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| IFFO1 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | IFFO1 , HOM-TES-103, IFFO, intermediate filament family orphan 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 610495; MGI: 2444516; HomoloGene: 18706; GeneCards: IFFO1; OMA:IFFO1 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Intermediate filament family orphan 1 is a protein that in humans is encoded by the IFFO1 gene. IFFO1 has uncharacterized function and a weight of 61.98 kDa. [5] IFFO1 proteins play an important role in the cytoskeleton and the nuclear envelope of most eukaryotic cell types. [6]
IFFO in human is located on the minus strand at Chromosome 12p13.3. The protein contains 17,709 nucleotide bases that encodes for 570 amino acids. The basal isoelectric point is 4.83. [7] IFFO1 contains a highly conserved filament domain that spans 299 amino acids from amino residue 230 to 529. [8] This region has been identified as pfam00038 conserved protein domain family. [9] Due to alternative splicing, there are 7 isoforms of IFFO1 in humans with 10 typical coding exons.
IFFO1 is also called Intermediate Filament Family Orphan Isoform X1, Intermediate Filament Family Orphan, HOM-TES-103, Intermediate Filament-Like MGC: 2625, and Tumor Antigen HOM-TES-10. [10]
The gene is found to be highly conserved. The most distant orthologs are found in fish and sharks (cartilaginous fishes) such as Callorhinchus milii. [11] Very low percentages of sequence coverage and identity of the gene's orthologs in fungi and invertebrates suggest that the gene was lost in those organisms. [12] Therefore, it is highly probable that IFFO1 originated in vertebrates.
| Genus/Species | Common Name | Divergence from Human (MYA) | Length (aa) | Similarity | Identity | NCBI Accession |
|---|---|---|---|---|---|---|
| Homo sapiens | Human | N/A | 570 | 100% | 100% | XP_006719036.1 |
| Mus musculus | Mouse | 92.3 | 563 | 93% | 95% | XP_006506337.2 |
| Lipotes vexillifer | Baiji dolphin | 94.2 | 573 | 92% | 95% | XP_007469487.1 |
| Loxodonta africana | African bush elephant | 98.7 | 574 | 94% | 96% | XP_003410688.1 |
| Chrysemys picta bellii | Painted turtle | 296 | 557 | 78% | 84% | XP_005291351.1 |
| Pseudopodoces humilis | Ground tit | 296 | 531 | 76% | 81% | XP_005523902.1 |
| Python bivittatus | Burmese python | 296 | 570 | 75% | 82% | XP_007429680.1 |
| Haliaeetus leucocephalus | Bald eagle | 296 | 537 | 74% | 79% | XP_010565842.1 |
| Rana catesbeiana | American bull frog | 371.2 | 511 | 25% | 44% | BAB63946.1 |
| Ambystoma mexicanum | Axolotl | 371.2 | 372 | 24% | 42% | AFN68290.1 |
| Notophthalmus viridescens | Eastern newt | 371.2 | 496 | 23% | 45% | CAA04656.1 |
| Danio Rerio | Zebra fish | 400.1 | 640 | 62% | 71% | XP_690165.5 |
| Poecilia formosa | Amazon molly | 400.1 | 640 | 57% | 65% | XP_007550181.1 |
| Callorhinchus milii | Australian ghostshark | 462.5 | 512 | 62% | 73% | XP_007896103.1 |
One paralog named IFFO2 has been found in humans. The paralog is found to have 99% similarity and 99% coverage when compared to IFFO1. The paralogous sequence is highly conserved, all the way back to fish and amphibians.
Multiple sequence alignments indicated that the Proline-Rich region from amino residues 39 to 61 near the 5' end of the sequence is highly conserved in both close and distant orthologs. [13] In addition, the filament region near the 3' end of the sequence is also highly conserved. Of the 42 conserved amino acid residues found within the IFFO1 sequence, 33 of them are found in the filament region.
