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 21361429 152 QSGQTSVGGSTALRCSSSeGAPKPVYNWVRLGTfPTPSPGSMvqdEVS-GQLILTNLSLTSSGTYRCVATNQMGS--ASC 228
Cdd:cd05728   7 SDTEADIGSSLRWECKAS-GNPRPAYRWLKNGQ-PLASENRI---EVEaGDLRITKLSLSDSGMYQCVAENKHGTiyASA 81

                ....
gi 21361429 229 ELTL 232
Cdd:cd05728  82 ELAV 85

Immunoglobulin (Ig)-like domain of protein zero (P0) and similar proteins; The members here are composed of the immunoglobulin (Ig) domain of protein zero (P0), a myelin membrane adhesion molecule. P0 accounts for over 50% of the total protein in peripheral nervous system (PNS) myelin. P0 is a single-pass transmembrane glycoprotein with a highly basic intracellular domain and an extracellular Ig domain. The extracellular domain of P0 (P0-ED) is similar to the Ig variable domain, carrying one acceptor sequence for N-linked glycosylation. P0 plays a role in membrane adhesion in the spiral wraps of the myelin sheath. The intracellular domain is thought to mediate membrane apposition of the cytoplasmic faces and may, through electrostatic interactions, interact directly with lipid headgroups. It is thought that homophilic interactions of the P0 extracellular domain mediate membrane juxtaposition in the extracellular space of PNS myelin. This group also contains the Ig domain of sodium channel subunit beta-2 (SCN2B), and of epithelial V-like antigen 1 (EVA). EVA, also known as myelin protein zero-like 2, is an adhesion molecule, which may play a role in structural organization of the thymus and early lymphocyte development. SCN2B subunits play a role in determining sodium channel density and function in neurons,and in control of electrical excitability in the brain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21361429  24 VEVKVPTEpLSTPLGKTAELTCTYSTS--VGDSFALEWSFVQPGKPISEShpILYFTNGHLYP--TGSKSKRVSLLQNPP 99
Cdd:cd05715   1 MEVYTPRE-LNVLNGSDVRLTCTFTSCytVGDAFSVTWTYQPEGGNTTES--MFHYSKGKPYIlkVGRFKDRVSWAGNPS 77

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 21361429 100 TVGvATLKLTDVHPSDTGTYLCQVNNPPDFyTNGLGLINLTV 141
Cdd:cd05715  78 KKD-ASIVISNLQFSDNGTYTCDVKNPPDI-VGGHGEIRLYV 117

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21361429     40 TAELTCTYSTSVGDSFALEWSFVQPGKPISesHPILYFTNGHLYPTGSKSKRVSLLQNPPTvGVATLKLTDVHPSDTGTY 119
Cdd:smart00406   1 SVTLSCKFSGSTFSSYYVSWVRQPPGKGLE--WLGYIGSNGSSYYQESYKGRFTISKDTSK-NDVSLTISNLRVEDTGTY 77

                   ....
gi 21361429    120 LCQV 123
Cdd:smart00406  78 YCAV 81

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21361429   151 SQSGQTSVGGSTALRCSSSeGAPKPVYNWVRLGTFPTPSP-GSMVQDEVSGQLILTNLSLTSSGTYRCVATNQMGSASCE 229
Cdd:pfam07679   7 PKDVEVQEGESARFTCTVT-GTPDPEVSWFKDGQPLRSSDrFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAGEAEAS 85

