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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 667714444 417 RARIRDRKAQQVFVDEGHTVQFVCRADGDPPPAILWLSPRKHLVSAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAANA 496
Cdd:cd20969    1 RAAIRDRKAQQVFVDEGHTVQFVCRADGDPPPAILWLSPRKHLVSAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAANA 80

                         90
                 ....*....|..
gi 667714444 497 GGNDSMPAHLHV 508
Cdd:cd20969   81 GGNDSMPAHLHV 92

polycystin cation channel protein; The Polycystin Cation Channel (PCC) Family (TC 1.A.5) Polycystin is a huge protein of 4303aas. Its repeated leucine-rich (LRR) segment is found in many proteins. It contains 16 polycystic kidney disease (PKD) domains, one LDL-receptor class A domain, one C-type lectin family domain, and 16-18 putative TMSs in positions between residues 2200 and 4100. Polycystin-L has been shown to be a cation (Na+, K+ and Ca2+) channel that is activated by Ca2+. Two members of the PCC family (polycystin 1 and 2) are mutated in autosomal dominant polycystic kidney disease, and polycystin-L is deleted in mice with renal and retinal defects. Note: this model is restricted to the amino half.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 667714444   335 NVSGNQLTTLEESVFHSVGNLETLILDSNPLACDCRLLWVFRRRWRLNFNRQQP---TCATPEFVQGKEFKDFPdvLLP- 410
Cdd:TIGR00864    1 DISNNKISTIEEGICANLCNLSEIDLSGNPFECDCGLARLPRWAEEKGVKVRQPeaaLCAGPGALAGQPLLGIP--LLDs 78

                   ....*....
gi 667714444   411 ----NYFTC 415
Cdd:TIGR00864   79 gcdeEYVAC 87

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 667714444 417 RARIRDRKAQQVFVDEGHTVQFVCRADGDPPPAILWLSPRKHLVSAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAANA 496
Cdd:cd20969    1 RAAIRDRKAQQVFVDEGHTVQFVCRADGDPPPAILWLSPRKHLVSAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAANA 80

                         90
                 ....*....|..
gi 667714444 497 GGNDSMPAHLHV 508
Cdd:cd20969   81 GGNDSMPAHLHV 92

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 667714444   426 QQVFVDEGHTVQFVCRADGDPPPAILWLspRKHLVSAKSNGRLTVFPDG---TLEVRYAQVQDNGTYLCIAANAGGNDSM 502
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWY--KQGGKLLAESGRFSVSRSGstsTLTISNVTPEDSGTYTCAATNSSGSASS 79

                   ....*.
gi 667714444   503 PAHLHV 508
Cdd:smart00410  80 GTTLTV 85

Leucine rich repeat;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 667714444  114 NLRTLGLRSNRLKLIPLGVFTGLSNLTKLDISENKIVILLDYMFQDLYNLKSLEVGDNDL 173
Cdd:pfam13855   2 NLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

leucine-rich repeat receptor-like protein kinase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 667714444  70 LDL-GKNRIKTLNQDEFaSFPHLEELELNENIVSAVEPGA-FNNLFNLRTLGLRSNRLK-LIPLGvftGLSNLTKLDISE 146
Cdd:PLN00113  74 IDLsGKNISGKISSAIF-RLPYIQTINLSNNQLSGPIPDDiFTTSSSLRYLNLSNNNFTgSIPRG---SIPNLETLDLSN 149

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 667714444 147 NkivILLDYMFQDL---YNLKSLEVGDNDLVYISHRAFSGLNSLEQLTLEKCNLT-SIPTEaLSHLHGLIVLRLRHLNIN 222
Cdd:PLN00113 150 N---MLSGEIPNDIgsfSSLKVLDLGGNVLVGKIPNSLTNLTSLEFLTLASNQLVgQIPRE-LGQMKSLKWIYLGYNNLS 225

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 667714444 223 AIRDYSFKRLYRLKVLEISH--------------------WPYLDTMT---PNCLYGL-NLTSLSITHCNLTA-VPYLaV 277
Cdd:PLN00113 226 GEIPYEIGGLTSLNHLDLVYnnltgpipsslgnlknlqylFLYQNKLSgpiPPSIFSLqKLISLDLSDNSLSGeIPEL-V 304

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 667714444 278 RHLVYLRFLNLSYNPISTIEGSMLHELLRLQEIQLVGGQLAVVEPYAFRGLNYLRVLNVSGNQLT-TLEESVFHSvGNLE 356
Cdd:PLN00113 305 IQLQNLEILHLFSNNFTGKIPVALTSLPRLQVLQLWSNKFSGEIPKNLGKHNNLTVLDLSTNNLTgEIPEGLCSS-GNLF 383

                        330       340       350
                 ....*....|....*....|....*....|....*
gi 667714444 357 TLILDSNPLA-------CDCRLLwvfrRRWRLNFN 384
Cdd:PLN00113 384 KLILFSNSLEgeipkslGACRSL----RRVRLQDN 414