When compared to fibrinogen and Cytochrome C (CYCS), IFFO1 is evolving at a moderate rate. The evolutionary history of fibrinogen demonstrates that it is a fast evolving gene, while cytochrome C has been found to be a slow evolving gene. With the most distant ortholog found to be in the Australian ghostshark, IFFO1 gene duplication took place in fish, which diverged from humans 462.5 million years ago. [14]
The predicted secondary structure of the protein consists mostly of alpha helices (47.19%) and random coils (44.74%). The building block of intermediate filaments are elongated coiled-coil dimer consisting of four consecutive alpha-helical segments. [15]
Structurally, it is most similar to 1GK4, which is chain A of the human vimentin coil 2b fragment (Cys2). [16] Vimentin is a class-II intermediate filament that is found in various non-epithelial cells, especially mesenchymal cells. [17] The vimentin protein is also responsible for maintaining cell shape, integrity of the cytoplasm, and stabilizing cytoskeletal interactions. [18] Its 1A subunit, most similar to IFFO1 protein, forms a single, amphipatic alpha-helix that's compatible with a coiled-coil geometry. It is speculated that this chain is involved in specific dimer-dimer interactions during intermediate filament assembly. A "YRKLLEGEE" domain on the C-terminus is found to be important for the formation of authentic tetrameric complexes and also for the control of filament width during assembly. [19]
Based on experimental data on normal tissues in the human body, IFFO1 gene is highly expressed in the cerebellum, cerebral cortex, and especially in the spleen. Medium expression is seen in several areas such as the adrenal gland, colon, lymph nodes, thymus, and ovary. The tissue areas that had the relatively low expression includes CD4 and CD8 T-cells, epidymal cells, the heart, and the stomach. Extremely low levels of expression were observed in tissues obtained from fetus, kidney, testis, thyroid, and especially in the salivary gland. However, the gene has been found to be highly expressed in chondrosarcoma. [20] Chondrosarcoma is the cancer of the cells that generate collagen. Therefore, there seems to be an association between IFFO1's filamentous characteristic and chondrosarcoma.
One nuclear export signal is predicted to be located at Leucine 141. [21] The IFFO1 protein is predicted to have one 11-amino acid long nuclear localization signal at 373. [22] Based on evidence, the protein is predicted to have high nuclear discrimination. [23] One negative charge acidic cluster was found from amino residue 435 to 447. One repetitive sequence PAPLSPAGP appears twice at 40 to 48 and then again from 159 to 166. This proline-rich region is found to be highly conserved. One long amino acid multiplets of 5 prolines is found at 549.
4 ubiquitination sites are found on Four different Lysine residues. They can be found at Lys78, Lys103, Lys113, Lys339. [24] Experimentally, there was evidence of 43 phosphorylation sites located on 31 serines, 7 threonines, and 5 tyrosines. [25] Furthermore, the evidence has shown with high confidence that Ser533 is a phosphorylation site specifically for protein kinase C. The phosphorylation site at Ser162 also acts as a )-glycosylated site. This type of glycosylation functions to have proteins fold properly, stabilizes the protein, and plays a role in cell-cell adhesion. [26] 4 sumolyated amino acids were found at Leu249, Leu293, Leu298, and Leu325. [27] Sumolation have several effects including interfering with the interaction between the protein’s target and its partner or provide a binding site for an interacting partner, causing conformational changes of the modified target, and facilitating or antagonizing ubiquitinization. [28] 5 glycation sites were predicted to be at Lys78, Lys256, Lys305, Lys380, and Lys478. End productions of glycation are involved in protein conformation changes, loss of function, and irreversible crosslinking. [29]
Evidence from two-hybrid screening exists for four protein interactions with IFFO1. [30]
Another protein interaction with ubiquitin C was found from affinity capture-MS assay. [37]
The IFFO1 gene has not been found to be associated with any particular diseases.
Intermediate filaments (IFs) are cytoskeletal structural components found in the cells of vertebrates, and many invertebrates. Homologues of the IF protein have been noted in an invertebrate, the cephalochordate Branchiostoma.
QRICH1, also known as Glutamine-rich protein 1, is a protein that in humans is encoded by the QRICH1 gene. One notable feature of this protein is that it contains a Caspase Activation Recruitment Domain, also known as a CARD domain. As a result of having this domain, QRICH1 is believed to be involved in apoptotic, inflammatory, and host-immune response pathways.