                  ....*
gi 21361429   230 LTLSV 234
Cdd:pfam07679  86 AELTV 90

Immunoglobulin (Ig)-like domain of protein zero (P0) and similar proteins; The members here are composed of the immunoglobulin (Ig) domain of protein zero (P0), a myelin membrane adhesion molecule. P0 accounts for over 50% of the total protein in peripheral nervous system (PNS) myelin. P0 is a single-pass transmembrane glycoprotein with a highly basic intracellular domain and an extracellular Ig domain. The extracellular domain of P0 (P0-ED) is similar to the Ig variable domain, carrying one acceptor sequence for N-linked glycosylation. P0 plays a role in membrane adhesion in the spiral wraps of the myelin sheath. The intracellular domain is thought to mediate membrane apposition of the cytoplasmic faces and may, through electrostatic interactions, interact directly with lipid headgroups. It is thought that homophilic interactions of the P0 extracellular domain mediate membrane juxtaposition in the extracellular space of PNS myelin. This group also contains the Ig domain of sodium channel subunit beta-2 (SCN2B), and of epithelial V-like antigen 1 (EVA). EVA, also known as myelin protein zero-like 2, is an adhesion molecule, which may play a role in structural organization of the thymus and early lymphocyte development. SCN2B subunits play a role in determining sodium channel density and function in neurons,and in control of electrical excitability in the brain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21361429  24 VEVKVPTEpLSTPLGKTAELTCTYSTS--VGDSFALEWSFVQPGKPISEShpILYFTNGHLYP--TGSKSKRVSLLQNPP 99
Cdd:cd05715   1 MEVYTPRE-LNVLNGSDVRLTCTFTSCytVGDAFSVTWTYQPEGGNTTES--MFHYSKGKPYIlkVGRFKDRVSWAGNPS 77

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 21361429 100 TVGvATLKLTDVHPSDTGTYLCQVNNPPDFyTNGLGLINLTV 141
Cdd:cd05715  78 KKD-ASIVISNLQFSDNGTYTCDVKNPPDI-VGGHGEIRLYV 117

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        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21361429 152 QSGQTSVGGSTALRCSSSeGAPKPVYNWVRLGTfPTPSPGSMvqdEVS-GQLILTNLSLTSSGTYRCVATNQMGS--ASC 228
Cdd:cd05728   7 SDTEADIGSSLRWECKAS-GNPRPAYRWLKNGQ-PLASENRI---EVEaGDLRITKLSLSDSGMYQCVAENKHGTiyASA 81

                ....
gi 21361429 229 ELTL 232
Cdd:cd05728  82 ELAV 85

Immunoglobulin variable domain (IgV); The members here are composed of the immunoglobulin variable domain (IgV). The IgV family contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology, and are components of immunoglobulin (Ig) and T cell receptors. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. Within the variable domain, there are regions of even more variability called the hypervariable or complementarity-determining regions (CDRs) which are responsible for antigen binding. A predominant feature of most Ig domains is the disulfide bridge connecting 2 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" strands in the other.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21361429  33 LSTPLGKTAELTCTYSTSVGDSfALEWSFVQPGKpisesHP--ILYFTNGHLYPTGSKSKRVSLLQNPPTVgvATLKLTD 110
Cdd:cd00099   8 LSVQEGESVTLSCEVSSSFSST-YIYWYRQKPGQ-----GPefLIYLSSSKGKTKGGVPGRFSGSRDGTSS--FSLTISN 79

                        90
                ....*....|...
gi 21361429 111 VHPSDTGTYLCQV 123
Cdd:cd00099  80 LQPEDSGTYYCAV 92

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21361429   151 SQSGQTSVGGSTALRCSSSeGAPKPVYNWVRLGTFPTPSP-GSMVQDEVSGQLILTNLSLTSSGTYRCVATNQMGSASCE 229
Cdd:pfam07679   7 PKDVEVQEGESARFTCTVT-GTPDPEVSWFKDGQPLRSSDrFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAGEAEAS 85

                  ....*
gi 21361429   230 LTLSV 234
Cdd:pfam07679  86 AELTV 90

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 21361429 151 SQSGQTSV-GGSTALRCSSsEGAPKPVYNWVRLGTfPTPsPGSMVQDEVSGQLILTNLSLTSSGTYRCVATNQMGSASCE 229
Cdd:cd05731   1 SESSTMVLrGGVLLLECIA-EGLPTPDIRWIKLGG-ELP-KGRTKFENFNKTLKIENVSEADSGEYQCTASNTMGSARHT 77

