Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 385298685  253 KPSVMTSATKIMSALGSNVLLRCDATGFPTPQITWTRSDSSPVNYTVIQESPEEGVrwSIMSLTGISSKDAGDYKCKAKN 332
Cdd:pfam13927   1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSN--STLTISNVTRSDAGTYTCVASN 78

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 385298685  253 KPSVMTSATKIMSALGSNVLLRCDATGFPTPQITWTRSDSSPVNYTVIQESPEEGVrwSIMSLTGISSKDAGDYKCKAKN 332
Cdd:pfam13927   1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSN--STLTISNVTRSDAGTYTCVASN 78

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 385298685   267 LGSNVLLRCDATGFPTPQITWTRSDSSPVNYTV-IQESPEEGvrWSIMSLTGISSKDAGDYKCKAKNLAGMSEAVVTVTV 345
Cdd:smart00410   8 EGESVTLSCEASGSPPPEVTWYKQGGKLLAESGrFSVSRSGS--TSTLTISNVTPEDSGTYTCAATNSSGSASSGTTLTV 85

protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 (PPP1R42), also known as leucine-rich repeat-containing protein 67 (lrrc67) or testis leucine-rich repeat (TLRR) protein, plays a role in centrosome separation. PPP1R42 has been shown to interact with the well-conserved signaling protein phosphatase-1 (PP1) and thereby increasing PP1's activity, which counters centrosome separation. Inhibition of PPP1R42 expression increases the number of centrosomes per cell while its depletion reduces the activity of PP1 leading to activation of NEK2, the kinase responsible for phosphorylation of centrosomal linker proteins promoting centrosome separation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 385298685  69 IRRIsaEAFYYLVELQYLWVTYNSVASIdpSSFYNLKQLHELRLDGNSLA-----AFPWASLLDM-PLLRTLDLHNNKIT 142
Cdd:cd21340   58 IEKI--ENLENLVNLKKLYLGGNRISVV--EGLENLTNLEELHIENQRLPpgeklTFDPRSLAALsNSLRVLNISGNNID 133

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 385298685 143 SVpnEALRYLKNLAYLDLSSNRLTTLPP--DFLESWTHL 179
Cdd:cd21340  134 SL--EPLAPLRNLEQLDASNNQISDLEEllDLLSSWPSL 170

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 385298685   486 AIENLRVVSETKESVTLTWNMINTTHNSAVTVLYSKYGGKDLLL---LNADSSKNQVTIDGLEPGGQY 550
Cdd:smart00060   3 PPSNLRVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEYREEGSEwkeVNVTPSSTSYTLTGLKPGTEY 70

Fibronectin type III domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 385298685  486 AIENLRVVSETKESVTLTWNmINTTHNSAVT---VLYSKYGGKDLLL-LNADSSKNQVTIDGLEPGGQYMACV 554
Cdd:pfam00041   2 APSNLTVTDVTSTSLTVSWT-PPPDGNGPITgyeVEYRPKNSGEPWNeITVPGTTTSVTLTGLKPGTEYEVRV 73

Leucine-rich repeat (LRR) protein [Transcription];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 385298685  75 EAFYYLVELQYLWVTYNSVASIdPSSFYNLKQLHELRLDGNSLAAFPwASLLDMPLLRTLDLHNNKITSVPnEALRYLKN 154
Cdd:COG4886  130 EELANLTNLKELDLSNNQLTDL-PEPLGNLTNLKSLDLSNNQLTDLP-EELGNLTNLKELDLSNNQITDLP-EPLGNLTN 206

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 385298685 155 LAYLDLSSNRLTTLPPDfLESWTHLVStpsgvLDLSPSRI 194
Cdd:COG4886  207 LEELDLSGNQLTDLPEP-LANLTNLET-----LDLSNNQL 240

Leucine rich repeat;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 385298685  106 QLHELRLDGNSLAAFPWASLLDMPLLRTLDLHNNKITSVPNEALRYLKNLAYLDLSSNRL 165
Cdd:pfam13855   2 NLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 385298685  268 GSNVLLRCDATGFPTPQITWTRSDSSpvnytvIQESPEEGVRWS--IMSLT--GISSKDAGDYKCKAKNLAGMSEAVVTV 343
Cdd:pfam07679  15 GESARFTCTVTGTPDPEVSWFKDGQP------LRSSDRFKVTYEggTYTLTisNVQPDDSGKYTCVATNSAGEAEASAEL 88

                  ..
gi 385298685  344 TV 345
Cdd:pfam07679  89 TV 90

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 385298685 267 LGSNVLLRCDATGFPTPQITWTRsDSSPVnytviqESPEEGVRW----SIMSLTGISSKDAGDYKCKAKNLAGMSEAVVT 342
Cdd:cd05730   17 LGQSVTLACDADGFPEPTMTWTK-DGEPI------ESGEEKYSFnedgSEMTILDVDKLDEAEYTCIAENKAGEQEAEIH 89

