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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24643236  76 QVLDFAHNQIPELrreEFLLAGLPNVHKIFLRNCTIQEVHrEAFKGLHILIELDLSGNRIRELhPGTFAGLEKLRNVIIN 155
Cdd:COG4886 116 ESLDLSGNQLTDL---PEELANLTNLKELDLSNNQLTDLP-EPLGNLTNLKSLDLSNNQLTDL-PEELGNLTNLKELDLS 190

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 24643236 156 NNEIEVLPNHLFvNLSFLSRIEFRNNRLRQVQLhVFAGTMALSAISLEQNRLSHLhkETFKDLQKLMHLSLQGN 229
Cdd:COG4886 191 NNQITDLPEPLG-NLTNLEELDLSGNQLTDLPE-PLANLTNLETLDLSNNQLTDL--PELGNLTNLEELDLSNN 260

Leucine rich repeat C-terminal domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 24643236    229 NAWNCSCELQDFRDFAISKRLYTPPTD--CQEPPQLRGKLWsEVPSENFAC 277
Cdd:smart00082   1 NPFICDCELRWLLRWLQANEHLQDPVDlrCASPSSLRGPLL-ELLHSEFKC 50

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24643236  76 QVLDFAHNQIPELrreEFLLAGLPNVHKIFLRNCTIQEVHrEAFKGLHILIELDLSGNRIRELhPGTFAGLEKLRNVIIN 155
Cdd:COG4886 116 ESLDLSGNQLTDL---PEELANLTNLKELDLSNNQLTDLP-EPLGNLTNLKSLDLSNNQLTDL-PEELGNLTNLKELDLS 190

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 24643236 156 NNEIEVLPNHLFvNLSFLSRIEFRNNRLRQVQLhVFAGTMALSAISLEQNRLSHLhkETFKDLQKLMHLSLQGN 229
Cdd:COG4886 191 NNQITDLPEPLG-NLTNLEELDLSGNQLTDLPE-PLANLTNLETLDLSNNQLTDL--PELGNLTNLEELDLSNN 260

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24643236   296 ISLPCRIVGSPRPNVTWVYNKRPLQQyDPRVRVlTSVEQmpeqpsqvlTSELRIVGVRASDKGAYTCVADNRGGRAEAEF 375
Cdd:pfam07679  18 ARFTCTVTGTPDPEVSWFKDGQPLRS-SDRFKV-TYEGG---------TYTLTISNVQPDDSGKYTCVATNSAGEAEASA 86

                  ....
gi 24643236   376 QLLV 379
Cdd:pfam07679  87 ELTV 90

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24643236    294 DNISLPCRIVGSPRPNVTWVYNKRPLQQYDPRVRVLtsveqmpeqpSQVLTSELRIVGVRASDKGAYTCVADNRGGRAEA 373
Cdd:smart00410  10 ESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVS----------RSGSTSTLTISNVTPEDSGTYTCAATNSSGSASS 79

                   ....*.
gi 24643236    374 EFQLLV 379
Cdd:smart00410  80 GTTLTV 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 24643236  72 SNEMQVLDFAHNQIPELRreefLLAGLPNVHKIFLRNCTIQEVHR--EAFKGLHILIELDLSGNRIRELHpgtfagleKL 149
Cdd:cd21340 119 SNSLRVLNISGNNIDSLE----PLAPLRNLEQLDASNNQISDLEEllDLLSSWPSLRELDLTGNPVCKKP--------KY 186

                        90
                ....*....|....
gi 24643236 150 R-NVIINNNEIEVL 162
Cdd:cd21340 187 RdKIILASKSLEVL 200

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24643236  76 QVLDFAHNQIPELrreEFLLAGLPNVHKIFLRNCTIQEVHrEAFKGLHILIELDLSGNRIRELhPGTFAGLEKLRNVIIN 155
Cdd:COG4886 116 ESLDLSGNQLTDL---PEELANLTNLKELDLSNNQLTDLP-EPLGNLTNLKSLDLSNNQLTDL-PEELGNLTNLKELDLS 190

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 24643236 156 NNEIEVLPNHLFvNLSFLSRIEFRNNRLRQVQLhVFAGTMALSAISLEQNRLSHLhkETFKDLQKLMHLSLQGN 229
Cdd:COG4886 191 NNQITDLPEPLG-NLTNLEELDLSGNQLTDLPE-PLANLTNLETLDLSNNQLTDL--PELGNLTNLEELDLSNN 260

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24643236   296 ISLPCRIVGSPRPNVTWVYNKRPLQQyDPRVRVlTSVEQmpeqpsqvlTSELRIVGVRASDKGAYTCVADNRGGRAEAEF 375
Cdd:pfam07679  18 ARFTCTVTGTPDPEVSWFKDGQPLRS-SDRFKV-TYEGG---------TYTLTISNVQPDDSGKYTCVATNSAGEAEASA 86

