*....|.
gi 569009785  104 GIYRCYASNKLGTAMSHEIQL 124
Cdd:cd04967    72 GHYQCLATNTVGSVLSREATL 92

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 409395 [Multi-domain] Cd Length: 96 Bit Score: 50.22 E-value: 1.99e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  421 RILTKDNQTymAVEGSTAYLLCKAFGAPVPSVQW-------LDEEGTTVLQDERFFPYANGTLSIRDLQANDTGRYFCQA 493
Cdd:cd05732     4 KITYLENQT--AVELEQITLTCEAEGDPIPEITWrratrgiSFEEGDLDGRIVVRGHARVSSLTLKDVQLTDAGRYDCEA 81


                  ..
gi 569009785  494 AN 495
Cdd:cd05732    82 SN 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.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 49.81 E-value: 2.15e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 569009785  341 GETARLDCQVQGRPQPEITWRINGMSMETVNKDQKYRIEQGSLILSNVQPSDTMVTQCEARN 402
Cdd:cd20970    17 GENATFMCRAEGSPEPEISWTRNGNLIIEFNTRYIVRENGTTLTIRNIRRSDMGIYLCIASN 78

Third 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 third 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 third 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 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, including vascular (VCAM), intercellular (ICAM), neural (NCAM) and mucosal addressin (MADCAM) cell adhesion molecules, as well as junction adhesion molecules (JAM).

Pssm-ID: 409569 Cd Length: 93 Bit Score: 49.70 E-value: 2.73e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  239 PTNSSSRLVALQGQSLILECIAEGFPTPTIKWLH---PSDPMPTDRVIYQNHN--KTLQLLNVGEEDDGEYTCLAENSLG 313
Cdd:cd20977     3 PQYVSKDMMAKAGDVTMIYCMYGSNPTAHPNYFKngkDVNGNPEDRITRHNRTsgKRLLFKTTLPEDEGVYTCEVDNGVG 82

                          90
                  ....*....|.
gi 569009785  314 -SARHAYYVTV 323
Cdd:cd20977    83 kPQKHSLKLTV 93

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.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 49.71 E-value: 2.97e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  327 PYWLQKPQSHLYGPGETARLDCQVQGRPQPEITWRINGMSMETVNKDQKYRIEQG--SLILSNVQPSDTMVTQCEARNQH 404
Cdd:cd20990     1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMLVRENGvhSLIIEPVTSRDAGIYTCIATNRA 80


                  .
gi 569009785  405 G 405
Cdd:cd20990    81 G 81

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.

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 49.66 E-value: 3.25e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 569009785  418 LPARILTKDnQTYMAVEGSTAYLLCKAFGAPVPSVQWLdEEGTTVLQDERFFPYAN---GTLSIRDLQANDTGRY 489
Cdd:cd05747     2 LPATILTKP-RSLTVSEGESARFSCDVDGEPAPTVTWM-REGQIIVSSQRHQITSTeykSTFEISKVQMSDEGNY 74

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.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 49.38 E-value: 3.38e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  519 RSAIEKKGARVTFTCQASFDPslQASITWRGDGRDLQErgDSDKYFIEDGKLVIQSLDYSDQGNYSCVASTELDEVESRA 598
Cdd:cd04969    10 KKILAAKGGDVIIECKPKASP--KPTISWSKGTELLTN--SSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGKANSTG 85


                  ....
gi 569009785  599 QLLV 602
Cdd:cd04969    86 SLSV 89

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.

Pssm-ID: 409443 [Multi-domain] Cd Length: 95 Bit Score: 49.47 E-value: 4.05e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  327 PYWL--QKPQSHLYG--PGETARLDCQVQGRPQPEITWRINGMSMETVNK--DQKYRIEQGSLILSNVQPSDTMVTQCEA 400
Cdd:cd05857     1 PYWTnpEKMEKKLHAvpAANTVKFRCPAAGNPTPTMRWLKNGKEFKQEHRigGYKVRNQHWSLIMESVVPSDKGNYTCVV 80


                  ....*
gi 569009785  401 RNQHG 405
Cdd:cd05857    81 ENEYG 85

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.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 49.11 E-value: 4.11e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  246 LVALQGQSLILECIAEGFPTPTIKWLHPSDPMPTDRVIY----QNHNKTLQLLNVGEEDDGEYTCLAENSLGSARHAYYV 321
Cdd:cd20973     7 KEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQidqdEDGLCSLIISDVCGDDSGKYTCKAVNSLGEATCSAEL 86


                  ..
gi 569009785  322 TV 323
Cdd:cd20973    87 TV 88

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth 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.

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 49.18 E-value: 4.76e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  332 KPQSHLYGPGETARLDCQVQGRPQPEITWRING-----MSMETVNKDQKYRIEQ-GSLILSNVQPSDTMVTQCEARNQHG 405
Cdd:cd05726     5 KPRDQVVALGRTVTFQCETKGNPQPAIFWQKEGsqnllFPYQPPQPSSRFSVSPtGDLTITNVQRSDVGYYICQALNVAG 84

                          90
                  ....*....|
gi 569009785  406 LLLANAYIYV 415
Cdd:cd05726    85 SILAKAQLEV 94

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 48.40 E-value: 4.83e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 569009785  434 EGSTAYLLCKAFGAPVPSVQWlDEEGTTVLQDERFFPYANGTLSIRDLQANDTGRYFCQAANDQNNVTILANLQV 508
Cdd:cd05745     1 EGQTVDFLCEAQGYPQPVIAW-TKGGSQLSVDRRHLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 48.73 E-value: 4.92e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  326 APYWLQKPQSHLYGPGETARLDCQVQGRPQPEITWRINGMSMETVNKDQkyrIEQG----SLILSNVQPSDTMVTQCEAR 401
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQ---IHQEgdlhSLIIAEAFEEDTGRYSCLAT 77

                          90
                  ....*....|....
gi 569009785  402 NQHGLLLANAYIYV 415
Cdd:cd20972    78 NSVGSDTTSAEIFV 91

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.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 49.09 E-value: 5.22e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  327 PYWLQKPQSHLYGPGETARLDCQVQGRPQPEITWRINGMSMETVNKDQKYR---IEQGSLILSNVQP-----SDTMVTQC 398
Cdd:cd07693     1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLETDKDDPRSHrivLPSGSLFFLRVVHgrkgrSDEGVYVC 80


                  ....*..
gi 569009785  399 EARNQHG 405
Cdd:cd07693    81 VAHNSLG 87

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 48.73 E-value: 5.32e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 569009785  244 SRLVAlQGQSLILECIAEGFPTPTIKW------LHPSdpmpTDRVIYQNHN-KTLQLLNVGEEDDGEYTCLAENSLGSA 315
Cdd:cd20972    10 SQEVA-EGSKVRLECRVTGNPTPVVRWfcegkeLQNS----PDIQIHQEGDlHSLIIAEAFEEDTGRYSCLATNSVGSD 83

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 48.39 E-value: 6.04e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 569009785  433 VEGSTAYLLCKAFGAPVPSVQWLDEEgTTVLQDERFFPYANGTLSIRDLQANDTGRYFCQAAN 495
Cdd:cd20968    12 IEGLKAVLPCTTMGNPKPSVSWIKGD-DLIKENNRIAVLESGSLRIHNVQKEDAGQYRCVAKN 73

IL-beta-binding protein; Provisional

Pssm-ID: 165149 [Multi-domain] Cd Length: 326 Bit Score: 52.71 E-value: 7.38e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  357 EITWRINGmsmetVNKDQKYRIEQGS--LILSNVQpSDTMVTQCEARNQHGLLLANAYIYVVQLPARILTKDNQTYMAVE 434
Cdd:PHA02785   62 DILWEKRG-----ADNDRIIPIDNGSnmLILNPTQ-SDSGIYICITKNETYCDMMSLNLTIVSVSESNIDLISYPQIVNE 135

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  435 GSTAYLLCKAFGAPVPS-----VQWldeEGTTVLQDERFFPYANGTLSIRDLQANDTGRYFC----QAANDQNNVTILAN 505
Cdd:PHA02785  136 RSTGEMVCPNINAFIASnvnadIIW---SGHRRLRNKRLKQRTPGIITIEDVRKNDAGYYTCvlkyIYGDKTYNVTRIVK 212

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  506 LQVKEAT--QITQGPRSAIEKKGARVTFTCQASF-DPSLQASITWRGDGRDLQE-RGDSD-------KYFIEDGKLVIQS 574
Cdd:PHA02785  213 LEVRDRIipPTMQLPEGVVTSIGSNLTIACRVSLrPPTTDADVFWISNGMYYEEdDEDGDgrisvanKIYTTDKRRVITS 292

                         250       260
                  ....*....|....*....|.
gi 569009785  575 ------LDYSDQGNYSCVAST 589
Cdd:PHA02785  293 rlninpVKEEDATTFTCMAFT 313

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.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 48.33 E-value: 7.96e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  432 AVEGSTAYLLCKAFGAPVPSVQWldEEGTTVL---QDERFFPyaNGTLSIRDLQ-ANDTGRYFCQAANDQNNvTILANLQ 507
Cdd:cd20958    12 AVAGQTLRLHCPVAGYPISSITW--EKDGRRLplnHRQRVFP--NGTLVIENVQrSSDEGEYTCTARNQQGQ-SASRSVF 86


                  ..
gi 569009785  508 VK 509
Cdd:cd20958    87 VK 88

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 143259 Cd Length: 88 Bit Score: 48.09 E-value: 8.74e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 569009785  341 GETARLDCQVQGRPQPEITWRingMSMETVNKDQKYRIEQGSLILSNVQPSDTMVTQCEARNQHGLLLANAYIYV 415
Cdd:cd05851    16 GQNVTLECFALGNPVPVIRWR---KILEPMPATAEISMSGAVLKIFNIQPEDEGTYECEAENIKGKDKHQARVYV 87

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.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 48.27 E-value: 8.84e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  513 QITQGPRSAIEKKGARVTFTCQASFDPslQASITWRGDGRDLQErGDSDKYFIEDGK-LVIQSLDYSDQGNYSCVASTEL 591
Cdd:cd20970     4 STPQPSFTVTAREGENATFMCRAEGSP--EPEISWTRNGNLIIE-FNTRYIVRENGTtLTIRNIRRSDMGIYLCIASNGV 80

                          90
                  ....*....|..
gi 569009785  592 D-EVESRAQLLV 602
Cdd:cd20970    81 PgSVEKRITLQV 92

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.

Pssm-ID: 409435 Cd Length: 96 Bit Score: 48.40 E-value: 9.22e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  327 PYWLQKPQSHLYGPGETAR---LDCQVQGRPQPEITWRINGMSMETvNKDQKYRIEQGSLILSNV-QPSDTMVTQCEARN 402
Cdd:cd05848     2 PVFVQEPDDAIFPTDSDEKkviLNCEARGNPVPTYRWLRNGTEIDT-ESDYRYSLIDGNLIISNPsEVKDSGRYQCLATN 80


                  ....*..
gi 569009785  403 QHGLLLA 409
Cdd:cd05848    81 SIGSILS 87

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.

