UniProt:Q6ZW49 PAXIP1

chain
  • chain:1-1069
checksum 78CD535A150E1FC1
comment
  • 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. Proposed to recruit PAGR1 to sites of DNA damage and the PAGR1:PAXIP1 complex is required for cell survival in response to DNA damage; the function is probably independent of MLL-containing histone methyltransferase (HMT) complexes. However, this function has been questioned (By similarity). 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 KMT2D/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. Conflictingly, its function in transcriptional regulation during immunoglobulin class switching is reported to be independent of the MLL2/MLL3 complex (By similarity).SUBUNIT Interacts with the C-terminal transactivation domain of PAX2 (By similarity). Forms a constitutive complex with PAGR1 independently of the MLL2/MLL3 complex (By similarity). Interacts with TP53BP1 (when phosphorylated at the N-terminus by ATM) (PubMed:15456759, PubMed:17690115, PubMed:23727112). Interacts with HLTF (PubMed:19723507). Component of the KMT2 family MLL2/MLL3 complex (also named ASCOM complex), at least composed of the HMTs KMT2D and/or KMT2C, the common subunits ASH2L, RBBP5, WDR5 and DPY30, and the complex type-specific subunits PAXIP1/PTIP, PAGR1, NCOA6 and KDM6A; required for the association of PAGR1 with the MLL2/MLL3 complex (PubMed:17178841, PubMed:17500065, PubMed:17761849, PubMed:17925232). Interacts with NUPR1; this interaction prevents PAXIP1 inhibition of PAX2 transcription factor activity (PubMed:11940591).INTERACTION Localizes to DNA damage foci upon ionizing radiation.ALTERNATIVE PRODUCTS The BRCT 1 and 2 domains mediate the interaction with PAGR1A.DOMAIN The BRCT 5 and 6 domains mediate the association with the MLL2/MLL3 complex (By similarity). 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.CAUTION The terminology of MLL proteins in mammalia is not consistent also concerning the terminology of MLL protein-containing complexes. The decribed MLL2/MLL3 complex is commonly described as MLL3/MLL4 complex in literature.SEQUENCE CAUTION Truncated N-terminus.SEQUENCE CAUTION Contaminating sequence.SEQUENCE CAUTION Intron retention.
created [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53
crossReference
databaseName UniProt
dbId 241743
description
  • recommendedName: PAX-interacting protein 1 alternativeName: PAX transactivation activation domain-interacting protein
displayName UniProt:Q6ZW49 PAXIP1
geneName
  • PAXIP1
  • PAXIP1L
  • PTIP
  • CAGF28
identifier Q6ZW49
isSequenceChanged false
keyword
  • 3D-structure
  • Alternative splicing
  • Chromosome
  • DNA damage
  • DNA recombination
  • DNA repair
  • Nucleus
  • Phosphoprotein
  • Proteomics identification
  • Reference proteome
  • Repeat
  • Transcription
  • Transcription regulation
modified [InstanceEdit:9926675] Weiser, Joel, 2024-11-03
moleculeType Protein
name
  • PAXIP1
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • PAXI1_HUMAN
  • O15404
  • Q6N099
  • Q6ZWH9
  • Q7Z315
  • Q86UN0
  • Q8N4P9
  • Q96HP2
sequenceLength 1069
species [Species:48887] Homo sapiens
stId uniprot:Q6ZW49
url http://purl.uniprot.org/uniprot/Q6ZW49
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