                ....*
gi 21361429 230 LTLSV 234
Cdd:cd05731  78 ISVTV 82

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21361429 155 QTSVGGSTALRCSSSEGAPKPVYNWVRLGtFPTPSPGSMVQDEVSGQLILTNLSLTSSGTYRCVATNQMGSASCELTLSV 234
Cdd:cd20952   9 QTVAVGGTVVLNCQATGEPVPTISWLKDG-VPLLGKDERITTLENGSLQIKGAEKSDTGEYTCVALNLSGEATWSAVLDV 87

Second Ig-like domain of Junctional adhesion molecule-1 (JAM1); a member of the I-set of IgSF domains; The members here are composed of the second Ig-like domain of Junctional adhesion molecule-1 (JAM1). JAM1 is an immunoglobulin superfamily (IgSF) protein with two Ig-like domains in its extracellular region; it plays a role in the formation of endothelial and epithelial tight junction and acts as a receptor for mammalian reovirus sigma-1. The IgSF is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. 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 second Ig-like domain of JAM1 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, the A strand of the I-set is discontinuous but lacks a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21361429 148 PLCSQSGQTSVGGSTALRCSSSEGAPKPVYNWVRLG----TFPTPSPG----SMVQDEVSGQLILTNLSLTSSGTYRCVA 219
Cdd:cd20950   1 PTVNIPSSATIGNRAVLTCSEPDGSPPSEYTWFKDGvvmpTNPKSTRAfsnsSYSLDPTTGELVFDPLSASDTGEYSCEA 80

                ....*..
gi 21361429 220 TNQMGSA 226
Cdd:cd20950  81 RNGYGTP 87

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21361429     31 EPLSTPLGKTAELTCTYSTSVGDSFalEWSFvQPGKPISEShpilyftnghlyptgsksKRVSLLQNPPTvgvATLKLTD 110
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEV--TWYK-QGGKLLAES------------------GRFSVSRSGST---STLTISN 57

                           90       100       110
                   ....*....|....*....|....*....|.
gi 21361429    111 VHPSDTGTYLCQVNNPPDFYTNGlglINLTV 141
Cdd:smart00410  58 VTPEDSGTYTCAATNSSGSASSG---TTLTV 85

First Ig-like domain of Junctional adhesion molecule-1 (JAM1)and similar domains; a member of the V-set of IgSF domains; The members here are composed of the first Ig-like domain of Junctional Adhesion Molecule-1 (JAM1)and similar domains. JAM1 is an immunoglobulin superfamily (IgSF) protein with two Ig-like domains in its extracellular region; it plays a role in the formation of endothelial and epithelial tight junction and acts as a receptor for mammalian reovirus sigma-1. The IgSF is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. 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 first Ig-like domain of JAM1 is a member of the V-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C'-C" in the other.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21361429  41 AELTCTYSTSVGDSfALEWSFVQpgkpisESHPILYFTNGHLypTGSKSKRVSLLQnpptvgvATLKLTDVHPSDTGTYL 120
Cdd:cd20946  17 VILSCKTPKKTSSP-RVEWKKLQ------RDVTFVVFQNNKI--QGDYKGRAEILG-------TNITIKNVTRSDSGKYR 80

                        90       100
                ....*....|....*....|..
gi 21361429 121 CQVNNPPDFYTNGLGLINLTVL 142
Cdd:cd20946  81 CEVSARSDGQNLGEVTVTLEVL 102

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 21361429  38 GKTAELTCTYSTSVGDSFAL--EWSFVQPGKpiSESHPILYFtNGHLYP--TGSKSKRVSLLQNPPTvGVATLKLTDVHP 113
Cdd:cd20960  15 GENVTLPCHHQLGLEDQGTLdiEWLLLPSDK--VEKVVITYS-GDRVYNhyYPALKGRVAFTSNDLS-GDASLNISNLKL 90