Pssm-ID: 143220 Cd Length: 78 Bit Score: 47.48 E-value: 9.66e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 569009785  251 GQSLILECIAEGFPTPTIKWLHPSDPMPTD-RVIYQNHN--KTLQLLNVGEEDDGEYTCLAENSLG 313
Cdd:cd05743     1 GETVEFTCVATGVPTPIINWRLNWGHVPDSaRVSITSEGgyGTLTIRDVKESDQGAYTCEAINTRG 66

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 47.98 E-value: 1.00e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  327 PYWLQ----KPQSHLYGPGETARLDCQVQGRPQPEITWRINGMSMETVNKDQKYRIEQG--SLILSNVQPSDTMVTQCEA 400
Cdd:cd05729     1 PRFTDtekmEEREHALPAANKVRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEEKgwSLIIERAIPRDKGKYTCIV 80


                  ....*
gi 569009785  401 RNQHG 405
Cdd:cd05729    81 ENEYG 85

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 48.12 E-value: 1.14e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569009785  330 LQKPQSHLYGPGETARLDCQVQGRPQPEITWRINGMSMETVNKDQKYRIEQGSLI-LSNVQPSD 392
Cdd:cd05747     7 LTKPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQITSTEYKSTFeISKVQMSD 70

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.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 47.93 E-value: 1.17e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785   30 PVITEQsPRRLVVFPTDDISLKCEARGRPQVEFRWTKDGIHFKPKEELGVVVHEAPYSGS---FTIEGNNSfAQRFQGIY 106
Cdd:cd07693     1 PRIVEH-PSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLETDKDDPRSHRIVLPSGSlffLRVVHGRK-GRSDEGVY 78

                          90
                  ....*....|....*...
gi 569009785  107 RCYASNKLGTAMSHEIQL 124
Cdd:cd07693    79 VCVAHNSLGEAVSRNASL 96

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143223 Cd Length: 69 Bit Score: 47.18 E-value: 1.24e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 569009785  440 LLCKAFGAPVPSVQWlDEEGTTVLQDERFFPYANGTLSIRDLQANDTGRYFCQAAN 495
Cdd:cd05746     3 IPCSAQGDPEPTITW-NKDGVQVTESGKFHISPEGYLAIRDVGVADQGRYECVARN 57

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 47.50 E-value: 1.29e-06

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785     37 PRRLVVFPTDDISLKCEARGRPQVEFRWTKDGIHfKPKEELGVVVHEAPYSGSFTIegnNSFAQRFQGIYRCYASNKLGT 116
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGK-LLAESGRFSVSRSGSTSTLTI---SNVTPEDSGTYTCAATNSSGS 76


                    ....*...
gi 569009785    117 AmSHEIQL 124
Cdd:smart00410   77 A-SSGTTL 83

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first 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. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409356 [Multi-domain] Cd Length: 96 Bit Score: 48.01 E-value: 1.29e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  327 PYWLQKPQSHLYgPGETAR----LDCQVQGRPQPEITWRINGMSMEtVNKDQKYRIEQGSLILSN-VQPSDTMVTQCEAR 401
Cdd:cd04967     2 PVFEEQPDDTIF-PEDSDEkkvaLNCRARANPVPSYRWLMNGTEID-LESDYRYSLVDGTLVISNpSKAKDAGHYQCLAT 79


                  ....*...
gi 569009785  402 NQHGLLLA 409
Cdd:cd04967    80 NTVGSVLS 87

Fifth immunoglobulin (Ig) domain of contactin-1; The members here are composed of the fifth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409438 Cd Length: 89 Bit Score: 47.69 E-value: 1.31e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 569009785  245 RLVALQGQSLILECIAEGFPTPTIKWLHPSDPMPTDRVIYQNHNKTLQLLNVGEEDDGEYTCLAENSLGSA 315
Cdd:cd05852    11 KILAAKGGRVIIECKPKAAPKPKFSWSKGTELLVNNSRISIWDDGSLEILNITKLDEGSYTCFAENNRGKA 81

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.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 47.53 E-value: 1.34e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 569009785  526 GARVTFTCQASFDPSlqASITWRGDGRDLQErgDSDKYFIEDGKLVIQSLDYSDQGNYSCVASTELDEVESRAQL 600
Cdd:cd20957    16 GRTAVFNCSVTGNPI--HTVLWMKDGKPLGH--SSRVQILSEDVLVIPSVKREDKGMYQCFVRNDGDSAQATAEL 86

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.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 47.57 E-value: 1.40e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 569009785   246 LVALQGQSLILECIAEGFPT-PTIKWLHPSD----PMPTDRVIYQNHNKTLQLLNVGEEDDGEYTCLAENSLGSA 315
Cdd:pfam00047    6 VTVLEGDSATLTCSASTGSPgPDVTWSKEGGtlieSLKVKHDNGRTTQSSLLISNVTKEDAGTYTCVVNNPGGSA 80

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.

Pssm-ID: 409435 Cd Length: 96 Bit Score: 47.63 E-value: 1.84e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785   41 VVFPTDD----ISLKCEARGRPQVEFRWTKDGIHfkpkeelgvVVHEAPYSGSFtIEGN----NSFAQRFQGIYRCYASN 112
Cdd:cd05848    11 AIFPTDSdekkVILNCEARGNPVPTYRWLRNGTE---------IDTESDYRYSL-IDGNliisNPSEVKDSGRYQCLATN 80

                          90
                  ....*....|..
gi 569009785  113 KLGTAMSHEIQL 124
Cdd:cd05848    81 SIGSILSREALL 92

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143223 Cd Length: 69 Bit Score: 46.41 E-value: 1.85e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  529 VTFTCQASFDPslQASITWRGDGRDLQERGdsdKYFI-EDGKLVIQSLDYSDQGNYSCVA 587
Cdd:cd05746     1 VQIPCSAQGDP--EPTITWNKDGVQVTESG---KFHIsPEGYLAIRDVGVADQGRYECVA 55

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.

Pssm-ID: 409534 Cd Length: 116 Bit Score: 47.65 E-value: 2.35e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 569009785  435 GSTAYLLCKAFGAPVPSVQWLDEEG-----TTVLQD----------ERFFPYANGTLSIRDLQANDTGRYFCQAAND 496
Cdd:cd20940    15 GDSVELHCEAVGSPIPEIQWWFEGQepneiCSQLWDgarldrvhinATYHQHATSTISIDNLTEEDTGTYECRASND 91

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

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 46.17 E-value: 2.54e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 569009785   48 ISLKCEARGRPQVEFRWTKDGIHFKPKEELGVVVHEapYSGSFTIegnNSFAQRFQGIYRCYASNKLGTAMSHEI 122
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSEL--GNGTLTI---SNVTLEDSGTYTCVASNSAGGSASASV 70

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third 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. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 46.77 E-value: 2.71e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569009785  432 AVEGSTAYLLCKAFGAPVPSVQWLDEEGTTVLQDERFfpYANGTLSIRDLQANDTGRYFCQAAN 495
Cdd:cd04968    13 ALKGQTVTLECFALGNPVPQIKWRKVDGSPSSQWEIT--TSEPVLEIPNVQFEDEGTYECEAEN 74

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.

Pssm-ID: 409444 Cd Length: 105 Bit Score: 47.26 E-value: 2.81e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  238 FPTNSSSRLvalqGQSLILECIAEGFPTPTIKWL---------HPSDPMPTDRVI----YQNHNKTLQLL---NVGEEDD 301
Cdd:cd05858     7 LPANTSVVV----GTDAEFVCKVYSDAQPHIQWLkhvekngskYGPDGLPYVEVLktagVNTTDKEIEVLylrNVTFEDA 82

                          90       100
                  ....*....|....*....|..
gi 569009785  302 GEYTCLAENSLGSARHAYYVTV 323
Cdd:cd05858    83 GEYTCLAGNSIGISHHSAWLTV 104

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.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 46.68 E-value: 2.90e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569009785  442 CKAFGAPVPSVQWldEEGTTVL-QDERFFPYANGTLSIRDLQANDTGRYFCQAANDQNNVTILANLQV 508
Cdd:cd04969    24 CKPKASPKPTISW--SKGTELLtNSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 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.

Pssm-ID: 409442 Cd Length: 92 Bit Score: 46.78 E-value: 3.02e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 569009785  341 GETARLDCQVQGRPQPEITWRINGMSMeTVNKDQKYRIEQGSLILSNVQPSDTMVTQCEARNQHG 405
Cdd:cd05856    19 GSSVRLKCVASGNPRPDITWLKDNKPL-TPPEIGENKKKKWTLSLKNLKPEDSGKYTCHVSNRAG 82

Seventh 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 seventh 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.

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 46.54 E-value: 3.37e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 569009785  432 AVEGSTAYLLCKAFGAPVPSVQWLDEEGTT------VLQDERFFPYANGTLSIRDLQANDTGRYFCQAAND 496
Cdd:cd20954    13 VAAGQDVMLHCQADGFPTPTVTWKKATGSTpgeykdLLYDPNVRILPNGTLVFGHVQKENEGHYLCEAKNG 83

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.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 46.44 E-value: 3.58e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  429 TYMAVeGSTAYLLCKAFGAPVPSVQWLdEEGTTVLQDERFFpYANGTLSIRDLQANDTGRYFCQAANDQNNVTILANLQV 508
Cdd:cd05728     9 TEADI-GSSLRWECKASGNPRPAYRWL-KNGQPLASENRIE-VEAGDLRITKLSLSDSGMYQCVAENKHGTIYASAELAV 85

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.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 46.64 E-value: 3.58e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  250 QGQSLILECIAEGFPTPTIKWLH---PSDPMPTDRvIYQNHNK----TLQLLNVGEEDDGEYTCLAENSLGSARHAYYVT 322
Cdd:cd20951    14 EKSDAKLRVEVQGKPDPEVKWYKngvPIDPSSIPG-KYKIESEygvhVLHIRRVTVEDSAVYSAVAKNIHGEASSSASVV 92


                  ..
gi 569009785  323 VE 324
Cdd:cd20951    93 VE 94

Seventh 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 seventh 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.

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 46.54 E-value: 3.61e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  327 PYWLQKPQSHLYGPGETARLDCQVQGRPQPEITWRINGMSMETVNKDQKYR-----IEQGSLILSNVQPSDTMVTQCEAR 401
Cdd:cd20954     2 PRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWKKATGSTPGEYKDLLYDpnvriLPNGTLVFGHVQKENEGHYLCEAK 81


                  .
gi 569009785  402 N 402
Cdd:cd20954    82 N 82

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. 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 Lingo-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.

Pssm-ID: 409561 Cd Length: 92 Bit Score: 46.61 E-value: 3.82e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569009785  250 QGQSLILECIAEGFPTPTIKWL----HPSDPMPTDRVIYQNhNKTLQLLNVGEEDDGEYTCLAENSLGSARHAYYVTV 323
Cdd:cd20969    16 EGHTVQFVCRADGDPPPAILWLsprkHLVSAKSNGRLTVFP-DGTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHLHV 92

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 51.16 E-value: 4.02e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  623 SQVHLSWSPAEDhnSPIEKYDIEfeDKEMAPEKWFSLGKVPGNQTSTTLKLSPYVHYTFRVTAINKYGPGEPSPVSETVV 702
Cdd:COG3401   341 SSITLSWTASSD--ADVTGYNVY--RSTSGGGTYTKIAETVTTTSYTDTGLTPGTTYYYKVTAVDAAGNESAPSEEVSAT 416

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  703 TPEAAPEKNPVDVRGEGNETNNMVITWKPLRWMDWNAPQIQYRVQWRPQGKQETWREQTV----------SDPFLVVSNT 772
Cdd:COG3401   417 TASAASGESLTASVDAVPLTDVAGATAAASAASNPGVSAAVLADGGDTGNAVPFTTTSSTvtatttdtttANLSVTTGSL 496

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 569009785  773 STFVPYEIKVQAVNNQGKGPEPQVTIGYSGEDYPQVSPELEDITIFNS--STVLVRWRPVDLAQVKGHLKGYNVTYW 847
Cdd:COG3401   497 VGGSGASSVTNSVSVIGASAAAAVGGAPDGTPNVTGASPVTVGASTGDvlITDLVSLTTSASSSVSGAGLGSGNLYL 573

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 46.33 E-value: 4.33e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  251 GQSLILECIAEGFPTPTIKWLHP--------SDPMPTDRVIYQNHNKTLQLLNVGEEDDGEYTCLAENSLGS-ARHAYYV 321
Cdd:cd05734    16 GKAVVLNCSADGYPPPTIVWKHSkgsgvpqfQHIVPLNGRIQLLSNGSLLIKHVLEEDSGYYLCKVSNDVGAdISKSMYL 95


                  ..
gi 569009785  322 TV 323
Cdd:cd05734    96 TV 97

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.

Pssm-ID: 409400 [Multi-domain] Cd Length: 91 Bit Score: 46.16 E-value: 4.36e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  258 CIAEGFPTPTIKWLH---PSDPMPTDRVIYQNHNKTLQLLNVGEEDDGEYTCLAENSLGS 314
Cdd:cd05738    21 CAASGNPDPEISWFKdflPVDTATSNGRIKQLRSGALQIENSEESDQGKYECVATNSAGT 80

Immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-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.

Pssm-ID: 409458 Cd Length: 95 Bit Score: 46.13 E-value: 4.54e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  331 QKPQSHLYGPGETARLDCQVQGRPQPEITWRINGMSMEtVNKDQKYRIE--QGSLIL--SNVQPSDTM--VTQCEARNQH 404
Cdd:cd05874     6 QSPKDYIVDPRENIVIQCEAKGKPPPSFSWTRNGTHFD-IDKDPKVTMKpnTGTLVIniMNGEKAEAYegVYQCTARNER 84


                  ....*.
gi 569009785  405 GLLLAN 410
Cdd:cd05874    85 GAAVSN 90

Second 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 second immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. 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.

