SERINC5

Last updated

Serine incorporator 5 is a protein that in humans is encoded by the SERINC5 gene. [1]

Contents

SERINC5
Identifiers
Aliases SERINC5 , C5orf12, TPO1, serine incorporator 5, chromosome 5 open reading frame 12, AIGP3, C86123, A130038L21Rik
External IDs OMIM: 614551 MGI: 2444223 HomoloGene: 65246 GeneCards: SERINC5
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001174071
NM_001174072
NM_178276

NM_172588

RefSeq (protein)

NP_001167542
NP_001167543
NP_840060

NP_766176

Location (UCSC) Chr 5: 80.11 – 80.26 Mb Chr 13: 92.61 – 92.71 Mb
PubMed search [4] [5]
Wikidata
View/Edit Human View/Edit Mouse

Properties

SERINC5 is a protein belonging to the serine incorporator (SERINC) family, in the predicted membrane proteins class. [6] It is believed that SERINC5 proteins help incorporate serine into certain lipid bilayer membranes; however, scientists are unsure of their primary function and physiology. [7] [8] Of the five proteins in the human SERINC family, their topologies are strikingly similar. Approximately 17% of amino acids are shared amongst these proteins. [8]

C-terminal Transmembrane Domain

SERINC proteins have about 10 to 11 transmembrane domains. For SERINC5 to localize itself to the plasma membrane to inhibit infectivity by viruses, an extra c-terminal transmembrane domain is required. [7] This extra transmembrane domain allows the protein to express itself stably.

Antagonistic Relationships

AP-2 Endocytic Pathway in the presence of Nef. AP-2 Endocytic Pathway with Nef.png
AP-2 Endocytic Pathway in the presence of Nef.
AP-2 Endocytic Pathway in the absence of Nef. AP-2 Endocytic Pathway in the absence of Nef.png
AP-2 Endocytic Pathway in the absence of Nef.

Nef, glycoGag, and S2 viral proteins are located throughout HIV-1 virions that aid in the facilitation of retrovirus release. When present, SERINC5, in the absence of certain virulence factors, prohibits HIV retrovirus particles from fusing to the cell membrane and incorporating their genetic information into target cells. [9] Because SERINC5 is primarily localized via the plasma membrane, and attaches to vesicles carrying virus particles, the restriction factor has the ability to greatly decrease viral infectivity in the early stages of infection. [10] It has been observed in past experiments that the highest SERINC5 concentration, regardless the expression of Nef, decreased infectivity approximately 250-fold. [8] Although poorly understood, it is believed that Nef is a primary cause for the destruction of SERINC5 and other restriction factors. When in the presence of virulence factors, specifically Nef, both SERINC5 and CD4 cells are downregulated through lysosomal degradation via the AP-2 endocytic pathway. [10] This causes rapid infectivity, and an increase in viral load.

Related Research Articles

HIV Human retrovirus, cause of AIDS

The human immunodeficiency viruses (HIV) are two species of Lentivirus that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive. Without treatment, average survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype. In most cases, HIV is a sexually transmitted infection and occurs by contact with or transfer of blood, pre-ejaculate, semen, and vaginal fluids. Research has shown that HIV is untransmittable through condomless sexual intercourse if the HIV-positive partner has a consistently undetectable viral load. Non-sexual transmission can occur from an infected mother to her infant during pregnancy, during childbirth by exposure to her blood or vaginal fluid, and through breast milk. Within these bodily fluids, HIV is present as both free virus particles and virus within infected immune cells.

Retrovirus Family of viruses

A retrovirus is a type of virus that inserts a copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. Once inside the host cell's cytoplasm, the virus uses its own reverse transcriptase enzyme to produce DNA from its RNA genome, the reverse of the usual pattern, thus retro (backwards). The new DNA is then incorporated into the host cell genome by an integrase enzyme, at which point the retroviral DNA is referred to as a provirus. The host cell then treats the viral DNA as part of its own genome, transcribing and translating the viral genes along with the cell's own genes, producing the proteins required to assemble new copies of the virus.

<i>Gammaretrovirus</i> Genus of viruses

Gammaretrovirus is a genus in the Retroviridae family. Example species are the murine leukemia virus and the feline leukemia virus. They cause various sarcomas, leukemias and immune deficiencies in mammals, reptiles and birds.

