Intercellular adhesion molecule (ICAM), N-terminal domain; ICAMs normally functions to promote intercellular adhesion and signalling. However, The N-terminal domain of the receptor binds to the rhinovirus 'canyon' surrounding the icosahedral 5-fold axes, during the viral attachment process. This family is a family that is part of the Ig superfamily and is therefore related to the family ig (pfam00047).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 159110562   32 EPFWADLQPRVALVERGGSLWLNCSTNCPRPERGGLETSLRRNGTQRGLRWLARQLVDIREpETQPVCFFRC 103
Cdd:pfam03921   2 GNFQVSVEPQKPILPAGGSVFVNCSTSCPQPEKLGLETSLNKIELESGQGWKAFELSNVSE-DSVPLCHFNC 72

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 159110562   499 PEHITWLEGTEASLSCVAHGVPPPSVSCVRSGKEEVMEGP---------------LRVAREHAGTYRCEAINARGSAAKN 563
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGrfsvsrsgststltiSNVTPEDSGTYTCAATNSSGSASSG 80

                   ....*
gi 159110562   564 VAVTV 568
Cdd:smart00410  81 TTLTV 85

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 159110562   416 PRSWTWPEGPEQTLHCEARGNPEPSVHCARPEGGAVLALG-------------LLGPVTRALAGTYRCTAVNGQGQAVKD 482
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGrfsvsrsgststlTISNVTPEDSGTYTCAATNSSGSASSG 80

                   ....*
gi 159110562   483 VTLTV 487
Cdd:smart00410  81 TTLTV 85

Intercellular adhesion molecule (ICAM), N-terminal domain; ICAMs normally functions to promote intercellular adhesion and signalling. However, The N-terminal domain of the receptor binds to the rhinovirus 'canyon' surrounding the icosahedral 5-fold axes, during the viral attachment process. This family is a family that is part of the Ig superfamily and is therefore related to the family ig (pfam00047).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 159110562   32 EPFWADLQPRVALVERGGSLWLNCSTNCPRPERGGLETSLRRNGTQRGLRWLARQLVDIREpETQPVCFFRC 103
Cdd:pfam03921   2 GNFQVSVEPQKPILPAGGSVFVNCSTSCPQPEKLGLETSLNKIELESGQGWKAFELSNVSE-DSVPLCHFNC 72

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 159110562   756 SVRPGGNFTLTCRAEAWPPAQISWR-------APPGALNLGLSSNNSTLSVAGAMGSHGGEYECAATNAHGRHARRITVR 828
Cdd:smart00410   5 TVKEGESVTLSCEASGSPPPEVTWYkqggkllAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTTLT 84

                   .
gi 159110562   829 V 829
Cdd:smart00410  85 V 85

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 159110562   499 PEHITWLEGTEASLSCVAHGVPPPSVSCVRSGKEEVMEGP---------------LRVAREHAGTYRCEAINARGSAAKN 563
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGrfsvsrsgststltiSNVTPEDSGTYTCAATNSSGSASSG 80

                   ....*
gi 159110562   564 VAVTV 568
Cdd:smart00410  81 TTLTV 85

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 159110562 760 GGNFTLTCRAEAWPPAQISWRAPPGAL---NLGLSSNNSTLSVAGAMGSHGGEYECAATNAHG--RHARRITV 827
Cdd:cd05876   10 GQSLVLECIAEGLPTPTVKWLRPSGPLppdRVKYQNHNKTLQLLNVGESDDGEYVCLAENSLGsaRHAYYVTV 82

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 159110562 664 PPQMdeSSCPSHQTWLEGAEATAlACSARGRPSPRVHCSREG---------------AARLERLQVSREDAGTYRCVATN 728
Cdd:cd20976    1 APSF--SSVPKDLEAVEGQDFVA-QCSARGKPVPRITWIRNAqplqyaadrstceagVGELHIQDVLPEDHGTYTCLAKN 77

                         90
                 ....*....|...
gi 159110562 729 AHGTDSRTVTVGV 741
Cdd:cd20976   78 AAGQVSCSAWVTV 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 159110562   416 PRSWTWPEGPEQTLHCEARGNPEPSVHCARPEGGAVLALG-------------LLGPVTRALAGTYRCTAVNGQGQAVKD 482
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGrfsvsrsgststlTISNVTPEDSGTYTCAATNSSGSASSG 80

                   ....*
gi 159110562   483 VTLTV 487
Cdd:smart00410  81 TTLTV 85

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 159110562 423 EGPEQTLHCEARGNPEPSVHCARPEGgavlalGLLGPVTRAL----------------AGTYRCTAVNGQGQAVKDVTLT 486
Cdd:cd05764   14 EGQRATLRCKARGDPEPAIHWISPEG------KLISNSSRTLvydngtldilittvkdTGAFTCIASNPAGEATARVELH 87

