Second immunoglobulin (Ig)-like C2-set domain of intercellular cell adhesion molecule 1 (ICAM-1), and similar domains; The members here are composed of the second immunoglobulin (Ig)-like domain of intercellular cell adhesion molecule 1 (ICAM-1; also known as domain of cluster of differentiation (CD) 54) and similar proteins. During the inflammation process, these molecules recruit leukocytes onto the vascular endothelium before extravasation to the injured tissues. ICAM-1 may be involved in organ targeted tumor metastasis. The interaction of ICAM-1 with leukocyte function-associated antigen-1 (LFA-1) plays a part in leukocyte-endothelial cell recognition. This group also contains ICAM-2 which also interacts with LFA-1. Transmigration of immature dendritic cells across resting endothelium is dependent on the interaction of ICAM-2 with, yet unidentified, ligand(s) on the dendritic cells. ICAM-1 has five Ig-like domains and ICAM-2 has two. ICAM-1 may also act as host receptor for viruses and parasites. The structures of this group show that the second Ig domain lacks a D strand and thus belonging to the C2-set of the IgSF

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 285026497 119 RPDRVELVPLPPWQPVGENFTLSCRVPGAGPRASLTLTLLRGGQELIRRSFVGEPPRARGAMLTATVLARREDHRANFSC 198
Cdd:cd05755    1 PPERVELTPLPSWQPVGKNFTLRCRVPGGAPRASLTLVLLRGNETLHRETFGGAAPAPQPAEATFTVLARREDHGANFSC 80

                         90       100
                 ....*....|....*....|.
gi 285026497 199 LAELDLRPHGLGLFANSSAPR 219
Cdd:cd05755   81 LAELDLRPQGLNLFHNHSAPR 101

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 285026497   756 SVRPGGNFTLTCRAEAWPPAQISWR-------APPGALNLGLSSNNSTLSVAGAMGSHGGEYECAATNAHGRHARRITVR 828
Cdd:smart00410   5 TVKEGESVTLSCEASGSPPPEVTWYkqggkllAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTTLT 84

                   .
gi 285026497   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 285026497   673 PSHQTWLEGAEATaLACSARGRPSPRVRCSREGAARL---ERLQVSR--------------EDAGTYLCVATNAHGTDSR 735
Cdd:smart00410   1 PPSVTVKEGESVT-LSCEASGSPPPEVTWYKQGGKLLaesGRFSVSRsgststltisnvtpEDSGTYTCAATNSSGSASS 79

                   ....
gi 285026497   736 TVTV 739
Cdd:smart00410  80 GTTL 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 285026497 580 PSNWTWVEGSGKLFSCEVDGKPEPRVECvgsegASEGVVL---PLVSSNSGSRNSMTPGNLSP---GIYLCNATNRHG 651
Cdd:cd04978    6 PPSLVLSPGETGELICEAEGNPQPTITW-----RLNGVPIepaPEDMRRTVDGRTLIFSNLQPndtAVYQCNASNVHG 78

Second immunoglobulin (Ig)-like C2-set domain of intercellular cell adhesion molecule 1 (ICAM-1), and similar domains; The members here are composed of the second immunoglobulin (Ig)-like domain of intercellular cell adhesion molecule 1 (ICAM-1; also known as domain of cluster of differentiation (CD) 54) and similar proteins. During the inflammation process, these molecules recruit leukocytes onto the vascular endothelium before extravasation to the injured tissues. ICAM-1 may be involved in organ targeted tumor metastasis. The interaction of ICAM-1 with leukocyte function-associated antigen-1 (LFA-1) plays a part in leukocyte-endothelial cell recognition. This group also contains ICAM-2 which also interacts with LFA-1. Transmigration of immature dendritic cells across resting endothelium is dependent on the interaction of ICAM-2 with, yet unidentified, ligand(s) on the dendritic cells. ICAM-1 has five Ig-like domains and ICAM-2 has two. ICAM-1 may also act as host receptor for viruses and parasites. The structures of this group show that the second Ig domain lacks a D strand and thus belonging to the C2-set of the IgSF

