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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665407514   113 PRNITTRTGHTAAINCRVDNLGDKSVSWIRKRDLHILtagiltytSDERFKVVRtaDSKDWTLHVKYAQPRDSGIYECQV 192
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLA--------ESGRFSVSR--SGSTSTLTISNVTPEDSGTYTCAA 70

                           90
                   ....*....|....*
gi 665407514   193 -NTEPKISMAFRLNV 206
Cdd:smart00410  71 tNSSGSASSGTTLTV 85

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665407514   113 PRNITTRTGHTAAINCRVDNLGDKSVSWIRKRDLHILtagiltytSDERFKVVRtaDSKDWTLHVKYAQPRDSGIYECQV 192
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLA--------ESGRFSVSR--SGSTSTLTISNVTPEDSGTYTCAA 70

                           90
                   ....*....|....*
gi 665407514   193 -NTEPKISMAFRLNV 206
Cdd:smart00410  71 tNSSGSASSGTTLTV 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 665407514 113 PRNITTRTGHTAAINCRVDNL-GDKSVSWIRKRDLHILTAgILTYTSD---------ERFKVVRTaDSKDWTLHVKYAQP 182
Cdd:cd00099    5 PRSLSVQEGESVTLSCEVSSSfSSTYIYWYRQKPGQGPEF-LIYLSSSkgktkggvpGRFSGSRD-GTSSFSLTISNLQP 82

                         90
                 ....*....|
gi 665407514 183 RDSGIYECQV 192
Cdd:cd00099   83 EDSGTYYCAV 92

Sixth immunoglobulin (Ig) domain of contactin; The members here are composed of the sixth 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665407514 212 DAKAIIAGPTDLYVKVGSSVTLTCHVkqpatsAQDigpiywyrgPYILTPFVAHPNDAAIDLQRISMESTLAEKLQS--R 289
Cdd:cd04970    1 DATRITLAPSNADITVGENATLQCHA------SHD---------PTLDLTFTWSFNGVPIDLEKIEGHYRRRYGKDSngD 65

                         90       100       110
                 ....*....|....*....|....*....|...
gi 665407514 290 LRIANAQLLDTGNYTCMPTT-----AEAASVVV 317
Cdd:cd04970   66 LEIVNAQLKHAGRYTCTAQTvvdsdSASATLVV 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 665407514   113 PRNITTRTGHTAAINCRVDNLGDKSVSWIRKRDLHILtagiltytSDERFKVVRtaDSKDWTLHVKYAQPRDSGIYECQV 192
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLA--------ESGRFSVSR--SGSTSTLTISNVTPEDSGTYTCAA 70

                           90
                   ....*....|....*
gi 665407514   193 -NTEPKISMAFRLNV 206
Cdd:smart00410  71 tNSSGSASSGTTLTV 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 665407514 113 PRNITTRTGHTAAINCRVDNL-GDKSVSWIRKRDLHILTAgILTYTSD---------ERFKVVRTaDSKDWTLHVKYAQP 182
Cdd:cd00099    5 PRSLSVQEGESVTLSCEVSSSfSSTYIYWYRQKPGQGPEF-LIYLSSSkgktkggvpGRFSGSRD-GTSSFSLTISNLQP 82

                         90
                 ....*....|
gi 665407514 183 RDSGIYECQV 192
Cdd:cd00099   83 EDSGTYYCAV 92

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 665407514  113 PRNITTRTGHTAAINCRVDNLGDK---SVSWIRKRDLHILTAGILTYTSD-------ERFKVVRTADSKDWTLHVKYAQP 182
Cdd:pfam07686   3 PREVTVALGGSVTLPCTYSSSMSEastSVYWYRQPPGKGPTFLIAYYSNGseegvkkGRFSGRGDPSNGDGSLTIQNLTL 82

                          90       100
                  ....*....|....*....|....*..
gi 665407514  183 RDSGIYECQVNTEPKISMAFRLNVIVT 209
Cdd:pfam07686  83 SDSGTYTCAVIPSGEGVFGKGTRLTVL 109

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 665407514  220 PTDLYVKVGSSVTLTCHVKQPATSAQdigpIYWYR-GPYILTPFVAHPNDAaidlqRISmestlaeklQSRLRIANAQLL 298
Cdd:pfam00047   3 PPTVTVLEGDSATLTCSASTGSPGPD----VTWSKeGGTLIESLKVKHDNG-----RTT---------QSSLLISNVTKE 64

