ID:PAXI1_HUMAN DESCRIPTION: RecName: Full=PAX-interacting protein 1; AltName: Full=PAX transactivation activation domain-interacting protein; FUNCTION: Involved in DNA damage response and in transcriptional regulation through histone methyltransferase (HMT) complexes. Plays a role in early development. In DNA damage response is required for cell survival after ionizing radiation. In vitro shown to be involved in the homologous recombination mechanism for the repair of double-strand breaks (DSBs). Its localization to DNA damage foci requires RNF8 and UBE2N. Recruits TP53BP1 to DNA damage foci and, at least in particular repair processes, effective DNA damage response appears to require the association with TP53BP1 phosphorylated by ATM at 'Ser-25'. Together with TP53BP1 regulates ATM association. Recruits PAGR1 to sites of DNA damage and the PAGR1:PAXIP1 complex is required for cell survival in response to DNA damage; the function is probbaly independent of MLL-containing histone methyltransferase (HMT) complexes. Promotes ubiquitination of PCNA following UV irradiation and may regulate recruitment of polymerase eta and RAD51 to chromatin after DNA damage. Proposed to be involved in transcriptional regulation by linking MLL-containing histone methyltransferase (HMT) complexes to gene promoters by interacting with promoter-bound transcription factors such as PAX2. Associates with gene promoters that are known to be regulated by MLL2. During immunoglobulin class switching in activated B-cells is involved in trimethylation of histone H3 at 'Lys-4' and in transcription initiation of downstream switch regions at the immunoglobulin heavy-chain (Igh) locus; this function appears to involve the recruitment of MLL- containing HMT complexes. SUBUNIT: Interacts with the C-terminal transactivation domain of PAX2 (By similarity). Interacts with PAGR1; the interaction is direct and also occurs independent of MLL-containing complexes. Interacts with TP53BP1 (phosphorylated at 'Ser-25'). Interacts with HLTF. Component of the MLL2/3 complex (also named ASCOM complex), at least composed of MLL2/ALR or MLL3, ASH2L, RBBP5, WDR5, NCOA6, DPY30, KDM6A, PAXIP1/PTIP, PAGR1 and alpha- and beta- tubulin. INTERACTION: Q9BTK6:PA1; NbExp=5; IntAct=EBI-743225, EBI-2372223; Q12888:TP53BP1; NbExp=4; IntAct=EBI-743225, EBI-396540; SUBCELLULAR LOCATION: Nucleus matrix (By similarity). Note=Localizes to DNA damage foci upon ionizing radiation. DOMAIN: The BRCT 5 and 6 domains function as a single module and are necessary and sufficient for in vitro phospho-specific binding (substrates phosphorylated by the kinases ataxia telangiectasia- mutated (ATM), ataxia telangiectasia and RAD3-related (ATR) in response to gamma irradiation). In contrast, in vivo two pairs of BRCT domains (3-6) bind to phosphorylated TP53BP1 much more efficiently. SIMILARITY: Contains 6 BRCT domains. SEQUENCE CAUTION: Sequence=AAB91434.1; Type=Frameshift; Positions=643, 662; Sequence=AAH33781.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=AAH33781.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence; Sequence=AAP21865.1; Type=Erroneous gene model prediction; Sequence=BAC85523.1; Type=Miscellaneous discrepancy; Note=Intron retention;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q6ZW49
