Affinage

POU2AF1

POU domain class 2-associating factor 1 · UniProt Q16633

Length
256 aa
Mass
27.4 kDa
Annotated
2026-06-10
100 papers in source corpus 39 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

POU2AF1 (OCA-B/OBF-1/Bob1) is a lymphoid-restricted transcriptional coactivator that lacks intrinsic sequence-specific DNA-binding activity and instead acts by docking onto DNA-bound octamer-binding factors Oct-1 and Oct-2 to drive immunoglobulin and other B-cell target genes (PMID:7859290, PMID:7623806, PMID:9632764). Structural and biophysical work shows it assembles a ternary complex in which an OCA-B peptide inserts into the octamer major groove, contacting an adenine at position 5, while an OCA-B α-helix engages a hydrophobic pocket on the POU-specific subdomain; OCA-B further clamps the POU-specific and POU homeodomain halves together on DNA and undergoes induced folding upon complex assembly (PMID:9819426, PMID:10541551, PMID:10329190). Octamer recognition is configuration-selective: OCA-B is stabilized on monomeric octamer sites and on PORE-type Oct dimers but is excluded from MORE-type dimers whose interface overlaps the OCA-B contact surface (PMID:11136971, PMID:38254723). Once recruited, OCA-B transactivates by engaging the general transcription machinery and B-cell-enriched cofactors—TBP and TFIIB, the USA cofactors PC2/PC4, and the TFIID subunit TAF(II)105—and mediates Igh enhancer-promoter looping through direct interaction with TFII-I while displacing repressive HDAC3 (PMID:7623806, PMID:9632764, PMID:8657574, PMID:10828057, PMID:21549311). In vivo, OCA-B is dispensable for early B-cell development and basal Ig transcription but is essential for antigen-dependent germinal center formation and the germinal-center transcriptional program (BCL6 up, IRF4 restrained) (PMID:8849727, PMID:8849728, PMID:8977324, PMID:11135581, PMID:33512466). Its abundance is set post-translationally by Siah-1/proteasome-dependent turnover acting through a C-terminal acidic degron, linking signaling to coactivator dosage (PMID:11483517, PMID:24061476). Beyond the nucleus, a myristoylated membrane isoform directly binds the tyrosine kinase SYK to stabilize it and support pre-BCR/BCR signaling during B-cell development (PMID:11239448, PMID:16713566). In T cells, OCA-B partners with Oct1/Oct2 and recruits the demethylase Jmjd1a to poise memory loci (Il2, Ifng), drives Tfh development via Bcl6/CXCR5, and licenses pathogenic autoreactive CD4+ responses, establishing it as a tractable target whose inhibition protects against autoimmune diabetes and EAE (PMID:26481684, PMID:26957522, PMID:33295943, PMID:40299553, PMID:41134666).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1995 High

    Established the founding mechanistic principle: OCA-B is a B-cell-specific coactivator with no intrinsic DNA binding that works by associating with the POU domains of Oct-1/Oct-2 to activate octamer-dependent Ig transcription.

    Evidence Yeast two-hybrid screen, co-association assays, and reconstituted in vitro transcription with recombinant protein and cofactor add-back

    PMID:7623806 PMID:7859290 PMID:9632764

    Open questions at the time
    • Did not define the atomic contacts with the POU domain
    • Required general cofactors (PC2/PC4) identified but mechanism of their contribution unresolved
  2. 1996 High

    Genetic loss-of-function pinned OCA-B's physiological role to antigen-dependent humoral immunity rather than basal Ig expression, by showing knockouts fail to form germinal centers while early B development and Ig rearrangement are intact.

    Evidence Three concurrent gene-targeted knockout mouse studies with immunization and histology

    PMID:8849727 PMID:8849728 PMID:8977324

    Open questions at the time
    • Did not explain why basal Ig transcription is spared
    • Downstream target genes mediating the GC defect not identified
  3. 1996 High

    Resolved how a DNA-binding-deficient coactivator gains octamer selectivity, showing OCA-B contacts the DNA major groove (requiring adenine at octamer position 5) and the POU-specific subdomain, forming ternary complexes only on a subset of octamer sequences.

    Evidence EMSA ternary complex assays, truncation/point mutagenesis, transcription reporters

    PMID:8654375 PMID:8769650

    Open questions at the time
    • Atomic-resolution geometry not yet determined
    • Functional consequence of sequence-selective recruitment in vivo unaddressed
  4. 1998 High

    Defined the dual-contact 'molecular clamp' mechanism in which OCA-B simultaneously grips the POU-specific and POU homeodomain subdomains and bridges separated POU halves on a promoter.

    Evidence POU domain chimeras, alanine scanning, methylation/phosphorothioate interference, in vivo transactivation

    PMID:8657574 PMID:9819426

    Open questions at the time
    • Connection to general transcription machinery recruitment incompletely mapped
  5. 1999 High

    Provided the structural and thermodynamic basis of complex assembly, visualizing OCA-B peptide-DNA and peptide-protein contacts and demonstrating cooperative, induced-folding ternary binding.

    Evidence 3.2 Å X-ray crystal structure plus gel filtration, calorimetry, CD, ITC

    PMID:10329190 PMID:10541551

    Open questions at the time
    • Crystallized peptide rather than full-length protein
    • Structure of OCA-B engaging Oct dimers not captured
  6. 2003 High

    Clarified which Oct configuration OCA-B preferentially targets, showing OCA-B stabilizes PORE-type Oct1/Oct2 dimers and overrides interface mutations, but cannot engage MORE-type dimers due to overlapping surfaces.

    Evidence EMSA ternary complex with mutant POU proteins and transcription reporters

    PMID:11136971 PMID:12727885

    Open questions at the time
    • Genome-wide proportion of monomer vs dimer targets unresolved at the time
    • Promoter-context determinants of dimer formation incompletely defined
  7. 2024 Medium

    Refined the DNA recognition model using unbiased selection, confirming dimer engagement but re-establishing monomeric Oct1/2 on classical octamers as primary OCA-B targets and showing OCA-B imposes its own sequence preference.

