Retinol-binding proteins (RBP) are a family of proteins with diverse functions. They are carrier proteins that bind retinol. Retinol and retinoic acid play crucial roles in the modulation of gene expression and overall development of an embryo. However, deficit or excess of either one of these substances can cause early embryo mortality or developmental malformations. Regulation of transport and metabolism of retinol necessary for a successful pregnancy is accomplished via RBP. Retinol binding proteins have been identified within the uterus, embryo, and extraembryonic tissue of the bovine, ovine, and porcine, clearly indicating that RBP plays a role in proper retinol exposure to the embryo and successful transport at the maternal-fetal interface.
The cadherin superfamily is a large family that engage in both homo- and heterotypic, calcium-dependent, cell-cell adhesion events, and can be divided into at least four subfamilies based on the extracellular (EC) regions and cytoplasmic domains, that is: classical cadherins, desmosomal cadherins, protocadherins, and cadherin-like molecules. Human cadherin 4, type 1, R-cadherin (retinal), also known as CDH4, CAD4 and RCAD, is a classical cadherin from the cadherin superfamily. It is a calcium-dependent adhesion molecule and a type I transmembrane glycoprotein composed of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. CDH4 is thought to play an important role during brain segmentation and neuronal outgrowth, and also exerts critical actions in kidney and muscle development. CDH4 is expressed in vascular smooth muscle, pancreatic β-cells, thyroid follicular cells, sensory neurons of the dorsal root ganglia, and, possibly, astrocytes and endothelium of the retina. As a classic cadherin, CDH4 forms both homodimers and heterodimers with N-cadherin. The extracellular region of human CDH4 is 96% aa identical to that of mouse CDH4.
RCAS1, also known as EBAG9, is a tumor-associated antigen that is expressed at high frequency in a variety of cancers. RCAS1 gene was identified as an estrogen-responsive gene. Regulation of transcription by estrogen is mediated by estrogen receptor which binds to the estrogen-responsive element (ERE) found in the 5'-flanking region of RCAS1 gene. Two transcript variants differing in the 5' UTR, but encoding the same protein, have been identified for RCAS1 gene. EBAG9 may participate in suppression of cell proliferation and induces apoptotic cell death through activation of interleukin-1-beta converting enzyme (ICE)-like proteases.
Reticulocalbin-2 (RCN2, also named as ERC-55), is a 55-kDa Ca2+-binding protein containing six EF-hands, which was identified to be localized in endoplasmic reticulum. RCN2 is belonging to Reticulocalbin (RCN) family, the family members could play oncogenic roles in human malignancies and facilitate tumor cell proliferation and metastasis. Recently, studies on RCN2 functions mainly focused on its role in differentiation and endocrine regulation in mouse. Another study has suggested that RCN2 could be a potential tumor-associated antigen for mammary cancer immunological prevention. Up to now, the experimental evidence uncovering the role of RCN2 in cancer is very limited.
Human epidermal growth factor receptor 2 (HER2) is a type of membrane glycoprotein, and belongs to the epidermal growth factor (EGF) receptor family. HER2 plays a key role in development, cell proliferation and differentiation. HER2 has been reported to associate with malignancy and a poor prognosis in numerous carcinomas, including breast, prostate, ovarian, lung cancers and so on. HER2 is activated by dimerization and not activated by EGF, TGF-alpha and amphiregulin. Interaction with PTK6 increases its intrinsic kinase activity.It is heterodimer with EGFR, ERBB3 and ERBB4. HER2 associates with the 5'-TCAAATTC-3' sequence in the PTGS2/COX-2 promoter and activates its transcription. It implicated in transcriptional activation of CDKN1A and the function of the protein involves STAT3 and SRC. And also it involved in the transcription of rRNA genes by RNA Pol I and enhances protein synthesis and cell growth.
Receptor tyrosine-protein kinase erbB-3 is an enzyme that in humans is encoded by the ERBB3 gene. This gene encodes a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. ERBB3 belongs to the protein kinase superfamily,tyr protein kinase family and EGF receptor subfamily.It contains 1 protein kinase domain and it is expressed in Epithelial tissues and brain. This membrane-bound protein has a neuregulin binding domain but not an active kinase domain. It therefore can bind this ligand but not convey the signal into the cell through protein phosphorylation. However, it does form heterodimers with other EGF receptor family members which do have kinase activity.
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