                  ....*...
gi 665407514  299 DTGNYTCM 306
Cdd:pfam00047  65 DAGTYTCV 72

Immunoglobulin (Ig) variable (V) domain of T-cell receptor (TCR) beta chain; The members here are composed of the immunoglobulin (Ig) variable domain of the beta chain of alpha/beta T-cell antigen receptors (TCRs). TCRs mediate antigen recognition by T lymphocytes, and are composed of alpha and beta, or gamma and delta, polypeptide chains with variable (V) and constant (C) regions. This group includes the variable domain of the alpha chain of alpha/beta TCRs. Alpha/beta TCRs recognize antigen as peptide fragments presented by major histocompatibility complex (MHC) molecules. The variable domain of TCRs is responsible for antigen recognition, and is located at the N-terminus of the receptor. Gamma/delta TCRs recognize intact protein antigens directly without antigen processing and recognize MHC independently of the bound peptide. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665407514 113 PRNITTRTGHTAAINCRVDNlGDKSVSWIRKRD------LHILTAGILTYTSD---ERFKVVRTADSKdWTLHVKYAQPR 183
Cdd:cd05899    5 PRYLIKRRGQSVTLRCSQKS-GHDNMYWYRQDPgkglqlLFYSYGGGLNEEGDlpgDRFSASRPSLTR-SSLTIKSAEPE 82

                 ....*..
gi 665407514 184 DSGIYEC 190
Cdd:cd05899   83 DSAVYLC 89

Immunoglobulin (Ig) variable (V) domain of Cluster of Differentiation (CD) 8 beta chain; The members here are composed of the immunoglobulin (Ig)-like domain in Cluster of Differentiation (CD) 8 beta. The CD8 glycoprotein plays an essential role in the control of T-cell selection, maturation, and the T-cell receptor (TCR)-mediated response to peptide antigen. CD8 is comprised of alpha and beta subunits and is expressed as either an alpha/alpha or alpha/beta dimer. Both dimeric isoforms can serve as a coreceptor for T cell activation and differentiation, however they have distinct physiological roles, different cellular distributions, unique binding partners, etc. Each CD8 subunit is comprised of an extracellular domain containing a V-type Ig-like domain, a single pass transmembrane portion, and a short intracellular domain. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665407514 113 PRNITTRTGHTAAINCRVDNL-GDKSVSWIRKR-----DLH-------ILTAGIlTY---TSDERFKVVRTADSKDWTLH 176
Cdd:cd07700    5 PGSLLVQTNQTVKMSCEAKTSpKNTRIYWLRQRqapskDSHfeflaswDPSKGI-VYgegVDQEKLIILSDSDSSRYILS 83

                         90
                 ....*....|....
gi 665407514 177 VKYAQPRDSGIYEC 190
Cdd:cd07700   84 LMSVKPEDSGTYFC 97

First (N-terminal) immunoglobulin (Ig)-like domain of nectin-like molecule-3; member of the V-set of Ig superfamily (IgSF) domains; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain of nectin-like molecule-3, Necl-3 (also known as cell adhesion molecule 2 (CADM2), SynCAM2, IGSF4D). Nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 - Necl-5). They all have an extracellular region containing three Ig-like domains, a transmembrane region, and a 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-3 accumulates in central and peripheral nervous system tissue, and has been shown to selectively interact with oligodendrocytes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665407514 110 FGMPRNITTRTGHTAAINCRVDNLGDKSVSWIRKRDlHILTAGILTYTSDERFKVVRtADSKDWTLHVKYAQPRDSGIYE 189
Cdd:cd07701    1 FPLTQNVTVVEGGTANLTCRVDQNDNTSLQWSNPAQ-QTLYFDDKKALRDNRIELVR-ASWHELSISISDVSLSDEGQYT 78

                         90
                 ....*....|....
gi 665407514 190 CQVNTEP-KISMAF 202
Cdd:cd07701   79 CSLFTMPvKTSKAY 92

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. 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 665407514 113 PRNITTRTGHTAAINCRVDNLGDKSVSWIRKrdlhiltAGILtyTSDERFKVVRTADSKdwTLHVKYAQPRDSGIYECQV 192
Cdd:cd05747   10 PRSLTVSEGESARFSCDVDGEPAPTVTWMRE-------GQII--VSSQRHQITSTEYKS--TFEISKVQMSDEGNYTVVV 78

                         90
                 ....*....|...
gi 665407514 193 -NTEPKISMAFRL 204
Cdd:cd05747   79 eNSEGKQEAQFTL 91

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. 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 Lingo-1 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 665407514 116 ITTRTGHTAAINCRVDNLGDKSVSWIRKRdLHILTAgiltyTSDERFKVVrtadsKDWTLHVKYAQPRDSGIYEC-QVNT 194
Cdd:cd20969   12 VFVDEGHTVQFVCRADGDPPPAILWLSPR-KHLVSA-----KSNGRLTVF-----PDGTLEVRYAQVQDNGTYLCiAANA 80

