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 971387048 288 PLITQHTHKLLVLEGQTATLKCKAIGDPTPIIHWVAPDDRLIGNSSRTSVYDNGTLDILITTSKDYGTFTCIAANAAGES 367
Cdd:cd05764    1 PLITRHTHELRVLEGQRATLRCKARGDPEPAIHWISPEGKLISNSSRTLVYDNGTLDILITTVKDTGAFTCIASNPAGEA 80

                 ....*...
gi 971387048 368 TATIELSI 375
Cdd:cd05764   81 TARVELHI 88

Leucine rich repeat C-terminal domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 971387048   241 NPLHCNCELLWLRRLDRDDDME------TCASPPGLKGRYFWYVReEEFVC 285
Cdd:smart00082   1 NPFICDCELRWLLRWLQANEHLqdpvdlRCASPSSLRGPLLELLH-SEFKC 50

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 971387048 288 PLITQHTHKLLVLEGQTATLKCKAIGDPTPIIHWVAPDDRLIGNSSRTSVYDNGTLDILITTSKDYGTFTCIAANAAGES 367
Cdd:cd05764    1 PLITRHTHELRVLEGQRATLRCKARGDPEPAIHWISPEGKLISNSSRTLVYDNGTLDILITTVKDTGAFTCIASNPAGEA 80

                 ....*...
gi 971387048 368 TATIELSI 375
Cdd:cd05764   81 TARVELHI 88

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971387048  288 PLITQHTHKLLVLEGQTATLKCKAIGDPTPIIHWVApDDRLIGNSSRTSV-YDNG--TLDILITTSKDYGTFTCIAANAA 364
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFK-DGQPLRSSDRFKVtYEGGtyTLTISNVQPDDSGKYTCVATNSA 79

                          90
                  ....*....|.
gi 971387048  365 GESTATIELSI 375
Cdd:pfam07679  80 GEAEASAELTV 90

Leucine rich repeat;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 971387048  124 NLQHLILNNNQLTSISDEAFEDfLLTLEDLDLSYNNLRSIPWESIRKMINLHQLSLDHNLI 184
Cdd:pfam13855   2 NLRSLDLSNNRLTSLDDGAFKG-LSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

Leucine rich repeat C-terminal domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 971387048   241 NPLHCNCELLWLRRLDRDDDME------TCASPPGLKGRYFWYVReEEFVC 285
Cdd:smart00082   1 NPFICDCELRWLLRWLQANEHLqdpvdlRCASPSSLRGPLLELLH-SEFKC 50

leucine-rich repeat receptor-like protein kinase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971387048  70 DFANMSGLVDLTLSRNTISYIQPYSFTDLESLRSLHLDSNRLPDIGEDILRGLINLQHLILNNNQLTSISDEAFEDFLLt 149
Cdd:PLN00113 470 DSFGSKRLENLDLSRNQFSGAVPRKLGSLSELMQLKLSENKLSGEIPDELSSCKKLVSLDLSHNQLSGQIPASFSEMPV- 548

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 971387048 150 LEDLDLSYNNLR-SIPwESIRKMINLHQLSLDHNLI 184
Cdd:PLN00113 549 LSQLDLSQNQLSgEIP-KNLGNVESLVQVNISHNHL 583

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 971387048 411 GPPERaVLVSEVTTTSALVKWTVSKSAP-RVKMYQLQY-NCSDDEVLIYRMIPATNKAFVVNNLVSGTGYDLCVLA 484
Cdd:cd00063    2 SPPTN-LRVTDVTSTSVTLSWTPPEDDGgPITGYVVEYrEKGSGDWKEVEVTPGSETSYTLTGLKPGTEYEFRVRA 76

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 971387048 288 PLITQHTHKLLVLEGQTATLKCKAIGDPTPIIHWVAPDDRLIGNSSRTSVYDNGTLDILITTSKDYGTFTCIAANAAGES 367
Cdd:cd05764    1 PLITRHTHELRVLEGQRATLRCKARGDPEPAIHWISPEGKLISNSSRTLVYDNGTLDILITTVKDTGAFTCIASNPAGEA 80

                 ....*...
gi 971387048 368 TATIELSI 375
Cdd:cd05764   81 TARVELHI 88

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971387048  46 PLDIDRRTVELRLGGNFIINISRQDFANMSGLVDLTLSRNTisyiqpySFTDLESLRSLHLDSNRLPDIGEDIlRGLINL 125
Cdd:COG4886   67 LLLSLLLLLLLSLLLLSLLLLGLTDLGDLTNLTELDLSGNE-------ELSNLTNLESLDLSGNQLTDLPEEL-ANLTNL 138