                        90
                ....*....|....
gi 21361429 114 SDTGTYLCQVNNPP 127
Cdd:cd20960  91 SDTGTYQCKVKKAP 104

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 21361429 159 GGSTALRCSSSeGAPKPVYNWVRLGTFPTP-SPGSMVQDEvSGQ--LILTNLSLTSSGTYRCVATNQMGSASCELTLSV 234
Cdd:cd05744  15 GRLCRFDCKVS-GLPTPDLFWQLNGKPVRPdSAHKMLVRE-NGRhsLIIEPVTKRDAGIYTCIARNRAGENSFNAELVV 91

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 21361429 159 GGSTALRCSSSeGAPKPVYNWVRLGTfPTPSPGSMVQDEV-SGQLILTNLSLTSSGTYRCVATNQMGSASCELTLSV 234
Cdd:cd20976  16 GQDFVAQCSAR-GKPVPRITWIRNAQ-PLQYAADRSTCEAgVGELHIQDVLPEDHGTYTCLAKNAAGQVSCSAWVTV 90

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and similar proteins; member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and related proteins. The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. The VEGFR family consists of three members: VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1) and VEGFR-3 (Flt-4). VEGF-A interacts with both VEGFR-1 and VEGFR-2. VEGFR-1 binds strongest to VEGF; VEGF-2 binds more weakly. VEGFR-3 appears not to bind VEGF, but binds other members of the VEGF family (VEGF-C and -D). VEGFRs bind VEGFs with high affinity with the IG-like domains. VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-2 is a major mediator of the mitogenic, angiogenic, and microvascular permeability-enhancing effects of VEGF-A. VEGFR-1 may play an inhibitory part in these processes by binding VEGF and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. VEGFR-3 has been shown to be involved in tumor angiogenesis and growth. This group also contains alpha-type platelet-derived growth factor receptor precursor (PDGFR)-alpha (CD140a), and PDGFR-beta (CD140b). PDGFRs alpha and beta have an extracellular component with five Ig-like domains, a transmembrane segment, and a cytoplasmic portion that has protein tyrosine kinase activity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21361429  24 VEVKVPTEPLSTPLGKTAELTCTYSTSVGDSFALEWSfvqpgkpiseshpilyftnghlYPTGSKSKRVSLLQ------N 97
Cdd:cd05742   3 LELSPNAEPTVLPQGETLVLNCTANVNLNEVVDFQWT----------------------YPSEKEGKLALLKPdikvdwS 60

                        90       100       110
                ....*....|....*....|....*....|....*
gi 21361429  98 PPTVGVATLKLTDVHPSDTGTYLCQVNNPPDFYTN 132
Cdd:cd05742  61 EPGEFVSTLTIPEATLKDSGTYTCAARSGVMKKEK 95

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 21361429   156 TSVGGSTALRCSSSeGAPKPVYNWVRLGTFPTPSPGSmvqdevsgqlILTNLSLTSSGTYRCVATNQMG---SASCELT 231
Cdd:pfam13895  11 VTEGEPVTLTCSAP-GNPPPSYTWYKDGSAISSSPNF----------FTLSVSAEDSGTYTCVARNGRGgkvSNPVELT 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 21361429 160 GSTA-LRCSSsEGAPKPVYNWVRLGTFPTPSPGSMVQDEVSGQLILTNLSLTSSGTYRCVATNQMG 224
Cdd:cd04978  14 GETGeLICEA-EGNPQPTITWRLNGVPIEPAPEDMRRTVDGRTLIFSNLQPNDTAVYQCNASNVHG 78

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21361429 156 TSVGGSTALRCSSSEGAPKPVYNWVRLGTFPTPSPG-SMVQDEVSG-QLILTNLSLTSSGTYRCVATNQMGSASCELTLS 233
Cdd:cd20973   8 EVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRfQIDQDEDGLcSLIISDVCGDDSGKYTCKAVNSLGEATCSAELT 87

                .
gi 21361429 234 V 234
Cdd:cd20973  88 V 88

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 21361429 157 SVGGSTALRCSSsEGAPKPVYNWVRLGTFPTPSPGSMVQdEVSGQLILTNLS-LTSSGTYRCVATNQMGSA-SCELTLS 233
Cdd:cd04967  17 SDEKKVALNCRA-RANPVPSYRWLMNGTEIDLESDYRYS-LVDGTLVISNPSkAKDAGHYQCLATNTVGSVlSREATLQ 93