Pssm-ID: 409545 Cd Length: 95 Bit Score: 46.38 E-value: 4.57e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  419 PARILTKDNQTYMAVEGSTAY-LLCKAFGAPVPSVQWLDE-EGTT-----VLQDErfFPYANGTLSIRDLQANDTGRYFC 491
Cdd:cd20953     1 APKIPGLSKSQPLTVSSASSIaLLCPAQGYPAPSFRWYKFiEGTTrkqavVLNDR--VKQVSGTLIIKDAVVEDSGKYLC 78


                  ....
gi 569009785  492 QAAN 495
Cdd:cd20953    79 VVNN 82

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. 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. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 46.07 E-value: 4.76e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569009785  256 LECIAEGFPTPTIKW---------------LHpsdPMPTDRVIYqnhnktlqLLNVGEEDDGEYTCLAENSLGS 314
Cdd:cd05763    19 LECAATGHPTPQIAWqkdggtdfpaarerrMH---VMPEDDVFF--------IVDVKIEDTGVYSCTAQNSAGS 81

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

Pssm-ID: 409408 [Multi-domain] Cd Length: 92 Bit Score: 45.97 E-value: 5.26e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 569009785  251 GQSLILECIAEG-FPTPTIKWLHPSDPM---PTDRVIYQNHNKT--LQLLNVGEEDDGEYTCLAENSLGSARHAYYVTV 323
Cdd:cd05750    14 GSKLVLKCEATSeNPSPRYRWFKDGKELnrkRPKNIKIRNKKKNseLQINKAKLEDSGEYTCVVENILGKDTVTGNVTV 92

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 46.08 E-value: 5.40e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  513 QITQGPRSAIEKKGARVTFTCQASFDPslQASITWRGDGRDLqERGDSDKYFIEDG-KLVIQSLDYSDQGNYSCVASTEL 591
Cdd:cd05730     5 RARQSEVNATANLGQSVTLACDADGFP--EPTMTWTKDGEPI-ESGEEKYSFNEDGsEMTILDVDKLDEAEYTCIAENKA 81

                          90
                  ....*....|.
gi 569009785  592 DEVESRAQLLV 602
Cdd:cd05730    82 GEQEAEIHLKV 92

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.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 45.65 E-value: 6.31e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 569009785   333 PQSHLYGPGETARLDCQV-QGRPQPEITWRINGMSMETVNK--DQKYRIEQGSLILSNVQPSDTMVTQCEARNQHGL 406
Cdd:pfam00047    3 PPTVTVLEGDSATLTCSAsTGSPGPDVTWSKEGGTLIESLKvkHDNGRTTQSSLLISNVTKEDAGTYTCVVNNPGGS 79

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. 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.

Pssm-ID: 409473 Cd Length: 92 Bit Score: 45.53 E-value: 7.23e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  327 PYWLQKPQSHLYGPGETARLDCQVQGRPQPEITWRINGmSMETVNKDQ--KYRIEQG--SLILSNVQPSDTMVTQCEARN 402
Cdd:cd05892     1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNN-EMLQYNTDRisLYQDNCGriCLLIQNANKKDAGWYTVSAVN 79


                  ....*....
gi 569009785  403 QHGLLLANA 411
Cdd:cd05892    80 EAGVVSCNA 88

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 45.48 E-value: 7.40e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 569009785  429 TYMAVEGSTAYLLCKAFGAPVPSVQWLDEEGTTvLQDERFFPYANGTLSIRDLQANDTGRYFCQAAN 495
Cdd:cd05731     4 STMVLRGGVLLLECIAEGLPTPDIRWIKLGGEL-PKGRTKFENFNKTLKIENVSEADSGEYQCTASN 69

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.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 45.72 E-value: 8.16e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569009785  435 GSTAYLLCKAFGAPVPSVQWL-DEEGTTVLQDERFFPYANGT-LSIRDLQANDTGRYFCQAAND 496
Cdd:cd05736    15 GVEASLRCHAEGIPLPRVQWLkNGMDINPKLSKQLTLIANGSeLHISNVRYEDTGAYTCIAKNE 78

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.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 45.52 E-value: 8.22e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 569009785  434 EGSTAYLLCKAFGAPVPSVQW------LDEEGT-TVLQDERffpyanGTLSIRDLQANDTGRYFCQAANDQNnvTILAN 505
Cdd:cd04978    13 PGETGELICEAEGNPQPTITWrlngvpIEPAPEdMRRTVDG------RTLIFSNLQPNDTAVYQCNASNVHG--YLLAN 83

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.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 45.22 E-value: 8.26e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  333 PQSHLYGPGETARLDCQVQGRPQPEITWRINGMSMetVNKDQKYRIEQGSLILSNVQPSDTMVTQCEARN 402
Cdd:cd20957     8 PPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGKPL--GHSSRVQILSEDVLVIPSVKREDKGMYQCFVRN 75

First immunoglobulin (Ig) domain of contactin-2; 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-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. 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. 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-2 is also expressed in retinal amacrine cells in the developing chick retina, corresponding to the period of formation and maturation of AC processes. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409437 [Multi-domain] Cd Length: 97 Bit Score: 45.69 E-value: 9.01e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785   30 PVITEQSPRrlVVFPT----DDISLKCEARGRPQVEFRWTKDGIHFKPKEElgvvVHEAPYSGSFTIegNNSFAQRFQGI 105
Cdd:cd05850     3 PVFEEQPSS--TLFPEgsaeEKVTLACRARASPPATYRWKMNGTELKMEPD----SRYRLVAGNLVI--SNPVKAKDAGS 74

                          90
                  ....*....|....*....
gi 569009785  106 YRCYASNKLGTAMSHEIQL 124
Cdd:cd05850    75 YQCLASNRRGTVVSREASL 93

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 45.18 E-value: 9.59e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 569009785  249 LQGQSLILECIAEGFPTPTIKWLHPSDPM-PTDR-VIYQNHN--KTLQLLNVGEEDDGEYTCLAENSLGSA 315
Cdd:cd05744    13 QEGRLCRFDCKVSGLPTPDLFWQLNGKPVrPDSAhKMLVRENgrHSLIIEPVTKRDAGIYTCIARNRAGEN 83

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.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 45.22 E-value: 1.02e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  251 GQSLILECIAEGFPTPTIKWLHPSDPMPTDRVIYQNHNKTLQLLNVGEEDDGEYTCLAEN 310
Cdd:cd20957    16 GRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILSEDVLVIPSVKREDKGMYQCFVRN 75

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.

Pssm-ID: 409454 Cd Length: 89 Bit Score: 44.97 E-value: 1.05e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785   36 SPRRLVVFPTDDISLKCEARGRPQVEFRWTKDgihfkpkeelGVVVHEAPYSGSFTIEGN----NSFAQRFQGIYRCYAS 111
Cdd:cd05868     5 APTNLVLSPGEDGTLICRANGNPKPSISWLTN----------GVPIEIAPTDPSRKVDGDtiifSKVQERSSAVYQCNAS 74


                  ....
gi 569009785  112 NKLG 115
Cdd:cd05868    75 NEYG 78

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.

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 45.04 E-value: 1.07e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 569009785  250 QGQSLILECIAEGFPTPTIKWLHPSDPMPTDR---VIYQNHNKTLQLLNVGEEDDGEYTCLAENSLGSARHAYYVT 322
Cdd:cd05747    17 EGESARFSCDVDGEPAPTVTWMREGQIIVSSQrhqITSTEYKSTFEISKVQMSDEGNYTVVVENSEGKQEAQFTLT 92

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 45.08 E-value: 1.08e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  247 VALQGQSLILECIA-EGFPTPTIKWLHPSDPMPTDRV-IYQNHNKTLQLLNVGEEDDGEYTCLAENSLGSARHAY-YVTV 323
Cdd:cd05724     8 QVAVGEMAVLECSPpRGHPEPTVSWRKDGQPLNLDNErVRIVDDGNLLIAEARKSDEGTYKCVATNMVGERESRAaRLSV 87

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 44.70 E-value: 1.28e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 569009785  431 MAVEGSTAYLLCKA-FGAPVPSVQWLDEEGTTVLQDERFFPYANGTLSIRDLQANDTGRYFCQAAN 495
Cdd:cd05724     8 QVAVGEMAVLECSPpRGHPEPTVSWRKDGQPLNLDNERVRIVDDGNLLIAEARKSDEGTYKCVATN 73

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.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 44.94 E-value: 1.42e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 569009785  251 GQSLILECIAEGFPTPTIKWL-HPSDPMP--TDRVIYQNHNKTLQLLNVGEEDDGEYTCLAENSLG 313
Cdd:cd05736    15 GVEASLRCHAEGIPLPRVQWLkNGMDINPklSKQLTLIANGSELHISNVRYEDTGAYTCIAKNEGG 80

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.

Pssm-ID: 409435 Cd Length: 96 Bit Score: 44.55 E-value: 1.70e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  236 LLFPTNSSSRLVALQgqslileCIAEGFPTPTIKWLHPSDPMPTDRVI-YQNHNKTLQLLNVGE-EDDGEYTCLAENSLG 313
Cdd:cd05848    11 AIFPTDSDEKKVILN-------CEARGNPVPTYRWLRNGTEIDTESDYrYSLIDGNLIISNPSEvKDSGRYQCLATNSIG 83


                  .
gi 569009785  314 S 314
Cdd:cd05848    84 S 84

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first 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. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409356 [Multi-domain] Cd Length: 96 Bit Score: 44.54 E-value: 1.71e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  518 PRSAIEKKgarVTFTCQASFDPSlqASITWRGDGRDLqERGDSDKYFIEDGKLVIQSLDYS-DQGNYSCVASTELDEVES 596
Cdd:cd04967    14 PEDSDEKK---VALNCRARANPV--PSYRWLMNGTEI-DLESDYRYSLVDGTLVISNPSKAkDAGHYQCLATNTVGSVLS 87


                  ....*...
gi 569009785  597 RAQLLVVG 604
Cdd:cd04967    88 REATLQFG 95

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth 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.

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 44.95 E-value: 1.72e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  435 GSTAYLLCKAFGAPVPSVQWlDEEGTTVL--------QDERFFPYANGTLSIRDLQANDTGRYFCQAANDQNNVTILANL 506
Cdd:cd05726    14 GRTVTFQCETKGNPQPAIFW-QKEGSQNLlfpyqppqPSSRFSVSPTGDLTITNVQRSDVGYYICQALNVAGSILAKAQL 92


                  ....*
gi 569009785  507 QVKEA 511
Cdd:cd05726    93 EVTDV 97

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.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 44.36 E-value: 1.89e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785   37 PRRLVVFPTDDISLKCEARGRPQVEFRWTKDgihfkpkeelGVVVHEAPYSGSFTIEGNN---SFAQRFQ-GIYRCYASN 112
Cdd:cd04978     6 PPSLVLSPGETGELICEAEGNPQPTITWRLN----------GVPIEPAPEDMRRTVDGRTlifSNLQPNDtAVYQCNASN 75


                  ....*.
gi 569009785  113 KLGTAM 118
Cdd:cd04978    76 VHGYLL 81

Immunoglobulin-like domain of human nephrin and similar proteins; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin-like domain in human nephrin and similar proteins. Nephrin is an integral component of the slit diaphragm and is a central component of the glomerular ultrafilter. Nephrin plays a structural role and has a role in signaling. Nephrin is a transmembrane protein having a short intracellular portion, an extracellular portion comprised of eight Ig-like domains, and one fibronectin type III-like domain. The extracellular portions of nephrin from neighboring foot processes of separate podocyte cells may interact with each other, and in association with other components of the slit diaphragm form a porous molecular sieve within the slit pore. The intracellular portion of nephrin is associated with linker proteins, which connect nephrin to the actin cytoskeleton. The intracellular portion is tyrosine phosphorylated, and mediates signaling from the slit diaphragm into the podocytes.