    Evidence EMSA-SELEX-Seq in vitro selection

    PMID:38254723

    Open questions at the time
    • Single study refining the prior dimer-centric model
    • In vivo correlation with occupancy not addressed in the same work
  8. 2000 Medium

    Connected OCA-B to the basal transcription apparatus by identifying the B-cell-enriched TFIID subunit TAF(II)105 as a C-terminal activation-domain partner required for octamer transcription.

    Evidence In vitro binding, dominant-negative and antibody inhibition, reporter assays

    PMID:10828057

    Open questions at the time
    • Stoichiometry within TFIID not defined
    • Relative contribution of TAF(II)105 versus TBP/TFIIB unclear
  9. 2001 High

    Showed OCA-B abundance is controlled post-translationally, identifying Siah-1-mediated proteasomal degradation as a switch that rises sharply upon B-cell activation independent of mRNA.

    Evidence Yeast two-hybrid, reciprocal co-IP, proteasome inhibitor and in vivo activation experiments

    PMID:11483517

    Open questions at the time
    • Whether Siah-1 directly ubiquitinates OCA-B not settled here
    • Upstream signals controlling Siah-1 engagement unknown
  10. 2013 Medium

    Refined the degradation mechanism, showing proteasomal turnover proceeds without OCA-B ubiquitination and is gated by a C-terminal acidic degron whose acidity (mimicking tyrosine phosphorylation) stabilizes the protein.

    Evidence Fluorescent reporter degradation assays, phosphomimetic mutagenesis, proteasome inhibitors, ubiquitination assay

    PMID:24061476

    Open questions at the time
    • Identity of the kinase generating the stabilizing modification not established
    • How a ubiquitin-independent substrate is delivered to the proteasome unresolved
  11. 2001 High

    Genetic epistasis defined the division of labor among octamer factors, showing Oct-1 can substitute for Oct-2/OBF-1 in basal Ig transcription while both are required for germinal centers, with OBF-1 most important for IgG.

    Evidence Compound Oct-2/OBF-1 knockout mice, bone marrow reconstitution, flow cytometry

    PMID:11135581

    Open questions at the time
    • Molecular basis of the GC-specific requirement not given
  12. 2006 Medium

    Uncovered non-transcriptional functions of OCA-B, identifying a myristoylated membrane isoform that binds and stabilizes the kinase SYK to support pre-BCR/BCR signaling, and an N-terminal interaction with galectin-1 modulating CD45/proliferation.

    Evidence Isoform purification with metabolic myristoylation labeling, fractionation, co-IP, SYK stability and rescue, CD45 phosphatase and proliferation assays

    PMID:11239448 PMID:16565088 PMID:16713566

    Open questions at the time
    • Structural basis of the SYK interaction unresolved
    • Relative in vivo contribution of nuclear vs membrane isoforms not quantified
  13. 2007 Medium

    Placed OCA-B in B-cell transcriptional and oncogenic networks by defining direct targets Spi-B and TNFRSF17/BCMA, and identifying XBP-1(S) as a direct upstream activator of the OCA-B gene during plasma cell differentiation.

    Evidence ChIP, EMSA, microarray, transgenic and knockout mice, siRNA/overexpression with growth assays

    PMID:16861304 PMID:17621271 PMID:17709512

    Open questions at the time
    • Full target-gene network not enumerated
    • Direct vs indirect myeloma growth dependence incompletely separated
  14. 2011 High

    Revealed an architectural role: OCA-B at the Igh 3' enhancer interacts with promoter-bound TFII-I to mediate enhancer-promoter looping and relieves HDAC3-mediated repression by competing for TFII-I.

    Evidence Co-IP, in vitro binding, 3C chromosome conformation capture, ChIP, competition assays

    PMID:21549311

    Open questions at the time
    • Generality of looping to non-Igh loci untested here
    • Dynamics of HDAC3 displacement during activation not resolved
  15. 2015 High

    Extended OCA-B to T-cell memory, showing it maintains a poised H3K4 chromatin state at memory loci and recruits the demethylase Jmjd1a to Il2/Ifng/Zbtb32 for rapid reactivation.

    Evidence Conditional knockout, ChIP-seq, OCA-B/Jmjd1a co-IP, viral infection model

    PMID:26481684

    Open questions at the time
    • How OCA-B selects memory loci versus naive-cell genes unclear
    • Direct chromatin-poising mechanism beyond Jmjd1a recruitment not fully defined
  16. 2016 Medium

    Defined OCA-B's role in Tfh differentiation by showing it directly transactivates Bcl6 (and Btla) with Oct1/Oct2 in a T-cell-intrinsic manner.

    Evidence ChIP, luciferase reporters, mixed bone marrow chimeras, flow cytometry

    PMID:26957522

    Open questions at the time
    • Relationship to the later Bhlhe40-CXCR5 circuit not yet integrated
  17. 2019 Medium

    Broadened the T-helper repertoire of OCA-B, showing it enhances RORγt-driven IL-17A in Th17 cells (requiring ternary-complex formation) and synergizes with MTA2/NuRD to repress pre-B genes Igll1/VpreB1.

    Evidence Co-IP, reporter assays, domain mapping, EAE knockout mice, compound knockout genetics with H3K27ac ChIP

    PMID:31103264 PMID:31291582

    Open questions at the time
    • Direct vs ternary-complex-dependent activation/repression mechanisms not fully separated
    • Single-lab findings per axis
  18. 2021 High

    Established OCA-B as a therapeutic target and central GC regulator: it co-occupies GC genes genome-wide with Oct1/Oct2 controlling BCL6/IRF4 balance, and its T-cell loss or peptide inhibition protects NOD mice from autoimmune diabetes; a peripheral adipogenesis role was also reported.