First immunoglobulin (Ig) domain of contactin-5; 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-5. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains, anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. In rats, a lack of contactin-5 (NB-2) results in an impairment of the neuronal activity in the auditory system. Contactin-5 is expressed specifically in the postnatal nervous system, peaking at about 3 weeks postnatal. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala; lower levels of expression have been detected in the corpus callosum, caudate nucleus, and spinal cord. This group belongs to the I-set of IgSF domains.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 21361429 163 ALRCSSsEGAPKPVYNWVRLGTfPTPSPGSMVQDEVSGQLILTNLS-LTSSGTYRCVATNQMGS 225
Cdd:cd05848  23 ILNCEA-RGNPVPTYRWLRNGT-EIDTESDYRYSLIDGNLIISNPSeVKDSGRYQCLATNSIGS 84

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 21361429 146 SNPLCSQSGQTSVGGSTALRCSSsEGAPKPVYNWVRLGTFPTPSPGSMVQDEVSGQLILTNLSLTSSGTYRCVATNQM-G 224
Cdd:cd20970   4 STPQPSFTVTAREGENATFMCRA-EGSPEPEISWTRNGNLIIEFNTRYIVRENGTTLTIRNIRRSDMGIYLCIASNGVpG 82

                        90
                ....*....|
gi 21361429 225 SASCELTLSV 234
Cdd:cd20970  83 SVEKRITLQV 92

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 21361429    28 VPTEPLSTPLGKTAELTCTYSTSVgDSFALEWSFVQPGKPISESHPilyftnghlyptgskskrvsllQNPPTVGVATLK 107
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSASTGS-PGPDVTWSKEGGTLIESLKVK----------------------HDNGRTTQSSLL 57

                          90       100
                  ....*....|....*....|....
gi 21361429   108 LTDVHPSDTGTYLCQVNNPPDFYT 131
Cdd:pfam00047  58 ISNVTKEDAGTYTCVVNNPGGSAT 81

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup 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. 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. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin 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. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21361429 158 VGGSTALRCSSsEGAPKPVYNWVRLGTFPTPSPGS-----MVQDEVsgqLILTNLSLTSSGTYRCVATNQMGSASCELTL 232
Cdd:cd05763  13 AGSTARLECAA-TGHPTPQIAWQKDGGTDFPAARErrmhvMPEDDV---FFIVDVKIEDTGVYSCTAQNSAGSISANATL 88

                ..
gi 21361429 233 SV 234
Cdd:cd05763  89 TV 90

Immunoglobulin (Ig)-like domain of protein zero (P0); The members here are composed of the immunoglobulin (Ig) domain of protein zero (P0), a myelin membrane adhesion molecule. P0 accounts for over 50% of the total protein in peripheral nervous system (PNS) myelin. P0 is a single-pass transmembrane glycoprotein with a highly basic intracellular domain and an Ig domain. The extracellular domain of P0 (P0-ED) is similar to the Ig variable domain, carrying one acceptor sequence for N-linked glycosylation. P0 plays a role in membrane adhesion in the spiral wraps of the myelin sheath. The intracellular domain is thought to mediate membrane apposition of the cytoplasmic faces and may, through electrostatic interactions, interact directly with lipid headgroups. It is thought that homophilic interactions of the P0 extracellular domain mediate membrane juxtaposition in the extracellular space of PNS myelin.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21361429  24 VEVKVPTEPLSTpLGKTAELTCTYSTS--VGDSFALEWSFVQPGKpiSESHPILYFTNGHLYP--TGSKSKRVSLLQNPP 99
Cdd:cd05879   1 IVVYTDREVYGT-VGSDVTLSCSFWSSewISDDISFTWHYQPDGS--RDAISIFHYGKGQPYIdnVGPFKERIEWVGNPS 77

