CD4, extracellular; Members of this family adopt an immunoglobulin-like beta-sandwich, with seven strands in 2 beta sheets, in a Greek key topology. They are predominantly found in the extracellular portion of CD4 proteins, where they enable interaction with major histocompatibility complex class II antigens.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843658083 152 ASSIVYKKEGEQVEFSFPLAFTVEKLtgSGELWWQAERASSSKSWITFDLKNKEVSVKRVTQDPKLQMGKKLPLHLTLPQ 231
Cdd:pfam09191   1 VSNTVYKKEGEQVEFSFPLTFEDENL--SGELRWQAEGASSSQSWITFSLKNRKVSVQKVTQDPKLQMKEKLPLTLTLPQ 78

                          90       100       110
                  ....*....|....*....|....*....|
gi 1843658083 232 ALPQYAGSGNLTLALEAktGKLHQEVNLVV 261
Cdd:pfam09191  79 ALLQYAGSGNLTLTLDK--GKLHQEVNLVV 106

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 1843658083  14 LQLGPSKLNDRADSRRSLWDQGNFPLIIKNLKIEDSDTYICEVEDQKEEVQLLV 67
Cdd:cd07690    44 LTKGPSKLNDRADSRRNLWDQGSFPLIIKNLKIEDSDTYICEVEDKKEEVELLV 97

Immunoglobulin C2-set domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1843658083 262 MRATQLQKNLTCEVWGPTSPK---LMLSLKLENKEAKVSKREKAVWVLNP---EAGMWQCLLSDSGQVLLESNIKVLPT 334
Cdd:pfam05790   1 VTVSCSNNLLTCEVLELTLPKgskMDPSLKLKGQEAKSLETKKLESTFQPtteDSGTWVCLASDNDQKKLESVIEVLVL 79

CD4, extracellular; Members of this family adopt an immunoglobulin-like beta-sandwich, with seven strands in 2 beta sheets, in a Greek key topology. They are predominantly found in the extracellular portion of CD4 proteins, where they enable interaction with major histocompatibility complex class II antigens.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843658083 152 ASSIVYKKEGEQVEFSFPLAFTVEKLtgSGELWWQAERASSSKSWITFDLKNKEVSVKRVTQDPKLQMGKKLPLHLTLPQ 231
Cdd:pfam09191   1 VSNTVYKKEGEQVEFSFPLTFEDENL--SGELRWQAEGASSSQSWITFSLKNRKVSVQKVTQDPKLQMKEKLPLTLTLPQ 78

                          90       100       110
                  ....*....|....*....|....*....|
gi 1843658083 232 ALPQYAGSGNLTLALEAktGKLHQEVNLVV 261
Cdd:pfam09191  79 ALLQYAGSGNLTLTLDK--GKLHQEVNLVV 106

Second immunoglobulin (Ig) domain of Cluster of Differentiation (CD) 4; member of the C2-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig) Constant 2 (C2)-set domain of Cluster of Differentiation (CD) 4. CD4 and CD8 are the two primary co-receptor proteins found on the surface of T cells, and the presence of either CD4 or CD8 determines the function of the T cell. CD4 is found on helper T cells, where it is required for the binding of MHC (major histocompatibility complex) class II molecules, while CD8 is found on cytotoxic T cells, where it is required for the binding of MHC class I molecules. CD4 contains four immunoglobulin domains, with the first three included in this hierarchy. The fourth domain has a general Ig architecture, but has slight topological changes in the arrangement of beta strands relative to the other structures in this family and is not specifically included in the hierarchy. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843658083  68 FGLTANSDTHLLQGQSLTLTLESPPGSSPSVQCRSPRGKNIQGG------KTLSVSQLELQDSGTWTCTVLQNQKKVEFK 141
Cdd:cd07694     1 FKLTATSSDHVLSGTNLTLTLHGSSNSLPAFKVEWRGPGNKSKQilnqdkKTLNLVQLGPNDSGTWDCIVSVNSSEKTLK 80

