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 386763736  382 PVFRQRPVSVEADLGATVSMRCDVAGNPEPEIEWISENSD---------QVVGVAAELKLK-VSSETAGRYFCKAvVNGF 451
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPlrssdrfkvTYEGGTYTLTISnVQPDDSGKYTCVA-TNSA 79

                          90
                  ....*....|.
gi 386763736  452 PEIGAEATLYV 462
Cdd:pfam07679  80 GEAEASAELTV 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 386763736    88 PQDQTAVVGSRVTLPCRV-MEKVGALQWTKDDFGLgqhrnLSGFERYSMVGSDeeGDFSLDIYPLMLDDDAKYQCQVGPG 166
Cdd:smart00410   1 PPSVTVKEGESVTLSCEAsGSPPPEVTWYKQGGKL-----LAESGRFSVSRSG--STSTLTISNVTPEDSGTYTCAATNS 73

                           90
                   ....*....|....*.
gi 386763736   167 pqgeQGIRSRFAKLTV 182
Cdd:smart00410  74 ----SGSASSGTTLTV 85

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386763736  382 PVFRQRPVSVEADLGATVSMRCDVAGNPEPEIEWISENSD---------QVVGVAAELKLK-VSSETAGRYFCKAvVNGF 451
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPlrssdrfkvTYEGGTYTLTISnVQPDDSGKYTCVA-TNSA 79

                          90
                  ....*....|.
gi 386763736  452 PEIGAEATLYV 462
Cdd:pfam07679  80 GEAEASAELTV 90

Second immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3 (also known as Neph2). This protein has five Ig-like domains, one transmembrane domain, and a cytoplasmic tail. Included in this group is mammalian Kirrel (Neph1), Kirrel2 (Neph3), and Drosophila RST (irregular chiasm C-roughest) protein. These proteins contain multiple Ig domains, have properties of cell adhesion molecules, and are important in organ development.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386763736 207 LECVSQGGKPAAEITWI-DGlgnVLTKGIEYVKEPLADSRRITARSILKLAPKKEHHNTTFTCQAQNTADRTYRSAKLLL 285
Cdd:cd05759   20 LTCRARGAKPAAEIIWFrDG---EQLEGAVYSKELLKDGKRETTVSTLLITPSDLDTGRTFTCRARNEAIPNGKETSITL 96

                 ..
gi 386763736 286 EV 287
Cdd:cd05759   97 DV 98

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386763736   388 PVSVEADLGATVSMRCDVAGNPEPEIEWISENSDQV----------VGVAAELKLK-VSSETAGRYFCkAVVNGFPEIGA 456
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLaesgrfsvsrSGSTSTLTISnVTPEDSGTYTC-AATNSSGSASS 79

                   ....*.
gi 386763736   457 EATLYV 462
Cdd:smart00410  80 GTTLTV 85

Immunoglobulin Variable (V) domain of the Coxsackievirus and Adenovirus Receptor (CAR), and similar proteins; The members here are composed of the Variable (V) domain of the Coxsackievirus and Adenovirus Receptor (CAR), and similar proteins. CAR, which is encoded by human CXADR gene, is a cell adhesion molecule of the Immunoglobulin (Ig) superfamily. The CAR acts as a type I membrane receptor for group B1-B6 coxsackie viruses and subgroup C adenoviruses. For instance, adenovirus interacts with the coxsackievirus and adenovirus receptor to enter epithelial airway cells. The CAR is also shown to be involved in physiological processes such as neuronal and heart development, epithelial tight junction integrity, and tumor suppression. The CAR is a component of the epithelial apical junction complex that may function as a homophilic cell adhesion molecule and is essential for tight junction integrity. The CAR is also involved in transepithelial migration of leukocytes through adhesive interactions with JAML a transmembrane protein of the plasma membrane of leukocytes. The interaction between both receptors also mediates the activation of gamma-delta T-cells, a subpopulation of T-cells residing in epithelia and involved in tissue homeostasis and repair. The CAR is composed of one V-set and one C2-set Ig module, a single transmembrane helix, and an intracellular domain. This group belongs to the V-set of IgSF domains, having A, B, E and D strands in one beta-sheet and A', G, F, C, C' and C" in the other

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386763736  94 VVGSRVTLPCRV---MEKVGAL--QWTKDDFGLGQ---------------HRNLSGfeRYSMVGSDEEGDFSLDIYPLML 153
Cdd:cd20960   13 VAGENVTLPCHHqlgLEDQGTLdiEWLLLPSDKVEkvvitysgdrvynhyYPALKG--RVAFTSNDLSGDASLNISNLKL 90