                         90
                 ....*....|..
gi 665407514 195 EPKISMAFRLNV 206
Cdd:cd20969   81 GGNDSMPAHLHV 92

Immunoglobulin (Ig)-like variable (V) domain of the Signal-Regulatory Protein (SIRP); The members here are composed of the immunoglobulin (Ig)-like domain of the Signal-Regulatory Protein (SIRP). The SIRPs belong to the "paired receptors" class of membrane proteins that comprise several genes coding for proteins with similar extracellular regions, but very different transmembrane/cytoplasmic regions with different (activating or inhibitory) signaling potentials. They are commonly on NK cells, but are also on many myeloid cells. Their extracellular region contains three immunoglobulin superfamily domains, a single V-set, and two C1-set IgSF domains. Their cytoplasmic tails that contain either ITIMs or transmembrane regions have positively charged residues that allow an association with adaptor proteins, such as DAP12/KARAP, containing ITAMs. There are 3 distinct SIRP members: alpha, beta, and gamma. SIRP alpha (also known as CD172a or SRC homology 2 domain-containing protein tyrosine phosphatase substrate 1/Shps-1) is a membrane receptor that interacts with a ligand CD47 expressed on many cells and gives an inhibitory signal through immunoreceptor tyrosine-based inhibition motifs in the cytoplasmic region that interact with phosphatases SHP-1 and SHP-2. SIRP beta has a short cytoplasmic region and associates with a transmembrane adapter protein DAP12 containing immunoreceptor tyrosine-based activation motifs to give an activating signal. SIRP gamma contains a very short cytoplasmic region lacking obvious signaling motifs, but also binds CD47 with much less affinity. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665407514 225 VKVGSSVTLTCHVkqpaTSAQDIGPIYWYRGpyiltpfvAHPNDAAIDLQR---------ISmESTLAEKLQSRLRIANA 295
Cdd:cd16097   11 VAAGESATLHCTV----TSLIPVGPIQWFRG--------AGPGRELIYNQKeghfprvttVS-DLTKRNNMDFSIRISNI 77

                         90
                 ....*....|.
gi 665407514 296 QLLDTGNYTCM 306
Cdd:cd16097   78 TPADAGTYYCV 88

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 665407514 113 PRNITTRTGHTAAINCRVDNLGDKSVSWIRKrdlhiltaGILTYTSDERFKVVRTAdskdwTLHVKYAQPRDSGIYEC 190
Cdd:cd20952    6 PQNQTVAVGGTVVLNCQATGEPVPTISWLKD--------GVPLLGKDERITTLENG-----SLQIKGAEKSDTGEYTC 70

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665407514  113 PRNITTRTGHTAAINCRVDNLGDKSVSWIRKrdlhiltaGILTYTSDERFKVVRTADSkdwTLHVKYAQPRDSGIYECQV 192
Cdd:pfam13927   8 PSSVTVREGETVTLTCEATGSPPPTITWYKN--------GEPISSGSTRSRSLSGSNS---TLTISNVTRSDAGTYTCVA 76

                  .
gi 665407514  193 N 193
Cdd:pfam13927  77 S 77

Immunoglobulin (Ig)-like domain of Programmed Cell Death 1 (PD1); The members here are composed of the immunoglobulin (Ig)-like domain of Programmed Cell Death 1 (PD1; also known as CD279/cluster of differentiation 279). PD1 is a cell surface receptor that is expressed on T cells and pro-B cells. The protein's structure includes an extracellular IgV domain followed by a transmembrane region and an intracellular tail. Activation of CD4+ T cells, CD8+ T cells, NKT cells, B cells, and monocytes induces PD-1 expression, immediately after which it binds two distinct ligands, PD-L1 (also known as B7-H1 or CD274/cluster of differentiation 274) and PD-L2, also known as B7-DC. PD-1 plays an important role in down regulating the immune system by preventing the activation of T-cells, reducing autoimmunity and promoting self-tolerance. The inhibitory effect of PD-1 is accomplished by promoting apoptosis in antigen specific T-cells in lymph nodes while simultaneously reducing apoptosis in regulatory T cells. A class of drugs that target PD-1, known as the PD-1 inhibitors, activate the immune system to attack tumors and treat cancer. Comparisons between the mouse PD-1 (mPD-1) and human PD-1 (hPD-1) reveals that unlike the mPD-1 which has a conventional IgSF V-set domain, hPD-1 lacks a C" strand, and instead the C' and D strands are connected by a long and flexible loop. In addition, the BC loop is not stabilized by disulfide bonding to the F strand of the ligand binding beta sheet. These differences result in different binding affinities of human and mouse PD-1 for their ligands.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 665407514 158 SDERFKVVRTADSKDWTLHVKYAQPRDSGIYEC---QVNTEPKISMAFRLNVIVT 209
Cdd:cd16088   58 QDWRFRVTQLPNGRDFHMSVVRARRNDSGTYLCgaiSLAPKAQIKESPRAELRVT 112

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665407514   123 TAAINCRV--DNLGDKSVSWIRKRD---LHILTAGILTYTS------DERFKVVRTADSKDWTLHVKYAQPRDSGIYECQ 191
Cdd:smart00406   1 SVTLSCKFsgSTFSSYYVSWVRQPPgkgLEWLGYIGSNGSSyyqesyKGRFTISKDTSKNDVSLTISNLRVEDTGTYYCA 80

                   .
gi 665407514   192 V 192
Cdd:smart00406  81 V 81