Pssm-ID: 143250 Cd Length: 109 Bit Score: 44.92 E-value: 1.92e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785   30 PVITEQSPRRLVVFPTD---DISLKCEARGRPQVEFRWTKDGIHFK---PKEElGVVVHEAPYSGSFTIEGNNSFAQRFq 103
Cdd:cd05773     5 PDLQKGPQLRKVASRGDgssDANLVCQAQGVPRVQFRWAKNGVPLDlgnPRYE-ETTEHTGTVHTSILTIINVSAALDY- 82

                          90       100
                  ....*....|....*....|....*..
gi 569009785  104 GIYRCYASNKLGTAmSHEIQLVAEGAP 130
Cdd:cd05773    83 ALFTCTAHNSLGED-SLDIQLVSTSRP 108

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 43.92 E-value: 2.16e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 569009785   329 WLQKPQSHLYgPGETARLDCQVQGRPQPEITWRINGmsmETVNKDQKYrieqgslILSNVQPSDTMVTQCEARNQHG 405
Cdd:pfam13895    3 VLTPSPTVVT-EGEPVTLTCSAPGNPPPSYTWYKDG---SAISSSPNF-------FTLSVSAEDSGTYTCVARNGRG 68

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.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 44.13 E-value: 2.25e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 569009785  526 GARVTFTCQASFDPslQASITWRGDGRDLQERGdsdKYFIEDGKLVIQSLDYSDQGNYSCVASTELDEVESRAQLLV 602
Cdd:cd05728    14 GSSLRWECKASGNP--RPAYRWLKNGQPLASEN---RIEVEAGDLRITKLSLSDSGMYQCVAENKHGTIYASAELAV 85

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.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 44.46 E-value: 2.43e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  513 QITQGPRSAIEKKGARVTFTCQASFDPSlqASITWRGDGRDLQERGD---SDKYFIEDGKLVIQSL-----DYSDQGNYS 584
Cdd:cd07693     2 RIVEHPSDLIVSKGDPATLNCKAEGRPT--PTIQWLKNGQPLETDKDdprSHRIVLPSGSLFFLRVvhgrkGRSDEGVYV 79

                          90
                  ....*....|...
gi 569009785  585 CVASTELDEVESR 597
Cdd:cd07693    80 CVAHNSLGEAVSR 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.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 44.09 E-value: 2.63e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  326 APYWLQKPQSHLYGPGETARLDCQVQGRPQPEITWRINGMSMETvnkDQKYRIEQ---------GSLILSNVQPSDTMVT 396
Cdd:cd20956     1 APVLLETFSEQTLQPGPSVSLKCVASGNPLPQITWTLDGFPIPE---SPRFRVGDyvtsdgdvvSYVNISSVRVEDGGEY 77


                  ....*....
gi 569009785  397 QCEARNQHG 405
Cdd:cd20956    78 TCTATNDVG 86

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.

Pssm-ID: 409402 [Multi-domain] Cd Length: 89 Bit Score: 43.92 E-value: 2.76e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 569009785  252 QSLILECIAEGfPTPTIKWLHPSDPMP-TDRVIYQNHNKTLQLLNVGEEDDGEYTCLAENSLGSAR 316
Cdd:cd05740    16 DAVTLTCEPET-QNTSYLWWFNGQSLPvTPRLTLSNGNRTLTLLNVTREDAGAYQCEISNPVSANR 80

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.

Pssm-ID: 409387 Cd Length: 97 Bit Score: 44.01 E-value: 3.36e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  237 LFPTNSSSRLVALQGQSLILECIAEGFPTPTIKWL----HPSDPMpTDRViYQNHNKTLQLLNV-----GEEDDGEYTCL 307
Cdd:cd05722     2 LYFLSEPSDIVAMRGGPVVLNCSAESDPPPKIEWKkdgvLLNLVS-DERR-QQLPNGSLLITSVvhskhNKPDEGFYQCV 79


                  ....*...
gi 569009785  308 AEN-SLGS 314
Cdd:cd05722    80 AQNeSLGS 87

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 43.35 E-value: 3.47e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  245 RLVALQGQSLILECIAEGFPTPTIKWLHPSDP-MPTDRVIYQNHNKTLQLL--NVGEEDDGEYTCLAENSLGSArhAYYV 321
Cdd:cd05748     1 TIVVRAGESLRLDIPIKGRPTPTVTWSKDGQPlKETGRVQIETTASSTSLVikNAKRSDSGKYTLTLKNSAGEK--SATI 78


                  ..
gi 569009785  322 TV 323
Cdd:cd05748    79 NV 80

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.

Pssm-ID: 409460 [Multi-domain] Cd Length: 83 Bit Score: 43.36 E-value: 3.55e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 569009785  429 TYMAVEGSTAYLLCKAFGAPVPSVQWLDEEGtTVLQDERFFPYANGTLSIRDLQANDTGRYFCQAANDQNNV 500
Cdd:cd05876     4 SLVALRGQSLVLECIAEGLPTPTVKWLRPSG-PLPPDRVKYQNHNKTLQLLNVGESDDGEYVCLAENSLGSA 74

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. 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. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 43.76 E-value: 3.56e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  435 GSTAYLLCKAFGAPVPSVQWLDEEGTTvlqderfFPYA----------NGTLSIRDLQANDTGRYFCQAANDQNNVTILA 504
Cdd:cd05763    14 GSTARLECAATGHPTPQIAWQKDGGTD-------FPAArerrmhvmpeDDVFFIVDVKIEDTGVYSCTAQNSAGSISANA 86


                  ....
gi 569009785  505 NLQV 508
Cdd:cd05763    87 TLTV 90

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule 1(NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-non-NCAM) interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143277 [Multi-domain] Cd Length: 97 Bit Score: 43.82 E-value: 3.71e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  421 RILTKDNQTYMAVEGSTAyLLCKAFGAPVPSVQW------LDEEGTT------VLQDERFfpyanGTLSIRDLQANDTGR 488
Cdd:cd05869     4 KITYVENQTAMELEEQIT-LTCEASGDPIPSITWrtstrnISSEEKTldghivVRSHARV-----SSLTLKYIQYTDAGE 77


                  ....*..
gi 569009785  489 YFCQAAN 495
Cdd:cd05869    78 YLCTASN 84

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 2 (NCAM-2); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule NCAM-2 (also known as OCAM/mamFas II and RNCAM). NCAM-2 is organized similarly to NCAM, including five N-terminal Ig-like domains and two fibronectin type III domains. NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE), and may function like NCAM, as an adhesion molecule. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143278 [Multi-domain] Cd Length: 98 Bit Score: 43.81 E-value: 3.73e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  422 ILTKDNQTymAVEGSTAYLLCKAFGAPVPSVQWLDEEGTTVLQDERFFP---------YANGTLSIRDLQANDTGRYFCQ 492
Cdd:cd05870     5 IIQLKNET--TVENGAATLSCKAEGEPIPEITWKRASDGHTFSEGDKSPdgrievkgqHGESSLHIKDVKLSDSGRYDCE 82


                  ...
gi 569009785  493 AAN 495
Cdd:cd05870    83 AAS 85

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.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 43.39 E-value: 3.82e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  521 AIEkkGARVTFTCQASFDPSlqASITWRGDGRDLQERGDSDKYFIEDGKLVIQSLDYSDQGNYSCVASTELDEVESRAQL 600
Cdd:cd20976    13 AVE--GQDFVAQCSARGKPV--PRITWIRNAQPLQYAADRSTCEAGVGELHIQDVLPEDHGTYTCLAKNAAGQVSCSAWV 88


                  ..
gi 569009785  601 LV 602
Cdd:cd20976    89 TV 90

Immunoglobulin (Ig)-like domain found in Perlecan and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in Perlecan. Perlecan is a large multi-domain heparin sulfate proteoglycan, important in tissue development and organogenesis. Perlecan can be represented as 5 major portions; its fourth major portion (domain IV) is a tandem repeat of immunoglobulin-like domains (Ig2-Ig15) which can vary in size due to alternative splicing. Perlecan binds many cellular and extracellular ligands. Its domain IV region has many binding sites. Some of these have been mapped at the level of individual Ig-like domains, including a site restricted to the Ig5 domain for heparin/sulfatide, a site restricted to the Ig3 domain for nidogen-1 and nidogen-2, a site restricted to Ig4-5 for fibronectin, and sites restricted to Ig2 and to Ig13-15 for fibulin-2. 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.

Pssm-ID: 409412 Cd Length: 85 Bit Score: 43.31 E-value: 4.09e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  518 PRSAIEKKGARVTFTCQA-SFDPSLqaSITW-RGDGRDLQERGDSDkyfiedGKLVIQSLDYSDQGNYSCVASTELDEVE 595
Cdd:cd05754     8 PRSQEVRPGADVSFICRAkSKSPAY--TLVWtRVNGTLPSRAMDFN------GILTIRNVQLSDAGTYVCTGSNMLDTDE 79


                  ....*
gi 569009785  596 SRAQL 600
Cdd:cd05754    80 ATATL 84

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 409395 [Multi-domain] Cd Length: 96 Bit Score: 43.67 E-value: 4.34e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  233 KPRLLFPTNSSsrlvALQGQSLILECIAEGFPTPTIKWLHPSDPM------PTDRVIYQNHNK--TLQLLNVGEEDDGEY 304
Cdd:cd05732     2 QPKITYLENQT----AVELEQITLTCEAEGDPIPEITWRRATRGIsfeegdLDGRIVVRGHARvsSLTLKDVQLTDAGRY 77

                          90
                  ....*....|....*....
gi 569009785  305 TCLAENSLGSARHAYYVTV 323
Cdd:cd05732    78 DCEASNRIGGDQQSMYLEV 96

First 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 first 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 first 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 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, including vascular (VCAM), intercellular (ICAM), neural (NCAM) and mucosal addressin (MADCAM) cell adhesion molecules, as well as junction adhesion molecules (JAM).

Pssm-ID: 409571 Cd Length: 91 Bit Score: 43.33 E-value: 4.57e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  327 PYWLQKPQSHLYGPGETARLDCQVQGRPQP-EITWRINGMSMETVNKDQKYRIEQGSLILSNVQPSDTMVTQCEARNQHG 405
Cdd:cd20979     1 PVLKEQPAEVLFREGQPTVLECVTEGGDQGvKYSWLKDGKSFNWQEHNVAQRKDEGSLVFLKPQASDEGQYQCFAETPAG 80


                  .
gi 569009785  406 L 406
Cdd:cd20979    81 V 81

Immunoglobulin (Ig)-like domain of human neurofascin (NF); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of human neurofascin (NF). NF 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 a cytoplasmic domain. NF has many alternatively spliced isoforms having different temporal expression patterns during development. NF participates in axon subcellular targeting and synapse formation, however little is known of the functions of the different isoforms. 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 lacks a C" strand.

Pssm-ID: 409459 Cd Length: 95 Bit Score: 43.43 E-value: 4.80e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569009785  253 SLILECIAEGFPTPTIKWLHPS-------DPmptdRVIYQNHNKTLQLLNVG----EEDDGEYTCLAENSLGSA 315
Cdd:cd05875    18 NILIECEAKGNPVPTFHWTRNGkffnvakDP----RVSMRRRSGTLVIDFRGggrpEDYEGEYQCFARNKFGTA 87

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule 1(NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-non-NCAM) interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143277 [Multi-domain] Cd Length: 97 Bit Score: 43.43 E-value: 5.64e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  233 KPRLLFPTNSSSrlVALQGQsLILECIAEGFPTPTIKWLHPSDPMPTD------RVIYQNHNK--TLQLLNVGEEDDGEY 304
Cdd:cd05869     2 KPKITYVENQTA--MELEEQ-ITLTCEASGDPIPSITWRTSTRNISSEektldgHIVVRSHARvsSLTLKYIQYTDAGEY 78

                          90
                  ....*....|....*....
gi 569009785  305 TCLAENSLGSARHAYYVTV 323
Cdd:cd05869    79 LCTASNTIGQDSQSMYLEV 97

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 43.00 E-value: 6.25e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 569009785  341 GETARLDCQVQGRPQPEITWRINGMSMEtvNKDQKYRI-EQGS-LILSNVQPSDTMVTQCEARNQHG 405
Cdd:cd05730    18 GQSVTLACDADGFPEPTMTWTKDGEPIE--SGEEKYSFnEDGSeMTILDVDKLDEAEYTCIAENKAG 82

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143223 Cd Length: 69 Bit Score: 42.17 E-value: 6.38e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 569009785  345 RLDCQVQGRPQPEITWRINGMSmetVNKDQKYRI-EQGSLILSNVQPSDTMVTQCEARNQHG 405
Cdd:cd05746     2 QIPCSAQGDPEPTITWNKDGVQ---VTESGKFHIsPEGYLAIRDVGVADQGRYECVARNTIG 60

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 42.86 E-value: 6.71e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 569009785  435 GSTAYLLCKAFGAPVPSVQWLDEEGTTVLQDE-------RFFPYANGTLSIRDLQANDTGRYFCQAAND 496
Cdd:cd05734    16 GKAVVLNCSADGYPPPTIVWKHSKGSGVPQFQhivplngRIQLLSNGSLLIKHVLEEDSGYYLCKVSND 84

Fifth immunoglobulin (Ig) domain of contactin-1; The members here are composed of the fifth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409438 Cd Length: 89 Bit Score: 42.68 E-value: 7.04e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 569009785  431 MAVEGSTAYLLCKAFGAPVPSVQWldEEGTTVL-QDERFFPYANGTLSIRDLQANDTGRYFCQAANDQNNVTILANLQV 508
Cdd:cd05852    13 LAAKGGRVIIECKPKAAPKPKFSW--SKGTELLvNNSRISIWDDGSLEILNITKLDEGSYTCFAENNRGKANSTGVLSV 89

Sixth 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 sixth 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.