                  ....
gi 24643236   376 QLLV 379
Cdd:pfam07679  87 ELTV 90

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24643236    294 DNISLPCRIVGSPRPNVTWVYNKRPLQQYDPRVRVLtsveqmpeqpSQVLTSELRIVGVRASDKGAYTCVADNRGGRAEA 373
Cdd:smart00410  10 ESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVS----------RSGSTSTLTISNVTPEDSGTYTCAATNSSGSASS 79

                   ....*.
gi 24643236    374 EFQLLV 379
Cdd:smart00410  80 GTTLTV 85

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24643236 296 ISLPCRIVGSPRPNVTWVYNKRPLQQYDPRVRVLTSVeqmpeqpsqvlTSELRIVGVRASDKGAYTCVADNR-GGRAEAE 374
Cdd:cd00096   1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELG-----------NGTLTISNVTLEDSGTYTCVASNSaGGSASAS 69

                .
gi 24643236 375 F 375
Cdd:cd00096  70 V 70

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 24643236 298 LPCRIVGSPRPNVTWVYNKRPLQQYDPRVRVltsveqmpeqpsQVLTSELRIVGVRASDKGAYTCVADNRGGRAEAEFQL 377
Cdd:cd20976  21 AQCSARGKPVPRITWIRNAQPLQYAADRSTC------------EAGVGELHIQDVLPEDHGTYTCLAKNAAGQVSCSAWV 88

                ..
gi 24643236 378 LV 379
Cdd:cd20976  89 TV 90

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24643236  94 LLAGLPNVHKIFLRNCTIQEVHREAFKGLHILIELDLSGNRirelhpgTFAGLEKLRNVIINNNEIEVLPNHLFvNLSFL 173
Cdd:COG4886  67 LLLSLLLLLLLSLLLLSLLLLGLTDLGDLTNLTELDLSGNE-------ELSNLTNLESLDLSGNQLTDLPEELA-NLTNL 138

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 24643236 174 SRIEFRNNRLRQVQLhVFAGTMALSAISLEQNRLSHLhKETFKDLQKLMHLSLQGN 229
Cdd:COG4886 139 KELDLSNNQLTDLPE-PLGNLTNLKSLDLSNNQLTDL-PEELGNLTNLKELDLSNN 192

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24643236 294 DNISLPCRIVGSPRPNVTWVYNKRPLQQYDPRVRVLtsveqmpeQPSQVLTseLRIVGVRASDKGAYTCVADNRGGRAEA 373
Cdd:cd05744  16 RLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLV--------RENGRHS--LIIEPVTKRDAGIYTCIARNRAGENSF 85

                ....*.
gi 24643236 374 EFQLLV 379
Cdd:cd05744  86 NAELVV 91

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24643236 294 DNISLPCRIVGSPRPNVTWVYNKRPLQQydprvrvltsveqmpEQPSQVLTSELRIVGVRASDKGAYTCVADNRGGRAEA 373
Cdd:cd05728  15 SSLRWECKASGNPRPAYRWLKNGQPLAS---------------ENRIEVEAGDLRITKLSLSDSGMYQCVAENKHGTIYA 79

                ....*.
gi 24643236 374 EFQLLV 379
Cdd:cd05728  80 SAELAV 85

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24643236 295 NISLPCRIVGSPRPNVTWVYNKRPLQQyDPRVRVLTSVeqmpeQPSQVLTSELRIVGVRASDKGAYTCVADNRGGRA 371
Cdd:cd20956  18 SVSLKCVASGNPLPQITWTLDGFPIPE-SPRFRVGDYV-----TSDGDVVSYVNISSVRVEDGGEYTCTATNDVGSV 88

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 24643236 295 NISLPCRIVGSPRPNVTWVYNKRPLQQYDPRVRVLTSveqmpeqpsqvlTSELRIVGVRASDKGAYTCVADNRGGRAEAE 374
Cdd:cd05730  20 SVTLACDADGFPEPTMTWTKDGEPIESGEEKYSFNED------------GSEMTILDVDKLDEAEYTCIAENKAGEQEAE 87

                ....*
gi 24643236 375 FQLLV 379
Cdd:cd05730  88 IHLKV 92

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24643236 297 SLPCRIVGSPRPNVTWVYNKRPLqqydprvrvltsveqMPEQPSQVLT----SELRIVGVRASDKGAYTCVADNRGG 369
Cdd:cd05736  19 SLRCHAEGIPLPRVQWLKNGMDI---------------NPKLSKQLTLiangSELHISNVRYEDTGAYTCIAKNEGG 80