    Evidence ChIP-seq, shRNA, epistasis in GC lymphoma cells; conditional knockout and membrane-penetrating peptide inhibitor pharmacology; adenoviral overexpression in MSCs

    PMID:33295943 PMID:33512466 PMID:33949290

    Open questions at the time
    • Adipogenesis link is low-confidence with no direct OCA-B-HDAC1 binding shown
    • Mechanism of peptide inhibitor disruption of complexes not fully detailed
  19. 2025 Medium

    Detailed OCA-B's role in pathogenic and migratory T-cell programs, showing it is required for pathogenic maturation of stem-like CD4+ T cells in EAE, drives Tfh CXCR5/GC migration via a Bhlhe40-Pou2af1 axis independent of Bcl6, and restrains Th2 differentiation through indirect association with GATA3.

    Evidence T-cell-specific conditional knockouts, relapsing-remitting EAE, RNA-seq, proximity labeling (BioID), ChIP-seq, recombinant DNA binding, allergy model

    PMID:40299553 PMID:40364837 PMID:41134666

    Open questions at the time
    • Direct vs indirect GATA3 association not biochemically resolved
    • How one coactivator both activates and restrains lineage programs mechanistically unexplained
    • Single-lab findings per phenotype
  20. 2026 Medium

    Consolidated the recruitment-and-activation model, adding MEF2B as a secondary recruiting factor and the Mediator complex as an activation interface, with GC B-cell-specific inactivation reproducing GC defects.

    Evidence Mechanistic review citing primary data; GC B-cell-specific conditional inactivation

    PMID:41939912

    Open questions at the time
    • MEF2B and Mediator contacts not structurally mapped here
    • Relative weighting of Oct1/2 vs MEF2B recruitment unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single coactivator dynamically partitions between its nuclear octamer-coactivator role and cytoplasmic/membrane signaling functions, and how it switches between gene activation and lineage restriction in different T-helper subsets, remains unresolved.
  • No integrated model linking isoform choice to functional output
  • Structural basis of MEF2B, Mediator, and SYK interactions undetermined
  • Determinants of context-dependent activation versus repression unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0003677 DNA binding 4 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 5 GO:0005829 cytosol 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-4839726 Chromatin organization 3 R-HSA-162582 Signal Transduction 2
Partners
JMJD1APOU2F1POU2F2SIAH1SYKTAF1CTBPTFII-I