Pssm-ID: 409551 Cd Length: 94 Bit Score: 42.86 E-value: 7.89e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569009785   55 RGRPQVEFRWTKDGIHFkpKEELGVVVHE-APYSGSFTIEgnnSFAQRFQGIYRCYASNKLGTA 117
Cdd:cd20959    28 GGDLPLNIRWTLDGQPI--SDDLGITVSRlGRRSSILSID---SLEASHAGNYTCHARNSAGSA 86

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.

Pssm-ID: 409400 [Multi-domain] Cd Length: 91 Bit Score: 42.69 E-value: 7.92e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785   32 ITEQSPRRLVVFPTDDISLKCEARGRPQVEFRWTKDGIHFKPKEELGVVvhEAPYSGSFTIEGNNsfaQRFQGIYRCYAS 111
Cdd:cd05738     1 IIDMGPQLKVVEKARTATMLCAASGNPDPEISWFKDFLPVDTATSNGRI--KQLRSGALQIENSE---ESDQGKYECVAT 75

                          90
                  ....*....|...
gi 569009785  112 NKLGTAMSHEIQL 124
Cdd:cd05738    76 NSAGTRYSAPANL 88

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.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 42.63 E-value: 8.17e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  518 PRSAIEKKGARVTFTCQASFDPSLQasITWRGDGRDLQERgDSDKY-FIEDG-KLVIQSLDYSDQGNYSCVASTELDEVE 595
Cdd:cd05736     7 PEFQAKEPGVEASLRCHAEGIPLPR--VQWLKNGMDINPK-LSKQLtLIANGsELHISNVRYEDTGAYTCIAKNEGGVDE 83


                  ....*..
gi 569009785  596 SRAQLLV 602
Cdd:cd05736    84 DISSLFV 90

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.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 42.62 E-value: 8.19e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569009785  432 AVEGSTAYLLCKAFGAPVPSVQWL-DEEGTTVLQDERFFPYANGTLSIRDLQANDTGRYFCQAANDQNNVTILANLQV 508
Cdd:cd20976    13 AVEGQDFVAQCSARGKPVPRITWIrNAQPLQYAADRSTCEAGVGELHIQDVLPEDHGTYTCLAKNAAGQVSCSAWVTV 90

First immunoglobulin (Ig) domain of contactin-2; 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-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. 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. 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-2 is also expressed in retinal amacrine cells in the developing chick retina, corresponding to the period of formation and maturation of AC processes. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409437 [Multi-domain] Cd Length: 97 Bit Score: 42.60 E-value: 9.64e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  327 PYWLQKPQSHLYGPG---ETARLDCQVQGRPQPEITWRINGMSMEtVNKDQKYRIEQGSLILSN-VQPSDTMVTQCEARN 402
Cdd:cd05850     3 PVFEEQPSSTLFPEGsaeEKVTLACRARASPPATYRWKMNGTELK-MEPDSRYRLVAGNLVISNpVKAKDAGSYQCLASN 81


                  ....*..
gi 569009785  403 QHGLLLA 409
Cdd:cd05850    82 RRGTVVS 88

Second Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the second 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.

Pssm-ID: 409392 Cd Length: 88 Bit Score: 42.17 E-value: 1.15e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 569009785  150 LPCNPPPSAAPLRIYWM-NSKILHIKQDERVSMGQ-NGDLYFANVLTSDnHSDYICNAHFP 208
Cdd:cd05727    15 LFCDPPPHYPDLSYRWLlNEFPNFIPEDGRRFVSQtNGNLYIAKVEASD-RGNYSCFVSSP 74

Immunoglobulin (Ig)-like domain of class III semaphorin Sema3; The members here are composed of the immunoglobulin (Ig)-like domain of Sema3 and similar proteins. Semaphorins are classified based on structural features additional to the Sema domain. Sema3 is a Class III semaphorin that is secreted. It is a vertebrate class having a Sema domain, an Ig domain, a short basic domain. They have been shown to be axonal guidance cues and have a part in the regulation of the cardiovascular, immune, and respiratory systems. Sema3A, the prototype member of this class III subfamily, induces growth cone collapse and is an inhibitor of axonal sprouting. In perinatal rat cortex, it acts as a chemoattractant and functions to direct the orientated extension of apical dendrites. It may play a role, prior to the development of apical dendrites, in signaling the radial migration of newborn cortical neurons towards the upper layers. Sema3A selectively inhibits vascular endothelial growth factor receptor (VEGF)-induced angiogenesis and induces microvascular permeability. This group also includes Sema3B, -C, -D, -E, -G.

Pssm-ID: 409455 Cd Length: 92 Bit Score: 42.33 E-value: 1.17e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 569009785  540 SLQASITW---RGDGRDLQERGDSDKYFIEDGKLVIQSLDYSDQGNYSCVA 587
Cdd:cd05871    23 SPQATVKWlfqRGGDQRKEEVKSEERLIVTDRGLLLRSLQRSDAGVYTCQA 73

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.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 41.61 E-value: 1.45e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569009785  432 AVEGSTAYLLCKAFGAPVPSVQWLdeEGTTVLQDERF-FPYANGTLSIRDLQANDTGRYFCQAANDQNNVTILANLQV 508
Cdd:cd20978    13 VKGGQDVTLPCQVTGVPQPKITWL--HNGKPLQGPMErATVEDGTLTIINVQPEDTGYYGCVATNEIGDIYTETLLHV 88

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 41.93 E-value: 1.51e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 569009785  524 KKGARVTFTCQASFDPslQASITWRGDGRDL-QERGDSDKYFIEDGKLVIQSLDYSDQGNYSCVA 587
Cdd:cd20949    12 KEGQSATILCEVKGEP--QPNVTWHFNGQPIsASVADMSKYRILADGLLINKVTQDDTGEYTCRA 74

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 41.71 E-value: 1.71e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  517 GPRSAIEKKGARvtFTCQASFDPSLQasITWRGDGRDLQERGDSDKYFIEDGK--LVIQSLDYSDQGNYSCVASTELDEV 594
Cdd:cd05744     8 GDLEVQEGRLCR--FDCKVSGLPTPD--LFWQLNGKPVRPDSAHKMLVRENGRhsLIIEPVTKRDAGIYTCIARNRAGEN 83


                  ....*...
gi 569009785  595 ESRAQLLV 602
Cdd:cd05744    84 SFNAELVV 91

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule 1(NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-non-NCAM) interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143277 [Multi-domain] Cd Length: 97 Bit Score: 41.89 E-value: 1.85e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 569009785  528 RVTFTCQASFDPSlqASITWRGDGRDLQERGDSdkyfiEDGKLVIQS-----------LDYSDQGNYSCVAS 588
Cdd:cd05869    19 QITLTCEASGDPI--PSITWRTSTRNISSEEKT-----LDGHIVVRSharvssltlkyIQYTDAGEYLCTAS 83

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.

Pssm-ID: 409387 Cd Length: 97 Bit Score: 41.69 E-value: 2.00e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 569009785  431 MAVEGSTAYLLCKAFGAPVPSVQWLdEEGTTV--LQDERFFPYANGTLSIRDLQAN-----DTGRYFCQAAND 496
Cdd:cd05722    12 VAMRGGPVVLNCSAESDPPPKIEWK-KDGVLLnlVSDERRQQLPNGSLLITSVVHSkhnkpDEGFYQCVAQNE 83

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.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 41.41 E-value: 2.13e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785   524 KKGARVTFTCQASFDPSlQASITWRGDG----RDLQERGDSDKYFIEDgkLVIQSLDYSDQGNYSCVASTELDEVESRAQ 599
Cdd:pfam00047    9 LEGDSATLTCSASTGSP-GPDVTWSKEGgtliESLKVKHDNGRTTQSS--LLISNVTKEDAGTYTCVVNNPGGSATLSTS 85


                   .
gi 569009785   600 L 600
Cdd:pfam00047   86 L 86

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 41.23 E-value: 2.14e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 569009785   239 PTNSSSRLVALQGQSLILECIAEGFPTPTIKWLHPSDPMPTdrviyqnhNKTLQLLNVGEEDDGEYTCLAENSLGS 314
Cdd:pfam13895    2 PVLTPSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDGSAISS--------SPNFFTLSVSAEDSGTYTCVARNGRGG 69

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 41.44 E-value: 2.41e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785   33 TEQSPRRLVVFPTDD-ISLKCEARGRPQVEFRWTKDGIHFKPKEELGVV-VHEAPYsgSFTIEgnnSFAQRFQGIYRCYA 110
Cdd:cd05729     6 TEKMEEREHALPAANkVRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTkVEEKGW--SLIIE---RAIPRDKGKYTCIV 80


                  ....*.
gi 569009785  111 SNKLGT 116
Cdd:cd05729    81 ENEYGS 86

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.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 41.08 E-value: 2.55e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  346 LDCQVQGRPQPEITWRINGMSMETVNKDQKYRIEQGSLILSNVQPSDTMVTQCEARNQHGLLLANAYIYV 415
Cdd:cd20976    21 AQCSARGKPVPRITWIRNAQPLQYAADRSTCEAGVGELHIQDVLPEDHGTYTCLAKNAAGQVSCSAWVTV 90

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.

Pssm-ID: 409442 Cd Length: 92 Bit Score: 41.38 E-value: 2.59e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 569009785  435 GSTAYLLCKAFGAPVPSVQWLDEEGTTVLQDERFFPYANGTLSIRDLQANDTGRYFCQAAN 495
Cdd:cd05856    19 GSSVRLKCVASGNPRPDITWLKDNKPLTPPEIGENKKKKWTLSLKNLKPEDSGKYTCHVSN 79

Sixth 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 sixth 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.

Pssm-ID: 409551 Cd Length: 94 Bit Score: 41.32 E-value: 2.62e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  248 ALQGQSLILECIAEGFPTP-TIKWLHPSDPMPTDRVI----YQNHNKTLQLLNVGEEDDGEYTCLAENSLGSARHAYYVT 322
Cdd:cd20959    14 AQVGMRAQLHCGVPGGDLPlNIRWTLDGQPISDDLGItvsrLGRRSSILSIDSLEASHAGNYTCHARNSAGSASYTAPLT 93


                  .
gi 569009785  323 V 323
Cdd:cd20959    94 V 94

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.