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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24643236 303 VGSPRPNVTWVYNKRPLQQYDPRVRVLTSveqmpeqpsqvltSELRIVGVRASDKGAYTCVADNRGGRAEAE 374
Cdd:cd05724  23 RGHPEPTVSWRKDGQPLNLDNERVRIVDD-------------GNLLIAEARKSDEGTYKCVATNMVGERESR 81

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24643236 294 DNISLPCRIVGSPRPNVTWVYNKRPLqqydPRVRVltsvEQMPEQpsqvltsELRIVGVRASDKGAYTCVADNRGGRAEA 373
Cdd:cd05725  13 DSAEFQCEVGGDPVPTVRWRKEDGEL----PKGRY----EILDDH-------SLKIRKVTAGDMGSYTCVAENMVGKIEA 77

                ....*.
gi 24643236 374 EFQLLV 379
Cdd:cd05725  78 SATLTV 83

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24643236 296 ISLPCRIVGSPRPNVTWVYNKRPLqqydprvrvltsveqmPEQPSQVLTSE-----LRIVGVRASDKGAYTCVADNRGGR 370
Cdd:cd05743   4 VEFTCVATGVPTPIINWRLNWGHV----------------PDSARVSITSEggygtLTIRDVKESDQGAYTCEAINTRGM 67

Fourth immunoglobulin (Ig)-like domain of platelet-derived growth factor receptor (PDGFR); The members here are composed of the fourth immunoglobulin (Ig)-like domain of platelet-derived growth factor receptor (PDGFR; also known as cluster of differentiation (CD) 140a) alpha and beta. PDGF is a potent mitogen for connective tissue cells. PDGF-stimulated processes are mediated by three different PDGFs (PDGF-A,PDGF-B, and PDGF-C). PDGFR alpha binds to all three PDGFs, whereas the PDGFR beta binds only to PDGF-B. PDGF alpha is organized as an extracellular component having five Ig-like domains, a transmembrane segment, and a cytoplasmic portion having protein tyrosine kinase activity. In mice, PDGFR alpha and PDGFR beta are essential for normal development.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24643236 280 RILGSVRSFIEAN-HDNISLPCRIVGSPRPNVTWVYNKRPLQQydPRVRVLTSVEQMPEQPSQvltSELRIVGVRASDKG 358
Cdd:cd05859   4 ALKPTFGQLEFANlHEVKEFVVEVEAYPPPQIRWLKDNRTLIE--NLTEITTSTRNVQETRYV---SKLKLIRAKEEDSG 78

                        90       100
                ....*....|....*....|.
gi 24643236 359 AYTCVADNRGGRAEAEFQLLV 379
Cdd:cd05859  79 LYTALAQNEDAVKSYTFALQI 99

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24643236 294 DNISLPCRIVGSPRPNVTWVynkrplQQYDPRVRVLTSVEQMpeQPSQVLTS--ELRIVGVRASDKGAYTCVADNRGGRA 371
Cdd:cd05765  16 ETASFHCDVTGRPQPEITWE------KQVPGKENLIMRPNHV--RGNVVVTNigQLVIYNAQPQDAGLYTCTARNSGGLL 87

                ....*...
gi 24643236 372 EAEFQLLV 379
Cdd:cd05765  88 RANFPLSV 95

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24643236 295 NISLPCRIVGSPRPNVTWVYNKRPLQqydPRVRvltsveQMPEQPSQVLtSELRIVGVRASDKGAYTCVADNRGGRAEAE 374
Cdd:cd20975  17 DVIMSIRVQGEPKPVVSWLRNRQPVR---PDQR------RFAEEAEGGL-CRLRILAAERGDAGFYTCKAVNEYGARQCE 86

                ....*
gi 24643236 375 FQLLV 379
Cdd:cd20975  87 ARLEV 91

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24643236 300 CRIVGSPRPNVTWVYNKRPLQQyDPRVRVLTSveqmpeqpsqvltSELRIVGVRASDKGAYTCVADNRGGRAE--AEFQL 377
Cdd:cd20957  23 CSVTGNPIHTVLWMKDGKPLGH-SSRVQILSE-------------DVLVIPSVKREDKGMYQCFVRNDGDSAQatAELKL 88

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24643236 279 PRILGSVRSFIEANHDNISLPCRIVGSPRPNVTWVYNKRPLQ--QYDPRVR--VLtsveqmpeqPSQVLTSeLRIVGVR- 353
Cdd:cd07693   1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLEtdKDDPRSHriVL---------PSGSLFF-LRVVHGRk 70

