ZNF730 or zinc finger protein 730 is a protein which in humans is encoded by the ZNF730 gene. It is located on the short arm of chromosome 19. [1] Zinc finger protein 730 is speculated to play a role in transcriptional regulation in acute myeloid leukemia and endometrial cancer. This is because ZNF730 was found to be expressed in higher levels in endometrial cancerous tumor samples and has been reported as a core binding factor in acute myeloid leukemia. [2] Zinc Finger protein 730 is a C2H2-type zinc finger protein containing a β/β/α structure, held in place by a Zinc ion. The C2H2-type protein motifs can regulate transcription by recognizing and binding to DNA sequences. [3]
The human ZNF730 gene is 5533 nucleotides long and it encodes transcript variant 1 which is the longest isoform. [4] The gene locus is 19p12 and it is found on the plus strand. [4] ZNF730 consists of 14 exons, it encodes for one Kruppel Associated Box (KRAB), and 12 C2H2 Zinc Fingers. [5]
The mRNA isoform 1 encoded by the human ZNF730 gene is 514 nucleotides long. [4] There are 7 isoforms of the ZNF839 mRNA. [1]
Through an HPA-RNA sequencing analysis of 12 different human tissues, protein ZNF730 has been found in high levels within the testis. [1] High expression in the testis is likely because of C2H2-zinc fingers playing a role in spermatogenesis, which occurs inside the seminiferous tubules. [6]
ZNF730 was also found to be expressed in high levels within the brain, lymph nodes, and placenta. [7] The high expression of ZNF730 in the brain, specifically the cerebellum, may be related to zinc finger proteins (Zin1 and Zinc2) being present in the cerebellum for the development of the central nervous system and regulation signaling pathways. [8]
The molecular weight of ZNF730 Isoform 1 has a theoretical molecular weight of 60296.34 Da. The protein's isoelectric point is predicted to be 9.5 in humans. The average isoelectric point in Homo sapiens is 6.64, so this value is higher than average. [9] Based on the SAPS tool, there are no positive, negative or neutral charge custers. It has been predicted that ZNF730 X1 has higher amounts of Histidine and Lysine than normal, and lower amounts of Valine.
ZNF730 X1 was found to have 10 predicted sites of glycosylation and 16 phosphorylation. The protein has been predicted to contain two LIM domains at 267-335 aa and also 407-475 aa. This double-zinc finger motif is specific to zinc-finger proteins, made up of three genes: LIN-11, Isl-1 and MEC-3. [10] [11]
The human Zinc Finger Protein 730 has been predicted to be localized in the nucleus of the cell, due to its transcription factor role. It is predicted to be localized 95.7% to the nucleus and 4.3% to the mitochondria. [12]
The structure is composed of 17 alpha helices, 12 beta sheets, and 38 coil-coils.
ZNF730 was found to have 3 interacting proteins: MOD_CK1_1, MOD_GSK3_1 and MOD_SUMO_rev_2. [13] It was found that MOD_CK1_1 is a Casein kinase 1 (CK1) phosphorylation site, found in the cytosl and nucleus, responsible for regulating signal transduction pathways in eukaryotes. The CK1 family are serine/threonine-selective enzymes. MOD_GSK3_ is a Glycogen Synthase Kinase 3 (GSK-3) site that phosphorylates threonine or serine. MOD_SUMO_rev_2 is an inverted version of SUMOylation motif recognized for modification by SUMO-1. SUMOylation occurs when SUMO proteins covalently bind to lysine residues in a target protein. It is a post-translational modification process that likely occurs in ZNF730.
A relationship has been found between ZNF730 protein mutations and endometrial cancer tumor protein composition. 2.1% of endometrial tumor samples have been shown to have ZNF730 oncogenic missense mutations. 0.4% of breast cancer tumors were also found to have ZNF730 missense mutations. [14]
Zinc Finger Protein 730 is predicted to have 25 SUMOylation sites, 10 predicted sites of glycosylation and 16 predicted sites of phosphorylation. [15]
ZNF730 has 3 orthologs that are all mammals. Zinc Finger Protein 730 Belongs to the Krueppel C2H2-type zinc-finger protein family and first appeared in mammals 28.8 million years ago in both Rhinopithecus bieti and Colobus angolensis palliatus. It later diverged into a different primate, Pongo pygmaeus, 15.2 million years ago.
ZNF730 has many paralogs. The 10 paralogs with the highest similarity to ZNF730 X1 were chosen for Table 3.
The following figure visualizes the rate of divergence as compared to the fibrinogen alpha chain and the cytochrome C chain. Based on the graph, ZNF730 evolved at a rate similar to that of Cytochrome C because they have similar slopes. ZNF730 evolved at a slower rate than the Fibrinogen Alpha chain, which had a much higher slope.
Zinc finger protein 684 is a protein that in humans is encoded by the ZNF684 gene.
Coiled-coil domain containing protein 180 (CCDC180) is a protein that in humans is encoded by the CCDC180 gene. This protein is known to localize to the nucleus and is thought to be involved in regulation of transcription as are many proteins containing coiled-coil domains. As it is expressed most highly in the testes and is regulated by SRY and SOX transcription factors, it could be involved in sex determination.
Leukocyte Receptor Cluster Member 9 is an uncharacterized protein encoded by the LENG9 gene. In humans, LENG9 is predicted to play a role in fertility and reproductive disorders associated with female endometrium structures.
BEND2 is a protein that in humans is encoded by the BEND2 gene. It is also found in other vertebrates, including mammals, birds, and reptiles. The expression of BEND2 in Homo sapiens is regulated and occurs at high levels in the skeletal muscle tissue of the male testis and in the bone marrow. The presence of the BEN domains in the BEND2 protein indicates that this protein may be involved in chromatin modification and regulation.