                  ....*...
gi 1843658083 142 IDIVVLAF 149
Cdd:cd07694    81 LDIKVLAF 88

cytoplasmic domain of T-cell surface glycoprotein CD4 and similar proteins; CD4, also called T-cell surface antigen T4/Leu-3, is an integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, CD4 functions primarily as a coreceptor for MHC class II molecule:peptide complex. In other cells such as macrophages or NK cells, it plays a role in differentiation/activation, cytokine expression and cell migration in a TCR/LCK-independent pathway. CD4 participates in the development of T-helper cells in the thymus and triggers the differentiation of monocytes into functional mature macrophages. The model corresponds to cytoplasmic domain of CD4, which is responsible for the interaction with HIV-1 Nef protein that suppresses multiple immune surveillance mechanisms to promote viral pathogenesis.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1843658083 346 VLGGVAGLLLFIGLGIFFCVRCRHRRRQAERMSQIKRLLSEKKT 389
Cdd:cd22570     1 VLGGAAGLLLFIGLCIFCCVRCRHRRRQAERMSQIKRLLSEKKT 44

Immunoglobulin C2-set domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1843658083 262 MRATQLQKNLTCEVWGPTSPK---LMLSLKLENKEAKVSKREKAVWVLNP---EAGMWQCLLSDSGQVLLESNIKVLPT 334
Cdd:pfam05790   1 VTVSCSNNLLTCEVLELTLPKgskMDPSLKLKGQEAKSLETKKLESTFQPtteDSGTWVCLASDNDQKKLESVIEVLVL 79

T cell CD4 receptor C terminal region; This domain is the C terminal domain of the CD4 T cell receptor. The C terminal domain is the cytoplasmic domain which relays the signal for T cell activation. This process involves co-receptor internalization. This domain is involved in binding to the N terminal of Lck co-receptor in a Zn2+ clasp structure.

                          10        20
                  ....*....|....*....|....*...
gi 1843658083 371 RRQAERMSQIKRLLSEKKTCQCPHRFQK 398
Cdd:pfam12104   1 RKRARRMAQAKQYLLEKKTCQCQRRMYK 28

CD4, extracellular; Members of this family adopt an immunoglobulin-like beta-sandwich, with seven strands in 2 beta sheets, in a Greek key topology. They are predominantly found in the extracellular portion of CD4 proteins, where they enable interaction with major histocompatibility complex class II antigens.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843658083 152 ASSIVYKKEGEQVEFSFPLAFTVEKLtgSGELWWQAERASSSKSWITFDLKNKEVSVKRVTQDPKLQMGKKLPLHLTLPQ 231
Cdd:pfam09191   1 VSNTVYKKEGEQVEFSFPLTFEDENL--SGELRWQAEGASSSQSWITFSLKNRKVSVQKVTQDPKLQMKEKLPLTLTLPQ 78

                          90       100       110
                  ....*....|....*....|....*....|
gi 1843658083 232 ALPQYAGSGNLTLALEAktGKLHQEVNLVV 261
Cdd:pfam09191  79 ALLQYAGSGNLTLTLDK--GKLHQEVNLVV 106

Second immunoglobulin (Ig) domain of Cluster of Differentiation (CD) 4; member of the C2-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig) Constant 2 (C2)-set domain of Cluster of Differentiation (CD) 4. CD4 and CD8 are the two primary co-receptor proteins found on the surface of T cells, and the presence of either CD4 or CD8 determines the function of the T cell. CD4 is found on helper T cells, where it is required for the binding of MHC (major histocompatibility complex) class II molecules, while CD8 is found on cytotoxic T cells, where it is required for the binding of MHC class I molecules. CD4 contains four immunoglobulin domains, with the first three included in this hierarchy. The fourth domain has a general Ig architecture, but has slight topological changes in the arrangement of beta strands relative to the other structures in this family and is not specifically included in the hierarchy. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843658083  68 FGLTANSDTHLLQGQSLTLTLESPPGSSPSVQCRSPRGKNIQGG------KTLSVSQLELQDSGTWTCTVLQNQKKVEFK 141
Cdd:cd07694     1 FKLTATSSDHVLSGTNLTLTLHGSSNSLPAFKVEWRGPGNKSKQilnqdkKTLNLVQLGPNDSGTWDCIVSVNSSEKTLK 80