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 OBF-1/OCA-B (POU2AF1) is a B cell-specific transcriptional coactivator with no intrinsic DNA-binding activity that physically associates with the POU domains of Oct-1 and Oct-2 (but not Oct-4 or Oct-6) and stimulates immunoglobulin promoter activity in an octamer site-dependent manner. Yeast two-hybrid screen, biochemical co-association assays, HeLa cell transcription reporter assay Cell High 7623806 7859290
1995 A single OCA-B polypeptide (34–35 kDa) is sufficient for B cell-specific activation of Ig promoters; POU domains of Oct-1 or Oct-2 are sufficient for OCA-B interaction, but an additional Oct activation domain is also required for full functional synergy with OCA-B. OCA-B additionally requires USA-derived general cofactors (including PC2 and PC4) for optimal activity in a reconstituted cell-free system, and directly interacts with PC4. Recombinant protein biochemical reconstitution, in vitro transcription assay, cofactor fractionation and add-back Molecular and cellular biology High 7623806 9632764
1996 OBF-1/OCA-B-deficient mice (generated by gene targeting) show severe defects in antigen-dependent B cell responses and completely fail to develop germinal centers after immunization, while immunoglobulin gene rearrangement/transcription and early B cell development are largely unaffected. Gene targeting / knockout mouse, immunization, histology, serum Ig measurement Nature High 8849727 8849728 8977324
1996 OCA-B binds DNA directly in the major groove between the two POU subdomains, requiring both an adenine at position 5 of the octamer element and contact with the POU domain; an amino-terminal fragment of OCA-B can bind the octamer site independently of a POU domain with the same sequence specificity, suggesting a POU-dependent conformational change exposes the OCA-B N-terminus. Electrophoretic mobility shift assay (EMSA), DNA binding assays with truncation mutants Genes & development Medium 8769650
1996 Bob1/OBF-1 forms ternary complexes with Oct-1 or Oct-2 bound to DNA in a sequence-selective manner; the N-terminal region (amino acids 26–32) of Bob1 contacts the POU-specific subdomain of Oct-1/Oct-2, and ternary complex formation occurs only on a subset of octamer sequences, conferring differential promoter activation. Mutational analysis, EMSA ternary complex assays, transcription reporter assays The EMBO journal High 8654375
1998 OCA-B makes selective contacts with both the POU-specific domain (residues L6, E7) and the POU homeodomain (residues K155, I159) of Oct-1, acting as a molecular clamp that holds together the two moieties of the POU domain on DNA; in vivo, OCA-B can recruit two artificially separated POU domain halves to a promoter to achieve transactivation. Oct-1/Pit-1 POU domain chimeras, alanine-scanning mutagenesis, methylation interference, phosphorothioate EMSA, in vivo transactivation assay Molecular and cellular biology High 9819426
1997 OCA-B is a functional analog of VP16 in that it provides a transcriptional activation domain and stabilizes Oct-1 on the octamer sequence, but contacts a different surface of the Oct-1 POU domain (both POU-specific and POU homeodomain plus center of octamer DNA); OCA-B and VP16 can bind the Oct-1 POU domain simultaneously. In vitro binding assays, transcription reporter assays, competition binding experiments Molecular and cellular biology Medium 9372961
1998 OBF-1 interacts with the general transcription factors TBP and TFIIB in the absence of DNA, in addition to its interactions with Oct-1/Oct-2 POU domains. OBF-1 activates promoter octamer sites but not enhancer octamer sites. In vitro protein interaction assay, transcription reporter assay Nucleic acids research Medium 8657574
1999 Crystal structure (3.2 Å) of OCA-B peptide/Oct-1 POU domain/octamer DNA ternary complex shows: OCA-B peptide binds in the major groove near the center of the octamer, forming hydrogen bonds with adenine at position 5; an alpha-helix of OCA-B binds a hydrophobic pocket on the POU-specific domain; both peptide-DNA and peptide-protein contacts provide structural specificity. X-ray crystallography (3.2 Å resolution) Genes & development High 10541551
1999 Bob1 binds specifically as a monomer to the complex of Oct-1 POU domain and Igκ promoter DNA, but binds weakly to either component alone, indicating both are required for avid binding; ternary complex formation requires defined DNA sequence and is sensitive to single base-pair changes; Bob1 undergoes partial folding upon ternary complex formation (induced folding). Biophysical characterization (gel filtration, calorimetry, circular dichroism, ITC) Journal of molecular biology High 10329190
2000 The POU dimer assembled on the PORE sequence (ATTTGAAATGCAAAT) can recruit OBF-1, whereas POU dimers formed on the MORE sequence cannot interact with OBF-1 because the same Oct-1 residues that form the MORE dimerization interface are also used for OBF-1/Oct-1 interactions on the PORE. Thus specific POU dimer configurations differentially recruit OBF-1. EMSA ternary complex formation assays, dimerization interface mutagenesis, transcription reporter assays Cell High 11136971
2001 The RING finger E3 ubiquitin ligase Siah-1 directly interacts with OBF-1 (via Siah-1 C-terminus and OBF-1 N-terminus, partly distinct from the Oct/DNA interaction surface); this interaction leads to downregulation of OBF-1 protein level (not mRNA) and reduction in octamer-dependent transcription; inhibition of the ubiquitin-proteasome pathway in B cells elevates OBF-1 protein; OBF-1 protein dramatically increases in primary activated B cells upon immunization without change in mRNA. Yeast two-hybrid, co-immunoprecipitation, protein level analysis, proteasome inhibitor treatment, in vivo B cell activation experiments The EMBO journal High 11483517