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 285026497 119 RPDRVELVPLPPWQPVGENFTLSCRVPGAGPRASLTLTLLRGGQELIRRSFVGEPPRARGAMLTATVLARREDHRANFSC 198
Cdd:cd05755    1 PPERVELTPLPSWQPVGKNFTLRCRVPGGAPRASLTLVLLRGNETLHRETFGGAAPAPQPAEATFTVLARREDHGANFSC 80

                         90       100
                 ....*....|....*....|.
gi 285026497 199 LAELDLRPHGLGLFANSSAPR 219
Cdd:cd05755   81 LAELDLRPQGLNLFHNHSAPR 101

N-terminal immunoglobulin domain of the intercellular adhesion molecules ICAM-1 (Cluster of Differentiation 54 or CD54), ICAM-2 (CD102) and ICAM-3 (CD50); members of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain found in the N-terminus of the intercellular adhesion molecules ICAM-1 (Cluster of Differentiation 54 or CD54), ICAM-2 (CD102), and ICAM-3 (CD50). ICAM-1, ICAM-2, 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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 285026497  38 LQPRVALVERGGSLWLNCSTNCPRPERGGLETSLRRNGTQRGLRWLARQLVDIREpETQPVCFFRC 103
Cdd:cd20944    3 VSPSKVILPRGGSLLVNCSTSCDQPELLGLETSLPKKLLLLPGNWKVYELSNVQE-DSQPMCYSNC 67

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 285026497  753 SPPSVRPGGNFTLTCRAEAWPPAQISWR------APPGALNLGLSSNNSTLSVAGAMGSHGGEYECAATN 816
Cdd:pfam13927   9 SSVTVREGETVTLTCEATGSPPPTITWYkngepiSSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

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 285026497 760 GGNFTLTCRAEAWPPAQISWRAPPGAL---NLGLSSNNSTLSVAGAMGSHGGEYECAATNAHG--RHARRITV 827
Cdd:cd05876   10 GQSLVLECIAEGLPTPTVKWLRPSGPLppdRVKYQNHNKTLQLLNVGESDDGEYVCLAENSLGsaRHAYYVTV 82

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 285026497  673 PSHQTWLEGAEATaLACSARGRPSPRV-------------RCS---REGAARLERLQVSREDAGTYLCVATNAHGTDSRT 736
Cdd:pfam07679   7 PKDVEVQEGESAR-FTCTVTGTPDPEVswfkdgqplrssdRFKvtyEGGTYTLTISNVQPDDSGKYTCVATNSAGEAEAS 85

                  ....*
gi 285026497  737 VTVGV 741
Cdd:pfam07679  86 AELTV 90

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 285026497 499 PERITWLEGTEASLSCVAHGVPPPSVSCVR-------SGKEEVME-GPLR---VAREHAGTYRCEAINARGSA-AKNVAV 566
Cdd:cd20968    6 PTNVTIIEGLKAVLPCTTMGNPKPSVSWIKgddlikeNNRIAVLEsGSLRihnVQKEDAGQYRCVAKNSLGIAySKPVTI 85

                 ...
gi 285026497 567 TVE 569
Cdd:cd20968   86 EVE 88

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 285026497  499 PERITWLEGTEASLSCVAHGVPPPSVS-----------CVRSGKEEVMEGPLR---VAREHAGTYRCEAIN 555
Cdd:pfam13927   8 PSSVTVREGETVTLTCEATGSPPPTITwykngepissgSTRSRSLSGSNSTLTisnVTRSDAGTYTCVASN 78

