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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11067395 109 PPEQVILDLQPEWVAIDEAFTVKCHVPSVAPLQSLTLTLLQGDQELHRKDFLSLSLVSQRAEVTVNVRAQRENDRHNFSC 188
Cdd:cd05755   1 PPERVELTPLPSWQPVGKNFTLRCRVPGGAPRASLTLVLLRGNETLHRETFGGAAPAPQPAEATFTVLARREDHGANFSC 80

                        90       100
                ....*....|....*....|.
gi 11067395 189 RAELDLSPHGGGLFHGSSATK 209
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 11067395    408 PGNQIWVEGMDQMLACIPEGNPIPALVCIWNGMTFDLEVP---------------QKATQNHTGTYSCTATNSLGSVSKD 472
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGrfsvsrsgststltiSNVTPEDSGTYTCAATNSSGSASSG 80

                   ....*
gi 11067395    473 IAVLV 477
Cdd:smart00410  81 TTLTV 85

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 11067395 109 PPEQVILDLQPEWVAIDEAFTVKCHVPSVAPLQSLTLTLLQGDQELHRKDFLSLSLVSQRAEVTVNVRAQRENDRHNFSC 188
Cdd:cd05755   1 PPERVELTPLPSWQPVGKNFTLRCRVPGGAPRASLTLVLLRGNETLHRETFGGAAPAPQPAEATFTVLARREDHGANFSC 80

                        90       100
                ....*....|....*....|.
gi 11067395 189 RAELDLSPHGGGLFHGSSATK 209
Cdd:cd05755  81 LAELDLRPQGLNLFHNHSAPR 101

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 11067395  25 FQVSVHPNQALVEFGHSLTINCSTTCPDPGPSGIETFLKKTQLSKGSQWKEFLLEGITENSVLQCFFSCAGVQKDTALDI 104
Cdd:cd20995   1 FEVYIRSEKQIVEATESWEVNCSTSCAQPEVGGLETPTNKILLEEQAQWKHYLVSNVSHDTVLLCHFTCSGKQESESFNI 80

                ...
gi 11067395 105 TMY 107
Cdd:cd20995  81 SVY 83

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11067395 410 NQIWVEGMDQMLACIPEGNPIPALVciWNGMTFDL--EVPQKATQNHT-----------GTYSCTATNSLGSVSKDIAVL 476
Cdd:cd05731   4 STMVLRGGVLLLECIAEGLPTPDIR--WIKLGGELpkGRTKFENFNKTlkienvseadsGEYQCTASNTMGSARHTISVT 81

                ..
gi 11067395 477 VQ 478
Cdd:cd05731  82 VE 83

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 11067395 109 PPEQVILDLQPEWVAIDEAFTVKCHVPSVAPLQSLTLTLLQGDQELHRKDFLSLSLVSQRAEVTVNVRAQRENDRHNFSC 188
Cdd:cd05755   1 PPERVELTPLPSWQPVGKNFTLRCRVPGGAPRASLTLVLLRGNETLHRETFGGAAPAPQPAEATFTVLARREDHGANFSC 80

                        90       100
                ....*....|....*....|.
gi 11067395 189 RAELDLSPHGGGLFHGSSATK 209
Cdd:cd05755  81 LAELDLRPQGLNLFHNHSAPR 101

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 11067395  25 FQVSVHPNQALVEFGHSLTINCSTTCPDPGPSGIETFLKKTQLSKGSQWKEFLLEGITENSVLQCFFSCAGVQKDTALDI 104
Cdd:cd20995   1 FEVYIRSEKQIVEATESWEVNCSTSCAQPEVGGLETPTNKILLEEQAQWKHYLVSNVSHDTVLLCHFTCSGKQESESFNI 80

                ...
gi 11067395 105 TMY 107
Cdd:cd20995  81 SVY 83

N-terminal immunoglobulin domain of the intercellular adhesion molecules ICAM-1 (Cluster of Differentiation 54 or CD54); 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-1 (Cluster of Differentiation 54 or CD54). The intercellular adhesion molecules ICAM-1, ICAM-2 (Cluster of Differentiation 102 or CD102) 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 11067395  26 QVSVHPNQALVEFGHSLTINCSTTCPDPGPSGIETFLKKTQLSKGSQWKEFLLEGITENSVLQCFFSCAGVQKDTALDIT 105
Cdd:cd20996   1 QTSIHPSKAILPRGGSVQVNCSTSCDQPLLLGLETPLPKKELLLGGNWKVFELSNVQEDSQPMCYSNCPDGQSSASTFLT 80

                ..
gi 11067395 106 MY 107
Cdd:cd20996  81 VY 82

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11067395    408 PGNQIWVEGMDQMLACIPEGNPIPALVCIWNGMTFDLEVP---------------QKATQNHTGTYSCTATNSLGSVSKD 472
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGrfsvsrsgststltiSNVTPEDSGTYTCAATNSSGSASSG 80

                   ....*
gi 11067395    473 IAVLV 477
Cdd:smart00410  81 TTLTV 85

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 11067395 403 QESDCPGNQIWVEGMDQMLACIPEGNPIPALVCIWNGMtfDLEVP---------------QKATQNHTGTYSCTATNSLG 467
Cdd:cd20976   3 SFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQ--PLQYAadrstceagvgelhiQDVLPEDHGTYTCLAKNAAG 80

                        90
                ....*....|
gi 11067395 468 SVSKDIAVLV 477
Cdd:cd20976  81 QVSCSAWVTV 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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 11067395 408 PGNQIWVEGMDQMLACIPEGNPIPALVCIWNGMTFDLEVPQKATQNH------------TGTYSCTATNSLGSVS 470
Cdd:cd20952   6 PQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTLENgslqikgaeksdTGEYTCVALNLSGEAT 80

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 11067395 400 PRFQESdcPGNQIWVEGMDQMLACIPEGNPIPALVCIWNGM----TFDLEVPQ----------KATQNHTGTYSCTATNS 465
Cdd:cd20972   2 PQFIQK--LRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKelqnSPDIQIHQegdlhsliiaEAFEEDTGRYSCLATNS 79

                        90
                ....*....|..
gi 11067395 466 LGSVSKDIAVLV 477
Cdd:cd20972  80 VGSDTTSAEIFV 91