2001 Mice whose lymphoid compartment is reconstituted with cells lacking both Oct-2 and OBF-1 still develop B cells to the IgM+ stage with essentially unaffected Ig gene transcription, implying that ubiquitous Oct-1 can substitute for Oct-2 and OBF-1 in basic Ig transcription; both factors are essential for germinal center formation, with OBF-1 being more important for IgG production. Genetic epistasis via compound knockout mice, bone marrow reconstitution, flow cytometry, Ig transcription analysis Nature immunology High 11135581
2001 OCA-B has a novel membrane-associated isoform (p35/p40) that is myristoylated in vivo; myristoylation leads to localization of p35 to membrane compartments, distinct from the nuclear p34 isoform, suggesting a non-transcriptional signaling function in late B cell development. Biochemical purification, metabolic labeling for myristoylation, subcellular fractionation, isoform characterization Immunity Medium 11239448
2000 TAF(II)105 (a B cell-enriched TFIID subunit) specifically interacts with the C-terminal activation domain of OCA-B and is required for OCA-B-dependent octamer-mediated transcription in B cells; this interaction links TFIID to B cell-specific transcription. In vitro binding assays, dominant-negative overexpression, antibody inhibition of transcription, reporter assays The Journal of biological chemistry Medium 10828057
2003 OBF1 stabilizes POU dimer–DNA interactions on PORE-type sequences and overrides Oct1 interface mutations that would otherwise abolish PORE-mediated dimerization; the PORE-type Oct1/Oct2 dimer (not the monomer) is the primary target of OBF1, and OBF1 alleviates DNA sequence requirements of the Oct1 dimer on PORE-related sequences. EMSA, in vitro ternary complex formation with mutant POU proteins, transcription reporter assays The EMBO journal Medium 12727885
2006 OCA-B directly interacts with the tyrosine kinase SYK in the cytoplasm and directly regulates SYK protein stability; this non-transcriptional function is required for pre-BCR and BCR signaling at multiple stages of B cell development (pre-B1 to pre-B2 transition). Co-immunoprecipitation, subcellular fractionation, SYK stability assays, genetic rescue experiments Cell High 16713566
2006 OCA-B directly interacts with galectin-1 (and related galectins) via its N-terminal domain; in OCA-B-deficient B cells, increased galectin-1 expression and cell surface association correlates with reduced CD45 phosphatase activity and negative regulation of B cell proliferation upon BCR stimulation. Co-immunoprecipitation (in vivo and in vitro), domain mapping, CD45 phosphatase activity assay, B cell proliferation assay The Journal of biological chemistry Medium 16565088
2006 The Ets transcription factor Spi-B is a direct transcriptional target of OBF-1; OBF-1 binds to the Spi-B promoter and OBF-1 deficiency reduces Spi-B expression; transgenic T cell expression of OBF-1 reveals Spi-B as a critical downstream mediator linking OBF-1 to B cell receptor signaling and germinal center formation. Transgenic mouse overexpression, microarray analysis, chromatin immunoprecipitation (ChIP), knockout mouse experiments Proceedings of the National Academy of Sciences of the United States of America High 16861304
2007 XBP-1(S) directly binds to the OBF-1/BOB-1/OCA-B promoter (at a UPR element conserved in mouse and human) in plasmacytoma cells and in primary B cells, both during plasma cell differentiation and in response to UPR activation, identifying OCA-B as a direct transcriptional target of XBP-1(S). Chromatin immunoprecipitation (ChIP), gel shift assay (EMSA), shRNA knockdown, promoter-reporter assay Journal of immunology Medium 17709512
2007 POU2AF1/OCA-B directly binds to an octamer site within the 5' regulatory region of TNFRSF17 (BCMA) and transactivates its expression; knockdown of POU2AF1 by siRNA inhibits multiple myeloma cell growth, while ectopic expression promotes it. siRNA knockdown, ectopic overexpression, ChIP, promoter reporter assay, cell growth assay Oncogene Medium 17621271
2011 OCA-B directly interacts with transcription factor TFII-I; OCA-B bound to the Igh 3' enhancer interacts with promoter-bound TFII-I to mediate promoter-enhancer looping (in cis and trans), and OCA-B also relieves HDAC3-mediated Igh promoter repression by competing with HDAC3 for binding to TFII-I. Co-immunoprecipitation, chromatin conformation capture (3C), ChIP, in vitro binding assay Molecular cell High 21549311
2013 Bob1 protein degradation is proteasome-mediated but does not require ubiquitination of Bob1; a C-terminal acidic region of Bob1 regulates the activity of degron signals elsewhere in the protein; tyrosine phosphorylation-mimetic mutations that make the C terminus more acidic stabilize the Bob1 protein, suggesting signaling pathways regulate Bob1 stability through this mechanism. Expression of a stable Bob1 mutant in B cells suppresses cell proliferation and induces differentiation markers. Fluorescent protein reporter degradation assay, proteasome inhibitor treatment, mutagenesis (phosphomimetic substitutions), ubiquitination assay Molecular and cellular biology Medium 24061476
2015 OCA-B is required for CD4+ T cell memory: it is needed to maintain a poised (H3K4me1/H3K4me3) chromatin state at the Il2 locus in resting previously stimulated CD4+ T cells, and recruits the histone lysine demethylase Jmjd1a to target loci including Il2, Ifng, and Zbtb32, enabling rapid gene reactivation upon antigen re-encounter. Conditional knockout mice, ChIP-seq, co-immunoprecipitation (OCA-B with Jmjd1a), flow cytometry, in vivo viral infection model The Journal of experimental medicine High 26481684