                 .
gi 159110562 487 V 487
Cdd:cd05764   88 I 88

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 159110562 580 PSNWTWVEGSGKLFSCEVDGKPEPRVECvgsegASEGIVL---PLVSSNSGPRNSMTPGNLSP---GIYLCNATNRHG 651
Cdd:cd04978    6 PPSLVLSPGETGELICEAEGNPQPTITW-----RLNGVPIepaPEDMRRTVDGRTLIFSNLQPndtAVYQCNASNVHG 78

Intercellular adhesion molecule (ICAM), N-terminal domain; ICAMs normally functions to promote intercellular adhesion and signalling. However, The N-terminal domain of the receptor binds to the rhinovirus 'canyon' surrounding the icosahedral 5-fold axes, during the viral attachment process. This family is a family that is part of the Ig superfamily and is therefore related to the family ig (pfam00047).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 159110562   32 EPFWADLQPRVALVERGGSLWLNCSTNCPRPERGGLETSLRRNGTQRGLRWLARQLVDIREpETQPVCFFRC 103
Cdd:pfam03921   2 GNFQVSVEPQKPILPAGGSVFVNCSTSCPQPEKLGLETSLNKIELESGQGWKAFELSNVSE-DSVPLCHFNC 72

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 159110562   756 SVRPGGNFTLTCRAEAWPPAQISWR-------APPGALNLGLSSNNSTLSVAGAMGSHGGEYECAATNAHGRHARRITVR 828
Cdd:smart00410   5 TVKEGESVTLSCEASGSPPPEVTWYkqggkllAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTTLT 84

                   .
gi 159110562   829 V 829
Cdd:smart00410  85 V 85

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 159110562   499 PEHITWLEGTEASLSCVAHGVPPPSVSCVRSGKEEVMEGP---------------LRVAREHAGTYRCEAINARGSAAKN 563
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGrfsvsrsgststltiSNVTPEDSGTYTCAATNSSGSASSG 80

                   ....*
gi 159110562   564 VAVTV 568
Cdd:smart00410  81 TTLTV 85

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 159110562   673 PSHQTWLEGAEATaLACSARGRPSPRVHCSREGAARL---ERLQVSR--------------EDAGTYRCVATNAHGTDSR 735
Cdd:smart00410   1 PPSVTVKEGESVT-LSCEASGSPPPEVTWYKQGGKLLaesGRFSVSRsgststltisnvtpEDSGTYTCAATNSSGSASS 79

                   ....
gi 159110562   736 TVTV 739
Cdd:smart00410  80 GTTL 83

N-terminal immunoglobulin domain of the intercellular adhesion molecules ICAM-2 (Cluster of Differentiation 102 or CD102); member of the I-set of IgSF domains; The members here are composed of the N-terminal immunoglobulin domain of the intercellular adhesion molecules ICAM-2 (Cluster of Differentiation 102 or CD102). The intercellular adhesion molecules ICAM-1 (Cluster of Differentiation 54 or CD54), ICAM-2 and ICAM-3 (Cluster of Differentiation 50 or CD50) mediate a variety of critical intercellular adhesion events in the immune system through interactions with their counter-receptors, the beta2-integrins LFA-1 (CD11a/CD18), Mac-1 (CD11b/CD18), p150,95 (CD11c/CD18), and CD11d/CD18. The ICAMs are type I transmembrane glycoproteins belonging to the immunoglobulin superfamily (IgSF). The binding of the ICAM family members with the beta2-integrins physically stabilizes interactions between pairs of T and B cells, T cells and antigen-presenting cells (APCs), and brings effector cells such as cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells into close proximity to their target cells. All three ICAMs share a common polypeptide homology and structural motif, and the ability to bind LFA-1. The distinct functional role of each ICAM is affected by their relative affinities for LFA-1 (ICAM-1 > ICAM-2 > ICAM-3). ICAM-1 is expressed in most tissues at low levels, and expression is increased by inflammatory cytokines. In contrast, ICAM-2 is expressed predominantly on endothelium and leukocytes (except neutrophils), and its expression generally is not responsive to cytokines. ICAM-3 is expressed on leukocytes and Langerhans cells, but not on resting, cytokine-induced endothelium, or nonhematopoietic tissues.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 159110562  33 PFWADLQprvaLVERGGSLWLNCSTNCPRPERGGLETSLRRNGTQRGLRWLARQLVDIREpETQPVCFFRCARRTLQARG 112
Cdd:cd20995    4 YIRSEKQ----IVEATESWEVNCSTSCAQPEVGGLETPTNKILLEEQAQWKHYLVSNVSH-DTVLLCHFTCSGKQESESF 78

