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C3d is derived from human C3 after a series of proteolytic cleavages.C3d is prepared from purified human C3. The C3 is converted to C3b by treatment with the natural human C3 convertase and this C3b is converted to iC3b. Finally, this iC3b is cleaved with trypsin to yield C3d.If the C3b precursor was attached to a surface (as occurs during complement activation) the iC3b, C3dg and C3d fragments would remain covalently attached to that surface.C3d is able to attach to a surfaceonly during complement activation on a surface. Surface-bound C3d is linked to the target through an ester or an amide covalent bond. Ester bonds are unstable, thusC3d releasesfrom the particle.

SIL1 is localized to endoplasmic reticulum (ER). SIL1 is an N-linked glycoprotein with an N-terminal ER targeting sequence, 2 putative N-glycosylation sites, and a C-terminal ER retention signal. SIL1 acts as a nucleotide exchange factor for another unfolded protein response protein. Mutations in SIL1 are linked to Marinesco-Sjogren syndrome.

Regulation of nuclear pre-mRNA domain-containing protein 1B (RPRD1B) interacts with phosphorylated C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit POLR2A, and participates in dephosphorylation of the CTD. RPRD1B stimulates binding of RNA polymerase II to the CCDN1 promoter and to the termination region before the poly-A site but decreases its binding after the poly-A site. RPRD1B inhibits RNA polymerase II from reading through the 3' end termination site and may allow it to be drafted back to the promoter through promotion of the formation of a chromatin loop. In addition, RPRD1B enhances the transcription of several other cell cycle-related genes including CDK2, CDK4, CDK6 and cyclin-E but not CDKN1A, CDKN1B or cyclin-A. RPRD1B also promotes cell proliferation.

BID is a pro-apoptotic Bcl-2 protein having only the BH3 domain. In reaction to apoptotic signaling, BID interacts with another Bcl-2 family of cell death regulators, called Bax, they form a heterodimer resulting to the insertion of Bax into the outer mitochondrial membrane. Bax induces the opening of the mitochondrial voltage-dependent anion channel which lead to the release of cytochrome c and other pro-apoptotic factors from the mitochondria resulting in activation of caspases. BID is a mediator of mitochondrial damage induced by caspase-8 (CASP8). CASP8 cleaves BID, and the COOH-terminal part translocates to mitochondria where it triggers cytochrome c release. The major proteolytic product p15 BID releasea cytochrome c. Isoform 1, Isoform 2 and Isoform 4 induce ice-like proteases and apoptosis while Isoform 3 does not induce apoptosis.

LASP1 has a vital part in the regulation of dynamic actin-based, cytoskeletal activities. Agonist-dependent changes in LASP1 phosphorylation can additionally assist in regulation of actin-associated ion transport activities in the parietal cell and in several other F-actin-rich secretory epithelial cell types.

LIN28 plays an important role as a 'translational enhancer', leading specific mRNAs to polysomes and therefore increasing the competence of protein synthesis. LIN28 is a marker of undifferentiated human embryonic stem cells and it enhances the efficiency of the formation of induced pluripotent stem (iPS) cells from human fibroblasts. LIN28 binds to the let-7 pre-miRNA and blocks production of the mature let-7 microRNA in mouse embryonic stem cells. Overexpression of LIN28 is associated with human germ-cell tumors.

Hepatitis A virus cellular receptor 1 (HAVCR1) is a membrane receptor for both human hepatitis A virus (HHAV) and TIMD4. HAVCR1 is a type I trans-membrane structural glycoprotein located in the renal proximal tubule epithelial cells. HAVCR1 protein may be involved in the control of asthma and allergic diseases. The reference genome represents an allele which retains a MTTVP amino acid segment that presents defense against atopy in HHAV seropositive individuals.

LZIC is a member of the CTNNBIP1 family. LZIC protein is universally expressed, with largest levels in kidney and up-regulated in various cases of gastric cancers. LZIC has no interaction with CTNNB1.

Fibronectin Type III Domain Containing 5 (Irisin) is a newly discovered hormone, secreted into circulation by muscle, which acts on white adipocytes and promotes WAT “browning”. r-Irisin can reduce body weight and cause induction of brown adipocyte in vivo, including a capacity for thermogenic energy expenditure mediated by uncoupling protein 1 (UCP-1). Irisin mature protein is comprised of 110 amino acid residues and two potential glycosylation sites. High levels of Irisin can be found in the heart whereas Very low expression is found in the colon, pancreas and spleen, if any.

