BANF1

The protein encoded by this gene was first identified by its ability to protect retroviruses from intramolecular integration and therefore promote intermolecular integration into the host cell genome. The protein forms a homodimer which localizes to both the nucleus and cytoplasm and is specifically associated with chromosomes during mitosis. This protein binds to double stranded DNA in a non-specific manner and also binds to LEM-domain containing proteins of the nuclear envelope. This protein is thought to facilitate nuclear reassembly by binding with both DNA and inner nuclear membrane proteins and thereby recruit chromatin to the nuclear periphery. Alternative splicing results in multiple transcript variants encoding the same protein

Full Name

barrier to autointegration factor 1

Function

Plays fundamental roles in nuclear assembly, chromatin organization, gene expression and gonad development. May potently compress chromatin structure and be involved in membrane recruitment and chromatin decondensation during nuclear assembly. Contains 2 non-specific dsDNA-binding sites which may promote DNA cross-bridging.
(Microbial infection) Exploited by retroviruses for inhibiting self-destructing autointegration of retroviral DNA, thereby promoting integration of viral DNA into the host chromosome. EMD and BAF are cooperative cofactors of HIV-1 infection. Association of EMD with the viral DNA requires the presence of BAF and viral integrase. The association of viral DNA with chromatin requires the presence of BAF and EMD.
(Microbial infection) In case of poxvirus infection, has an antiviral activity by blocking viral DNA replication.

Biological Process

Chromosome condensation Source: GO_Central
Chromosome segregation Source: GO_Central
DNA integration Source: Ensembl
Establishment of integrated proviral latency Source: Reactome
Mitotic nuclear envelope reassembly Source: Reactome
Negative regulation of viral genome replication Source: UniProtKB
Nuclear transport Source: Reactome
Response to virus Source: ProtInc

Cellular Location

Barrier-to-autointegration factor: Nucleus; Nucleus envelope; Cytoplasm; Chromosome. Significantly enriched at the nuclear inner membrane, diffusely throughout the nucleus during interphase and concentrated at the chromosomes during the M-phase. The phosphorylated form (by VRK1 or vaccinia virus B1 kinase) shows a cytoplasmic localization whereas the unphosphorylated form locates almost exclusively in the nucleus (PubMed:24600006, PubMed:16495336). May be included in HIV-1 virions via its interaction with viral GAG polyprotein.

Involvement in disease

Nestor-Guillermo progeria syndrome (NGPS): An atypical progeroid syndrome characterized by normal development in the first years of life, later followed by the emergence of generalized lipoatrophy, severe osteoporosis, and marked osteolysis. The atrophic facial subcutaneous fat pad and the marked osteolysis of the maxilla and mandible result in a typical pseudosenile facial appearance with micrognathia, prominent subcutaneous venous patterning, a convex nasal ridge, and proptosis. Cognitive development is completely normal. Patients do not have cardiovascular dysfunction, atherosclerosis, or metabolic anomalies.

PTM

Ser-4 is the major site of phosphorylation as compared to Thr-2 and Thr-3. Phosphorylation on Thr-2; Thr-3 and Ser-4 disrupts its ability to bind DNA and reduces its ability to bind LEM domain-containing proteins. Non phosphorylated BAF seems to enhance binding between EMD and LMNA. Dephosphorylated by protein phosphatase 2A (PP2A) following interaction with ANKLE2/LEM4 during mitotic exit, leading to mitotic nuclear envelope reassembly.
(Microbial infection) Phosphorylated at the N-terminus by vaccinia virus (VacV) B1 kinase, leading to BANF1 relocalization to the cytoplasm, loss of dimerization and impaired DNA binding activity (PubMed:24600006, PubMed:16495336). Hyperphosphorylation is linked to the loss of ability to suppress vaccinia virus replication (PubMed:24600006).