                 ....*
gi 159110562 113 LIRTF 117
Cdd:cd20995   79 NISVY 83

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 159110562 763 FTLTCRAEAWPPAQISWR------APPGALNLGLSSNNSTLSVAGAMGSHGGEYECAATNAHGRHARRIT 826
Cdd:cd00096    1 VTLTCSASGNPPPTITWYkngkplPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

N-terminal immunoglobulin domain of the intercellular adhesion molecules ICAM-3 (Cluster of Differentiation 50 or CD50); member of the I-set of IgSF domains; The members here are composed of the N-terminal immunoglobulin domain of the intercellular adhesion molecules ICAM-3 (Cluster of Differentiation 50 or CD50). The intercellular adhesion molecules ICAM-1 (Cluster of Differentiation 54 or CD54), ICAM-2 (Cluster of Differentiation 102 or CD102) and ICAM-3 mediate a variety of critical intercellular adhesion events in the immune system through interactions with their counter-receptors, the beta2-integrins LFA-1 (CD11a/CD18), Mac-1 (CD11b/CD18), p150,95 (CD11c/CD18), and CD11d/CD18. The ICAMs are type I transmembrane glycoproteins belonging to the immunoglobulin superfamily (IgSF). The binding of the ICAM family members with the beta2-integrins physically stabilizes interactions between pairs of T and B cells, T cells and antigen-presenting cells (APCs), and brings effector cells such as cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells into close proximity to their target cells. All three ICAMs share a common polypeptide homology and structural motif, and the ability to bind LFA-1. The distinct functional role of each ICAM is affected by their relative affinities for LFA-1 (ICAM-1 > ICAM-2 > ICAM-3). ICAM-1 is expressed in most tissues at low levels, and expression is increased by inflammatory cytokines. In contrast, ICAM-2 is expressed predominantly on endothelium and leukocytes (except neutrophils), and its expression generally is not responsive to cytokines. ICAM-3 is expressed on leukocytes and Langerhans cells, but not on resting, cytokine-induced endothelium, or nonhematopoietic tissues.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 159110562  32 EPFWADLQPRVALVERGGSLWLNCSTNCPRPERGGLETSLRRNGTQRGLRWLARQLVDI 90
Cdd:cd20997    1 QEFLLRVEPQNPVLSAGGSLFVNCSTDCPSSEKIALETSLSKELVASGMGWAAFNLSNV 59

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 159110562  749 ELAASPPSVRPGGNFTLTCRAEAWPPAQISWRAPPGALNlglSSNNSTLSVAGAmgSHGGEYECAATNAHGRH 821
Cdd:pfam13895   3 VLTPSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDGSAIS---SSPNFFTLSVSA--EDSGTYTCVARNGRGGK 70

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 159110562   416 PRSWTWPEGPEQTLHCEARGNPEPSVHCARPEGGAVLALG-------------LLGPVTRALAGTYRCTAVNGQGQAVKD 482
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGrfsvsrsgststlTISNVTPEDSGTYTCAATNSSGSASSG 80

                   ....*
gi 159110562   483 VTLTV 487
Cdd:smart00410  81 TTLTV 85

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 159110562 673 PSHQTWLEGAEATaLACSARGRPSPRVHCSREGA-----ARLERLQ--------VSREDAGTYRCVATNAHGTD-SRTVT 738
Cdd:cd20968    6 PTNVTIIEGLKAV-LPCTTMGNPKPSVSWIKGDDlikenNRIAVLEsgslrihnVQKEDAGQYRCVAKNSLGIAySKPVT 84

                 ....
gi 159110562 739 VGVE 742
Cdd:cd20968   85 IEVE 88

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 159110562  750 LAASPPSVRPGGNFTLTCRA-EAWPPAQISWRAPPGALNLGL-------SSNNSTLSVAGAMGSHGGEYECAATNAHGRH 821
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSAsTGSPGPDVTWSKEGGTLIESLkvkhdngRTTQSSLLISNVTKEDAGTYTCVVNNPGGSA 80

                  ....*.
gi 159110562  822 ARRITV 827
Cdd:pfam00047  81 TLSTSL 86

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 159110562 687 LACSARGRPSPRVHCSREGA----------------ARLERLQVSREDAGTYRCVATNAH-GTDSRTV 737
Cdd:cd00096    3 LTCSASGNPPPTITWYKNGKplppssrdsrrselgnGTLTISNVTLEDSGTYTCVASNSAgGSASASV 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 159110562 490 APALDSVgcPEHITWLEGTEASLSCVAHGVPPPSVSCVRSGKE----------EVMEGPLR---VAREHAGTYRCEAINA 556
Cdd:cd20976    1 APSFSSV--PKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPlqyaadrstcEAGVGELHiqdVLPEDHGTYTCLAKNA 78

                         90
                 ....*....|..
gi 159110562 557 RGSAAKNVAVTV 568
Cdd:cd20976   79 AGQVSCSAWVTV 90

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.