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971387048 126 QHLILNNNQLTSISDEAFEdfLLTLEDLDLSYNNLRSIPwESIRKMINLHQLSLDHNLIDYITEgTFADLQKLARLDLTS 205
Cdd:COG4886  139 KELDLSNNQLTDLPEPLGN--LTNLKSLDLSNNQLTDLP-EELGNLTNLKELDLSNNQITDLPE-PLGNLTNLEELDLSG 214

                 ....*....
gi 971387048 206 NRLQKLPPD 214
Cdd:COG4886  215 NQLTDLPEP 223

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971387048  55 ELRLGGNFIINISrQDFANMSGLVDLTLSRNTISYIqPYSFTDLESLRSLHLDSNRLPDIGEdiLRGLINLQHLILNNNQ 134
Cdd:COG4886  186 ELDLSNNQITDLP-EPLGNLTNLEELDLSGNQLTDL-PEPLANLTNLETLDLSNNQLTDLPE--LGNLTNLEELDLSNNQ 261

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971387048 135 LTSISDEAFedfLLTLEDLDLSYNNLRSIPWESIRKMINLHQLSLDHNLIDYITEgtFADLQKLARLDLTSNRLQKLPPD 214
Cdd:COG4886  262 LTDLPPLAN---LTNLKTLDLSNNQLTDLKLKELELLLGLNSLLLLLLLLNLLEL--LILLLLLTTLLLLLLLLKGLLVT 336

                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 971387048 215 PIFARSQVIPLAVTPFSPPLSLSFGGNPLHCNCELLWL 252
Cdd:COG4886  337 LTTLALSLSLLALLTLLLLLNLLSLLLTLLLTLGLLGL 374

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 971387048  287 PPLITQHTHKLLVLEGQTATLKCKAIGDPTPIIHWVAPDDRLIGNSSR--TSVYDNGTLDILITTSKDYGTFTCIAAN 362
Cdd:pfam13927   1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRsrSLSGSNSTLTISNVTRSDAGTYTCVASN 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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971387048 289 LITQHTHKLLVLEGQTATLKCKAIGDPTPIIHWVAPDDRLIGNSSRTSVYDNGTLDILITTSKDYGTFTCIAANAAGEST 368
Cdd:cd20952    1 IILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTLENGSLQIKGAEKSDTGEYTCVALNLSGEAT 80

                 ....*..
gi 971387048 369 ATIELSI 375
Cdd:cd20952   81 WSAVLDV 87

Leucine rich repeat;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 971387048  100 SLRSLHLDSNRLPDIGEDILRGLINLQHLILNNNQLTSISDEAFEDfLLTLEDLDLSYNNL 160
Cdd:pfam13855   2 NLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSG-LPSLRYLDLSGNRL 61

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971387048  55 ELRLGGNFIINISrQDFANMSGLVDLTLSRNTISYIQpySFTDLESLRSLHLDSNRLPDIGEdiLRGLINLQHLILNNNQ 134
Cdd:COG4886  209 ELDLSGNQLTDLP-EPLANLTNLETLDLSNNQLTDLP--ELGNLTNLEELDLSNNQLTDLPP--LANLTNLKTLDLSNNQ 283

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971387048 135 LTSISDEAFEDFLLTLEDLDLSYNNLRSIPWESIRKMINLHQLSLDHNLIDYITEGTFADLQKLARLDLTSNRLQKLPPD 214
Cdd:COG4886  284 LTDLKLKELELLLGLNSLLLLLLLLNLLELLILLLLLTTLLLLLLLLKGLLVTLTTLALSLSLLALLTLLLLLNLLSLLL 363

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 971387048 215 PIFARSQVIPLAVTPFSPPLSLSFGGNPLHCNCELLWLRRLDRDDD 260
Cdd:COG4886  364 TLLLTLGLLGLLEATLLTLALLLLTLLLLLLTTTAGVLLLTLALLD 409

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971387048 297 LLVLEGQTATLKCKAIGDPTPIIHWVAPDDRLIGNssRTSV-YDNGTLDILITTSKDYGTFTCIAANAAGES----TATI 371
Cdd:cd05876    5 LVALRGQSLVLECIAEGLPTPTVKWLRPSGPLPPD--RVKYqNHNKTLQLLNVGESDDGEYVCLAENSLGSArhayYVTV 82