2016 Bob1 (OBF1) directly binds to and transactivates the Bcl6 and Btla promoters in CD4+ T cells together with Oct1/Oct2; mixed bone marrow chimeras demonstrated this is a T cell-intrinsic requirement for Bcl6 expression and Tfh cell development/pool size. Chromatin immunoprecipitation (ChIP), luciferase reporter assay, mixed bone marrow chimeras, flow cytometry The EMBO journal Medium 26957522
2019 Bob1 interacts with RORγt (via the ligand-binding domain of RORγt) and enhances RORγt-mediated IL-17A transcription in Th17 cells; this enhancement requires the ability of Bob1 to form a DNA-Oct1-Bob1 ternary complex. Co-immunoprecipitation, reporter gene assay, Bob1 knockout mice (EAE model), domain mapping Biochemical and biophysical research communications Medium 31103264
2019 MTA2/NuRD complex and OCA-B synergistically repress Igll1 and VpreB1 at the pre-B cell stage; MTA2 deficiency leads to increased H3K27 acetylation at these promoters; OCA-B and MTA2 cooperate to regulate the pre-B to immature B cell transition. Compound knockout mouse genetics, ChIP (H3K27ac), gene expression profiling Cell reports Medium 31291582
2021 OBF1, OCT1, and OCT2 colocalize genome-wide (ChIP-seq) at promoters and enhancers of GC regulatory genes (BCL6, IRF4, etc.) in GC B cells; OBF1 downregulation (shRNA) disrupts the GC transcriptional program: GC maintenance genes (e.g., BCL6) are downregulated and GC exit genes (e.g., IRF4) are upregulated; ectopic BCL6 does not rescue proliferation of OBF1-depleted GC lymphoma cells unless IRF4 is also depleted. ChIP-seq, shRNA knockdown, ectopic expression, cell proliferation assay Blood High 33512466
2021 T cell-specific conditional OCA-B knockout protects NOD mice from spontaneous autoimmune diabetes; rationally designed membrane-penetrating OCA-B peptide inhibitors normalized blood glucose and reduced T cell infiltration and proinflammatory cytokine expression in newly diabetic NOD mice, demonstrating pharmacologic inhibitability. Conditional knockout mouse (Cre-lox), peptide inhibitor pharmacology, histology, flow cytometry, cytokine measurement The Journal of experimental medicine High 33295943
2021 POU2AF1/OCA-B promotes MSC adipogenesis by inhibiting nuclear translocation and mRNA expression of HDAC1; overexpression of OCA-B promoted spontaneous adipogenesis, and co-transfection with HDAC1 partially reversed this effect. Adenoviral overexpression, siRNA knockdown, Oil-red O staining, Western blot, subcellular fractionation Adipocyte Low 33949290
2024 OCA-B expression is sufficient to improve CD4+ T cell antiviral memory recall responses; high endogenous OCA-B expression early in viral infection prospectively identifies memory precursor cells with increased survival and memory recall potential (using OCA-B mCherry reporter mouse). Ectopic overexpression in vivo (retroviral), OCA-B-mCherry reporter mouse, viral infection model, flow cytometry Proceedings of the National Academy of Sciences of the United States of America Medium 38386711
2024 EMSA-SELEX-Seq analysis reaffirms that BOB1 selectively engages the dimer configuration of OCT1/2, but clarifies that monomeric OCT1/2 assembled on the classical octamer ATGCAAAT and related motifs are also primary BOB1 targets; BOB1 imposes a specific DNA sequence preference on OCT1/2 in monomeric configuration. EMSA-SELEX-Seq (in vitro selection combined with sequencing) Biomolecules Medium 38254723
2025 OCA-B is required for pathogenic maturation of stem-like CD4+ T cells in EAE; T cell-intrinsic OCA-B loss nearly eliminates CNS infiltration and clinical disease upon autoantigen re-encounter; OCA-B promotes Tcf7, Slamf6, and Sell expression in proliferating CNS T cell populations during remission, and its loss at relapse results in accumulation of immunomodulatory (Ccr9+Bach2+) CD4+ T cells. T cell-specific conditional knockout (Cre-lox), relapsing-remitting EAE model, flow cytometry, gene expression analysis The Journal of clinical investigation Medium 40299553
2025 Pou2af1/OCA-B in Tfh cells promotes optimal CXCR5 expression and GC migration through a Bhlhe40-Pou2af1 axis: Pou2af1 upregulates CXCR5 but not Bcl6, while Bhlhe40 represses Pou2af1 expression; this circuit operates independently of the Bcl6-Blimp1 fate-determination axis. Conditional knockout, RNA-seq of antigen-specific Tfh cells, flow cytometry, CXCR5 expression analysis Cell reports Medium 41134666
2025 OCA-B restricts Th2 differentiation: proximity labeling shows OCA-B indirectly associates with GATA3; ChIP-seq reveals co-enrichment of GATA3 and Oct1 (OCA-B partner) at the Th2 locus control region (Il4, Il13, Il5, Gata3, Irf4); recombinant protein DNA binding and reporter assays are consistent with OCA-B restraining transcription at these loci. Proximity labeling (BioID), ChIP-seq, recombinant protein DNA binding assay, reporter assay, in vivo papain allergy model with T cell-specific OCA-B deletion Frontiers in immunology Medium 40364837
2026 OCA-B is recruited to target genes through primary interactions with DNA-binding transcription factors OCT1/OCT2 as well as secondary interactions with MEF2B; its transcriptional activation involves interactions with the Mediator coactivator complex; GC B cell-specific inactivation of Oca-B is sufficient to cause GC defects. Mechanistic review citing primary experimental data; GC B cell-specific conditional inactivation Frontiers in immunology Medium 41939912