                        90       100
                ....*....|....*....|....*....
gi 21361429 100 TVGvATLKLTDVHPSDTGTYLCQVNNPPD 128
Cdd:cd05879  78 RKD-GSIVIHNLDYTDNGTFTCDVKNPPD 105

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 21361429 159 GGSTALRCSSsEGAPKPVYNWVRLGTfPTPSPGSMVQDEvSGQLILTNLSLTSSGTYRCVATNQMGSASCELTLSV 234
Cdd:cd05876  10 GQSLVLECIA-EGLPTPTVKWLRPSG-PLPPDRVKYQNH-NKTLQLLNVGESDDGEYVCLAENSLGSARHAYYVTV 82

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
                ....*....|....*....|....*
gi 21361429 102 GVATLKLTDVHPSDTGTYLCQVNNP 126
Cdd:cd00096  37 GNGTLTISNVTLEDSGTYTCVASNS 61

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        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21361429 158 VGGSTALRCSSSeGAPKPVYNWV-------RLGTFPTPSPGSMVQDEVsGQLILTNLSLTSSGTYRCVATNQMGSASCEL 230
Cdd:cd05765  14 VGETASFHCDVT-GRPQPEITWEkqvpgkeNLIMRPNHVRGNVVVTNI-GQLVIYNAQPQDAGLYTCTARNSGGLLRANF 91

                ....
gi 21361429 231 TLSV 234
Cdd:cd05765  92 PLSV 95

Immunoglobulin Variable (IgV) domain of B7-H4; The members here are composed of the immunoglobulin variable (IgV) domain of B7-H4 (also known as B7-S1, B7x, or Vtcn1). B7-H4 is one of the B7 family of immune-regulatory ligands that act as negative regulators of T cell function; it contains one IgV domain and one IgC domain. The B7-family consists of structurally related cell-surface protein ligands, which bind to receptors on lymphocytes that regulate immune responses. The binding of B7-H4 to unidentified receptors results in the inhibition of TCR-mediated T cell proliferation, cell-cycle progression and IL-2 production. As a co-inhibitory molecule, B7-H4 is widely expressed in tumor tissues and its expression is significantly associated with poor prognosis in human cancers such as glioma, pancreatic cancer, oral squamous cell carcinoma, renal cell carcinoma, and lung cancer.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 21361429  91 RVSLLQNPPTVGVATLKLTDVHPSDTGTYLCQVNNppdfyTNGLGLINLTV 141
Cdd:cd20984  63 RTSLFADQVHVGNASLRLKNVQLTDAGTYLCIISN-----SKGTGNANMEY 108

Immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), neurocan; The members here are composed of the immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), neurocan. In CSPGs, the Ig-like domain is followed by hyaluronan (HA)-binding tandem repeats, and a C-terminal region with epidermal growth factor-like, lectin-like, and complement regulatory protein-like domains. Separating these N- and C-terminal regions is a nonhomologous glycosaminoglycan attachment region. In cartilage, the CSPG aggrecan (not included in this group) forms cartilage link protein stabilized aggregates with HA. These aggregates contribute to the tissue's load bearing properties. Unlike aggrecan which is widely distributed in connective tissue and extracellular matrices, neurocan is localized almost exclusively in nervous tissue. Aggregates having other CSPGs substituting for aggrecan may contribute to the structural integrity of many different tissues. Members of the vertebrate HPLN (hyaluronan/HA and proteoglycan binding link) protein family are physically linked adjacent to CSPG genes.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21361429  27 KVPTEPLSTPLGKTAELTCTYS-----TSVGDSFALEWSFVQPGKpISESHPILYFTNGHLYPTGSKSKRVSLLQNPPTV 101
Cdd:cd05902   1 RVTAPPVRRPLSSSVLLPCVFTlppsaSSPPEGPRIKWTKLSTSG-GQQQRPVLVARDNVVRVAKAFQGRVSLPGYPKNR 79

                        90       100
                ....*....|....*....|..
gi 21361429 102 GVATLKLTDVHPSDTGTYLCQV 123
Cdd:cd05902  80 YNASLVLSRLRYSDSGTYRCEV 101