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 285026497 580 PSNWTWVEGSGKLFSCEVDGKPEPRVECvgsegASEGVVL---PLVSSNSGSRNSMTPGNLSP---GIYLCNATNRHG 651
Cdd:cd04978    6 PPSLVLSPGETGELICEAEGNPQPTITW-----RLNGVPIepaPEDMRRTVDGRTLIFSNLQPndtAVYQCNASNVHG 78

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 285026497  420 TWPEGPEQTLHCEARGNPEPSV----------HCARPDGGAVLALGLL--GPVTRALAGTYRCTAIN 474
Cdd:pfam13927  12 TVREGETVTLTCEATGSPPPTItwykngepisSGSTRSRSLSGSNSTLtiSNVTRSDAGTYTCVASN 78

Second immunoglobulin (Ig)-like C2-set domain of intercellular cell adhesion molecule 1 (ICAM-1), and similar domains; The members here are composed of the second immunoglobulin (Ig)-like domain of intercellular cell adhesion molecule 1 (ICAM-1; also known as domain of cluster of differentiation (CD) 54) and similar proteins. During the inflammation process, these molecules recruit leukocytes onto the vascular endothelium before extravasation to the injured tissues. ICAM-1 may be involved in organ targeted tumor metastasis. The interaction of ICAM-1 with leukocyte function-associated antigen-1 (LFA-1) plays a part in leukocyte-endothelial cell recognition. This group also contains ICAM-2 which also interacts with LFA-1. Transmigration of immature dendritic cells across resting endothelium is dependent on the interaction of ICAM-2 with, yet unidentified, ligand(s) on the dendritic cells. ICAM-1 has five Ig-like domains and ICAM-2 has two. ICAM-1 may also act as host receptor for viruses and parasites. The structures of this group show that the second Ig domain lacks a D strand and thus belonging to the C2-set of the IgSF

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 285026497 119 RPDRVELVPLPPWQPVGENFTLSCRVPGAGPRASLTLTLLRGGQELIRRSFVGEPPRARGAMLTATVLARREDHRANFSC 198
Cdd:cd05755    1 PPERVELTPLPSWQPVGKNFTLRCRVPGGAPRASLTLVLLRGNETLHRETFGGAAPAPQPAEATFTVLARREDHGANFSC 80

                         90       100
                 ....*....|....*....|.
gi 285026497 199 LAELDLRPHGLGLFANSSAPR 219
Cdd:cd05755   81 LAELDLRPQGLNLFHNHSAPR 101

N-terminal immunoglobulin domain of the intercellular adhesion molecules ICAM-1 (Cluster of Differentiation 54 or CD54), ICAM-2 (CD102) and ICAM-3 (CD50); members of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain found in the N-terminus of the intercellular adhesion molecules ICAM-1 (Cluster of Differentiation 54 or CD54), ICAM-2 (CD102), and ICAM-3 (CD50). ICAM-1, ICAM-2, 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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 285026497  38 LQPRVALVERGGSLWLNCSTNCPRPERGGLETSLRRNGTQRGLRWLARQLVDIREpETQPVCFFRC 103
Cdd:cd20944    3 VSPSKVILPRGGSLLVNCSTSCDQPELLGLETSLPKKLLLLPGNWKVYELSNVQE-DSQPMCYSNC 67

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 285026497  753 SPPSVRPGGNFTLTCRAEAWPPAQISWR------APPGALNLGLSSNNSTLSVAGAMGSHGGEYECAATN 816
Cdd:pfam13927   9 SSVTVREGETVTLTCEATGSPPPTITWYkngepiSSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 285026497   499 PERITWLEGTEASLSCVAHGVPPPSVSCVRSGKEEVMEGP---------------LRVAREHAGTYRCEAINARGSAAKN 563
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGrfsvsrsgststltiSNVTPEDSGTYTCAATNSSGSASSG 80