Leucine rich repeat C-terminal domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 667714444   363 NPLACDCRLLWvFRRRWRLNF---NRQQPTCATPEFVQGK 399
Cdd:smart00082   1 NPFICDCELRW-LLRWLQANEhlqDPVDLRCASPSSLRGP 39

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 667714444 417 RARIRDRKAQQVFVDEGHTVQFVCRADGDPPPAILWLSPRKHLVSAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAANA 496
Cdd:cd20969    1 RAAIRDRKAQQVFVDEGHTVQFVCRADGDPPPAILWLSPRKHLVSAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAANA 80

                         90
                 ....*....|..
gi 667714444 497 GGNDSMPAHLHV 508
Cdd:cd20969   81 GGNDSMPAHLHV 92

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 667714444  56 FVAVPEGIPTETRLLDLGKNRIKTLNQDEFASFPHLEELELNENIVSAVEPGAFNNLFNLRTLGLRSNRLkliplgvFTG 135
Cdd:COG4886   39 LLSLLSLLLLLTLLLSLLLRDLLLSSLLLLLSLLLLLLLSLLLLSLLLLGLTDLGDLTNLTELDLSGNEE-------LSN 111

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 667714444 136 LSNLTKLDISENKIViLLDYMFQDLYNLKSLEVGDNDLVYIShRAFSGLNSLEQLTLEKCNLTSIPtEALSHLHGLIVLR 215
Cdd:COG4886  112 LTNLESLDLSGNQLT-DLPEELANLTNLKELDLSNNQLTDLP-EPLGNLTNLKSLDLSNNQLTDLP-EELGNLTNLKELD 188

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 667714444 216 LRHLNINAIrdysfkrlyrlkvleishwpyldtmtPNCLYGL-NLTSLSITHCNLTAVPyLAVRHLVYLRFLNLSYNPIS 294
Cdd:COG4886  189 LSNNQITDL--------------------------PEPLGNLtNLEELDLSGNQLTDLP-EPLANLTNLETLDLSNNQLT 241

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 667714444 295 TIEgsmlhellrlqeiqlvggqlavvepyAFRGLNYLRVLNVSGNQLTTLEESVfhSVGNLETLILDSNPL 365
Cdd:COG4886  242 DLP--------------------------ELGNLTNLEELDLSNNQLTDLPPLA--NLTNLKTLDLSNNQL 284

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 667714444 423 RKAQQVFVDEGHTVQFVCRADGDPPPAILWLSPRKHLVSAKSngRLTVFPDGTLEVRYAQVQDNGTYLCIAANAGGNDSM 502
Cdd:cd05764    5 RHTHELRVLEGQRATLRCKARGDPEPAIHWISPEGKLISNSS--RTLVYDNGTLDILITTVKDTGAFTCIASNPAGEATA 82

                 ....*.
gi 667714444 503 PAHLHV 508
Cdd:cd05764   83 RVELHI 88

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 667714444 420 IRDRKAQQVfVDEGHTVQFVCRADGDPPPAILWLSpRKHLVSAKsNGRLTVFPDGTLEVRYAQVQDNGTYLCIAANAGGN 499
Cdd:cd20952    2 ILQGPQNQT-VAVGGTVVLNCQATGEPVPTISWLK-DGVPLLGK-DERITTLENGSLQIKGAEKSDTGEYTCVALNLSGE 78

                 ....*....
gi 667714444 500 DSMPAHLHV 508
Cdd:cd20952   79 ATWSAVLDV 87

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 667714444  422 DRKAQQVFVDEGHTVQFVCRADGDPPPAILWLSPRKHLvsaKSNGRLTVFPDG---TLEVRYAQVQDNGTYLCIAANAGG 498
Cdd:pfam07679   4 TQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPL---RSSDRFKVTYEGgtyTLTISNVQPDDSGKYTCVATNSAG 80

                          90
                  ....*....|
gi 667714444  499 NDSMPAHLHV 508
Cdd:pfam07679  81 EAEASAELTV 90

Leucine rich repeat;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 667714444  114 NLRTLGLRSNRLKLIPLGVFTGLSNLTKLDISENKIVILLDYMFQDLYNLKSLEVGDNDL 173
Cdd:pfam13855   2 NLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

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 667714444 184 LNSLEQLTLEKCNLTSIptEALSHLHGLIVLRLRHLNINAIRDysfkrlyrlkvleishwpyLDTMTpnclyglNLTSLS 263
Cdd:cd21340    1 LKRITHLYLNDKNITKI--DNLSLCKNLKVLYLYDNKITKIEN-------------------LEFLT-------NLTHLY 52

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 667714444 264 ITHCNLTAVPYLAvrHLVYLRFLNLSYNPISTIEGsmLHELLRLQEIQLVGGQLAVVEPYAF--RGLNY----LRVLNVS 337
Cdd:cd21340   53 LQNNQIEKIENLE--NLVNLKKLYLGGNRISVVEG--LENLTNLEELHIENQRLPPGEKLTFdpRSLAAlsnsLRVLNIS 128

                        170       180
                 ....*....|....*....|....*...
gi 667714444 338 GNQLTTLEEsvFHSVGNLETLILDSNPL 365
Cdd:cd21340  129 GNNIDSLEP--LAPLRNLEQLDASNNQI 154