                         90
                 ....*....|....*
gi 386763736 154 DDDAKYQCQVGPGPQ 168
Cdd:cd20960   91 SDTGTYQCKVKKAPG 105

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386763736  466 PIITSH-KVQFGGVGGRVKIDCLAFSIPKAEhILWSFEGKIINmSSADPDIYIfeehhlpEGVRAALIIRDSKATHFGKY 544
Cdd:pfam13927   2 PVITVSpSSVTVREGETVTLTCEATGSPPPT-ITWYKNGEPIS-SGSTRSRSL-------SGSNSTLTISNVTRSDAGTY 72

                  ....*.
gi 386763736  545 NCTVMN 550
Cdd:pfam13927  73 TCVASN 78

Third immunoglobulin domain of Nectin-like Protein-5, and similar domains; The members here are composed of the third immunoglobulin domain of Nectin-like Protein-5 (also known as Cluster of Differentiation 155 (CD155)). Nectin-like Protein-5 mediates NK (Natural Killer) cell adhesion and triggers NK cell effector functions. CD155 binds two different NK cell receptors: CD96 and CD226. These interactions accumulate at the cell-cell contact site, leading to the formation of a mature immunological synapse between NK cell and target cell. This may trigger adhesion and secretion of lytic granules and IFN-gamma and activate cytotoxicity of activated NK cells. CD155 may also promote NK cell-target cell modular exchange, and PVR transfer to the NK cell. This transfer is more important in some tumor cells expressing a lot of PVR, and may trigger fratricide NK cell activation, providing tumors with a mechanism of immunoevasion. Moreover, CD155 plays a role in mediating tumor cell invasion and migration.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 386763736 312 EVILSCQADANPHELSYRWfindELMTGDFTT-------KMIIHNVSRQYHDAIVkCEVVNAVG--KSEQS 373
Cdd:cd20930   18 EATLTCDVRSNPEPTGYDW----STTSGPFPTsavaqgpQLLIHSVDRLVNTTFI-CTVTNAVGtgRAEQT 83

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386763736  382 PVFRQRPVSVEADLGATVSMRCDVAGNPEPEIEWISENSD---------QVVGVAAELKLK-VSSETAGRYFCKAvVNGF 451
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPlrssdrfkvTYEGGTYTLTISnVQPDDSGKYTCVA-TNSA 79

                          90
                  ....*....|.
gi 386763736  452 PEIGAEATLYV 462
Cdd:pfam07679  80 GEAEASAELTV 90

Second immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3 (also known as Neph2). This protein has five Ig-like domains, one transmembrane domain, and a cytoplasmic tail. Included in this group is mammalian Kirrel (Neph1), Kirrel2 (Neph3), and Drosophila RST (irregular chiasm C-roughest) protein. These proteins contain multiple Ig domains, have properties of cell adhesion molecules, and are important in organ development.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386763736 207 LECVSQGGKPAAEITWI-DGlgnVLTKGIEYVKEPLADSRRITARSILKLAPKKEHHNTTFTCQAQNTADRTYRSAKLLL 285
Cdd:cd05759   20 LTCRARGAKPAAEIIWFrDG---EQLEGAVYSKELLKDGKRETTVSTLLITPSDLDTGRTFTCRARNEAIPNGKETSITL 96

                 ..
gi 386763736 286 EV 287
Cdd:cd05759   97 DV 98

Second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 - Necl-4; member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 (also known as cell adhesion molecule 3 or CADM3), Necl-2 (also known as CADM1), Necl-3 (also known as CADM2) and Necl-4 (also known as CADM4). These nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1 and Necl-2 have Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue and is important to the formation of synapses, axon bundles, and myelinated axons. Necl-2 is expressed in a wide variety of tissues, and is a putative tumour suppressor gene, which is downregulated in aggressive neuroblastoma. Necl-3 has been shown to accumulate in tissues of the central and peripheral nervous system, where it is expressed in ependymal cells and myelinated axons. It is observed at the interface between the axon shaft and the myelin sheath. Necl-4 is expressed on Schwann cells, and plays a key part in initiating peripheral nervous system (PNS) myelination. Necl-4 participates in cell-cell adhesion and is proposed to play a role in tumor suppression.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386763736 183 LVPPEAPKIT-QGDYLVttEDREIELECVSQGGKPAAEITWIDglGNVLTKGIEYVKEplADSRRI-TARSILKLAPKKE 260
Cdd:cd05761    1 LGVPEKPVITgFTSPVV--EGDEITLTCTTSGSKPAADIRWFK--NDKELKGVKEVQE--SGAGKTfTVTSTLRFRVDRD 74