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 OBF-1, a novel B cell-specific coactivator that stimulates immunoglobulin promoter activity through association with octamer-binding proteins. Cell 351 7859290
1995 Cloning, functional characterization, and mechanism of action of the B-cell-specific transcriptional coactivator OCA-B. Molecular and cellular biology 245 7623806
1996 B-cell-specific coactivator OBF-1/OCA-B/Bob1 required for immune response and germinal centre formation. Nature 239 8849727
1997 mcm5/cdc46-bob1 bypasses the requirement for the S phase activator Cdc7p. Proceedings of the National Academy of Sciences of the United States of America 222 9096361
1996 The B-cell-specific transcription coactivator OCA-B/OBF-1/Bob-1 is essential for normal production of immunoglobulin isotypes. Nature 207 8849728
2012 B and T cells collaborate in antiviral responses via IL-6, IL-21, and transcriptional activator and coactivator, Oct2 and OBF-1. The Journal of experimental medicine 171 23045607
1996 The B cell coactivator Bob1 shows DNA sequence-dependent complex formation with Oct-1/Oct-2 factors, leading to differential promoter activation. The EMBO journal 123 8654375
1996 B lymphocytes are impaired in mice lacking the transcriptional co-activator Bob1/OCA-B/OBF1. European journal of immunology 119 8977324
2000 Synergism with the coactivator OBF-1 (OCA-B, BOB-1) is mediated by a specific POU dimer configuration. Cell 118 11136971
2001 Oct-2 and Bob-1 deficiency in Hodgkin and Reed Sternberg cells. Cancer research 109 11280769
2001 B cell development and immunoglobulin gene transcription in the absence of Oct-2 and OBF-1. Nature immunology 88 11135581
1998 OCA-B integrates B cell antigen receptor-, CD40L- and IL 4-mediated signals for the germinal center pathway of B cell development. The EMBO journal 87 9724642
1996 Sequence-specific DNA binding of the B-cell-specific coactivator OCA-B. Genes & development 81 8769650
1999 Crystal structure of an OCA-B peptide bound to an Oct-1 POU domain/octamer DNA complex: specific recognition of a protein-DNA interface. Genes & development 78 10541551
2001 The RING finger protein Siah-1 regulates the level of the transcriptional coactivator OBF-1. The EMBO journal 69 11483517
1998 Coactivator OBF-1 makes selective contacts with both the POU-specific domain and the POU homeodomain and acts as a molecular clamp on DNA. Molecular and cellular biology 64 9819426
2007 POU2AF1, an amplification target at 11q23, promotes growth of multiple myeloma cells by directly regulating expression of a B-cell maturation factor, TNFRSF17. Oncogene 58 17621271
1998 Downstream activation of a TATA-less promoter by Oct-2, Bob1, and NF-kappaB directs expression of the homing receptor BLR1 to mature B cells. The Journal of biological chemistry 54 9786883
2011 Direct interactions of OCA-B and TFII-I regulate immunoglobulin heavy-chain gene transcription by facilitating enhancer-promoter communication. Molecular cell 52 21549311
2005 Differential requirement for OBF-1 during antibody-secreting cell differentiation. The Journal of experimental medicine 51 15867091
2003 Lack of the transcriptional coactivator OBF-1 prevents the development of systemic lupus erythematosus-like phenotypes in Aiolos mutant mice. Journal of immunology (Baltimore, Md. : 1950) 51 12574333
2017 TCR-based therapy for multiple myeloma and other B-cell malignancies targeting intracellular transcription factor BOB1. Blood 50 28053195
2003 OCA-B regulation of B-cell development and function. Trends in immunology 50 14552839
1998 The Oct-1 POU domain activates snRNA gene transcription by contacting a region in the SNAPc largest subunit that bears sequence similarities to the Oct-1 coactivator OBF-1. Genes & development 50 9832505
1989 The OBF1 protein and its DNA-binding site are important for the function of an autonomously replicating sequence in Saccharomyces cerevisiae. Molecular and cellular biology 50 2674674
2015 Oct1 and OCA-B are selectively required for CD4 memory T cell function. The Journal of experimental medicine 47 26481684
2004 CD86 and beta2-adrenergic receptor signaling pathways, respectively, increase Oct-2 and OCA-B Expression and binding to the 3'-IgH enhancer in B cells. The Journal of biological chemistry 47 15024018
1997 OCA-B is a functional analog of VP16 but targets a separate surface of the Oct-1 POU domain. Molecular and cellular biology 46 9372961
2016 The transcriptional coactivator Bob1 promotes the development of follicular T helper cells via Bcl6. The EMBO journal 45 26957522
1996 The B cell transcriptional coactivator BOB1/OBF1 gene fuses to the LAZ3/BCL6 gene by t(3;11)(q27;q23.1) chromosomal translocation in a B cell leukemia line (Karpas 231). Leukemia 43 8618432
1996 Gene structure and characterization of the murine homologue of the B cell-specific transcriptional coactivator OBF-1. Nucleic acids research 43 8657574
1999 Oct-1 POU and octamer DNA co-operate to recognise the Bob-1 transcription co-activator via induced folding. Journal of molecular biology 41 10329190
2016 POU2AF1 Functions in the Human Airway Epithelium To Regulate Expression of Host Defense Genes. Journal of immunology (Baltimore, Md. : 1950) 40 26927796
1998 Coactivation by OCA-B: definition of critical regions and synergism with general cofactors. Molecular and cellular biology 39 9632764
2000 Role of OCA-B in 3'-IgH enhancer function. Journal of immunology (Baltimore, Md. : 1950) 38 10799892
2006 The Ets factor Spi-B is a direct critical target of the coactivator OBF-1. Proceedings of the National Academy of Sciences of the United States of America 36 16861304
2005 Identification of a potential role for POU2AF1 and BTG4 in the deletion of 11q23 in chronic lymphocytic leukemia. Genes, chromosomes & cancer 34 15672409
2019 MTA2/NuRD Regulates B Cell Development and Cooperates with OCA-B in Controlling the Pre-B to Immature B Cell Transition. Cell reports 33 31291582
2000 Cutting edge: lack of peripheral B cells and severe agammaglobulinemia in mice simultaneously lacking Bruton's tyrosine kinase and the B cell-specific transcriptional coactivator OBF-1. Journal of immunology (Baltimore, Md. : 1950) 32 10604987
1991 The multifunctional protein OBF1 is phosphorylated at serine and threonine residues in Saccharomyces cerevisiae. Proceedings of the National Academy of Sciences of the United States of America 32 2034654
2002 The mcm5-bob1 bypass of Cdc7p/Dbf4p in DNA replication depends on both Cdk1-independent and Cdk1-dependent steps in Saccharomyces cerevisiae. Genetics 31 12019222
2001 Identification and characterization of a novel OCA-B isoform. implications for a role in B cell signaling pathways. Immunity 31 11239448
2021 OBF1 and Oct factors control the germinal center transcriptional program. Blood 30 33512466
1989 Purification and characterization of OBF1: a Saccharomyces cerevisiae protein that binds to autonomously replicating sequences. Molecular and cellular biology 29 2674673
2006 Nontranscriptional regulation of SYK by the coactivator OCA-B is required at multiple stages of B cell development. Cell 28 16713566
1997 The B cell-specific coactivator OBF-1 (OCA-B, Bob-1) is inducible in T cells and its expression is dispensable for IL-2 gene induction. Immunobiology 28 9442392
2007 Identification of ERdj3 and OBF-1/BOB-1/OCA-B as direct targets of XBP-1 during plasma cell differentiation. Journal of immunology (Baltimore, Md. : 1950) 26 17709512
2006 Interaction of the B cell-specific transcriptional coactivator OCA-B and galectin-1 and a possible role in regulating BCR-mediated B cell proliferation. The Journal of biological chemistry 26 16565088
2016 Natalizumab-induced POU2AF1/Spi-B upregulation: A possible route for PML development. Neurology(R) neuroimmunology & neuroinflammation 25 27088119