Pssm-ID: 409400 [Multi-domain] Cd Length: 91 Bit Score: 41.15 E-value: 2.96e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  430 YMAVEGS-TAYLLCKAFGAPVPSVQWLDE--EGTTVLQDERFFPYANGTLSIRDLQANDTGRYFCQAANDQ-NNVTILAN 505
Cdd:cd05738     8 LKVVEKArTATMLCAASGNPDPEISWFKDflPVDTATSNGRIKQLRSGALQIENSEESDQGKYECVATNSAgTRYSAPAN 87


                  ....
gi 569009785  506 LQVK 509
Cdd:cd05738    88 LYVR 91

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.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 40.95 E-value: 3.15e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785   30 PVIT-EQSPRRLVVFPTDDISLKCEARGRPQVEFRWTKDGIHFKPKEElGVVVHEapySGS-FTIEgnnSFAQRFQGIYR 107
Cdd:cd20970     1 PVIStPQPSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNT-RYIVRE---NGTtLTIR---NIRRSDMGIYL 73

                          90
                  ....*....|....*...
gi 569009785  108 CYASNKLGTAMSHEIQLV 125
Cdd:cd20970    74 CIASNGVPGSVEKRITLQ 91

First immunoglobulin (Ig) domain of contactin-2; 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-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. 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. 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-2 is also expressed in retinal amacrine cells in the developing chick retina, corresponding to the period of formation and maturation of AC processes. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409437 [Multi-domain] Cd Length: 97 Bit Score: 41.06 E-value: 3.52e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  518 PRSAIEKKgarVTFTCQASFDPSlqASITWRGDGRDLQERGDSdKYFIEDGKLVIQS-LDYSDQGNYSCVASTELDEVES 596
Cdd:cd05850    15 PEGSAEEK---VTLACRARASPP--ATYRWKMNGTELKMEPDS-RYRLVAGNLVISNpVKAKDAGSYQCLASNRRGTVVS 88


                  ....*...
gi 569009785  597 RAQLLVVG 604
Cdd:cd05850    89 REASLRFG 96

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

Pssm-ID: 409360 Cd Length: 96 Bit Score: 40.85 E-value: 3.73e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 569009785  258 CI---AEGFPTPTIKWLH------PSDPMPTDRVIYQN----HNKTLQLLNVGEEDDGEYTCLAENSLGSAR 316
Cdd:cd04971    17 CIpftVRGNPKPTLTWYHngavlnESDYIRTEIHYEAAtpteYHGCLKFDNPTHVNNGNYTLVASNEYGQDS 88

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 40.69 E-value: 3.79e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  341 GETARLDCQVQGRPQPEITWrINGMSMETVNKdqkyRI---EQGSLILSNVQPSDTMVTQCEARNQHGLLLANAYIYVVQ 417
Cdd:cd20968    14 GLKAVLPCTTMGNPKPSVSW-IKGDDLIKENN----RIavlESGSLRIHNVQKEDAGQYRCVAKNSLGIAYSKPVTIEVE 88

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.

Pssm-ID: 143220 Cd Length: 78 Bit Score: 40.17 E-value: 3.92e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  435 GSTAYLLCKAFGAPVPSVQWLDEEGTtvLQDERFFPYAN----GTLSIRDLQANDTGRYFCQAANDQNNV 500
Cdd:cd05743     1 GETVEFTCVATGVPTPIINWRLNWGH--VPDSARVSITSeggyGTLTIRDVKESDQGAYTCEAINTRGMV 68

Immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains NrCAM [Ng(neuronglia)CAM-related cell adhesion molecule], which is primarily expressed in the nervous system, and human neurofascin. 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 lacks a C" strand.

Pssm-ID: 409396 [Multi-domain] Cd Length: 94 Bit Score: 40.85 E-value: 4.15e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  331 QKPQSHLYGPGETARLDCQVQGRPQPEITWRINGMSMEtVNKDQKY--RIEQGSLILS--NVQPSDTM-VTQCEARNQHG 405
Cdd:cd05733     6 QSPKDYIVDPRDNITIKCEAKGNPQPTFRWTKDGKFFD-PAKDPRVsmRRRSGTLVIDnhNGGPEDYQgEYQCYASNELG 84


                  ....*
gi 569009785  406 LLLAN 410
Cdd:cd05733    85 TAISN 89

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143223 Cd Length: 69 Bit Score: 39.86 E-value: 4.55e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  256 LECIAEGFPTPTIKWLHPSDPMPTDRVIYQNHNKTLQLLNVGEEDDGEYTCLAENSLGSA 315
Cdd:cd05746     3 IPCSAQGDPEPTITWNKDGVQVTESGKFHISPEGYLAIRDVGVADQGRYECVARNTIGYA 62

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 409395 [Multi-domain] Cd Length: 96 Bit Score: 40.59 E-value: 5.11e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 569009785  341 GETARLDCQVQGRPQPEITWR--INGMSMETVNKDQ----KYRIEQGSLILSNVQPSDTMVTQCEARNQHG 405
Cdd:cd05732    16 LEQITLTCEAEGDPIPEITWRraTRGISFEEGDLDGrivvRGHARVSSLTLKDVQLTDAGRYDCEASNRIG 86

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third 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. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 40.22 E-value: 5.42e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 569009785  341 GETARLDCQVQGRPQPEITWR-INGMSMETvnkdQKYRIEQGSLILSNVQPSDTMVTQCEARNQHGLLLANAYIYV 415
Cdd:cd04968    16 GQTVTLECFALGNPVPQIKWRkVDGSPSSQ----WEITTSEPVLEIPNVQFEDEGTYECEAENSRGKDTVQGRIIV 87

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 40.26 E-value: 6.02e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569009785  434 EGSTAYLLCKAFGAPVPSVQWLdEEGTTVLQDERFFPYANG---TLSIRDLQANDTGRYFCQAANDQNNVTILANLQV 508
Cdd:cd20972    15 EGSKVRLECRVTGNPTPVVRWF-CEGKELQNSPDIQIHQEGdlhSLIIAEAFEEDTGRYSCLATNSVGSDTTSAEIFV 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.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 40.12 E-value: 6.68e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  518 PRSAIEKKGARVTFTCQASFDPslQASITWRGDGRDLQERGDSDKYFIEDGKLVIQSLDYSDQGNYSCVASTELDEVESR 597
Cdd:cd04978     6 PPSLVLSPGETGELICEAEGNP--QPTITWRLNGVPIEPAPEDMRRTVDGRTLIFSNLQPNDTAVYQCNASNVHGYLLAN 83


                  ....*.
gi 569009785  598 AQLLVV 603
Cdd:cd04978    84 AFLHVL 89

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.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 39.69 E-value: 6.81e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  517 GPRSAIEKKGARVTFTCQASFDPSlqASITWRGDGRDLQERgdsdKYFI-EDGKLVIQSLDYSDQGNYSCVASTELDEVE 595
Cdd:cd05725     3 RPQNQVVLVDDSAEFQCEVGGDPV--PTVRWRKEDGELPKG----RYEIlDDHSLKIRKVTAGDMGSYTCVAENMVGKIE 76


                  ....*..
gi 569009785  596 SRAQLLV 602
Cdd:cd05725    77 ASATLTV 83

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

Pssm-ID: 409408 [Multi-domain] Cd Length: 92 Bit Score: 39.80 E-value: 7.22e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 569009785   48 ISLKCEARGR-PQVEFRWTKDGIHFKPKEELGVVVHEAPYSGSFTIegnNSFAQRFQGIYRCYASNKLG 115
Cdd:cd05750    17 LVLKCEATSEnPSPRYRWFKDGKELNRKRPKNIKIRNKKKNSELQI---NKAKLEDSGEYTCVVENILG 82

First immunoglobulin (Ig) domain of contactin-1; 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-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409436 [Multi-domain] Cd Length: 95 Bit Score: 39.94 E-value: 8.08e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785   30 PVITEQSPRrlVVFPTDD----ISLKCEARGRPQVEFRWTKDGIHFKPKEElgvvvHEAPYSGSFTIegNNSFAQRFQGI 105
Cdd:cd05849     2 PVFEEQPID--TIYPEEStegkVSVNCRARANPFPIYKWRKNNLDIDLTND-----RYSMVGGNLVI--NNPDKYKDAGR 72

                          90
                  ....*....|....*....
gi 569009785  106 YRCYASNKLGTAMSHEIQL 124
Cdd:cd05849    73 YVCIVSNIYGKVRSREATL 91

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. 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.

Pssm-ID: 409473 Cd Length: 92 Bit Score: 39.75 E-value: 8.16e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 569009785  248 ALQGQSLILECIAEGFPTPTIKWLHPSDPMP--TDRV-IYQNHNKTLQLL--NVGEEDDGEYTCLAENSLG 313
Cdd:cd05892    12 VLEGDPVRLECQISAIPPPQIFWKKNNEMLQynTDRIsLYQDNCGRICLLiqNANKKDAGWYTVSAVNEAG 82

Second 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 second 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. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of this group show that the second Ig domain lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules, including vascular (VCAM), intercellular (ICAM), neural (NCAM) and mucosal addressin (MADCAM) cell adhesion molecules, as well as junction adhesion molecules (JAM).

Pssm-ID: 409557 Cd Length: 101 Bit Score: 39.92 E-value: 8.66e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  236 LLFPTNSSSRLVALQGQSLILEC-IAEGFPTPTIKW---LHPSDPMPT---DRVIYQNHNKTLQLLNVGEED---DGEYT 305
Cdd:cd20965     2 LLDPQVKTKEKKPVEGKPFKLDCnVPPGYPKPTIEWkkqLVSDSSKADtilDRRITISPNGDLYFTNVTKEDvstDYKYV 81


                  ....*
gi 569009785  306 CLAEN 310
Cdd:cd20965    82 CVAKT 86

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 2 (NCAM-2); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule NCAM-2 (also known as OCAM/mamFas II and RNCAM). NCAM-2 is organized similarly to NCAM, including five N-terminal Ig-like domains and two fibronectin type III domains. NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE), and may function like NCAM, as an adhesion molecule. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143278 [Multi-domain] Cd Length: 98 Bit Score: 39.96 E-value: 8.78e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 569009785  341 GETARLDCQVQGRPQPEITWR--INGMSMETVNKDQKYRIE------QGSLILSNVQPSDTMVTQCEARNQHG 405
Cdd:cd05870    16 NGAATLSCKAEGEPIPEITWKraSDGHTFSEGDKSPDGRIEvkgqhgESSLHIKDVKLSDSGRYDCEAASRIG 88

Immunoglobulin (Ig)-like domain of human neurofascin (NF); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of human neurofascin (NF). NF 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 a cytoplasmic domain. NF has many alternatively spliced isoforms having different temporal expression patterns during development. NF participates in axon subcellular targeting and synapse formation, however little is known of the functions of the different isoforms. 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 lacks a C" strand.

Pssm-ID: 409459 Cd Length: 95 Bit Score: 39.57 E-value: 9.87e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  331 QKPQSHLYGPGETARLDCQVQGRPQPEITWRINGmSMETVNKDQK--YRIEQGSLIL---SNVQPSD-TMVTQCEARNQH 404
Cdd:cd05875     6 QSAKDYIVDPRDNILIECEAKGNPVPTFHWTRNG-KFFNVAKDPRvsMRRRSGTLVIdfrGGGRPEDyEGEYQCFARNKF 84


                  ....*.
gi 569009785  405 GLLLAN 410
Cdd:cd05875    85 GTALSN 90

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

Pssm-ID: 462230 Cd Length: 109 Bit Score: 40.13 E-value: 9.88e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785   431 MAVEGSTAYLLCKA---FGAPVPSVQWL----DEEGTTVL-----------QDERF-----FPYANGTLSIRDLQANDTG 487
Cdd:pfam07686    7 TVALGGSVTLPCTYsssMSEASTSVYWYrqppGKGPTFLIayysngseegvKKGRFsgrgdPSNGDGSLTIQNLTLSDSG 86

                           90
                   ....*....|...
gi 569009785   488 RYFCQAANDQNNV 500
Cdd:pfam07686   87 TYTCAVIPSGEGV 99

Immunoglobulin (Ig)-like domain of class III semaphorin Sema3; The members here are composed of the immunoglobulin (Ig)-like domain of Sema3 and similar proteins. Semaphorins are classified based on structural features additional to the Sema domain. Sema3 is a Class III semaphorin that is secreted. It is a vertebrate class having a Sema domain, an Ig domain, a short basic domain. They have been shown to be axonal guidance cues and have a part in the regulation of the cardiovascular, immune, and respiratory systems. Sema3A, the prototype member of this class III subfamily, induces growth cone collapse and is an inhibitor of axonal sprouting. In perinatal rat cortex, it acts as a chemoattractant and functions to direct the orientated extension of apical dendrites. It may play a role, prior to the development of apical dendrites, in signaling the radial migration of newborn cortical neurons towards the upper layers. Sema3A selectively inhibits vascular endothelial growth factor receptor (VEGF)-induced angiogenesis and induces microvascular permeability. This group also includes Sema3B, -C, -D, -E, -G.

Pssm-ID: 409455 Cd Length: 92 Bit Score: 39.64 E-value: 9.93e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 569009785  433 VEGSTAYLLCKAfGAPVPSVQWL-----DEEGTTVLQDERFFPYANGTLsIRDLQANDTGRYFCQA 493
Cdd:cd05871    10 VEGNSTFLECLP-KSPQATVKWLfqrggDQRKEEVKSEERLIVTDRGLL-LRSLQRSDAGVYTCQA 73

Third immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F (also known as LAR), type IIa; member of the I-set of IgSF domains; The members here are composed of the third 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. Included in this group is Drosophila LAR (DLAR).