                         90       100
                 ....*....|....*....|....*...
gi 386763736 261 HHNTTFTCQAQNTA-DRTYRSAKLLLEV 287
Cdd:cd05761   75 DDGVAVICRVDHESlTSTPKQTQQVLEV 102

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 386763736  382 PVFRQRPVSVEADLGATVSMRCDVAGNPEPEIEWISEN---------SDQVVGVAAELKLK-VSSETAGRYFCKA 446
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGepissgstrSRSLSGSNSTLTISnVTRSDAGTYTCVA 76

Second immunoglobulin (Ig)-like domain of nectin-like molecule-3 (Necl-3); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molecule-3 (Necl-3; also known as cell adhesion molecule 2 (CADM2)). Nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. Necl-3 has been shown to accumulate in tissues of the central and peripheral nervous system where it is expressed in ependymal cells and myelinated axons. It is observed at the interface between the axon shaft and the myelin sheath. Ig domains are likely to participate in ligand binding and recognition.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386763736 182 VLVPPEAPKITQGDYLVTTEDReIELECVSQGGKPAAEITWIDGLGNVltKGIEYVKEPLADSRRITARSILKLAPKKEH 261
Cdd:cd05884    1 VLGVPEKPQISGFTSPVMEGDH-IQLTCKTSGSKPAADIRWFKNDKEV--KDVKYLKAEDANRKTFTVSSSLDFHVDRDD 77

                         90       100
                 ....*....|....*....|....*..
gi 386763736 262 HNTTFTCQAQNTA-DRTYRSAKLLLEV 287
Cdd:cd05884   78 DGVAITCRVDHESlTATPQIAMQVLEI 104

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386763736   87 EPQDQTAVVGSRVTLPCRVM----EKVGALQWTKDDFGLGQHRNLSGF----------ERYSMVGSDEEGDFSLDIYPLM 152
Cdd:pfam07686   2 TPREVTVALGGSVTLPCTYSssmsEASTSVYWYRQPPGKGPTFLIAYYsngseegvkkGRFSGRGDPSNGDGSLTIQNLT 81

                          90       100       110
                  ....*....|....*....|....*....|.
gi 386763736  153 LDDDAKYQCQVGPGPQGEQGirsRFAKLTVL 183
Cdd:pfam07686  82 LSDSGTYTCAVIPSGEGVFG---KGTRLTVL 109

Second immunoglobulin (Ig)-like domain of nectin-like molecule 2 (Necl-2); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molecule 2 (Necl-2; also known as cell adhesion molecule 1 (CADM1)). Nectin-like molecules (Necls) have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. Necl-2 has Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is expressed in a wide variety of tissues and is a putative tumour suppressor gene which is downregulated in aggressive neuroblastoma. Ig domains are likely to participate in ligand binding and recognition.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386763736 183 LVPPEAPKI-TQGDYLVttEDREIELECVSQGGKPAAEITWIDglGNVLTKGIEYVKEplADSRRITARSILKLAPKKEH 261
Cdd:cd05883    1 LVPPRNLVIdIQKDTAV--EGEEIELNCTAMASKPAATIRWFK--GNKELTGKSEVEE--WYSRMFTVTSQLMLKVTKED 74

                         90
                 ....*....|...
gi 386763736 262 HNTTFTCQAQNTA 274
Cdd:cd05883   75 DGVPVICLVDHPA 87

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386763736   83 HFAMEPQDQTAVVGSRVTLPCRVMekvGA----LQWTKDDfglgqhRNLSGFERYSMvgSDEEGDFSLDIYPLMLDDDAK 158
Cdd:pfam07679   2 KFTQKPKDVEVQEGESARFTCTVT---GTpdpeVSWFKDG------QPLRSSDRFKV--TYEGGTYTLTISNVQPDDSGK 70