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gi 159110562 757 VRPGGNFTLTCRAEAWPPAQISWRAPPGALNLGL--------SSNN---STLSVAGAMGSHGGEYECAATNAHG--RHAR 823
Cdd:cd20956   13 LQPGPSVSLKCVASGNPLPQITWTLDGFPIPESPrfrvgdyvTSDGdvvSYVNISSVRVEDGGEYTCTATNDVGsvSHSA 92

                 ....
gi 159110562 824 RITV 827
Cdd:cd20956   93 RINV 96

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 159110562 510 ASLSCVAHGVPPPSVSCVRSGKEEVMEGPLR--------------VAREHAGTYRCEAIN-ARGSAAKNV 564
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSrrselgngtltisnVTLEDSGTYTCVASNsAGGSASASV 70

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 159110562 674 SHQTWLEGaEATALACSARGRPSPRVHCSREG---------------AARLErlQVSREDAGTYRCVATNAHGTDSRTVT 738
Cdd:cd05731    3 SSTMVLRG-GVLLLECIAEGLPTPDIRWIKLGgelpkgrtkfenfnkTLKIE--NVSEADSGEYQCTASNTMGSARHTIS 79

                 ....
gi 159110562 739 VGVE 742
Cdd:cd05731   80 VTVE 83

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.

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gi 159110562 423 EGPEQTLHCEARGNPEPSVHCARPEGgavlalGLLGPVTRAL----------------AGTYRCTAVNGQGQAVKDVTLT 486
Cdd:cd05764   14 EGQRATLRCKARGDPEPAIHWISPEG------KLISNSSRTLvydngtldilittvkdTGAFTCIASNPAGEATARVELH 87

                 .
gi 159110562 487 V 487
Cdd:cd05764   88 I 88

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.

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gi 159110562 674 SHQTW-LEGAEATaLACSARGRPSPRVH-----------CSREGAAR---LERLQVSREDAGTYRCVATNAHGTDSRTVT 738
Cdd:cd05764    7 THELRvLEGQRAT-LRCKARGDPEPAIHwispegklisnSSRTLVYDngtLDILITTVKDTGAFTCIASNPAGEATARVE 85

                 ...
gi 159110562 739 VGV 741
Cdd:cd05764   86 LHI 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.

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gi 159110562 665 PQMDESSCPSHQTWLEGAEATaLACSARGRPSPRVHCSREGAAR---------------LERLQVSREDAGTYRCVATN- 728
Cdd:cd20970    1 PVISTPQPSFTVTAREGENAT-FMCRAEGSPEPEISWTRNGNLIiefntryivrengttLTIRNIRRSDMGIYLCIASNg 79

                         90
                 ....*....|...
gi 159110562 729 AHGTDSRTVTVGV 741
Cdd:cd20970   80 VPGSVEKRITLQV 92

Immunoglobulin I-set domain;

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gi 159110562  499 PEHITWLEGTEASLSCVAHGVPPPSVSCVRSGKE---------EVMEGP-----LRVAREHAGTYRCEAINARGSAAKNV 564
Cdd:pfam07679   7 PKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPlrssdrfkvTYEGGTytltiSNVQPDDSGKYTCVATNSAGEAEASA 86

                  ....
gi 159110562  565 AVTV 568
Cdd:pfam07679  87 ELTV 90

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

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gi 159110562 757 VRPGGNFTLTCRAEAWPPAQISWRAPpGALNLGLSS-----NNSTLSVAGAMGSHGGEYECAATNAHGRHARRITVRV 829
Cdd:cd20952   11 VAVGGTVVLNCQATGEPVPTISWLKD-GVPLLGKDErittlENGSLQIKGAEKSDTGEYTCVALNLSGEATWSAVLDV 87

First immunoglobulin (Ig) domain of contactin-2; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module by contacts between IG domains 1 and 4, and domains 2 and 3. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-2 is also expressed in retinal amacrine cells in the developing chick retina, corresponding to the period of formation and maturation of AC processes. This group belongs to the I-set of IgSF domains.