PAXI1_BOVIN
ID PAXI1_BOVIN Reviewed; 984 AA.
AC A0JNA8;
DT 24-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 12-DEC-2006, sequence version 1.
DT 03-AUG-2022, entry version 92.
DE RecName: Full=PAX-interacting protein 1;
DE AltName: Full=PAX transactivation activation domain-interacting protein;
GN Name=PAXIP1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Fetal liver;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Involved in DNA damage response and in transcriptional
CC regulation through histone methyltransferase (HMT) complexes. Plays a
CC role in early development. In DNA damage response is required for cell
CC survival after ionizing radiation. In vitro shown to be involved in the
CC homologous recombination mechanism for the repair of double-strand
CC breaks (DSBs). Its localization to DNA damage foci requires RNF8 and
CC UBE2N. Recruits TP53BP1 to DNA damage foci and, at least in particular
CC repair processes, effective DNA damage response appears to require the
CC association with TP53BP1 phosphorylated by ATM at 'Ser-25'. Together
CC with TP53BP1 regulates ATM association. Proposed to recruit PAGR1 to
CC sites of DNA damage and the PAGR1:PAXIP1 complex is required for cell
CC survival in response to DNA damage; the function is probably
CC independent of MLL-containing histone methyltransferase (HMT)
CC complexes. However, this function has been questioned (By similarity).
CC Promotes ubiquitination of PCNA following UV irradiation and may
CC regulate recruitment of polymerase eta and RAD51 to chromatin after DNA
CC damage. Proposed to be involved in transcriptional regulation by
CC linking MLL-containing histone methyltransferase (HMT) complexes to
CC gene promoters by interacting with promoter-bound transcription factors
CC such as PAX2. Associates with gene promoters that are known to be
CC regulated by KMT2D/MLL2. During immunoglobulin class switching in
CC activated B-cells is involved in trimethylation of histone H3 at 'Lys-
CC 4' and in transcription initiation of downstream switch regions at the
CC immunoglobulin heavy-chain (Igh) locus; this function appears to
CC involve the recruitment of MLL-containing HMT complexes. Conflictingly,
CC its function in transcriptional regulation during immunoglobulin class
CC switching is reported to be independent of the MLL2/MLL3 complex (By
CC similarity). {ECO:0000250|UniProtKB:Q6NZQ4,
CC ECO:0000250|UniProtKB:Q6ZW49}.
CC -!- SUBUNIT: Interacts with the C-terminal transactivation domain of PAX2
CC (By similarity). Forms a constitutive complex with PAGR1 independently
CC of the MLL2/MLL3 complex. Interacts with TP53BP1 (when phosphorylated
CC at the N-terminus by ATM). Interacts with HLTF. Component of the KMT2
CC family MLL2/MLL3 complex (also named ASCOM complex), at least composed
CC of the HMTs KMT2D and/or KMT2C, the common subunits ASH2L, RBBP5, WDR5
CC and DPY30, and the complex type-specific subunits PAXIP1/PTIP, PAGR1,
CC NCOA6 and KDM6A; required for the association of PAGR1 with the
CC MLL2/MLL3 complex (By similarity). Interacts with NUPR1; this
CC interaction prevents PAXIP1 inhibition of PAX2 transcription factor
CC activity (By similarity). {ECO:0000250|UniProtKB:Q6NZQ4,
CC ECO:0000250|UniProtKB:Q6ZW49}.
CC -!- SUBCELLULAR LOCATION: Nucleus matrix {ECO:0000250|UniProtKB:Q6NZQ4}.
CC Chromosome {ECO:0000250|UniProtKB:Q6ZW49}. Note=Localizes to DNA damage
CC foci upon ionizing radiation. {ECO:0000250|UniProtKB:Q6ZW49}.
CC -!- DOMAIN: The BRCT 1 and 2 domains mediate the interaction with PAGR1A.
CC {ECO:0000250|UniProtKB:Q6NZQ4}.
CC -!- DOMAIN: The BRCT 5 and 6 domains mediate the association with the
CC MLL2/MLL3 complex (By similarity). The BRCT 5 and 6 domains function as
CC a single module and are necessary and sufficient for in vitro phospho-
CC specific binding (substrates phosphorylated by the kinases ataxia
CC telangiectasia-mutated (ATM), ataxia telangiectasia and RAD3-related
CC (ATR) in response to gamma irradiation). In contrast, in vivo two pairs
CC of BRCT domains (3-6) bind to phosphorylated TP53BP1 much more
CC efficiently. {ECO:0000250|UniProtKB:Q6NZQ4}.
CC -!- CAUTION: The terminology of MLL proteins in mammalia is not consistent
CC also concerning the terminology of MLL protein-containing complexes.
CC The decribed MLL2/MLL3 complex is commonly described as MLL3/MLL4
CC complex in literature. {ECO:0000305}.
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DR EMBL; BC126589; AAI26590.1; -; mRNA.
DR RefSeq; NP_001071385.1; NM_001077917.1.
DR AlphaFoldDB; A0JNA8; -.
DR SMR; A0JNA8; -.
DR STRING; 9913.ENSBTAP00000055051; -.
DR PaxDb; A0JNA8; -.
DR PRIDE; A0JNA8; -.
DR Ensembl; ENSBTAT00000023287; ENSBTAP00000023287; ENSBTAG00000017505.