                        90
                ....*....|....*....
gi 24643236 354 -ASDKGAYTCVADNRGGRA 371
Cdd:cd07693  71 gRSDEGVYVCVAHNSLGEA 89

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24643236 294 DNISLPCRIVGSPRPNVTWvynKRPlqqydprVRVLTSVEQMP----EQPSQVLTSELRIVGVRASDKGAYTCVADNRGG 369
Cdd:cd05732  17 EQITLTCEAEGDPIPEITW---RRA-------TRGISFEEGDLdgriVVRGHARVSSLTLKDVQLTDAGRYDCEASNRIG 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24643236   293 HDNISLPCRIV-GSPRPNVTWVYNKRplqqydprvrVLTSVEQMPEQPSQVLTSELRIVGVRASDKGAYTCVADNRGGRA 371
Cdd:pfam00047  11 GDSATLTCSAStGSPGPDVTWSKEGG----------TLIESLKVKHDNGRTTQSSLLISNVTKEDAGTYTCVVNNPGGSA 80

                  ....*.
gi 24643236   372 EAEFQL 377
Cdd:pfam00047  81 TLSTSL 86

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24643236 298 LPCRIVGSPRPNVTWVYNKRPLQQYDprvrvltsveqmPEQPSQVLTSELRIVGVRASDKGAYTCVADNRGG 369
Cdd:cd05867  19 LDCQVEGIPTPNITWSINGAPIEGTD------------PDPRRHVSSGALILTDVQPSDTAVYQCEARNRHG 78

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24643236 296 ISLPCRIVGSPRPNVTWVYNKRPLQQYDPrvrvltsveQMPEQPSQVLTselrIVGVRASDKGAYTCVADNRGGRAEAEF 375
Cdd:cd05856  22 VRLKCVASGNPRPDITWLKDNKPLTPPEI---------GENKKKKWTLS----LKNLKPEDSGKYTCHVSNRAGEINATY 88

                ....
gi 24643236 376 QLLV 379
Cdd:cd05856  89 KVDV 92

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24643236 294 DNISLPCRIVGSPRPNVTWVYNKRPLQQyDPRVRVLTSVEqmpeqpsqvlTSELRIVGVRASDKGAYTCVADNRGGRAEA 373
Cdd:cd05748   8 ESLRLDIPIKGRPTPTVTWSKDGQPLKE-TGRVQIETTAS----------STSLVIKNAKRSDSGKYTLTLKNSAGEKSA 76

                ....*.
gi 24643236 374 EFQLLV 379
Cdd:cd05748  77 TINVKV 82

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 24643236 274 NFACRPRilgsvrSFIEANHDNISLPCRIVGSPRPNVTWvynkrplQQYDPRVRVLTSveqMPEQPSQVL----TSELRI 349
Cdd:cd05726   1 QFVVKPR------DQVVALGRTVTFQCETKGNPQPAIFW-------QKEGSQNLLFPY---QPPQPSSRFsvspTGDLTI 64

                        90       100       110
                ....*....|....*....|....*....|..
gi 24643236 350 VGVRASDKGAYTCVADNRGGRAEAEFQLLVSG 381
Cdd:cd05726  65 TNVQRSDVGYYICQALNVAGSILAKAQLEVTD 96

Immunoglobulin Variable (IgV) domain in HERV-H LTR-associating 2 (HHLA2); The members here are composed of the immunoglobulin variable (IgV) region in HERV-H LTR-associating 2 (HHLA2; also known as B7-H7/B7 homolog 7). HHLA2 is a member of the B7 family of immune regulatory proteins. Mature human HHLA2 consists of an extracellular domain (ECD) with three immunoglobulin-like domains, a transmembrane segment, and a cytoplasmic domain. HHLA2 is widely expressed in human cancers including non-small cell lung carcinoma (NSCLS), triple negative breast cancer (TNBC), and melanoma, but has limited expression on normal tissues. Interestingly, unlike other members of B7 family, HHLA2 is not expressed in mice or rats. HHLA2 functions as a T cell coinhibitory molecules as it inhibits the proliferation of activated CD4(+) and CD8(+) T cells and their cytokine production. Furthermore, HHLA2 is constitutively expressed on the surface of human monocytes and is induced on B cells after stimulation, however it is not inducible on T cells.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24643236 293 HDNISLPCRIVGSPRPNVTWV------------YNKRPLQQYDPRVRVLTSVeqMPEQPSQVLTSeLRIVGVRASDKGAY 360
Cdd:cd16091  12 SEDCILPCSFTPGSEVVIHWYkqdsdikvhsyyYGKDQLESQDQRYRNRTSL--FKDQISNGNAS-LLLRRVQLQDEGRY 88

                        90
                ....*....|....*....
gi 24643236 361 TCVADNRGGRAEAEFQLLV 379
Cdd:cd16091  89 KCYTSTIIGNQESFVNLKV 107