                   ....*
gi 285026497   564 VAVTV 568
Cdd:smart00410  81 TTLTV 85

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 285026497  33 PFWADLQprvaLVERGGSLWLNCSTNCPRPERGGLETSLRRNGTQRGLRWLARQLVDIREpETQPVCFFRCARRTLQARG 112
Cdd:cd20995    4 YIRSEKQ----IVEATESWEVNCSTSCAQPEVGGLETPTNKILLEEQAQWKHYLVSNVSH-DTVLLCHFTCSGKQESESF 78

                 ....*
gi 285026497 113 LIRTF 117
Cdd:cd20995   79 NISVY 83

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 285026497   673 PSHQTWLEGAEATaLACSARGRPSPRVRCSREGAARL---ERLQVSR--------------EDAGTYLCVATNAHGTDSR 735
Cdd:smart00410   1 PPSVTVKEGESVT-LSCEASGSPPPEVTWYKQGGKLLaesGRFSVSRsgststltisnvtpEDSGTYTCAATNSSGSASS 79

                   ....
gi 285026497   736 TVTV 739
Cdd:smart00410  80 GTTL 83

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 285026497  32 EPFWADLQPRVALVERGGSLWLNCSTNCPRPERGGLETSLRRNGTQRGLRWLARQLVDI 90
Cdd:cd20997    1 QEFLLRVEPQNPVLSAGGSLFVNCSTDCPSSEKIALETSLSKELVASGMGWAAFNLSNV 59

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 285026497  749 ELAASPPSVRPGGNFTLTCRAEAWPPAQISWRAPPGALNlglSSNNSTLSVAGAmgSHGGEYECAATNAHGRHARR---I 825
Cdd:pfam13895   3 VLTPSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDGSAIS---SSPNFFTLSVSA--EDSGTYTCVARNGRGGKVSNpveL 77

                  ..
gi 285026497  826 TV 827
Cdd:pfam13895  78 TV 79

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 285026497 499 PERITWLEGTEASLSCVAHGVPPPSVSCVR-------SGKEEVME-GPLR---VAREHAGTYRCEAINARGSA-AKNVAV 566
Cdd:cd20968    6 PTNVTIIEGLKAVLPCTTMGNPKPSVSWIKgddlikeNNRIAVLEsGSLRihnVQKEDAGQYRCVAKNSLGIAySKPVTI 85

                 ...
gi 285026497 567 TVE 569
Cdd:cd20968   86 EVE 88

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 285026497  499 PERITWLEGTEASLSCVAHGVPPPSVS-----------CVRSGKEEVMEGPLR---VAREHAGTYRCEAIN 555
Cdd:pfam13927   8 PSSVTVREGETVTLTCEATGSPPPTITwykngepissgSTRSRSLSGSNSTLTisnVTRSDAGTYTCVASN 78

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 285026497  750 LAASPPSVRPGGNFTLTCRA-EAWPPAQISWRAPPGALNLGL-------SSNNSTLSVAGAMGSHGGEYECAATNAHGRH 821
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSAsTGSPGPDVTWSKEGGTLIESLkvkhdngRTTQSSLLISNVTKEDAGTYTCVVNNPGGSA 80

                  ....*.
gi 285026497  822 ARRITV 827
Cdd:pfam00047  81 TLSTSL 86

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 285026497 673 PSHQTWLEGAEATALACSARGRPSPRVRCSREG---AARLERLQVSR----------EDAGTYLCVATNAHGTDSRTVTV 739
Cdd:cd20978    7 PEKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGkplQGPMERATVEDgtltiinvqpEDTGYYGCVATNEIGDIYTETLL 86

                 ..
gi 285026497 740 GV 741
Cdd:cd20978   87 HV 88

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 285026497 490 APALDSVgcPERITWLEGTEASLSCVAHGVPPPSVSCVRSGKE----------EVMEGPLR---VAREHAGTYRCEAINA 556
Cdd:cd20976    1 APSFSSV--PKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPlqyaadrstcEAGVGELHiqdVLPEDHGTYTCLAKNA 78