                  ....*
gi 386763736  159 YQCQV 163
Cdd:pfam07679  71 YTCVA 75

Second immunoglobulin domain of Cluster of Differentiation (CD) 33 and related Siglecs; member of the C2-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig) domain of Cluster of Differentiation (CD) 33 (also known as sialic-acid binding immunoglobulin type-lectin 3 (Siglec-3)) and related Siglecs. CD33, a Siglec family member, is a well-known immunotherapeutic target in acute myeloid leukemia (AML). It is an inhibitory sialoadhesin expressed in human leukocytes of the myeloid lineage and some lymphoid subsets, including natural killer (NK) cells. Siglecs are primarily expressed on immune cells and recognize sialic acid-containing glycan ligands. Siglecs are organized as an extracellular module composed of Ig-like domains (an N-terminal variable set of Ig-like carbohydrate recognition domains, and 1 to 16 constant Ig-like domains), followed by transmembrane and short cytoplasmic domains. Human Siglecs are classified into two subgroups, one subgroup is comprised of sialoadhesin (Siglec-1), CD22 (Siglec-2), and MAG (Siglec-4, myelin-associated glycoprotein), the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11. CD33 (Siglec-3) is the smallest Siglec member. It preferentially binds to alpha2-6- and alpha2-3-sialylated glycans and strongly binds to sialylated ligands on leukemic cell lines. 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. This group includes CD33-related Siglecs which belong to the C2-set of IgSF domains. Unlike the C1-set, the C2-set structures do not have a D strand.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386763736 202 DREIELECVSQGGKPA--AEITWidgLGNVLTKGIEyVKEPLADSRRITARSILKLAPKKEHHNTTFTCQA--QNTADRT 277
Cdd:cd20987   12 GQEVTLTCSVPDNCPAlsPEFSW---LGAALTPLPP-VLGRLEEEGTTTHSSVLTFTPRPEDHGTNLTCQVkfPGATVTT 87

                 ....*.
gi 386763736 278 YRSAKL 283
Cdd:cd20987   88 ERTIQL 93

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386763736 387 RPVSVEADLGATVSMRCDVAGNPEPEIEWISENSDQVVGVAA-----ELKL-KVSSETAGRYFCKAvVNGFPEIGAEATL 460
Cdd:cd05725    3 RPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPKGRYEilddhSLKIrKVTAGDMGSYTCVA-ENMVGKIEASATL 81

                 ..
gi 386763736 461 YV 462
Cdd:cd05725   82 TV 83

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386763736 369 KSEQSKKLdisfgpvfRQRpvSVEADLGATVSMRCDVAGNPEPEIEWISENSDQVVGVAAE-------LKLK-VSSETAG 440
Cdd:cd05856    2 RFTQPAKM--------RRR--VIARPVGSSVRLKCVASGNPRPDITWLKDNKPLTPPEIGEnkkkkwtLSLKnLKPEDSG 71

                         90
                 ....*....|....*.
gi 386763736 441 RYFCKaVVNGFPEIGA 456
Cdd:cd05856   72 KYTCH-VSNRAGEINA 86

First immunoglobulin (Ig) domain of contactin-1; 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-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386763736 381 GPVFRQRPVSV---EADLGATVSMRCDVAGNPEPEIEWISENSD--------QVVGVAAELKLKVSSETAGRYFCkAVVN 449
Cdd:cd05849    1 GPVFEEQPIDTiypEESTEGKVSVNCRARANPFPIYKWRKNNLDidltndrySMVGGNLVINNPDKYKDAGRYVC-IVSN 79

                         90
                 ....*....|..
gi 386763736 450 GFPEI-GAEATL 460
Cdd:cd05849   80 IYGKVrSREATL 91

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 386763736 398 TVSMRCDVAGNPEPEIEWISE--------NSDQVVGVAAELKLKVSSETA--GRYFCKAVVNGFPEIGAEATLYVK 463
Cdd:cd05738   16 TATMLCAASGNPDPEISWFKDflpvdtatSNGRIKQLRSGALQIENSEESdqGKYECVATNSAGTRYSAPANLYVR 91

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386763736 386 QRPVSVEADLGATVSMRCDVAGNPEPEIEW---------ISENSdQVVGVAAELK-LKVSSETAGRYFCKAVVNGFPEIG 455
Cdd:cd20970    7 QPSFTVTAREGENATFMCRAEGSPEPEISWtrngnliieFNTRY-IVRENGTTLTiRNIRRSDMGIYLCIASNGVPGSVE 85

                 ....*..
gi 386763736 456 AEATLYV 462
Cdd:cd20970   86 KRITLQV 92

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 386763736 382 PVFRQRPVSVEADLGATVSMRCDVAGNPEPEIEW--------------ISENSDQVVGVAAElklkVSSETAGRYFCKA 446
Cdd:cd20972    2 PQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWfcegkelqnspdiqIHQEGDLHSLIIAE----AFEEDTGRYSCLA 76