Zinc-alpha-2-glycoprotein (ZAG) is found in body fluids such as serum, sweat, and seminal and breast cyst fluids. It is identical in amino acid sequence to tumor-derived lipid mobilizing factor (LMF), a protein associated with the dramatic loss of adipose body stores in cancer cachexia, and has been shown to stimulate lipolysis by adipocytes in vivo and in vitro. A role for ZAG has been proposed in the regulation of body weight, and age-dependent changes in genetically influenced obesity, and also it regulates melanin production by normal and malignant melanocytes. It has also recently been classified as a novel adipokine in that it is produced by both white and brown fat adipocytes and may act in a local autocrine fashion in the reduction of adiposity in cachexia. Controlling ZAG/LMF's activity could be life-saving in the management of certain cancers and other cachexiainducing conditions, and its possible normal role in body fat store homeostasis is deserving of understanding in its own right. ZAG exhibits a class I major histocompatibility complex (MHC) fold but is a soluble protein rather than being anchored to plasma membranes and does not associate with alpha-2-microglobulin in humans. Like antigen-presenting MHC class I proteins, ZAG has an open apical groove, and X-ray crystallography of human derived ZAG revealed an unidentifiable electron density in a similar position to that occupied by antigenic peptides in classical MHC proteins and glycolipids in isoforms of CD1. This presumptive ligand is not a peptide, and the groove is too small to hold a glycolipid such as is presented by CD1 isoforms. By analogy with all other MHC class I-related proteins that have an open apical groove [some do not ], occupancy by a ligand is probably crucial to ZAG's biological function. Despite all of the structural and biochemical evidence that ZAG binds a ligand, none has so far been found by extraction from protein isolated from biological fluids. This difficulty could be because the ligand is labile, heterogeneous, or readily lost during purification procedures. Knowing more about how ZAG interacts with the compounds it has been found to bind, both natural and artificial, will inform searches for the elusive ligand(s) and its/their role in ZAG's signaling function.

THAP Domain Containing, Apoptosis Associated Protein 7 (THAP7) holds one THAP-type zinc finger. THAP7 is a chromatin-associated, histone tail-binding protein which represses transcription by recruiting HDAC3 and nuclear hormone receptor corepressors.

Pyroglutamyl-Peptidase I (PGPEP1) is an omega peptidase which detaches pyroglutamyl residues from the amino termini of peptides and proteins. PGPEP1 is a cytosolic cysteine peptidase which is expressed in most cell types. PGPEP1 enzyme has need of s a thiol-reducing agent for activity. PGPEP1 is possibly involved in the inactivation of biologically active peptides which have an amino terminal pyroglutamyl group, for instance peptides as neurotensin, luteinizing hormone releasing hormone, and thyrotropinreleasing hormone.

PPIL1 belongs to the cyclophilin family of peptidylprolyl isomerases (PPIases).
The cyclophilins are a well conserved, ubiquitous family, members of which take an significant part in protein folding, immunosuppression by cyclosporin A, and infection of HIV-1 virions. PPIL1 protein increases the folding of proteins and catalyze the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. PPIL1 is involved in proliferation of cancer cells through modulation of phosphorylation of stathmin. PPIL1 is a novel molecular target for colon-cancer therapy.

THAP3 is an element of a THAP1/THAP3-HCFC1-OGT complex which is essential for the regulation of the transcriptional activity of RRM1. THAP3 is vastly produced in placenta, skeletal muscle and heart.

Leucine Rich Repeats And Immunoglobulin Like Domains 1 or LRIG1 is a protein, acting as is a pan-negative regulator of EGFR signal transduction. When studied along with ErbB proteins and Met kinase, LRIG1 was found to have regulation activities such as ubiquitination and lysosomal degradation increment of the receptors. Therefore, LRIG1 acts as a suppressor for tumors via cell proliferation control via negative regulation of tyrosine kinase receptors that belongs to the EGF protein family. LRIG1 expression is downregulated in cancer, and acts a prognostic tool for cancer development.

Kelch Domain Containing 8B, also known as KLHDC8B shapes a distinct beta-propeller protein structure of kelch domains which allow for protein-protein interactions. In addition,mutations in KLHDC8B have been connected with Hodgkin lymphoma.

Fibronectin Leucine Rich Transmembrane Protein 3, also known as FLRT3 is a member of the fibronectin leucine rich transmembrane protein (FLRT) family. FLRT3 contains one fibronectin type-III domain as well as 10 LRR (leucine-rich) repeats and is expressed in the kidney, brain, pancreas, skeletal muscle, lung, liver, placenta, and heart. In addition, the members of the FLRT family play a role in cell adhesion as well as receptor signaling. FLRT3 has been implicated in neurite outgrowth after nerve damage, as a positive regulator of FGF signalling and in homotypic cell adhesion. Furthermore, FLRT3 has an essential function in regulating cellular adhesion among the epithelial apical ridge and the underlying mesenchyme and also in the establishment of the dorso-ventral position of the ridge.

RWD Domain Containing 1 (RWDD1) is a member of the RWDD1/GIR2 family. The RWDD1 protein protects DRG2 (developmentally regulated GTP binding protein 2), from proteolytic degradation. RWD domain refers to 3 signature motifs in proteins: RING finger, WD-repeats, and yeast DEAD (DEXD)-like motif. Current evidence proposes that RWD domain may be required for protein-protein interaction.