Pssm-ID: 409401 Cd Length: 82 Bit Score: 39.11 E-value: 1.08e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 569009785  433 VEGSTAYLLCKAFGAPVPSVQWLdeEGTTVLQDERFFPYANGTLSIRDLQanDTGRYFCQAANDQNNVTILANLQVK 509
Cdd:cd05739    10 MPGGSVNLTCVAVGAPMPYVKWM--KGGEELTKEDEMPVGRNVLELTNIY--ESANYTCVAISSLGMIEATAQVTVK 82

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.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 39.37 E-value: 1.12e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 569009785  346 LDCQVQGRPQPEITWRINGmsmETVNKDQKYRI-EQGSLILSNVQPSDTMVTQCEARNQHG 405
Cdd:cd04969    22 IECKPKASPKPTISWSKGT---ELLTNSSRICIlPDGSLKIKNVTKSDEGKYTCFAVNFFG 79

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.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 39.24 E-value: 1.17e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 569009785  427 NQTYMAV-EGSTAYLLCKAFGAPVPSVQWL---DEEGTTVLQDERFFPYANGtLSIRDLQANDTGRYFCQAAN 495
Cdd:cd20949     5 NAYVTTVkEGQSATILCEVKGEPQPNVTWHfngQPISASVADMSKYRILADG-LLINKVTQDDTGEYTCRAYQ 76

First immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR). 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 all FGFs.

Pssm-ID: 409362 Cd Length: 94 Bit Score: 39.49 E-value: 1.19e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785   22 IPDEllEPPVITEQSPRRLVVFPTDDISLKCEARGRPQVeFRWTKDGIHFKPKEELGVVVHEAPYSGSftiegnnsfAQR 101
Cdd:cd04973     3 LPPE--APPTYQISEVESYSAHPGDLLQLRCRLRDDVQS-INWTKDGVQLGENNRTRITGEEVQIKDA---------VPR 70

                          90
                  ....*....|....*
gi 569009785  102 FQGIYRCYASNKLGT 116
Cdd:cd04973    71 DSGLYACVTSSPSGS 85

Second Ig-like domain of Junctional adhesion molecule-1 (JAM1); a member of the I-set of IgSF domains; The members here are composed of the second Ig-like domain of Junctional adhesion molecule-1 (JAM1). JAM1 is an immunoglobulin superfamily (IgSF) protein with two Ig-like domains in its extracellular region; it plays a role in the formation of endothelial and epithelial tight junction and acts as a receptor for mammalian reovirus sigma-1. The 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 second Ig-like domain of JAM1 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, the A strand of the I-set is discontinuous but lacks 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.

Pssm-ID: 409542 Cd Length: 97 Bit Score: 39.61 E-value: 1.24e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569009785  341 GETARLDCQVQ-GRPQPEITWRINGMSMETVNK------DQKYRI--EQGSLILSNVQPSDTMVTQCEARNQHG 405
Cdd:cd20950    12 GNRAVLTCSEPdGSPPSEYTWFKDGVVMPTNPKstrafsNSSYSLdpTTGELVFDPLSASDTGEYSCEARNGYG 85

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 39.13 E-value: 1.33e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 569009785  526 GARVTFTCQASFDPslQASITWRGDGRDLQERGDSDKYFIEDGK--LVIQSLDYSDQGNYSCVASTELDEVE 595
Cdd:cd05729    19 ANKVRLECGAGGNP--MPNITWLKDGKEFKKEHRIGGTKVEEKGwsLIIERAIPRDKGKYTCIVENEYGSIN 88

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 409395 [Multi-domain] Cd Length: 96 Bit Score: 39.04 E-value: 1.52e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 569009785  525 KGARVTFTCQASFDPSlqASITWRGDGRDLQ-ERGDSDKYFIEDGK-----LVIQSLDYSDQGNYSCVAST 589
Cdd:cd05732    15 ELEQITLTCEAEGDPI--PEITWRRATRGISfEEGDLDGRIVVRGHarvssLTLKDVQLTDAGRYDCEASN 83

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 39.13 E-value: 1.65e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 569009785  435 GSTAYLLCKAFGAPVPSVQWLdEEGTTVLQDERFFPYANG----TLSIRDLQANDTGRYFCQAAN 495
Cdd:cd05729    19 ANKVRLECGAGGNPMPNITWL-KDGKEFKKEHRIGGTKVEekgwSLIIERAIPRDKGKYTCIVEN 82

Second immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R), and similar domains; The members here are composed of the second immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R; also known as cluster of differentiation (CD) 121). IL-1 alpha and IL-1 beta are cytokines which participate in the regulation of inflammation, immune responses, and hematopoiesis. These cytokines bind to the IL-1 receptor type 1 (IL1R1), which is activated on additional association with interleukin-1 receptor accessory protein (IL1RAP). IL-1 also binds a second receptor designated type II (IL1R2). Mature IL1R1 consists of three IG-like domains, a transmembrane domain, and a large cytoplasmic domain. Mature IL1R2 is organized similarly except that it has a short cytoplasmic domain. The latter does not initiate signal transduction. A naturally occurring cytokine IL-1RA (IL-1 receptor antagonist) is widely expressed and binds to IL-1 receptors, inhibiting the binding of IL-1 alpha and IL-1 beta. This group also contains ILIR-like 1 (IL1R1L) which maps to the same chromosomal location as IL1R1 and IL1R2.

Pssm-ID: 409415 Cd Length: 92 Bit Score: 38.84 E-value: 1.71e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 569009785  537 FDPSLQASITWRGDGRDLQERGdsdKYFIEDGKLVIQSLDYSDQGNYSCVAS 588
Cdd:cd05757    24 KNENVLPPIQWYKDCKPLQGDK---RFIPKGSKLLIQNVTEEDAGNYTCKFT 72

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 38.53 E-value: 1.83e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569009785   525 KGARVTFTCQASFDPslQASITWRGDGRDLQERGDSdkyfiedgklVIQSLDYSDQGNYSCVAS 588
Cdd:pfam13895   13 EGEPVTLTCSAPGNP--PPSYTWYKDGSAISSSPNF----------FTLSVSAEDSGTYTCVAR 64

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 38.14 E-value: 1.94e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785    30 PVITEQSPrrlVVFPTDDISLKCEARGRPQVEFRWTKDgihfkpkeelGVVVHEAPYSGSFTIEGNNSfaqrfqGIYRCY 109
Cdd:pfam13895    2 PVLTPSPT---VVTEGEPVTLTCSAPGNPPPSYTWYKD----------GSAISSSPNFFTLSVSAEDS------GTYTCV 62

                           90
                   ....*....|....*.
gi 569009785   110 ASNKLGTAMSHEIQLV 125
Cdd:pfam13895   63 ARNGRGGKVSNPVELT 78

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth 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.

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 38.78 E-value: 2.36e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  518 PRSAIEKKGARVTFTCQASFDPslQASITWRGDGRDL-----QERGDSDKYFI-EDGKLVIQSLDYSDQGNYSCVASTEL 591
Cdd:cd05726     6 PRDQVVALGRTVTFQCETKGNP--QPAIFWQKEGSQNllfpyQPPQPSSRFSVsPTGDLTITNVQRSDVGYYICQALNVA 83

                          90
                  ....*....|...
gi 569009785  592 DEVESRAQLLVVG 604
Cdd:cd05726    84 GSILAKAQLEVTD 96

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first 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. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409356 [Multi-domain] Cd Length: 96 Bit Score: 38.38 E-value: 2.55e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  237 LFPTNSSSRLVALQgqslileCIAEGFPTPTIKWLHPS---DPMPTDRviYQNHNKTLQLLN-VGEEDDGEYTCLAENSL 312
Cdd:cd04967    12 IFPEDSDEKKVALN-------CRARANPVPSYRWLMNGteiDLESDYR--YSLVDGTLVISNpSKAKDAGHYQCLATNTV 82


                  ....
gi 569009785  313 GSAR 316
Cdd:cd04967    83 GSVL 86

First immunoglobulin (Ig)-like domain of Tyro3 receptor tyrosine kinase (RTK), and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain of Tyro3 receptor tyrosine kinase (RTK). Tyro3 together with Axl and Mer form 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, in the lymphatic and vascular systems, and in the 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.

Pssm-ID: 409553 Cd Length: 87 Bit Score: 38.20 E-value: 2.57e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 569009785  434 EGSTAYLLCKAFGAPVPSVQWLDEEGTTVLQDERFFPYAN----GTLSIRDLQANDTGRYFCQAAN 495
Cdd:cd20961     7 QGQPVKLNCSVEGMEEPDIQWVKDGAVVQNLDQLYIPVSEqhwiGFLSLKSVERSDAGRYWCQVED 72

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.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 38.54 E-value: 2.64e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 569009785  246 LVALQGQSLILECIAEGFPTPTIKWLHPSDPMPTDR----VIYQNHNKTLQLLNVGEEDDGEYTCLAENSLG 313
Cdd:cd20990    10 LTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSahkmLVRENGVHSLIIEPVTSRDAGIYTCIATNRAG 81

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

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 38.25 E-value: 2.81e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785   32 ITEQSPRRLVVFPTDDISLKCEARGRPQVEFRWTKDGIHFKPKEElgvvvheapysgSFTIEGNNSFAQRF-----QGIY 106
Cdd:cd20952     1 IILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDE------------RITTLENGSLQIKGaeksdTGEY 68

                          90
                  ....*....|....
gi 569009785  107 RCYASNKLGTAMSH 120
Cdd:cd20952    69 TCVALNLSGEATWS 82

Phage-related protein, tail protein J [Mobilome: prophages, transposons];

Pssm-ID: 443767 [Multi-domain] Cd Length: 978 Bit Score: 41.85 E-value: 2.87e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  622 QSQVHLSWSPAEDHNSpiekYDIEFEDkemAPEKWFSLGKVpgnqTSTTLKLSPYV--HYTFRVTAINKYG-PGEPSPVS 698
Cdd:COG4733   551 VTTLTVSWDAPAGAVA----YEVEWRR---DDGNWVSVPRT----SGTSFEVPGIYagDYEVRVRAINALGvSSAWAASS 619

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  699 ETVVTPEAAPEKNPVDVRGEGNeTNNMVITWKplrwMDWNAPQIQYRVQWRPQGkqeTWREQTVsDPFLVVSNTSTFVP- 777
Cdd:COG4733   620 ETTVTGKTAPPPAPTGLTATGG-LGGITLSWS----FPVDADTLRTEIRYSTTG---DWASATV-AQALYPGNTYTLAGl 690

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 569009785  778 -----YEIKVQAVNNQGKGPEPQVtigySGEDYPQVSPELEDIT 816
Cdd:COG4733   691 kagqtYYYRARAVDRSGNVSAWWV----SGQASADAAGILDAIT 730

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.

Pssm-ID: 409443 [Multi-domain] Cd Length: 95 Bit Score: 38.30 E-value: 2.99e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785   33 TEQSPRRLVVFPT-DDISLKCEARGRPQVEFRWTKDGIHFKPKEEL-GVVVHEAPYSGSFtiegnNSFAQRFQGIYRCYA 110
Cdd:cd05857     6 PEKMEKKLHAVPAaNTVKFRCPAAGNPTPTMRWLKNGKEFKQEHRIgGYKVRNQHWSLIM-----ESVVPSDKGNYTCVV 80

                          90
                  ....*....|....
gi 569009785  111 SNKLGTaMSHEIQL 124
Cdd:cd05857    81 ENEYGS-INHTYHL 93

CD80-like C2-set immunoglobulin domain; These domains belong to the immunoglobulin superfamily.