The genome and proteins of HIV have been the subject of extensive research since the discovery of the virus in 1983. "In the search for the causative agent, it was initially believed that the virus was a form of the Human T-cell leukemia virus (HTLV), which was known at the time to affect the human immune system and cause certain leukemias. However, researchers at the Pasteur Institute in Paris isolated a previously unknown and genetically distinct retrovirus in patients with AIDS which was later named HIV." Each virion comprises a viral envelope and associated matrix enclosing a capsid, which itself encloses two copies of the single-stranded RNA genome and several enzymes. The discovery of the virus itself occurred two years following the report of the first major cases of AIDS-associated illnesses.

Viral infectivity factor

Viral infectivity factor, or Vif, is an accessory protein found in HIV and other lentiviruses. Its role is to disrupt the antiviral activity of the human enzyme APOBEC by targeting it for ubiquitination and cellular degradation. APOBEC is a cytidine deaminase enzyme that mutates viral nucleic acids.

The murine leukemia viruses are retroviruses named for their ability to cause cancer in murine (mouse) hosts. Some MLVs may infect other vertebrates. MLVs include both exogenous and endogenous viruses. Replicating MLVs have a positive sense, single-stranded RNA (ssRNA) genome that replicates through a DNA intermediate via the process of reverse transcription.

APOBEC3G

APOBEC3G is a human enzyme encoded by the APOBEC3G gene that belongs to the APOBEC superfamily of proteins. This family of proteins has been suggested to play an important role in innate anti-viral immunity. APOBEC3G belongs to the family of cytidine deaminases that catalyze the deamination of cytidine to uridine in the single stranded DNA substrate. The C-terminal domain of A3G renders catalytic activity, several NMR and crystal structures explain the substrate specificity and catalytic activity

The Simian foamy virus (SFV) is a species of the genus Spumavirus, which belongs to the family of Retroviridae. It has been identified in a wide variety of primates, including pro-simians, New World and Old World monkeys as well as apes, and each species has been shown to harbor a unique (species-specific) strain of SFV, including African green monkeys, baboons, macaques and chimpanzees. As it is related to the more well-known retrovirus human immunodeficiency virus (HIV), its discovery in primates has led to some speculation that HIV may have been spread to the human species in Africa through contact with blood from apes, monkeys, and other primates, most likely through bushmeat hunting practices.

Group-specific antigen, or gag, is the polyprotein that contains the core structural proteins of an Ortervirus. It was named as such because scientists used to believe it was antigenic. Now it is known that it makes up the inner shell, not the envelope exposed outside. It makes up all the structural units of viral conformation and provides supportive framework for mature virion.

Visna virus from the genus Lentivirus and subfamily Orthoretrovirinae, is a "prototype" retrovirus that causes encephalitis and chronic pneumonitis in sheep. It is known as visna when found in the brain, and maedi when infecting the lungs. Lifelong, persistent infections in sheep occur in the lungs, lymph nodes, spleen, joints, central nervous system, and mammary glands; The condition is sometimes known as "ovine progressive pneumonia" (OPP), particularly in the United States, or "Montana sheep disease". White blood cells of the monocyte/macrophage lineage are the main target of visna virus.

AP1S1

AP-1 complex subunit sigma-1A is a protein that in humans is encoded by the AP1S1 gene.

AP1S2

AP-1 complex subunit sigma-2 is a protein that in humans is encoded by the AP1S2 gene.

SERINC3

Serine incorporator 3 is a protein that in humans is encoded by the SERINC3 gene. It has been demonstrated that SERINC3 acts as a retrovirus restriction factor.

Tetherin

Tetherin, also known as bone marrow stromal antigen 2, is a lipid raft associated protein that in humans is encoded by the BST2 gene. In addition, tetherin has been designated as CD317. This protein is constitutively expressed in mature B cells, plasma cells and plasmacytoid dendritic cells, and in many other cells, it is only expressed as a response to stimuli from IFN pathway.

Vpu protein

Vpu is an accessory protein that in HIV is encoded by the vpu gene. Vpu stands for "Viral Protein U". The Vpu protein acts in the degradation of CD4 in the endoplasmic reticulum and in the enhancement of virion release from the plasma membrane of infected cells. Vpu induces the degradation of the CD4 viral receptor and therefore participates in the general downregulation of CD4 expression during the course of HIV infection. Vpu-mediated CD4 degradation is thought to prevent CD4-Env binding in the endoplasmic reticulum in order to facilitate proper Env assembly into virions. It is found in the membranes of infected cells, but not the virus particles themselves.

