SLX4IP | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Aliases | SLX4IP, C20orf94, bA204H22.1, bA254M13.1, dJ1099D15.3, SLX4 interacting protein | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 615958; MGI: 1921493; HomoloGene: 49913; GeneCards: SLX4IP; OMA: SLX4IP - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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SLX4 interacting protein is a protein that in humans is encoded by the SLX4IP gene. [5]
SLX4 interacting protein (SLX4IP) exists in a monomeric form, and interacts with the SLX4- XPF- ERCC1 multiprotein complex, which is responsible for the assembly of a Holliday junction resolvase in the role of DNA repair and maintenance. [6]
SLX4IP has been shown to directly interact with the N-terminal end of the SLX4 protein, which plays a role in the coordination of multiple different DNA structure-specific endonucleases. [7]
SLX4IP has also been shown to be involved in the control of alternative lengthening of telomeres, through its accumulation and interactions with the SLX4, BLM and XPF proteins. [8]
The SLX4IP gene is located on the short arm (p) of chromosome 20 at position 12.2 (20p12.2). [9] The human SLX4IP gene contains 14 exons, with the cDNA being 204,000 base pairs orientated on the plus strand. [9] This codes for a protein of 408 amino acids with a molecular mass of 45,552 daltons. [10]
Homologs of the SLX4IP gene have been found to be conserved in several non-human species including mice, rats, frogs, chickens, dogs, rhesus monkeys and chimpanzees. [11] Orthologs for the human SLX4IP gene have also been identified in 283 other organisms. [11]
The SLX4IP protein is expressed at its highest level in the skin and the testis, along with being expressed in 26 other tissues. [12]
Somatic and monoallelic deletions of the 5’ region of SLX4IP was shown to occur in 30% of patients with childhood acute lymphoblastic leukemia (ALL) and in cases of ETV6/ RUNX1-rearranged acute lymphoblastic leukemia, deletions were found in greater than 60% of cases. [13] By analyzing the breakpoints of SLX4IP, characteristic illegitimate V(D)J mediated recombination was revealed. [13] These deletions were found to be significantly biased towards the male gender. [13]
In order for cancer cells to retain their ability to proliferate without limitations, they can regulate the telomeres of their chromosomes by recombination via a process known as alternative lengthening of telomeres (ALT). [14] This recombination has been shown to require the accumulation of SLX4IP at ALT telomeres due to its antagonization of promiscuous BLM activity. [8] BLM is responsible for the extension of telomeres as it is a RecQ helicase vital to homologous recombination and DNA replication. [15]
In DNA, Interstrand crosslinks (ICLs) are required to be repaired due to their high toxicity, often leading to diseases such as Fanconi anaemia. [16] SLX4IP plays a role in the ICL repair functionality of the SLX4-XPF-ERCC1 complex, due to its simultaneous binding of both SLX4 and XPF-ERCC1, which maintains the stability of the complex and promotes interaction between the SLX4 and the XPF-ERCC1 regions. [6] [17] When SLX4IP was depleted from treated cells, they were found to accumulate in the G2/M phase of the cell cycle where the resolution of holiday junctions during ICL repair regularly occurs. [17] [18]
The HIV-1 auxiliary protein Vpr potently stops the host cells progression through its natural cycle at the G2/M transition stage. [19] This arrest was found to be caused from its premature activation of the SLX4 structure-specific endonuclease complex, which SLX4IP directly interacts with. [20] Through this research the SLX4 complex was also discovered to be involved with the regulation of innate immunity, due to its negative regulation of type 1 interferon production, both when induced spontaneously and HIV-1-mediated. [20]
SLX4IP | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
Aliases | SLX4IP, C20orf94, bA204H22.1, bA254M13.1, dJ1099D15.3, SLX4 interacting protein | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 615958; MGI: 1921493; HomoloGene: 49913; GeneCards: SLX4IP; OMA: SLX4IP - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
|
SLX4 interacting protein is a protein that in humans is encoded by the SLX4IP gene. [5]
SLX4 interacting protein (SLX4IP) exists in a monomeric form, and interacts with the SLX4- XPF- ERCC1 multiprotein complex, which is responsible for the assembly of a Holliday junction resolvase in the role of DNA repair and maintenance. [6]
SLX4IP has been shown to directly interact with the N-terminal end of the SLX4 protein, which plays a role in the coordination of multiple different DNA structure-specific endonucleases. [7]
SLX4IP has also been shown to be involved in the control of alternative lengthening of telomeres, through its accumulation and interactions with the SLX4, BLM and XPF proteins. [8]
The SLX4IP gene is located on the short arm (p) of chromosome 20 at position 12.2 (20p12.2). [9] The human SLX4IP gene contains 14 exons, with the cDNA being 204,000 base pairs orientated on the plus strand. [9] This codes for a protein of 408 amino acids with a molecular mass of 45,552 daltons. [10]
Homologs of the SLX4IP gene have been found to be conserved in several non-human species including mice, rats, frogs, chickens, dogs, rhesus monkeys and chimpanzees. [11] Orthologs for the human SLX4IP gene have also been identified in 283 other organisms. [11]
The SLX4IP protein is expressed at its highest level in the skin and the testis, along with being expressed in 26 other tissues. [12]
Somatic and monoallelic deletions of the 5’ region of SLX4IP was shown to occur in 30% of patients with childhood acute lymphoblastic leukemia (ALL) and in cases of ETV6/ RUNX1-rearranged acute lymphoblastic leukemia, deletions were found in greater than 60% of cases. [13] By analyzing the breakpoints of SLX4IP, characteristic illegitimate V(D)J mediated recombination was revealed. [13] These deletions were found to be significantly biased towards the male gender. [13]
In order for cancer cells to retain their ability to proliferate without limitations, they can regulate the telomeres of their chromosomes by recombination via a process known as alternative lengthening of telomeres (ALT). [14] This recombination has been shown to require the accumulation of SLX4IP at ALT telomeres due to its antagonization of promiscuous BLM activity. [8] BLM is responsible for the extension of telomeres as it is a RecQ helicase vital to homologous recombination and DNA replication. [15]
In DNA, Interstrand crosslinks (ICLs) are required to be repaired due to their high toxicity, often leading to diseases such as Fanconi anaemia. [16] SLX4IP plays a role in the ICL repair functionality of the SLX4-XPF-ERCC1 complex, due to its simultaneous binding of both SLX4 and XPF-ERCC1, which maintains the stability of the complex and promotes interaction between the SLX4 and the XPF-ERCC1 regions. [6] [17] When SLX4IP was depleted from treated cells, they were found to accumulate in the G2/M phase of the cell cycle where the resolution of holiday junctions during ICL repair regularly occurs. [17] [18]
The HIV-1 auxiliary protein Vpr potently stops the host cells progression through its natural cycle at the G2/M transition stage. [19] This arrest was found to be caused from its premature activation of the SLX4 structure-specific endonuclease complex, which SLX4IP directly interacts with. [20] Through this research the SLX4 complex was also discovered to be involved with the regulation of innate immunity, due to its negative regulation of type 1 interferon production, both when induced spontaneously and HIV-1-mediated. [20]