Sushi repeat (SCR repeat);

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 528510477  129 CGQPPSFPHSHLQG-KTGLDLGDELLYACDPGHKLPNGETAFsllCDSCGEWYGLVQHC 186
Cdd:pfam00084   1 CPPPPDIPNGKVSAtKNEYNYGASVSYECDPGYRLVGSPTIT---CQEDGTWSPPFPEC 56

K+-dependent Na+/Ca+ exchanger; [Transport and binding proteins, Cations and iron carrying compounds]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528510477   321 DPPTEEPSSPNVEATDDSWLDGYPVGQEEDKAGGGSTGEAGPEHEAETETGQSEVEVFEDAASKKPVEEETGGLIGSPDE 400
Cdd:TIGR00927  650 ERPTEAEGENGEESGGEAEQEGETETKGENESEGEIPAERKGEQEGEGEIEAKEADHKGETEAEEVEHEGETEAEGTEDE 729

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 528510477   401 EDSIHIKGDEEQLTRLEEESVGIHEDTTEGITKDGEVHTPEKTALEFD 448
Cdd:TIGR00927  730 GEIETGEEGEEVEDEGEGEAEGKHEVETEGDRKETEHEGETEAEGKED 777

Extracellular link domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528510477   28 RVFLLElesfSKGGQEDGFEAAAQACMAQGARVASGADLHHAVlECAFSACSRAWLSGPSVG------STVCSGvpghLR 101
Cdd:pfam00193   1 GVFHLE----SPGRYKLTFQEAQAACAALGATLATPEQLYAAW-KAGLDTCDAGWLADGTVRypittpRPNCGG----NM 71

                          90       100
                  ....*....|....*....|
gi 528510477  102 PVDVQLENSTANTESLGVFC 121
Cdd:pfam00193  72 PGVRQYGFRDPLSERYDAYC 91

Transmembrane domain of ErbB2, a Protein Tyrosine Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. ErbB2 (HER2, HER2/neu) is a member of the EGFR (HER, ErbB) subfamily of proteins, which 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. It is activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. ErbB2 does not bind to any known EGFR subfamily ligands, but contributes to the kinase activity of all possible heterodimers. It acts as the preferred partner of other ligand-bound EGFR proteins and functions as a signal amplifier, with the ErbB2-ErbB3 heterodimer being the most potent pair in mitogenic signaling. 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 ErbB2 have been associated with increased breast cancer risk. ErbB2 plays an important role in cell development, proliferation, survival and motility. Overexpression of ErbB2 results in its activation and downstream signaling, even in the absence of ligand. ErbB2 overexpression, mainly due to gene amplification, has been shown in a variety of human cancers. Its role in breast cancer is especially well-documented. ErbB2 is up-regulated in about 25% of breast tumors and is associated with increases in tumor aggressiveness, recurrence and mortality. ErbB2 is a target for monoclonal antibodies and small molecule inhibitors, which are being developed as treatments for cancer. The first humanized antibody approved for clinical use is Trastuzumab (Herceptin), which is being used in combination with other therapies to improve the survival rates of patients with HER2-overexpressing breast cancer.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 528510477 577 CHGAGHGPMIAAIIVGVVAALAGVVLGV---WCYKKRQQK 613
Cdd:cd12094    2 CPAEQRASPLTSIIAGVVGILLVVVLLVvfgILIKRRRQK 41

Domain abundant in complement control proteins; SUSHI repeat; short complement-like repeat (SCR); The complement control protein (CCP) modules (also known as short consensus repeats SCRs or SUSHI repeats) contain approximately 60 amino acid residues and have been identified in several proteins of the complement system. A missense mutation in seventh CCP domain causes deficiency of the b subunit of factor XIII.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 528510477   129 CGQPPSFPHSHLQGKTG-LDLGDELLYACDPGHKLPNGETAFsllCDSCGEWYGLVQHC 186
Cdd:smart00032   1 CPPPPDIENGTVTSSSGtYSYGDTVTYSCDPGYTLIGSSTIT---CLENGTWSPPPPTC 56

Extracellular link domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528510477   28 RVFLLElesfSKGGQEDGFEAAAQACMAQGARVASGADLHHAVlECAFSACSRAWLSGPSVG------STVCSGvpghLR 101
Cdd:pfam00193   1 GVFHLE----SPGRYKLTFQEAQAACAALGATLATPEQLYAAW-KAGLDTCDAGWLADGTVRypittpRPNCGG----NM 71

                          90       100
                  ....*....|....*....|
gi 528510477  102 PVDVQLENSTANTESLGVFC 121
Cdd:pfam00193  72 PGVRQYGFRDPLSERYDAYC 91

Transmembrane domain of ErbB2, a Protein Tyrosine Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. ErbB2 (HER2, HER2/neu) is a member of the EGFR (HER, ErbB) subfamily of proteins, which 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. It is activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. ErbB2 does not bind to any known EGFR subfamily ligands, but contributes to the kinase activity of all possible heterodimers. It acts as the preferred partner of other ligand-bound EGFR proteins and functions as a signal amplifier, with the ErbB2-ErbB3 heterodimer being the most potent pair in mitogenic signaling. 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 ErbB2 have been associated with increased breast cancer risk. ErbB2 plays an important role in cell development, proliferation, survival and motility. Overexpression of ErbB2 results in its activation and downstream signaling, even in the absence of ligand. ErbB2 overexpression, mainly due to gene amplification, has been shown in a variety of human cancers. Its role in breast cancer is especially well-documented. ErbB2 is up-regulated in about 25% of breast tumors and is associated with increases in tumor aggressiveness, recurrence and mortality. ErbB2 is a target for monoclonal antibodies and small molecule inhibitors, which are being developed as treatments for cancer. The first humanized antibody approved for clinical use is Trastuzumab (Herceptin), which is being used in combination with other therapies to improve the survival rates of patients with HER2-overexpressing breast cancer.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 528510477 577 CHGAGHGPMIAAIIVGVVAALAGVVLGV---WCYKKRQQK 613
Cdd:cd12094    2 CPAEQRASPLTSIIAGVVGILLVVVLLVvfgILIKRRRQK 41

Domain abundant in complement control proteins; SUSHI repeat; short complement-like repeat (SCR); The complement control protein (CCP) modules (also known as short consensus repeats SCRs or SUSHI repeats) contain approximately 60 amino acid residues and have been identified in several proteins of the complement system. A missense mutation in seventh CCP domain causes deficiency of the b subunit of factor XIII.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 528510477   129 CGQPPSFPHSHLQGKTG-LDLGDELLYACDPGHKLPNGETAFsllCDSCGEWYGLVQHC 186
Cdd:smart00032   1 CPPPPDIENGTVTSSSGtYSYGDTVTYSCDPGYTLIGSSTIT---CLENGTWSPPPPTC 56

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
                 ....*....|....*....|....*....|....
gi 528510477 583 GPMIAAIIVGVVAALAGVVLGVWCYKKRQQKSSH 616
Cdd:cd12087    5 TTSIAAGVVGGLLVLVILGLIVFLFRRRRHIKRK 38