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 667714444 424 KAQQVFVDEGHTVQFVCRADGDPPPAILW--------LSPRKhlvSAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAAN 495
Cdd:cd05726    5 KPRDQVVALGRTVTFQCETKGNPQPAIFWqkegsqnlLFPYQ---PPQPSSRFSVSPTGDLTITNVQRSDVGYYICQALN 81

                         90
                 ....*....|...
gi 667714444 496 AGGNDSMPAHLHV 508
Cdd:cd05726   82 VAGSILAKAQLEV 94

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 667714444 427 QVFVDEGHTVQFVCRADGDPPPAILWLSPRKHLVSakSNGRLTvFPDGTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHL 506
Cdd:cd20978   10 NVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQG--PMERAT-VEDGTLTIINVQPEDTGYYGCVATNEIGDIYTETLL 86

                 ..
gi 667714444 507 HV 508
Cdd:cd20978   87 HV 88

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 667714444 428 VFVDEGHTVQFVCRADGDPPPAILWLspRKHLVSAKSNGRLTVFPDGT-LEVRYAQVQDNGTYLCIAAN-AGGNDSMPAH 505
Cdd:cd20970   12 VTAREGENATFMCRAEGSPEPEISWT--RNGNLIIEFNTRYIVRENGTtLTIRNIRRSDMGIYLCIASNgVPGSVEKRIT 89

                 ...
gi 667714444 506 LHV 508
Cdd:cd20970   90 LQV 92

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 667714444 432 EGHTVQFVCRADGDPPPAILWLSPRKHLvsaKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHLHV 508
Cdd:cd05745    1 EGQTVDFLCEAQGYPQPVIAWTKGGSQL---SVDRRHLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 667714444 424 KAQQVFVDEGHTVQFVCRADGDPPPAILWLSPRKHLVSAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAANAGG 498
Cdd:cd05747    9 KPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQITSTEYKSTFEISKVQMSDEGNYTVVVENSEG 83

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 667714444 436 VQFVCRADGDPPPAILWLSPRKHLVSAKS--NGRLTVFPD---GTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHLHV 508
Cdd:cd05869   20 ITLTCEASGDPIPSITWRTSTRNISSEEKtlDGHIVVRSHarvSSLTLKYIQYTDAGEYLCTASNTIGQDSQSMYLEV 97

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 667714444 433 GHTVQFVCRADGDPPPAILWLSPR-----KHLVSAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAANAGGND-SMPAHL 506
Cdd:cd05734   16 GKAVVLNCSADGYPPPTIVWKHSKgsgvpQFQHIVPLNGRIQLLSNGSLLIKHVLEEDSGYYLCKVSNDVGADiSKSMYL 95

                 ..
gi 667714444 507 HV 508
Cdd:cd05734   96 TV 97

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 667714444 430 VDEGHTVQFVCRADGDPPPAILW--LSPRKHLVSAKSN---GRLTVFPDGTLEVRYAQVQDNGTYLCIAANAGG 498
Cdd:cd05765   12 VKVGETASFHCDVTGRPQPEITWekQVPGKENLIMRPNhvrGNVVVTNIGQLVIYNAQPQDAGLYTCTARNSGG 85

BspA type Leucine rich repeat region (6 copies); This family includes a number of leucine rich repeats. This family contains a large number of BSPA-like surface antigens from Trichomonas vaginalis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 667714444   75 NRIKTLNQDEFASFPHLEELELNENIVSaVEPGAFNNlFNLRTLGLRSNrLKLIPLGVFTGLSNLTKLDISENkIVILLD 154
Cdd:pfam13306  20 SSLTSIGEYAFSNCTSLKSITLPSSLTS-IGSYAFYN-CSLTSITIPSS-LTSIGEYAFSNCSNLKSITLPSN-LTSIGS 95

                          90       100       110
                  ....*....|....*....|....*....|....
gi 667714444  155 YMFQDLyNLKSLEVGDNdLVYISHRAFSGLNSLE 188
Cdd:pfam13306  96 YAFSNC-SLKSITIPSS-VTTIGSYAFSNCSNLK 127

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 667714444 428 VFVDEGHTVQFVCRADGDPPPAILWLSPRKHLVSAKSNGRL--TVFPDGTL------EVRYAQvQDNGTYLCIAANAGGN 499
Cdd:cd07693   10 LIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLETDKDDPRShrIVLPSGSLfflrvvHGRKGR-SDEGVYVCVAHNSLGE 88

                         90
                 ....*....|
gi 667714444 500 D-SMPAHLHV 508
Cdd:cd07693   89 AvSRNASLEV 98

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 667714444 423 RKAQQVFVDEGHTVQFVCRADGDPPPAILWLSPRKHLVSA-----KSNGRLTvfpdgTLEVRYAQVQDNGTYLCIAANAG 497
Cdd:cd20972    6 QKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSpdiqiHQEGDLH-----SLIIAEAFEEDTGRYSCLATNSV 80

                         90
                 ....*....|.
gi 667714444 498 GNDSMPAHLHV 508
Cdd:cd20972   81 GSDTTSAEIFV 91