                 .
gi 971387048 372 E 372
Cdd:cd05876   83 E 83

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 971387048 301 EGQTATLKCKAIGDPTPIIHWVAPDDRLIGNSS--RTSVYDNGTLDILITTSKDYGTFTCIAANAAGESTATIELSI 375
Cdd:cd20969   16 EGHTVQFVCRADGDPPPAILWLSPRKHLVSAKSngRLTVFPDGTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHLHV 92

Leucine rich repeat;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 971387048   51 RRTVELRLGGNFIINISRQDFANMSGLVDLTLSRNTISYIQPYSFTDLESLRSLHLDSNRL 111
Cdd:pfam13855   1 PNLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971387048 296 KLLVLEGQTATLKCKAIGDPTPIIHWVAPDDRLIgNSSRTSVYDNGTLDILITTSKDYGTFTCIAANAAGESTATIELSI 375
Cdd:cd05852   11 KILAAKGGRVIIECKPKAAPKPKFSWSKGTELLV-NNSRISIWDDGSLEILNITKLDEGSYTCFAENNRGKANSTGVLSV 89

Leucine rich repeat;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 971387048   75 SGLVDLTLSRNTISYIQPYSFTDLESLRSLHLDSNRLPDIGEDILRGLINLQHLILNNNQL 135
Cdd:pfam13855   1 PNLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 971387048 290 ITQHTHKLLVLEGQTATLKCKAIGDPTPIIHWVAPDDrLIGNSSRTSVYDNGTLDILITTSKDYGTFTCIAANAAG 365
Cdd:cd20968    2 ITRPPTNVTIIEGLKAVLPCTTMGNPKPSVSWIKGDD-LIKENNRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLG 76

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 971387048 287 PPLITQHTHKLLVLEGQTATLKCKAIGDPTPIIHWVApDDRLIGNSSRTSVYDNGTLDILITTS---KDYGTFTCIAANA 363
Cdd:cd20972    1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFC-EGKELQNSPDIQIHQEGDLHSLIIAEafeEDTGRYSCLATNS 79

                         90
                 ....*....|..
gi 971387048 364 AGESTATIELSI 375
Cdd:cd20972   80 VGSDTTSAEIFV 91

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

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gi 971387048 305 ATLKCKAIGDPTPIIHWVAPDDRLIGNS--SRTSVYDNGTLDILITTSKDYGTFTCIAANAAGESTATI 371
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPLPPSSrdSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASAS 69

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.

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gi 971387048 302 GQTATLKCKAIGDPTPIIHWVAPDDRLIGNSSRTSV-YDNGTLDILITTSKDYGTFTCIAANAAGESTATIELSI 375
Cdd:cd05730   18 GQSVTLACDADGFPEPTMTWTKDGEPIESGEEKYSFnEDGSEMTILDVDKLDEAEYTCIAENKAGEQEAEIHLKV 92

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

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gi 971387048 291 TQHTHKLLVLEGQTATLKCKAIGDPTPIIHWVApDDRLIGNSSR-TSVYDNGTLDILITTS---KDYGTFTCIAANAAGE 366
Cdd:cd20973    1 IQTLRDKEVVEGSAARFDCKVEGYPDPEVKWMK-DDNPIVESRRfQIDQDEDGLCSLIISDvcgDDSGKYTCKAVNSLGE 79

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gi 971387048 367 STATIELSI 375
Cdd:cd20973   80 ATCSAELTV 88

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 971387048 296 KLLVLEGQTATLKCKAIGDPTPIIHWvAPDDRLIGNSSRTSVYDNGTLDILITTSKDYGTFTCIAANAAGESTATIELSI 375
Cdd:cd04969   11 KILAAKGGDVIIECKPKASPKPTISW-SKGTELLTNSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89

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

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gi 971387048 298 LVLEGQTATLKCKAIGDPTPIIHWVapddRLIGN--SSRTSVYD-NGTLDILITTSKDYGTFTCIAANAAGESTATI 371
Cdd:cd05731    6 MVLRGGVLLLECIAEGLPTPDIRWI----KLGGElpKGRTKFENfNKTLKIENVSEADSGEYQCTASNTMGSARHTI 78

First immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-1, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-1. NCAM-1 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-nonNCAM) 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 the Ig1, Ig2, and Ig3 domains. 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). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

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gi 971387048 302 GQTATLKCKAIGDPTPiIHWVAPD-DRLIGNSSRTSVYDNG----TLDILITTSKDYGTFTCIAANAAG-ESTATIELSI 375
Cdd:cd04977   15 GESKFFLCKVSGDAKN-INWVSPNgEKVLTKHGNLKVVNHGsvlsSLTIYNANINDAGIYKCVATNGKGtESEATVKLDI 93