                 ...
gi 385298685 343 VTV 345
Cdd:cd05730   90 LKV 92

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 385298685 254 PSVMTSATKIMSALGSNVLLRCDATGFPTPQITWTRsDSSPVNYTVIQESPEEGVrwSIMSLTGISSKDAGDYKCKAKNL 333
Cdd:cd20976    2 PSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIR-NAQPLQYAADRSTCEAGV--GELHIQDVLPEDHGTYTCLAKNA 78

                         90
                 ....*....|..
gi 385298685 334 AGMSEAVVTVTV 345
Cdd:cd20976   79 AGQVSCSAWVTV 90

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 385298685 271 VLLRCDATGFPTPQITWTRSDSSPVNYTVIQESPEEGvrWSIMSLTGISSKDAGDYKCKAKNLAGMSEAVVT 342
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELG--NGTLTISNVTLEDSGTYTCVASNSAGGSASASV 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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 385298685 265 SALGSNVLLRCDATGFPTPQITWTRSDSSPVNYTVIQESpeEGVrwsiMSLTGISSKDAGDYKCKAKNLAG 335
Cdd:cd04968   13 ALKGQTVTLECFALGNPVPQIKWRKVDGSPSSQWEITTS--EPV----LEIPNVQFEDEGTYECEAENSRG 77

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 385298685 259 SATKIMSALGSNVLLRCDATGFPTPQITWTRSDSSPVNYTVIQESPEEGVRwsimsLTGISSKDAGDYKCKAKNLAGMSE 338
Cdd:cd05731    1 SESSTMVLRGGVLLLECIAEGLPTPDIRWIKLGGELPKGRTKFENFNKTLK-----IENVSEADSGEYQCTASNTMGSAR 75

                 ....*..
gi 385298685 339 AVVTVTV 345
Cdd:cd05731   76 HTISVTV 82

Leucine rich repeat;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 385298685   82 ELQYLWVTYNSVASIDPSSFYNLKQLHELRLDGNSLAAFPWASLLDMPLLRTLDLHNNKI 141
Cdd:pfam13855   2 NLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 385298685 268 GSNVLLRCDATGFPTPQITWTRS-DSSPVNYTVIQESPEEGV-RWSIMSLTGISSKDAGDYKCKAKNL--AGMSeAVVTV 343
Cdd:cd20954   16 GQDVMLHCQADGFPTPTVTWKKAtGSTPGEYKDLLYDPNVRIlPNGTLVFGHVQKENEGHYLCEAKNGigSGLS-KVIFL 94

                 ..
gi 385298685 344 TV 345
Cdd:cd20954   95 KV 96

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 385298685 268 GSNVLLRCDATGFPTPQITWTRSDSspvnytviqeSPEEGV-RWSIMS------LTGISSKDAGDYKCKAKNLAG 335
Cdd:cd20970   17 GENATFMCRAEGSPEPEISWTRNGN----------LIIEFNtRYIVREngttltIRNIRRSDMGIYLCIASNGVP 81

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 385298685 266 ALGSNVLLRCDATGFPTPQITWTRSDSSpvNYTVIQESPEEGVRWSI-----MSLTGISSKDAGDYKCKAKNLAG--MSE 338
Cdd:cd05726   12 ALGRTVTFQCETKGNPQPAIFWQKEGSQ--NLLFPYQPPQPSSRFSVsptgdLTITNVQRSDVGYYICQALNVAGsiLAK 89

                 ....*.
gi 385298685 339 AVVTVT 344
Cdd:cd05726   90 AQLEVT 95

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 385298685 268 GSNVLLRCDATGFPTPQITWTR------SDSSPVNYTViqeSPEEGVrwSIMSLTGISSKDAGDYKCKAKNLAGMSEAVV 341
Cdd:cd20951   15 KSDAKLRVEVQGKPDPEVKWYKngvpidPSSIPGKYKI---ESEYGV--HVLHIRRVTVEDSAVYSAVAKNIHGEASSSA 89

                 ....
gi 385298685 342 TVTV 345
Cdd:cd20951   90 SVVV 93

type III secretion system effector E3 ubiquitin transferase SlrP;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 385298685  38 SRLVLCNDMdmNELPTNLPVDTVKLRIEKTVIRRISAEAFYYLVELqylWVTYNSVASIDPSSFYNLKQLHElrlDGNSL 117
Cdd:PRK15370 266 SLDLFHNKI--SCLPENLPEELRYLSVYDNSIRTLPAHLPSGITHL---NVQSNSLTALPETLPPGLKTLEA---GENAL 337