Pssm-ID: 400489 Cd Length: 89 Bit Score: 38.17 E-value: 3.11e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 569009785   329 WLQKPQSHLYGPGETARLDCQVQ-GRPQPEITWRINGMSMETVNKDQKYRIEQGsliLSNVQPSDTMVTQCEARNQ 403
Cdd:pfam08205    2 TIEPPASLLEGEGPEVVATCSSAgGKPAPRITWYLDGKPLEAAETSSEQDPESG---LVTVTSELKLVPSRSDHGQ 74

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.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 37.93 E-value: 3.49e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 569009785  517 GPRSAIEkkGARVTFTCQASFDPSlqASITWRGDGRDLQErGDSDKYFiEDGKLVIQSLD-YSDQGNYSCVA 587
Cdd:cd20958     8 GNLTAVA--GQTLRLHCPVAGYPI--SSITWEKDGRRLPL-NHRQRVF-PNGTLVIENVQrSSDEGEYTCTA 73

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 37.57 E-value: 3.64e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 569009785  341 GETARLDCQVQGRPQPEITWRINGMsmeTVNKDQKYRIEQG----SLILSNVQPSDTMVTQCEARNQHG 405
Cdd:cd05748     7 GESLRLDIPIKGRPTPTVTWSKDGQ---PLKETGRVQIETTasstSLVIKNAKRSDSGKYTLTLKNSAG 72

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 37.37 E-value: 3.90e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 569009785   422 ILTKDNQTYMavEGSTAYLLCKAFGAPVPSVQWlDEEGTTVLQDERFFpyangTLSIRdlqANDTGRYFCQAANDQ 497
Cdd:pfam13895    3 VLTPSPTVVT--EGEPVTLTCSAPGNPPPSYTW-YKDGSAISSSPNFF-----TLSVS---AEDSGTYTCVARNGR 67

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.

Pssm-ID: 409388 Cd Length: 84 Bit Score: 37.56 E-value: 3.90e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 569009785  529 VTFTCQASFDPSlqASITWRGDGrDLQERGDsdkYF--IEDGKLVIQSLDYSDQGNYSCVASTELDEVESRAQLLV 602
Cdd:cd05723    15 IVFECEVTGKPT--PTVKWVKNG-DVVIPSD---YFkiVKEHNLQVLGLVKSDEGFYQCIAENDVGNAQASAQLII 84

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.

Pssm-ID: 409435 Cd Length: 96 Bit Score: 38.00 E-value: 3.97e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 569009785  442 CKAFGAPVPSVQWLdEEGTTV-LQDERFFPYANGTLSIRDL-QANDTGRYFCQAAN 495
Cdd:cd05848    26 CEARGNPVPTYRWL-RNGTEIdTESDYRYSLIDGNLIISNPsEVKDSGRYQCLATN 80

Immunoglobulin (Ig)-like domain found in Perlecan and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in Perlecan. Perlecan is a large multi-domain heparin sulfate proteoglycan, important in tissue development and organogenesis. Perlecan can be represented as 5 major portions; its fourth major portion (domain IV) is a tandem repeat of immunoglobulin-like domains (Ig2-Ig15) which can vary in size due to alternative splicing. Perlecan binds many cellular and extracellular ligands. Its domain IV region has many binding sites. Some of these have been mapped at the level of individual Ig-like domains, including a site restricted to the Ig5 domain for heparin/sulfatide, a site restricted to the Ig3 domain for nidogen-1 and nidogen-2, a site restricted to Ig4-5 for fibronectin, and sites restricted to Ig2 and to Ig13-15 for fibulin-2. 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.

Pssm-ID: 409412 Cd Length: 85 Bit Score: 37.54 E-value: 5.04e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  421 RILTKDNQTYMAVEGSTAYLLCKAFG-APVPSVQWLDEEGTTVLQDERFfpyaNGTLSIRDLQANDTGRYFCQAANDQNN 499
Cdd:cd05754     2 QVTVEEPRSQEVRPGADVSFICRAKSkSPAYTLVWTRVNGTLPSRAMDF----NGILTIRNVQLSDAGTYVCTGSNMLDT 77


                  ....*..
gi 569009785  500 VTILANL 506
Cdd:cd05754    78 DEATATL 84

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.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 37.40 E-value: 5.10e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  434 EGSTAYLLCKAFGAPVPSVQWLDE----EGTTVLQDERFFP-YANGTLSIRDLQANDTGRYFCQAANDQNNVTILANLQV 508
Cdd:cd20951    14 EKSDAKLRVEVQGKPDPEVKWYKNgvpiDPSSIPGKYKIESeYGVHVLHIRRVTVEDSAVYSAVAKNIHGEASSSASVVV 93


                  .
gi 569009785  509 K 509
Cdd:cd20951    94 E 94

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.

Pssm-ID: 409388 Cd Length: 84 Bit Score: 37.18 E-value: 5.24e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 569009785  442 CKAFGAPVPSVQWLdEEGTTVLQDERFFPYANGTLSIRDLQANDTGRYFCQAANDQNNVTILANLQV 508
Cdd:cd05723    19 CEVTGKPTPTVKWV-KNGDVVIPSDYFKIVKEHNLQVLGLVKSDEGFYQCIAENDVGNAQASAQLII 84

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.

Pssm-ID: 409453 [Multi-domain] Cd Length: 89 Bit Score: 37.18 E-value: 5.70e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  515 TQGPRSAIEKKGARVTFTCQASFDPslQASITWRGDGRDLQERGDSDKYFIEDGKLVIQSLDYSDQGNYSCVASTELDEV 594
Cdd:cd05867     3 TRRPQSHLYGPGETARLDCQVEGIP--TPNITWSINGAPIEGTDPDPRRHVSSGALILTDVQPSDTAVYQCEARNRHGNL 80


                  ....*....
gi 569009785  595 ESRAQLLVV 603
Cdd:cd05867    81 LANAHVHVV 89

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.

Pssm-ID: 409563 Cd Length: 93 Bit Score: 37.45 E-value: 5.72e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  430 YMAVEGSTAYLLCKAFGAPVPSVQWLdEEGTTVLQDERF------FPYANGTLSIRDLQANdTGRYFCQAANDQNNVTIL 503
Cdd:cd20971    11 LNVRYQSNATLVCKVTGHPKPIVKWY-RQGKEIIADGLKyriqefKGGYHQLIIASVTDDD-ATVYQVRATNQGGSVSGT 88


                  ....*
gi 569009785  504 ANLQV 508
Cdd:cd20971    89 ASLEV 93

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.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 37.17 E-value: 5.95e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  515 TQGPRSAIEKKGARVTFTCQASFDPslQASITWRGDGRDLQERGDSDKYFIEDG--KLVIQSLDYSDQGNYSCVASTELD 592
Cdd:cd20973     1 IQTLRDKEVVEGSAARFDCKVEGYP--DPEVKWMKDDNPIVESRRFQIDQDEDGlcSLIISDVCGDDSGKYTCKAVNSLG 78

                          90
                  ....*....|
gi 569009785  593 EVESRAQLLV 602
Cdd:cd20973    79 EATCSAELTV 88

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.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 37.16 E-value: 6.21e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 569009785  341 GETARLDCQVQGRPQPEITWRINGMSMeTVNKDQKYrIEQGSLILSNVQP-SDTMVTQCEARNQHGL 406
Cdd:cd20958    15 GQTLRLHCPVAGYPISSITWEKDGRRL-PLNHRQRV-FPNGTLVIENVQRsSDEGEYTCTARNQQGQ 79

Immunoglobulin (Ig)-like domain of semaphorin 4D (Sema4D) and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of semaphorin 4D (Sema4D) and similar proteins. Sema4D is a Class IV semaphorin. Semaphorins are classified based on structural features additional to the Sema domain. Sema4D has extracellular Sema and Ig domains, a transmembrane domain, and a short cytoplasmic domain. Sema4D plays a part in the development of GABAergic synapses. Sema4D in addition is an immune semaphorin. It is abundant on resting T cells; its expression is weak on resting B cells and antigen presenting cells (APCs), but is upregulated by various stimuli. The receptor used by Sema4D in the immune system is CD72. Sem4D enhances the activation of B cells and DCs through binding CD72, perhaps by reducing CD72s inhibitory signals. The receptor used by Sema4D in the non-lymphatic tissues is plexin-B1. Sem4D is anchored to the cell surface but its extracellular domain can be released from the cell surface by a metalloprotease-dependent process. Sem4D may mediate its effects in its membrane-bound form and/or its cleaved form.

Pssm-ID: 409457 Cd Length: 87 Bit Score: 37.10 E-value: 6.22e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 569009785  333 PQSHLYGPGETARLDCqVQGRPQPEITWRINGMSMETvnKDQKYRIEQGSLILSNVQPSDTMVTQC 398
Cdd:cd05873     3 PRQRTFKLGGNAELKC-SPKSNLARVVWKFQGKVLKA--ESPKYGLYGDGLLIFNASEADAGRYQC 65

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.

Pssm-ID: 409563 Cd Length: 93 Bit Score: 37.45 E-value: 6.62e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569009785  251 GQSLILECIAEGFPTPTIKWLHPSDPMPTDR--VIYQNHNKTLQLLNVG---EEDDGEYTCLAENSLGSA 315
Cdd:cd20971    16 QSNATLVCKVTGHPKPIVKWYRQGKEIIADGlkYRIQEFKGGYHQLIIAsvtDDDATVYQVRATNQGGSV 85

Immunoglobulin (Ig)-like domain at the C-terminus of semaphorins; The members here are composed of the immunoglobulin (Ig)-like domain in semaphorins. Semaphorins are transmembrane protein that have important roles in a variety of tissues. Functionally, semaphorins were initially characterized for their importance in the development of the nervous system and in axonal guidance. Later they have been found to be important for the formation and functioning of the cardiovascular, endocrine, gastrointestinal, hepatic, immune, musculoskeletal, renal, reproductive, and respiratory systems. Semaphorins function through binding to their receptors and transmembrane semaphorins also serves as receptors themselves. Although molecular mechanism of semaphorins is poorly understood, the Ig-like domains may be involved in ligand binding or dimerization.

Pssm-ID: 409368 Cd Length: 88 Bit Score: 37.05 E-value: 6.71e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 569009785  331 QKPQSHLYGPGETARLDCQVQGRPQPEiTWRINGMSMETVNKDQKYRIEQGSLILSNVQPSDTMVTQCEARN 402
Cdd:cd04979     1 TSFKQISVKEGDTVILSCSVKSNNAPV-TWIHNGKKVPRYRSPRLVLKTERGLLIRSAQEADAGVYECHSGE 71

First immunoglobulin-like domain of vascular endothelial cell adhesion molecule-1 (VCAM-1), and similar domains; member of the I-set of IgSF domains; The members here include the first immunoglobulin-like domain of vascular endothelial cell adhesion molecule-1 (VCAM-1; also known as Cluster of Differentiation 106 (CD106)) and similar proteins. During the inflammation process, these molecules recruit leukocytes onto the vascular endothelium before extravasation to the injured tissues. The interaction of VCAM-1 binding to the beta1 integrin very late antigen (VLA-4) expressed by lymphocytes and monocytes mediates the adhesion of leucocytes to blood vessel walls, and regulates migration across the endothelium. During metastasis, some circulating cancer cells extravasate to a secondary site by a similar process. VCAM-1 may be involved in organ targeted tumor metastasis and may also act as host receptors for viruses and parasites. VCAM-1 contains seven Ig domains. 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 first Ig-like domain of VCAM-1 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, the A strand of the I-set is discontinuous, but lacks a C" strand.

Pssm-ID: 409536 Cd Length: 89 Bit Score: 36.88 E-value: 9.05e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 569009785  240 TNSSSRLVALQGQSLILECIAEGFPTPTIKWLHPSDPMPTDRVIYQNHNKTLQLLNVGEEDDGEYTCLA 308
Cdd:cd20943     5 ISPGSRYAAQIGDSVSLTCSTTGCESPSFSWRTQIDSPLNGKVRNEGTTSTLTLSPVSFENEHSYLCTV 73

C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein (also known as myomesin-2). Myomesin and M-protein are both structural proteins localized to the M-band, a transverse structure in the center of the sarcomere, and are candidates for M-band bridges. Both proteins are modular, consisting mainly of repetitive Ig-like and fibronectin type III (FnIII) domains. Myomesin is expressed in all types of vertebrate striated muscle; M-protein has a muscle-type specific expression pattern. Myomesin is present in both slow and fast fibers; M-protein is present only in fast fibers. It has been suggested that myomesin acts as a molecular spring with alternative splicing as a means of modifying its elasticity.

Pssm-ID: 319300 Cd Length: 92 Bit Score: 36.80 E-value: 9.36e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 569009785  249 LQGQSLILECIAEGFPTPTIKWLHPSDPMP-TDRV---IYQNHNKTLQLLNVGEEDDGEYTCLAENSLGSARHAYYVTV 323
Cdd:cd05737    14 MEGKTLNLTCNVWGDPPPEVSWLKNDQALAfLDHCnlkVEAGRTVYFTINGVSSEDSGKYGLVVKNKYGSETSDVTVSV 92