First immunoglobulin (Ig)-like domain of Tyro3 receptor tyrosine kinase (RTK), and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain of Tyro3 receptor tyrosine kinase (RTK). Tyro3 together with Axl and Mer form the Axl/Tyro3 family of receptor tyrosine kinases (RTKs). This family includes Axl (also known as Ark, Ufo, and Tyro7), Tyro3 (also known as Sky, Rse, Brt, Dtk, and Tif), and Mer (also known as Nyk, c-Eyk, and Tyro12). Axl/Tyro3 family receptors have an extracellular portion with two Ig-like domains followed by two fibronectin-types III (FNIII) domains, a membrane-spanning single helix, and a cytoplasmic tyrosine kinase domain. Axl, Tyro3 and Mer are widely expressed in adult tissues, though they show higher expression in the brain, in the lymphatic and vascular systems, and in the testis. Axl, Tyro3, and Mer bind the vitamin K dependent protein Gas6 with high affinity, and in doing so activate their tyrosine kinase activity. Axl/Gas6 signaling may play a part in cell adhesion processes, prevention of apoptosis, and cell proliferation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386763736 389 VSVEADLGATVSMRCDVAGNPEPEIEWIS-----ENSDQVVGVAAE------LKLK-VSSETAGRYFCKAVVNGFPEIGA 456
Cdd:cd20961    1 VKLTVSQGQPVKLNCSVEGMEEPDIQWVKdgavvQNLDQLYIPVSEqhwigfLSLKsVERSDAGRYWCQVEDGGETEISQ 80

                 ....*..
gi 386763736 457 EATLYVK 463
Cdd:cd20961   81 PVWLTVE 87

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 386763736  307 IPEGAEVILSCQADANPHElSYRWFINDELMTGdfTTKMIIHNVSrqYHDA-IVKCEVVNAVGkSEQSKKLDIS 379
Cdd:pfam13895  11 VTEGEPVTLTCSAPGNPPP-SYTWYKDGSAISS--SPNFFTLSVS--AEDSgTYTCVARNGRG-GKVSNPVELT 78

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
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 386763736 399 VSMRCDVAGNPEPEIEWI---------SENSDQVVGVAAELKLK-VSSETAGRYFCKA 446
Cdd:cd00096    1 VTLTCSASGNPPPTITWYkngkplppsSRDSRRSELGNGTLTISnVTLEDSGTYTCVA 58

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

                         10        20        30
                 ....*....|....*....|....*....|....
gi 386763736 382 PVFRQRPVSVEADLGATVSMRCDVAGNPEPEIEW 415
Cdd:cd05765    1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITW 34

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386763736 381 GPVFRQRPVSV---EADLGATVSMRCDVAGNPEPEIEWISENSDQVVGVAAELKL---------KVSSETAGRYFCKAVV 448
Cdd:cd04967    1 GPVFEEQPDDTifpEDSDEKKVALNCRARANPVPSYRWLMNGTEIDLESDYRYSLvdgtlvisnPSKAKDAGHYQCLATN 80

                         90
                 ....*....|..
gi 386763736 449 NGFPEIGAEATL 460
Cdd:cd04967   81 TVGSVLSREATL 92

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

                         10        20        30
                 ....*....|....*....|....*....|....*
gi 386763736 385 RQRPVSVEADLGATVSMRCDVAGNPEPEIEWISEN 419
Cdd:cd05730    7 RQSEVNATANLGQSVTLACDADGFPEPTMTWTKDG 41

Third immunoglobulin domain of Nectin-like Protein-5, and similar domains; The members here are composed of the third immunoglobulin domain of Nectin-like Protein-5 (also known as Cluster of Differentiation 155 (CD155)). Nectin-like Protein-5 mediates NK (Natural Killer) cell adhesion and triggers NK cell effector functions. CD155 binds two different NK cell receptors: CD96 and CD226. These interactions accumulate at the cell-cell contact site, leading to the formation of a mature immunological synapse between NK cell and target cell. This may trigger adhesion and secretion of lytic granules and IFN-gamma and activate cytotoxicity of activated NK cells. CD155 may also promote NK cell-target cell modular exchange, and PVR transfer to the NK cell. This transfer is more important in some tumor cells expressing a lot of PVR, and may trigger fratricide NK cell activation, providing tumors with a mechanism of immunoevasion. Moreover, CD155 plays a role in mediating tumor cell invasion and migration.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 386763736 312 EVILSCQADANPHELSYRWfindELMTGDFTT-------KMIIHNVSRQYHDAIVkCEVVNAVG--KSEQS 373
Cdd:cd20930   18 EATLTCDVRSNPEPTGYDW----STTSGPFPTsavaqgpQLLIHSVDRLVNTTFI-CTVTNAVGtgRAEQT 83