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 385298685 118 AAFPwASLldMPLLRTLDLHNNKITSVPnEALRylKNLAYLDLSSNRLTTLPPD------FLE-SWTHLVSTPSGVLDL- 189
Cdd:PRK15370 338 TSLP-ASL--PPELQVLDVSKNQITVLP-ETLP--PTITTLDVSRNALTNLPENlpaalqIMQaSRNNLVRLPESLPHFr 411

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 385298685 190 ----SPSRIIlgLQDNPwFCDCHISKMIELSKVVD 220
Cdd:PRK15370 412 gegpQPTRII--VEYNP-FSERTIQNMQRLMSSVG 443

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 385298685 267 LGSNVLLRCDATGFPTPQITWTRSDSS-----PVNYTVIQESPEegvrwsiMSLTGISSKDAGDYKCKAKNLAGMSEAVV 341
Cdd:cd05736   14 PGVEASLRCHAEGIPLPRVQWLKNGMDinpklSKQLTLIANGSE-------LHISNVRYEDTGAYTCIAKNEGGVDEDIS 86

                 ....
gi 385298685 342 TVTV 345
Cdd:cd05736   87 SLFV 90

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 385298685 267 LGSNVLLRCDATGFPTPQITWTRSDSSpvnytvIQESPEEGVRWSIMSLTGISSKDAGDYKCKAKNLAGM 336
Cdd:cd05851   15 KGQNVTLECFALGNPVPVIRWRKILEP------MPATAEISMSGAVLKIFNIQPEDEGTYECEAENIKGK 78

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

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gi 385298685 266 ALGSNVLLRCDATGFPTPQITWTRsDSSPVnytviqesPEEGVRWSI-----MSLTGISSKDAGDYKCKAKNLAGMSEAV 340
Cdd:cd20952   12 AVGGTVVLNCQATGEPVPTISWLK-DGVPL--------LGKDERITTlengsLQIKGAEKSDTGEYTCVALNLSGEATWS 82

                 ....*
gi 385298685 341 VTVTV 345
Cdd:cd20952   83 AVLDV 87

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

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gi 385298685  268 GSNVLLRCDATGFPTPQITWTRsDSSPVNYTviqespeegvrwSIMSLTGISSKDAGDYKCKAKNLAGM-SEAVVTVTV 345
Cdd:pfam13895  14 GEPVTLTCSAPGNPPPSYTWYK-DGSAISSS------------PNFFTLSVSAEDSGTYTCVARNGRGGkVSNPVELTV 79

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.

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gi 385298685 267 LGSNVLLRCDATGFPTPQITWTRSDsspvnyTVIQESPEEGVRWS-IMSLTGISSKDAGDYKCKAKNLAGMS-EAVVTVT 344
Cdd:cd20968   13 EGLKAVLPCTTMGNPKPSVSWIKGD------DLIKENNRIAVLESgSLRIHNVQKEDAGQYRCVAKNSLGIAySKPVTIE 86

                 .
gi 385298685 345 V 345
Cdd:cd20968   87 V 87

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.

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gi 385298685 254 PSVMTsatkIMSalGSNVLLRCDATGFPTPQITWTRSDSsPVNYTVIQESPEEGVRWSIMSLTGISSKDAGDYKCKAKNL 333
Cdd:cd05737    8 PDVVT----IME--GKTLNLTCNVWGDPPPEVSWLKNDQ-ALAFLDHCNLKVEAGRTVYFTINGVSSEDSGKYGLVVKNK 80

                         90
                 ....*....|..
gi 385298685 334 AGMSEAVVTVTV 345
Cdd:cd05737   81 YGSETSDVTVSV 92

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.

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gi 385298685 268 GSNVLLRCDATGFPTPQITWTRSDSSPVNYTVIQESPEEGVRWSIMsLTGISSKDAGDYKCKAKNLAGMSEAVVTVTV 345
Cdd:cd05729   19 ANKVRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEEKGWSLI-IERAIPRDKGKYTCIVENEYGSINHTYDVDV 95

Leucine rich repeat;

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gi 385298685   61 KLRIEKTVIRRISAEAFYYLVELQYLWVTYNSVASIDPSSFYNLKQLHELRLDGNSL 117
Cdd:pfam13855   5 SLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

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.

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gi 385298685 262 KIMSALGSNVLLRCDATGFPTPQITWTRSDSSPVNYTVIQESPEEGVRwsimsLTGISSKDAGDYKCKAKNLAGMSEAVV 341
Cdd:cd04969   11 KILAAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICILPDGSLK-----IKNVTKSDEGKYTCFAVNFFGKANSTG 85

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gi 385298685 342 TVTV 345
Cdd:cd04969   86 SLSV 89