# A Newly Characterized, Two BRCT Domain-Containing Isoform of PAX-Interacting Protein (PTIP) Generated via Frame Shift and Alternative Pre-mRNA Splicing

**Authors:** Ching-Jung Huang, Chuan Li, Danyang Yu, Hyein Cho, Kangsan Kim, Y. Jessie Zhang, Daechan Park, Haley O. Tucker

PMC · DOI: 10.33696/signaling.6.143 · Journal of cellular signaling · 2026-01-31

## TL;DR

Researchers discovered a new, shorter version of the PTIP protein that affects B and T cell development in mice.

## Contribution

A novel PTIP isoform, PTIP576, is identified through a unique frameshift and splicing mechanism.

## Key findings

- PTIP576 is expressed in progenitor and activated mature B lymphocytes.
- Overexpression of PTIP576 increases bone marrow B cells and thymocyte CD4 T cells.
- PTIP576 retains only the BRCT domains and has a unique disordered C-terminus.

## Abstract

In an effort to clone polyglutamine-rich factors from activated B lymphocytes of mice, we discovered and describe here a previously uncharacterized isoform of PTIP/PAXIP1. By virtue of a two-nucleotide frameshift followed by alternative pre-mRNA splicing, this shorter isoform of 576 amino acids (termed PTIP576) retained only the two central BRCT domains of previously characterized PTIP and encodes a unique and structurally disordered 50 residue C-terminus. PTIP576 is expressed primarily in nuclei of progenitor and activated mature B lymphocytes. Transgenic overexpression of PTIP576 in murine B and T cells led to increased lineages of bone marrow B cells and thymocyte CD4 T cells. We conclude by addressing potential functions of PTIP576 resulting from the relatively unique mechanism by which it is engendered.