                         90
                 ....*....|..
gi 285026497 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 285026497 757 VRPGGNFTLTCRAEAWPPAQISWRAPPGALNLGL--------SSNN---STLSVAGAMGSHGGEYECAATNAHG--RHAR 823
Cdd:cd20956   13 LQPGPSVSLKCVASGNPLPQITWTLDGFPIPESPrfrvgdyvTSDGdvvSYVNISSVRVEDGGEYTCTATNDVGsvSHSA 92

                 ....
gi 285026497 824 RITV 827
Cdd:cd20956   93 RINV 96

Fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains; member of the C2-set IgSF domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains. The CEA family is a group of anchored or secreted glycoproteins, expressed by epithelial cells, leukocytes, endothelial cells and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), also known as CD66e (Cluster of Differentiation 66e), is a cell surface glycoprotein that plays a role in cell adhesion, intracellular signaling and tumor progression. Diseases associated with CEACAM5 include lung cancer and rectum cancer. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 285026497 753 SPPSVRPGGNFTLTCRAEAWPPAQISWRappgaLNLGLSSNNSTLSVAGAMGSHGGEYECAATN-AHGR 820
Cdd:cd20948    3 SDTYYLSGENLNLSCHAASNPPAQYSWT-----INGTFQTSSQELFLPAITENNEGTYTCSAHNsLTGK 66

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 285026497 502 ITWLEGTEASLSCVAHGVPPPSVSCVRSGKE--------EVMEGPLR---VAREHAGTYRCEAINARGSAAKNVAVTVE 569
Cdd:cd05731    5 TMVLRGGVLLLECIAEGLPTPDIRWIKLGGElpkgrtkfENFNKTLKienVSEADSGEYQCTASNTMGSARHTISVTVE 83

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 285026497  673 PSHQTWLEGAEATaLACSARGRPSPRVRCSREGAARLERLQ----------------VSREDAGTYLCVATN 728
Cdd:pfam13927   8 PSSVTVREGETVT-LTCEATGSPPPTITWYKNGEPISSGSTrsrslsgsnstltisnVTRSDAGTYTCVASN 78

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 285026497 664 PPQMDESscPSHQTWLEGAEATaLACSARGRPSPRVRCSREGA-------------ARLERLQVSR---EDAGTYLCVAT 727
Cdd:cd20972    1 PPQFIQK--LRSQEVAEGSKVR-LECRVTGNPTPVVRWFCEGKelqnspdiqihqeGDLHSLIIAEafeEDTGRYSCLAT 77

                         90
                 ....*....|....
gi 285026497 728 NAHGTDSRTVTVGV 741
Cdd:cd20972   78 NSVGSDTTSAEIFV 91

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 285026497  499 PERITWLEGTEASLSCVAHGVPPPSVSCVRSGKE---------EVMEGP-----LRVAREHAGTYRCEAINARGSAAKNV 564
Cdd:pfam07679   7 PKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPlrssdrfkvTYEGGTytltiSNVQPDDSGKYTCVATNSAGEAEASA 86

                  ....
gi 285026497  565 AVTV 568
Cdd:pfam07679  87 ELTV 90

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 285026497 689 CSARGRPSPRVRCSREGA--ARLERLQV----------SREDAGTYLCVATNAHGT 732
Cdd:cd05728   21 CKASGNPRPAYRWLKNGQplASENRIEVeagdlritklSLSDSGMYQCVAENKHGT 76

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 285026497 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 285026497 743 YRPVVAELAASP--PSVRPGGNFTLTCRAEAWPPAQISWRAPPGALNLGLSSNNSTlsVAGAM-------GSHGGEYECA 813
Cdd:cd05850    1 YGPVFEEQPSSTlfPEGSAEEKVTLACRARASPPATYRWKMNGTELKMEPDSRYRL--VAGNLvisnpvkAKDAGSYQCL 78