                  ....*...
gi 1843658083 142 IDIVVLAF 149
Cdd:cd07694    81 LDIKVLAF 88

cytoplasmic domain of T-cell surface glycoprotein CD4 and similar proteins; CD4, also called T-cell surface antigen T4/Leu-3, is an integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, CD4 functions primarily as a coreceptor for MHC class II molecule:peptide complex. In other cells such as macrophages or NK cells, it plays a role in differentiation/activation, cytokine expression and cell migration in a TCR/LCK-independent pathway. CD4 participates in the development of T-helper cells in the thymus and triggers the differentiation of monocytes into functional mature macrophages. The model corresponds to cytoplasmic domain of CD4, which is responsible for the interaction with HIV-1 Nef protein that suppresses multiple immune surveillance mechanisms to promote viral pathogenesis.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1843658083 346 VLGGVAGLLLFIGLGIFFCVRCRHRRRQAERMSQIKRLLSEKKT 389
Cdd:cd22570     1 VLGGAAGLLLFIGLCIFCCVRCRHRRRQAERMSQIKRLLSEKKT 44

Immunoglobulin C2-set domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1843658083 262 MRATQLQKNLTCEVWGPTSPK---LMLSLKLENKEAKVSKREKAVWVLNP---EAGMWQCLLSDSGQVLLESNIKVLPT 334
Cdd:pfam05790   1 VTVSCSNNLLTCEVLELTLPKgskMDPSLKLKGQEAKSLETKKLESTFQPtteDSGTWVCLASDNDQKKLESVIEVLVL 79

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1843658083  74 SDTHLLQGQSLTLTLESPPGSSPSVQCRSPrGKNIQGGKTLSVSQLELQDSGTWTCTV-LQNQKKVEFKIDIVV 146
Cdd:pfam13895   7 SPTVVTEGEPVTLTCSAPGNPPPSYTWYKD-GSAISSSPNFFTLSVSAEDSGTYTCVArNGRGGKVSNPVELTV 79

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1843658083   32 WDQGNFPLIIKNLKIEDSDTYICEVE----DQKEEVQLLV 67
Cdd:smart00410  46 RSGSTSTLTISNVTPEDSGTYTCAATnssgSASSGTTLTV 85

Transmembrane domain of the Epidermal Growth Factor Receptor family of Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EGFR (HER, ErbB) subfamily members include EGFR (HER1, ErbB1), HER2 (ErbB2), HER3 (ErbB3), HER4 (ErbB4), and similar proteins. They are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane (TM) helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. They are activated by ligand-induced dimerization, resulting in the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Collectively, they can recognize a variety of ligands including EGF, TGFalpha, and neuregulins, among others. All four subfamily members can form homo- or heterodimers. HER3 contains an impaired kinase domain and depends on its heterodimerization partner for activation. EGFR subfamily members are involved in signaling pathways leading to a broad range of cellular responses including cell proliferation, differentiation, migration, growth inhibition, and apoptosis. The TM domain not only serves as a membrane anchor, but also plays an important role in receptor dimerization and optimal activation. Mutations in the TM domain of EGFR family RTKs have been associated with increased breast cancer risk.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1843658083 333 PTWSTPVqpMALIVLGGVAGLLLfIGLGIFFCVRCRHRRRQ 373
Cdd:cd12087     1 RTSKTTS--IAAGVVGGLLVLVI-LGLIVFLFRRRRHIKRK 38