## Linked entities

- **Genes:** PAXIP1 (PAX interacting protein 1) [NCBI Gene 22976], PAXIP1 (PAX interacting protein 1) [NCBI Gene 22976]
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Trav6-3 (T cell receptor alpha variable 6-3) [NCBI Gene 328483] {aka Gm13948, Gm193, Gm4, TCR}, Ighd (immunoglobulin heavy constant delta) [NCBI Gene 380797] {aka IgD, Igh-5}, Kit (Kit proto-oncogene receptor tyrosine kinase) [NCBI Gene 16590] {aka Bs, CD117, Fdc, Gsfsco1, Gsfsco5, Gsfsow3}, Itgam (integrin alpha M) [NCBI Gene 16409] {aka CD11b/CD18, CR3, CR3A, Cd11b, F730045J24Rik, Ly-40}, Tlr4 (toll-like receptor 4) [NCBI Gene 21898] {aka Lps, Ly87, Ran/M1, Rasl2-8}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, Wt1 (WT1 transcription factor) [NCBI Gene 22431] {aka D630046I19Rik, Wt-1}, Cd3e (CD3 antigen, epsilon polypeptide) [NCBI Gene 12501] {aka CD3, CD3epsilon, T3e}, Ptprc (protein tyrosine phosphatase receptor type C) [NCBI Gene 19264] {aka B220, CD45R, Cd45, L-CA, Ly-5, Lyt-4}, Brca1 (breast cancer 1, early onset) [NCBI Gene 12189], Ccr5 (C-C motif chemokine receptor 5) [NCBI Gene 12774] {aka AM4-7, CD195, Cmkbr5}, Actb (actin, beta) [NCBI Gene 11461] {aka Actx, E430023M04Rik, beta-actin}, Il2ra (interleukin 2 receptor, alpha chain) [NCBI Gene 16184] {aka CD25, Il2r, Ly-43}, Ighm (immunoglobulin heavy constant mu) [NCBI Gene 16019] {aka Igh-6, Igh-M, Igh6, Igm, TC1460681, muH}, Sdc1 (syndecan 1) [NCBI Gene 20969] {aka CD138, Sstn, Synd, Synd1, syn-1}, Bcr (BCR activator of RhoGEF and GTPase) [NCBI Gene 110279] {aka 5133400C09Rik, mKIAA3017}, Paxip1 (PAX interacting (with transcription-activation domain) protein 1) [NCBI Gene 55982] {aka D5Ertd149e, PTIP}, PAXIP1 (PAX interacting protein 1) [NCBI Gene 22976] {aka CAGF28, CAGF29, PACIP1, PAXIP1L, PTIP, TNRC2}, Igkv4-74 (immunoglobulin kappa variable 4-74) [NCBI Gene 236047] {aka Gm10880, Gm192, IgVkai4}, Il5 (interleukin 5) [NCBI Gene 16191] {aka Il-5}, Ccnd1 (cyclin D1) [NCBI Gene 12443] {aka CycD1, Cyl-1, PRAD1, bcl-1, cD1}, Cacna1b (calcium channel, voltage-dependent, N type, alpha 1B subunit) [NCBI Gene 12287] {aka BIII, Cav2.2, Cchn1a, alpha(1B)}, Ldlr (low density lipoprotein receptor) [NCBI Gene 16835] {aka Hlb301}, Cd8a (CD8 subunit alpha) [NCBI Gene 12525] {aka Ly-2, Ly-35, Ly-B, Lyt-2}, Igh (immunoglobulin heavy chain complex) [NCBI Gene 111507], Meis1 (Meis homeobox 1) [NCBI Gene 17268] {aka C530044H18Rik, Evi8}, Spn (sialophorin) [NCBI Gene 20737] {aka A630014B01Rik, Cd43, Galgp, Ly-48, Ly48}, Il7 (interleukin 7) [NCBI Gene 16196] {aka A630026I06Rik, Il-7, hlb368}, Nr3c2 (nuclear receptor subfamily 3, group C, member 2) [NCBI Gene 110784] {aka MR, Mlr}, Tril (TLR4 interactor with leucine-rich repeats) [NCBI Gene 66873] {aka 1200009O22Rik, mKIAA0644}, Il2 (interleukin 2) [NCBI Gene 16183] {aka Il-2}, Cd79a (CD79A antigen (immunoglobulin-associated alpha)) [NCBI Gene 12518] {aka Ig-alpha, Iga, Igalpha, Ly-54, Ly54, mb-1}, Cd19 (CD19 antigen) [NCBI Gene 12478]
- **Diseases:** Hypertrophic Cardiomyopathy (MESH:D002312), inflammation (MESH:D007249), immunodeficiency (MESH:D007153), Hereditary Polyneuropathy (MESH:D009386), Charcot-Marie-Tooth Disease (MESH:D002607), Cystic Fibrosis (MESH:D003550), B cell leukemia (MESH:D015448), salt wasting (MESH:D013651), genetic disease disorders (MESH:D030342), cancer (MESH:D009369), HIV resistance (MESH:D015658), leukemic (MESH:D007938), B (MESH:D006509), Tay-Sachs Disease (MESH:D013661), Crohn's (MESH:D003424)
- **Chemicals:** NaCl (MESH:D012965), agar (MESH:D000362), phenol (MESH:D019800), FITC (MESH:D016650), sodium azide (MESH:D019810), chloroform (MESH:D002725), guanidinium thiocyanate (MESH:C054436), EDTA (MESH:D004492), SM (MESH:D012493), glutamine (MESH:D005973), NaAc (-), MgSO4 (MESH:D008278), azide (MESH:D001386), HCl (MESH:D006851), DSP (MESH:C018279), agarose (MESH:D012685), PC (MESH:D010767), ampicillin (MESH:D000667), SDS (MESH:D012967), cesium (MESH:D002586), formaldehyde (MESH:D005557)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090], Escherichia coli (E. coli, species) [taxon 562]
- **Mutations:** C for 15-20, C57A, Phe-Glu, 12 glutamine (CAG)
- **Cell lines:** XL1-Blue — Homo sapiens (Human), Burkitt lymphoma, Cancer cell line (CVCL_1967), C57BL/6 — Mus musculus (Mouse), Transformed cell line (CVCL_C0MU), CH12 — Mus musculus (Mouse), Mouse lymphoma, Cancer cell line (CVCL_6818), M12 — Mus musculus (Mouse), Mouse lymphoma, Cancer cell line (CVCL_IU99)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12857844/full.md

## References

44 references — full list in the complete paper: https://tomesphere.com/paper/PMC12857844/full.md

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Source: https://tomesphere.com/paper/PMC12857844