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000416 positive regulation of histone H3-K36 methylation GO:0001570 vasculogenesis GO:0006281 DNA repair GO:0006303 double-strand break repair via nonhomologous end joining GO:0006310 DNA recombination GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006974 cellular response to DNA damage stimulus GO:0010212 response to ionizing radiation GO:0030330 DNA damage response, signal transduction by p53 class mediator GO:0031398 positive regulation of protein ubiquitination GO:0035066 positive regulation of histone acetylation GO:0043542 endothelial cell migration GO:0045830 positive regulation of isotype switching GO:0048304 positive regulation of isotype switching to IgG isotypes GO:0051568 histone H3-K4 methylation GO:0051571 positive regulation of histone H3-K4 methylation GO:0060261 positive regulation of transcription initiation from RNA polymerase II promoter GO:0060612 adipose tissue development GO:0060717 chorion development GO:1902749 regulation of cell cycle G2/M phase transition GO:2001022 positive regulation of response to DNA damage stimulus
AK126674 - Homo sapiens cDNA FLJ44719 fis, clone BRACE3022303, highly similar to Homo sapiens PAX interacting (with transcription-activation domain) protein 1 (PAXIP1), mRNA. BX538201 - Homo sapiens mRNA; cDNA DKFZp686O11215 (from clone DKFZp686O11215). BC033781 - Homo sapiens PAX interacting (with transcription-activation domain) protein 1, mRNA (cDNA clone MGC:45592 IMAGE:4509264), complete cds. U80735 - Homo sapiens CAGF28 mRNA, partial cds. AK093584 - Homo sapiens cDNA FLJ36265 fis, clone THYMU2002841, highly similar to Mus musculus Pax transcription activation domain interacting protein PTIP mRNA. AX748215 - Sequence 1740 from Patent EP1308459. AK123600 - Homo sapiens cDNA FLJ41606 fis, clone CTONG3001123, highly similar to Mus musculus Pax transcription activation domain interacting protein PTIP mRNA. BX640616 - Homo sapiens mRNA; cDNA DKFZp686E06126 (from clone DKFZp686E06126). AK293744 - Homo sapiens cDNA FLJ58501 complete cds, highly similar to Homo sapiens PAX interacting (with transcription-activation domain) protein 1 (PAXIP1), mRNA. BC008328 - Homo sapiens PAX interacting (with transcription-activation domain) protein 1, mRNA (cDNA clone IMAGE:3503689), partial cds. JD555892 - Sequence 536916 from Patent EP1572962. JD541850 - Sequence 522874 from Patent EP1572962. JD543900 - Sequence 524924 from Patent EP1572962. JD368813 - Sequence 349837 from Patent EP1572962. JD463919 - Sequence 444943 from Patent EP1572962. JD251036 - Sequence 232060 from Patent EP1572962. JD048034 - Sequence 29058 from Patent EP1572962. JD510774 - Sequence 491798 from Patent EP1572962. JD113583 - Sequence 94607 from Patent EP1572962. JD066599 - Sequence 47623 from Patent EP1572962. JD292983 - Sequence 274007 from Patent EP1572962. JD534273 - Sequence 515297 from Patent EP1572962. JD206197 - Sequence 187221 from Patent EP1572962. JD156340 - Sequence 137364 from Patent EP1572962. JD509703 - Sequence 490727 from Patent EP1572962. JD091583 - Sequence 72607 from Patent EP1572962. JD137669 - Sequence 118693 from Patent EP1572962. JD140013 - Sequence 121037 from Patent EP1572962. JD553755 - Sequence 534779 from Patent EP1572962. JD549637 - Sequence 530661 from Patent EP1572962. JD554643 - Sequence 535667 from Patent EP1572962. JD162841 - Sequence 143865 from Patent EP1572962. JD375503 - Sequence 356527 from Patent EP1572962. AK307417 - Homo sapiens cDNA, FLJ97365. AK123044 - Homo sapiens cDNA FLJ41049 fis, clone PROST2008993, moderately similar to Mus musculus Pax transcription activation domain interacting protein PTIP mRNA.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q6ZW49 (Reactome details) participates in the following event(s):
R-HSA-5686685 RIF1 and PAX1IP bind TP53BP1 at DNA DSBs R-HSA-5693599 Association of Ku heterodimer with ends of DNA double-strand break R-HSA-5686900 TP53BP1 recruits DCLRE1C to ATM R-HSA-5686704 Activated ATM phosphorylates DCLRE1C R-HSA-5693571 Nonhomologous End-Joining (NHEJ) R-HSA-5617472 Activation of anterior HOX genes in hindbrain development during early embryogenesis R-HSA-5693532 DNA Double-Strand Break Repair R-HSA-5619507 Activation of HOX genes during differentiation R-HSA-73894 DNA Repair R-HSA-1266738 Developmental Biology
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