Coiled-coil domain containing 94 (CCDC94) is a protein that in humans is encoded by the CCDC94 gene. The CCDC94 protein contains a coiled-coil domain, a domain of unknown function (DUF572), an uncharacterized conserved protein (COG5134), and lacks a transmembrane domain.
Transmembrane protein 33 is a protein that in humans, is encoded by the TMEM33 gene, also known as SHINC3. Another name for the TMEM33 protein is DB83.
Coiled-coil domain-containing protein 138, also known as CCDC138, is a human protein encoded by the CCDC138 gene. The exact function of CCDC138 is unknown.
Coiled Coil Domain Containing protein 42B, also known as CCDC42B, is a protein encoded by the protein-coding gene CCDC42B.
EVI5L is a protein that in humans is encoded by the EVI5L gene. EVI5L is a member of the Ras superfamily of monomeric guanine nucleotide-binding (G) proteins, and functions as a GTPase-activating protein (GAP) with a broad specificity. Measurement of in vitro Rab-GAP activity has shown that EVI5L has significant Rab2A- and Rab10-GAP activity.
Uncharacterized protein C14orf80 is a protein which in humans is encoded by the chromosome 14 open reading frame 80, C14orf80, gene.
FAM76A is a protein that in Homo sapiens is encoded by the FAM76A gene. Notable structural characteristics of FAM76A include an 83 amino acid coiled coil domain as well as a four amino acid poly-serine compositional bias. FAM76A is conserved in most chordates but it is not found in other deuterostrome phlya such as echinodermata, hemichordata, or xenacoelomorpha—suggesting that FAM76A arose sometime after chordates in the evolutionary lineage. Furthermore, FAM76A is not found in fungi, plants, archaea, or bacteria. FAM76A is predicted to localize to the nucleus and may play a role in regulating transcription.
Uncharacterized protein C12orf60 is a protein that in humans is encoded by the C12orf60 gene. The gene is also known as LOC144608 or MGC47869. The protein lacks transmembrane domains and helices, but it is rich in alpha-helices. It is predicted to localize in the nucleus.
Chromosome 21 Open Reading Frame 58 (C21orf58) is a protein that in humans is encoded by the C21orf58 gene.
Testis-expressed protein 9 is a protein that in humans is encoded the TEX9 gene. TEX9 that encodes a 391-long amino acid protein containing two coiled-coil regions. The gene is conserved in many species and encodes orthologous proteins in eukarya, archaea, and one species of bacteria. The function of TEX9 is not yet fully understood, but it is suggested to have ATP-binding capabilities.
Chromosome 4 open reading frame 51 (C4orf51) is a protein which in humans is encoded by the C4orf51 gene.
Chromosome 1 open reading frame (C1orf167) is a protein which in humans is encoded by the C1orf167 gene. The NCBI accession number is NP_001010881. The protein is 1468 amino acids in length with a molecular weight of 162.42 kDa. The mRNA sequence was found to be 4689 base pairs in length.
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.
C16orf90 or chromosome 16 open reading frame 90 produces uncharacterized protein C16orf90 in homo sapiens. C16orf90's protein has four predicted alpha-helix domains and is mildly expressed in the testes and lowly expressed throughout the body. While the function of C16orf90 is not yet well understood by the scientific community, it has suspected involvement in the biological stress response and apoptosis based on expression data from microarrays and post-translational modification data.
ProteinFAM89A is a protein which in humans is encoded by the FAM89A gene. It is also known as chromosome 1 open reading frame 153 (C1orf153). Highest FAM89A gene expression is observed in the placenta and adipose tissue. Though its function is largely unknown, FAM89A is found to be differentially expressed in response to interleukin exposure, and it is implicated in immune responses pathways and various pathologies such as atherosclerosis and glioma cell expression.
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 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.
Secernin-3 (SCRN3) is a protein that is encoded by the human SCRN3 gene. SCRN3 belongs to the peptidase C69 family and the secernin subfamily. As a part of this family, the protein is predicted to enable cysteine-type exopeptidase activity and dipeptidase activity, as well as be involved in proteolysis. It is ubiquitously expressed in the brain, thyroid, and 25 other tissues. Additionally, SCRN3 is conserved in a variety of species, including mammals, birds, fish, amphibians, and invertebrates. SCRN3 is predicted to be an integral component of the cytoplasm.