Uncharacterized protein C2orf73 is a protein that in humans is encoded by the C2orf73 gene. The protein is predicted to be localized to the nucleus.
Chromosome 16 open reading frame 46 is a protein of yet to be determined function in Homo sapiens. It is encoded by the C16orf46 gene with NCBI accession number of NM_001100873. It is a protein-coding gene with an overlapping locus.
Zinc Finger Protein 800 or ZNF800 is a protein that in humans is encoded by the ZNF800 gene. The specific function of ZNF800 is not yet well understood by the scientific community.
Zinc finger CCHC-type containing 18 (ZCCHC18) is a protein that in humans is encoded by ZCCHC18 gene. It is also known as Smad-interacting zinc finger protein 2 (SIZN2), para-neoplastic Ma antigen family member 7b (PNMA7B), and LOC644353. Other names such as zinc finger, CCHC domain containing 12 pseudogene 1, P0CG32, ZCC18_HUMAN had been used to describe this protein.
Chromosome 9 open reading frame 43 is a protein that in humans is encoded by the C9orf43 gene. The gene is also known as MGC17358 and LOC257169. C9orf43 contains DUF 4647 and a polyglutamine repeat region although protein function is not well understood.
Cilia- and flagella-associated protein 299 (CFAP299), is a protein that in humans is encoded by the CFAP299 gene. CFAP299 is predicted to play a role in spermatogenesis and cell apoptosis.
WD Repeat and Coiled-coiled containing protein (WDCP) is a protein which in humans is encoded by the WDCP gene. The function of the protein is not completely understood, but WDCP has been identified in a fusion protein with anaplastic lymphoma kinase found in colorectal cancer. WDCP has also been identified in the MRN complex, which processes double-stranded breaks in DNA.
ZNF337, also known as zinc finger protein 337, is a protein that in humans is encoded by the ZNF337 gene. The ZNF337 gene is located on human chromosome 20 (20p11.21). Its protein contains 751 amino acids, has a 4,237 base pair mRNA and contains 6 exons total. In addition, alternative splicing results in multiple transcript variants. The ZNF337 gene encodes a zinc finger domain containing protein, however, this gene/protein is not yet well understood by the scientific community. The function of this gene has been proposed to participate in a processes such as the regulation of transcription (DNA-dependent), and proteins are expected to have molecular functions such as DNA binding, metal ion binding, zinc ion binding, which would be further localized in various subcellular locations. While there are no commonly associated or known aliases, an important paralog of this gene is ZNF875.
Coiled-coil domain containing 121 (CCDC121) is a protein encoded by the CCDC121 gene in humans. CCDC121 is located on the minus strand of chromosome 2 and encodes three protein isoforms. All isoforms of CCDC121 contain a domain of unknown function referred to as DUF4515 or pfam14988.
Chromosome 12 Open Reading Frame 50 (C12orf50) is a protein-encoding gene which in humans encodes for the C12orf50 protein. The accession id for this gene is NM_152589. The location of C12orf50 is 12q21.32. It covers 55.42 kb, from 88429231 to 88373811, on the reverse strand. Some of the neighboring genes to C12orf50 are RPS4XP15, LOC107984542, and C12orf29. RPS4XP15 is upstream C12orf50 and is on the same strand. LOC107984542 and C12orf29 are both downstream. LOC107984542 is on the opposite strand while C12orf29 is on the same strand. C12orf50 has six isoforms. This page is focusing on isoform X1. C12orf50 isoform X1 is 1711 nucleotides long and has a protein with a length of 414 aa.
Zinc Finger Protein 548 (ZNF548) is a human protein encoded by the ZNF548 gene which is located on chromosome 19. It is found in the nucleus and is hypothesized to play a role in the regulation of transcription by RNA Polymerase II. It belongs to the Krüppel C2H2-type zinc-finger protein family as it contains many zinc-finger repeats.
Chromosome 13 Open Reading Frame 46 is a protein which in humans is encoded by the C13orf46 gene. In humans, C13orf46 is ubiquitously expressed at low levels in tissues, including the lungs, stomach, prostate, spleen, and thymus. This gene encodes eight alternatively spliced mRNA transcript, which produce five different protein isoforms.
Transmembrane protein 248, also known as C7orf42, is a gene that in humans encodes the TMEM248 protein. This gene contains multiple transmembrane domains and is composed of seven exons.TMEM248 is predicted to be a component of the plasma membrane and be involved in vesicular trafficking. It has low tissue specificity, meaning it is ubiquitously expressed in tissues throughout the human body. Orthology analyses determined that TMEM248 is highly conserved, having homology with vertebrates and invertebrates. TMEM248 may play a role in cancer development. It was shown to be more highly expressed in cases of colon, breast, lung, ovarian, brain, and renal cancers.
FAM131A is a protein that is encoded by the FAM131A gene in humans. Aliases for FAM131A include C3orf40, FLAT715, and PRO1378.
ZNF839 or zinc finger protein 839 is a protein which in humans is encoded by the ZNF839 gene. It is located on the long arm of chromosome 14. Zinc finger protein 839 is speculated to play a role in humoral immune response to cancer as a renal carcinoma antigen (NY-REN-50). This is because NY-REN-50 was found to be over expressed in cancer patients, especially those with renal carcinoma. Zinc finger protein 839 also plays a role in transcription regulation by metal-ion binding since it binds to DNA via C2H2-type zinc finger repeats.
Zinc Finger Protein 62, also known as "ZNF62," "ZNF755," or "ZET," is a protein that in humans is encoded by the ZFP62 gene. ZFP62 is part of the C2H2 Zinc Finger family of genes.