2014 Oct2 and Obf1 as Facilitators of B:T Cell Collaboration during a Humoral Immune Response. Frontiers in immunology 25 24688485
2006 Linkage disequilibrium screening for multiple sclerosis implicates JAG1 and POU2AF1 as susceptibility genes in Europeans. Journal of neuroimmunology 25 16934875
2003 Identification of transcription coactivator OCA-B-dependent genes involved in antigen-dependent B cell differentiation by cDNA array analyses. Proceedings of the National Academy of Sciences of the United States of America 24 12857960
2001 Expression of the Oct-1 transcription factor and characterization of its interactions with the Bob1 coactivator. Biochemistry 23 11380252
2003 OBF1 enhances transcriptional potential of Oct1. The EMBO journal 21 12727885
1999 Catfish Oct2 binding affinity and functional preference for octamer motifs, and interaction with OBF-1. Developmental and comparative immunology 19 10402207
2002 Bob1 (OCA-B/OBF-1) differential transactivation of the B cell-specific B29 (Ig beta) and mb-1 (Ig alpha) promoters. Journal of immunology (Baltimore, Md. : 1950) 18 11907094
2021 Targeting transcriptional coregulator OCA-B/Pou2af1 blocks activated autoreactive T cells in the pancreas and type 1 diabetes. The Journal of experimental medicine 17 33295943
2008 Silencing and nuclear repositioning of the lambda5 gene locus at the pre-B cell stage requires Aiolos and OBF-1. PloS one 17 18974788
2006 Biochemical activities of the BOB1 mutant in Methanobacterium thermoautotrophicum MCM. Biochemistry 17 16401076
2000 Specific interaction of TAFII105 with OCA-B is involved in activation of octamer-dependent transcription. The Journal of biological chemistry 17 10828057
2000 Functional analysis of the OCA-B promoter. Journal of immunology (Baltimore, Md. : 1950) 17 10843692
2019 Bob1 enhances RORγt-mediated IL-17A expression in Th17 cells through interaction with RORγt. Biochemical and biophysical research communications 15 31103264
2016 Bob1 limits cellular frequency of T-follicular helper cells. European journal of immunology 15 27080143
2013 Germinal center-independent, IgM-mediated autoimmunity in sanroque mice lacking Obf1. Immunology and cell biology 15 24217807
2008 Enforced expression of the transcriptional coactivator OBF1 impairs B cell differentiation at the earliest stage of development. PloS one 15 19104664
2000 Genetic analyses of NFKB1 and OCA-B function: defects in B cells, serum IgM level, and antibody responses in Nfkb1-/-Oca-b-/- mice. Journal of immunology (Baltimore, Md. : 1950) 14 11120805
2009 Role of defective Oct-2 and OCA-B expression in immunoglobulin production and Kaposi's sarcoma-associated herpesvirus lytic reactivation in primary effusion lymphoma. Journal of virology 13 19224997
2007 Primary gastric Hodgkin's lymphoma expressing a B-Cell profile including Oct-2 and Bob-1 proteins. International journal of hematology 13 17562619
2016 Oct2 and Bob1 are sensitive and specific markers in lineage determination of B cell lymphomas with no expression of conventional B cell markers. Histopathology 12 27319306
2011 Evaluation of CARMA1/CARD11 and Bob1 as candidate genes in common variable immunodeficiency. Journal of investigational allergology & clinical immunology 11 21905497
2024 Structure of POU2AF1 recombinant protein and it affects the progression and treatment of liver cancer based on WGCNA and molecular docking analysis. International journal of biological macromolecules 10 39128756
2022 Alterations of the miR-126-3p/POU2AF1/Spi-B Axis and JCPyV Reactivation in Multiple Sclerosis Patients Receiving Natalizumab. Frontiers in neurology 10 35359635
2017 The Transcriptional Coactivator Bob1 Is Associated With Pathologic B Cell Responses in Autoimmune Tissue Inflammation. Arthritis & rheumatology (Hoboken, N.J.) 10 27907250
2000 The lymphoid-specific cofactor OBF-1 is essential for the expression of a V(H) promoter/HS1,2 enhancer-linked transgene in late B cell development. Molecular immunology 10 11282393
2024 Bob1 maintains T follicular helper cells for long-term humoral immunity. Communications biology 9 38360857
2017 Germline variation in the 3'-untranslated region of the POU2AF1 gene is associated with susceptibility to lymphoma. Molecular carcinogenesis 9 28345816
1996 Heterogeneity of breakpoints at the transcriptional co-activator gene, BOB-1, in lymphoproliferative disease. Leukemia 9 8751468
1995 Fusion of the LAZ3/BCL6 and BOB1/OBF1 genes by t(3; 11) (q27; q23) chromosomal translocation. Comptes rendus de l'Academie des sciences. Serie III, Sciences de la vie 9 8574789
2024 OCA-B/Pou2af1 is sufficient to promote CD4+ T cell memory and prospectively identifies memory precursors. Proceedings of the National Academy of Sciences of the United States of America 8 38386711
2021 POU2AF1 promotes MSCs adipogenesis by inhibiting HDAC1 expression. Adipocyte 8 33949290
2019 Evaluation of SUMO1 and POU2AF1 in whole blood from rheumatoid arthritis patients and at risk relatives. International journal of immunogenetics 8 30681271
2014 Cutting edge: The transcription factor Bob1 counteracts B cell activation and regulates miR-146a in B cells. Journal of immunology (Baltimore, Md. : 1950) 8 24719463
2003 Critical role for the Oct-2/OCA-B partnership in Ig-secreting cells. Journal of immunology (Baltimore, Md. : 1950) 8 14662861
1999 B-Cell coactivator OBF-1 exhibits unusual transcriptional properties and functions in a DNA-bound Oct-1-dependent fashion. Molecular and cellular biology 8 10330165
1996 Cloning and characterization of the murine B-cell specific transcriptional coactivator Bob1. Biological chemistry Hoppe-Seyler 8 8868069
2013 A C-terminal acidic domain regulates degradation of the transcriptional coactivator Bob1. Molecular and cellular biology 7 24061476
2007 OBF-1 is essential for the generation of antibody-secreting cells and the development of autoimmunity in MRL-lpr mice. Journal of autoimmunity 7 17574818
2003 The OBF-1 gene locus confers B cell-specific transcription by restricting the ubiquitous activity of its promoter. European journal of immunology 7 14515270
2022 OCA-B does not act as a transcriptional coactivator in T cells. Immunology and cell biology 5 35285071
2005 Alterations of loci encoding PU.1, BOB1, and OCT2 transcription regulators do not correlate with their suppressed expression in Hodgkin lymphoma. Cancer genetics and cytogenetics 5 15796964
2001 Bob1, a Gim5/MM-1/Pfd5 homolog, interacts with the MAP kinase kinase Byr1 to regulate sexual differentiation in the fission yeast, Schizosaccharomyces pombe. Differentiation; research in biological diversity 4 11683500
2025 OCA-B promotes pathogenic maturation of stem-like CD4+ T cells and autoimmune demyelination. The Journal of clinical investigation 2 40299553
2017 High frequency of Bob1lo T follicular helper cells in florid reactive follicular hyperplasia. Immunology letters 2 28756244
2007 Bob-1 is expressed in classic Hodgkin lymphoma. Diagnostic pathology 2 17346351
2002 Cloning and characterization of the chick Oct binding factor OBF-1. Biochimica et biophysica acta 2 12359338
2025 Transcriptional co-regulator OCA-B/Pou2af1 restricts Th2 differentiation. Frontiers in immunology 1 40364837
2025 Optimal CXCR5 expression during Tfh maturation involves the Bhlhe40-Pou2af1 axis. Cell reports 1 41134666
2024 Transcriptional Coactivator BOB1 (OBF1, OCA-B) Modulates the Specificity of DNA Recognition by the POU-Domain Factors OCT1 and OCT2 in a Monomeric Configuration. Biomolecules 1 38254723
2024 Optimal CXCR5 Expression during Tfh Maturation Involves the Bhlhe40-Pou2af1 Axis. bioRxiv : the preprint server for biology 1 38903096
2026 Regulation of B cell development and lymphocyte function by transcriptional coactivator OCA-B. Frontiers in immunology 0 41939912

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