Nef (protein)

Nef is a small 27-35 kDa myristoylated protein encoded by primate lentiviruses. These include Human Immunodeficiency Viruses and Simian Immunodeficiency Virus (SIV). Nef localizes primarily to the cytoplasm but also partially to the Plasma membrane (PM) and is one of many pathogen-expressed proteins, known as virulence factors, which function to manipulate the host's cellular machinery and thus allow infection, survival or replication of the pathogen. Nef stands for "Negative Factor" and although it is often considered indispensable for HIV-1 replication, in infected hosts the viral protein markedly elevates viral titers.

Mason-Pfizer monkey virus (M-PMV), formerly Simian retrovirus (SRV), is a species of retroviruses that usually infect and cause a fatal immune deficiency in Asian macaques. The ssRNA virus appears sporadically in mammary carcinoma of captive macaques at breeding facilities which expected as the natural host, but the prevalence of this virus in feral macaques remains unknown. M-PMV was transmitted naturally by virus-containing body fluids, via biting, scratching, grooming, and fighting. Cross contaminated instruments or equipment (fomite) can also spread this virus among animals.

Vpx is a virion-associated protein encoded by human immunodeficiency virus type 2 HIV-2 and most simian immunodeficiency virus (SIV) strains, but that is absent from HIV-1. It is similar in structure to the protein Vpr that is carried by SIV and HIV-2 as well as HIV-1. Vpx is one of five accessory proteins carried by lentiviruses that enhances viral replication by inhibiting host antiviral factors.

Host switch

In parasitology and epidemiology, a host switch is an evolutionary change of the host specificity of a parasite or pathogen. For example, the human immunodeficiency virus used to infect and circulate in non-human primates in West-central Africa, but switched to humans in the early 20th century.

Bovine foamy virus (BFV) is a ss(+)RNA retrovirus that belongs to the genus spumaviridae. Spumaviruses differ from the other six members of family retroviridae, both structurally and in pathogenic nature. Spumaviruses derive their name from spuma the latin for "foam". The 'foam' aspect of 'foamy virus' comes from syncytium formation and the rapid vacuolization of infected cells, creating a 'foamy' appearance.

References

  1. "SERINC5 (Gene)". GeneCards. Retrieved April 24, 2019.
  2. 1 2 3 GRCh38: Ensembl release 89: ENSG00000164300 - Ensembl, May 2017
  3. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000021703 - Ensembl, May 2017
  4. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  6. "SERINC5". The Human Protein Atlas.
  7. 1 2 Zhang, Xianfeng; Zhou, Tao; Yang, Jie; Lin, Yumei; Shi, Jing; Zhang, Xihe; Frabutt, Dylan A.; Zeng, Xiangwei; Li, Sunan (February 2017). Ross, Susan (ed.). "Identification of SERINC5-001 as the Predominant Spliced Isoform for HIV-1 Restriction". Journal of Virology. 91 (10): 1–13. doi:10.1128/JVI.00137-17. PMC   5411613 . PMID   28275190 via American Society for Microbiology.
  8. 1 2 3 Rosa, Annachiara; Chande, Ajit; Ziglio, Serena; De Sanctis, Veronica; Bertorelli, Roberto; Goh, Shih Lin; McCauley, Sean M.; Nowosielska, Anetta; Antonarakis, Stylianos E. (October 2015). "HIV-1 Nef promotes infection by excluding SERINC5 from virion incorporation". Nature. 526 (7572): 212–217. doi:10.1038/nature15399. PMC   4861059 . PMID   26416734.
  9. Kluge, Silvia F. (October 2015). "SnapShot: Antiviral Restriction Factors" (PDF). Cell. 163 (3): 774–774.e1. doi: 10.1016/j.cell.2015.10.019 . PMID   26496613. S2CID   32924308.
  10. 1 2 Zheng, Yong-Hui; Shi, Jing; Xiong, Ran; Zhou, Tao; Su, Peiyi; Zhang, Xihe; Qiu, Xusheng; Li, Hongmei; Li, Sunan (March 2018). "HIV-1 Nef Antagonizes SERINC5 Restriction by Downregulation of SERINC5 via the Endosome/Lysosome System". Journal of Virology. 92 (11): 16. doi:10.1128/JVI.00196-18. PMC   5952139 . PMID   29514909 via American Society for Microbiology.