DR GeneID; 513213; -.
DR KEGG; bta:513213; -.
DR CTD; 22976; -.
DR VEuPathDB; HostDB:ENSBTAG00000017505; -.
DR VGNC; VGNC:32602; PAXIP1.
DR eggNOG; KOG2043; Eukaryota.
DR GeneTree; ENSGT00940000155757; -.
DR HOGENOM; CLU_009382_0_0_1; -.
DR InParanoid; A0JNA8; -.
DR OrthoDB; 840249at2759; -.
DR Proteomes; UP000009136; Chromosome 4.
DR Bgee; ENSBTAG00000017505; Expressed in oocyte and 104 other tissues.
DR ExpressionAtlas; A0JNA8; baseline and differential.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0044666; C:MLL3/4 complex; IBA:GO_Central.
DR GO; GO:0016363; C:nuclear matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0006310; P:DNA recombination; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0051568; P:histone H3-K4 methylation; IBA:GO_Central.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0060261; P:positive regulation of transcription initiation from RNA polymerase II promoter; IBA:GO_Central.
DR Gene3D; 3.40.50.10190; -; 5.
DR InterPro; IPR001357; BRCT_dom.
DR InterPro; IPR036420; BRCT_dom_sf.
DR InterPro; IPR037886; Paxip1.
DR PANTHER; PTHR23196:SF31; PTHR23196:SF31; 2.
DR Pfam; PF00533; BRCT; 1.
DR Pfam; PF12738; PTCB-BRCT; 2.
DR Pfam; PF16770; RTT107_BRCT_5; 1.
DR SMART; SM00292; BRCT; 6.
DR SUPFAM; SSF52113; SSF52113; 5.
DR PROSITE; PS50172; BRCT; 5.
PE 2: Evidence at transcript level;
KW Chromosome; DNA damage; DNA recombination; DNA repair; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Transcription;
KW Transcription regulation.
FT CHAIN 1..984
FT /note="PAX-interacting protein 1"
FT /id="PRO_0000296261"
FT DOMAIN 8..93
FT /note="BRCT 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 94..183
FT /note="BRCT 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 516..609
FT /note="BRCT 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 616..704
FT /note="BRCT 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 781..862
FT /note="BRCT 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 883..924
FT /note="BRCT 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT REGION 94..183
FT /note="Interaction with PAGR1"
FT /evidence="ECO:0000250"
FT REGION 187..271
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 417..509
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 505..984
FT /note="Interaction with TP53BP1"
FT /evidence="ECO:0000250"
FT REGION 750..771
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 583..600
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 189..205
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 207..236
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 243..258
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 422..453
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 454..481
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 482..504
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 227
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6NZQ4"
FT MOD_RES 235
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6ZW49"
SQ SEQUENCE 984 AA; 109167 MW; 2ECFB31F6F7A2A7E CRC64;
MSGQVPRVPE EMFKEVKYYA VGDLDPQVIQ LLKAGKAKEV SYNALASHII SEDGDNPEVG
EAREVFDLPV VKPSWVILSV QCGALLPVNG FSPESCQIFF GITACLSQVS PEDRSALWAM
LTFHGGGCQL NLNRKCTHLV VPEPKGEKYE CALRRASIKI VTPDWVLDCI SEKTRKDEAL
YHPRLIVYEE EEEEEEEEEG AGNEEPDSPN EGSTDGKSSP ASSQEGSPSG EPPFSPKSSA
EKSKGELMFD DSSDSSPEKQ ERNLNWTPAE VPQLAAAKRR LPPGKEPGLI NLCANVPPVP
GGILPPEVRG SLLAPGQSLQ GPERPEVMAA WSPAMRTLRN ITNNADIQQM SSRPSNVAHI
LQSLSAPTKT LEQQVNHSQQ GPASAVLLGQ VKVAPEPAPA PQPILHLQPQ QLLQLQQQHL
AQQPYPPPPP HPFPPPPAHP HQFPQPPLQR PQPPLQQQQL SHLQQQQLQH LQRLQQMQPT
PTAQLPGPPA QALQPPPPQA QAQPPLFGHD PAVEIPEEGF LLGCVFAIAD YPEQMSDKQL
LATWKRIIQA HGGAVDPTFS SRCTHLLCES QVSGLFAQAM KERKRCITAH WLNTVLKKKK
LVPPHRALHF PVAFPPGGKP CSQHIISVTG FVDNDRDDLK LMAYLAGAKY TGYLCRSNTV
LICREPTGLK YEKAKEWRIP CVNAQWLGDI LLGNFEALRQ TQYGRYTAFG LQDPFAPTPQ
LVLSLLDAWR VPLKVSSELL MGVRLPPKPK QNEVTNVQPS SKRARIEDIP PPTKKLTPEL
TPFVLFTGFE PVQVQQYIKK LYILGGEVAE SAQKCTHLIA SKVTRTVKFL TAISVVKHIV
TPEWLEECFK CQKFVDEQNY LLRDAEAEVL FSFSLEESLR RAHASPLFKA KYFYITPGIC
PSLSTMKAIV ECAGGKVLSR QPSFRKLMEH KQNKSLSEIV LISCENDLHL CREYFARGID
VHNAEFVLTG VLTQTLDYES YKFN