Hypoxia-inducible factor-1 (HIF-1), identified as one of the transcription factors, has been found to play an essential role in cellular and systemic oxygen homeostasis. HIF-1 is a heterodimer composed of HIF-1b subunit and one of three subunits (Hif-1a, Hif-2 (or Hif-3)). The activation of Hif-1 (is closely associated with a variety of tumors and oncogenic pathways. Hif-1 (consists of DNA binding domain (DBD domain), Dimerization domain and C-terminal regulatory domains, including two transactivation domains (TAD), an oxygen-dependent degradation (ODD) domain, and inhibitory domains. Under hypoxic conditions HIF1A activates the transcription of more than 40 genes, including, erythropoietin, glucose transporters, glycolytic enzymes, VEGF, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. HIF-1A also plays a crucial role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. It binds to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) of target gene promoters. Activation involves recruitment of transcriptional coactivators such as CREBPB and EP300. Its activity is improved by interaction with both, NCOA1 or NCOA2. Interaction with redox regulatory protein APEX appears to activate CTAD and potentiates activation by NCOA1 and CREBBP. The induction is under reduced oxygen tension. HIF1A is also induced by a variety of receptor-mediated factors such as growth factors, cytokines, and circulatory factors for example PDGF, EGF, FGF-2, IGF-2, TGF-1 beta, HGF, TNF alpha, IL-1 beta, angiotensin-2 and thrombin. Nevertheless, this induction is less intense than that stimulated by hypoxia.

ASF1 Anti-Silencing Function 1 Homolog B (ASF1B) belongs to the H3/H4 family of histone chaperone proteins and is similar to the anti-silencing function-1 protein in yeast. ASF1B is the substrate of the tousled-like kinase family of cell cycle-regulated kinases, and may have a crucial role in modulating the nucleosome structure of chromatin by guaranteeing a regular supply of histones at sites of nucleosome assembly. ASF1B cooperates with CAF-1 (chromatin assembly factor 1) to stimulate replication-dependent chromatin assembly. ASF1B is highly expressed in the testis and at lower levels in colon, small intestine and thymus. ASF1B is necessary for spermatogenesis.

Podoplanin is a small mucin-like type-1 transmembrane protein, typically expressed in various specialized cell types throughout the body. Podoplanin is a type-I integral membrane glycoprotein with diverse distribution in human tissues. PDPN physiological function is related to its mucin-type character. The homologous protein in other species has been described as a differentiation antigen and influenza-virus receptor.
PDPN is expressed in lymphatic progenitor cells and afterwards during mouse development in lymphatic endothelial cells. Podoplanin is a specific marker for lymph vessel endothelial cells. Over-expression of podoplanin significantly elevates endothelial cell adhesion, migration, and tube formation. Inhibition of Podoplanin expression decreases cell adhesion in human dermal lymphatic endothelial cells. Podoplanin is used as a specific marker for lymphatic endothelium in histopathology.
Podoplanin expression is increased in nearly all human colon, rectum, and small intestine tumors. AGGRUS may serve as a diagnostic marker that distinguishes seminomas, the majority of which over express the protein, from embryonal carcinoma in testicular germ cell tumors.

Von Willebrand Factor A Domain Containing 2 (VWA2) is an extracellular matrix protein containing vWA-like domains. VWA2 contains a signal peptide sequence, an N-terminal VWA domain connected to 2 additional tandem vWA domains by a cysteine-rich sequence and an EGF-like domain. Also, another EGF-like domain is located at the C-terminus. Expression of VWA2 is induced in stage II, III and IV colon cancers and colon adenomas and is considered a novel serum marker for the diagnosis of early-stage colon cancer.

SNIP1 is smad nuclear interacting protein that contains a forkhead-associated (FHA) domain and acts as a nuclear inhibitor of CBP/p300. SNIP1 is an inhibitor of the TGF-beta signal transduction pathway and is significant in suppressing transcriptional activation dependent on the co-activators CBP and p300. Inhibition of NF-kappa B activity is a function of the N-terminal domain of SNIP1 and involves competition of SNIP1 and the NF-kappa B subunit, RelA/p65, for binding to p300, similar to the mechanism of inhibition of Smad signaling by SNIP1.

A human infecting coronavirus (viral pneumonia) called 2019 novel coronavirus, 2019-nCoV was found in the fish market at the city of Wuhan, Hubei province of China on December 2019.

The 2019-nCoV shares an 87% identity to the 2 bat-derived severe acute respiratory syndrome 2018 SARS-CoV-2 located in Zhoushan of eastern China. 2019-nCoV has an analogous receptor-BD-structure to that of 2018 SARS-CoV, even though there is a.a. diversity so thus the 2019-nCoV might bind to ACE2 receptor protein (angiotensin-converting enzyme 2) in humans.

While bats are possibly the host of 2019-nCoV, researchers suspect that animal from the ocean sold at the seafood market was an intermediate host. RSCU analysis proposes that the 2019-nCoV is a recombinant within the viral spike glycoprotein between the bat coronavirus and an unknown coronavirus.