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Protein

PAX-interacting protein 1

Gene

Paxip1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in DNA damage response and in transcriptional regulation through histone methyltransferase (HMT) complexes such as the MLL2/MLL3 complex. 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. Together with Tp53bp1 regulates Atm association (By similarity). Proposed to recruit Pagr1 to sites of DNA damage and the Pagr1:Paxip1 complex is required for cell survival in response to DNA damage independently of the MLL2/MLL3 complex. However, this function has been questioned (PubMed:19124460, PubMed:26744420). 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 (By similarity). 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 (PubMed:20671152, PubMed:26744420).By similarity7 Publications

GO - Biological processi

  • adipose tissue development Source: UniProtKB
  • cellular response to DNA damage stimulus Source: MGI
  • chorion development Source: UniProtKB
  • DNA damage response, signal transduction by p53 class mediator Source: Ensembl
  • DNA recombination Source: UniProtKB-KW
  • DNA repair Source: UniProtKB-KW
  • endothelial cell migration Source: UniProtKB
  • histone H3-K4 methylation Source: Ensembl
  • positive regulation of histone acetylation Source: UniProtKB
  • positive regulation of histone H3-K36 methylation Source: UniProtKB
  • positive regulation of histone H3-K4 methylation Source: UniProtKB
  • positive regulation of isotype switching Source: UniProtKB
  • positive regulation of isotype switching to IgG isotypes Source: UniProtKB
  • positive regulation of protein ubiquitination Source: UniProtKB
  • positive regulation of response to DNA damage stimulus Source: UniProtKB
  • positive regulation of transcription initiation from RNA polymerase II promoter Source: UniProtKB
  • regulation of cell cycle G2/M phase transition Source: UniProtKB
  • response to ionizing radiation Source: Ensembl
  • transcription, DNA-templated Source: UniProtKB-KW
  • vasculogenesis Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

DNA damage, DNA recombination, DNA repair, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-MMU-5617472. Activation of anterior HOX genes in hindbrain development during early embryogenesis.
R-MMU-5693571. Nonhomologous End-Joining (NHEJ).

Names & Taxonomyi

Protein namesi
Recommended name:
PAX-interacting protein 1
Alternative name(s):
PAX transactivation activation domain-interacting protein
Gene namesi
Name:Paxip1
Synonyms:Ptip
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:1890430. Paxip1.

Subcellular locationi

GO - Cellular componenti

  • histone methyltransferase complex Source: MGI
  • nuclear matrix Source: UniProtKB-SubCell
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice are developmentally retarded, disorganized, and embryonic lethal by day 9.5 of embryonic development (E9.5). Mutant cells appear to replicate DNA but show reduced levels of mitosis and widespread cell death by E8.5. DNA damage appears to precede nuclear condensation at E7. Reduced levels of histone H3 methylated at 'Lys-4 in developing tissues.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 10561056PAX-interacting protein 1PRO_0000296263Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei223 – 2231PhosphoserineCombined sources
Modified residuei230 – 2301PhosphoserineCombined sources

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ6NZQ4.
MaxQBiQ6NZQ4.
PaxDbiQ6NZQ4.
PeptideAtlasiQ6NZQ4.
PRIDEiQ6NZQ4.

PTM databases

iPTMnetiQ6NZQ4.
PhosphoSiteiQ6NZQ4.

Expressioni

Tissue specificityi

Expression detected in all tissues examined, including brain stem, cerebellum, cortex, heart, spleen, kidney, liver, thymus and lung.1 Publication

Developmental stagei

Highly expressed in embryonic kidney and brain.1 Publication

Gene expression databases

BgeeiENSMUSG00000002221.
ExpressionAtlasiQ6NZQ4. baseline and differential.
GenevisibleiQ6NZQ4. MM.

Interactioni

Subunit structurei

Interacts with the C-terminal transactivation domain of PAX2 (By similarity). Forms a constitutive complex with PAGR1 independently of the MLL2/MLL3 complex. Interacts with TP53BP1 (phosphorylated at 'Ser-25'). Interacts with HLTF. 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 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
PAGR1Q9BTK65EBI-1395317,EBI-2372223From a different organism.
Pagr1aQ99L0211EBI-1395317,EBI-11667455
Pax2P321143EBI-1395317,EBI-1395232
Pax2P32114-22EBI-1395317,EBI-1395250
Pax5Q026503EBI-1395317,EBI-296260
TP53BP1Q128885EBI-1395317,EBI-396540From a different organism.

Protein-protein interaction databases

BioGridi207754. 3 interactions.
IntActiQ6NZQ4. 41 interactions.
MINTiMINT-4131297.
STRINGi10090.ENSMUSP00000002291.

Structurei

3D structure databases

ProteinModelPortaliQ6NZQ4.
SMRiQ6NZQ4. Positions 847-1056.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini8 – 9386BRCT 1PROSITE-ProRule annotationAdd
BLAST
Domaini94 – 18390BRCT 2PROSITE-ProRule annotationAdd
BLAST
Domaini588 – 68194BRCT 3PROSITE-ProRule annotationAdd
BLAST
Domaini688 – 77689BRCT 4PROSITE-ProRule annotationAdd
BLAST
Domaini853 – 93482BRCT 5PROSITE-ProRule annotationAdd
BLAST
Domaini955 – 98935BRCT 6PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni94 – 18390Interaction with PAGR12 PublicationsAdd
BLAST
Regioni577 – 1056480Interaction with TP53BP1By similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi655 – 67218Nuclear localization signalSequence analysisAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi189 – 1979Poly-Glu
Compositional biasi367 – 577211Gln-richAdd
BLAST

Domaini

The BRCT 1 and 2 domains mediate the interaction with PAGR1A.1 Publication
The BRCT 5 and 6 domains mediate the association with the MLL2/MLL3 complex (PubMed:26744420). 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.1 Publication

Sequence similaritiesi

Contains 6 BRCT domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG2043. Eukaryota.
ENOG410XSGS. LUCA.
GeneTreeiENSGT00600000084454.
HOGENOMiHOG000115463.
HOVERGENiHBG061191.
InParanoidiQ6NZQ4.
KOiK14972.
OMAiMEHKQNS.
OrthoDBiEOG091G0YK0.
PhylomeDBiQ6NZQ4.
TreeFamiTF329580.

Family and domain databases

Gene3Di3.40.50.10190. 4 hits.
InterProiIPR001357. BRCT_dom.
[Graphical view]
PfamiPF00533. BRCT. 1 hit.
PF12738. PTCB-BRCT. 2 hits.
PF16770. RTT107_BRCT_5. 1 hit.
[Graphical view]
SMARTiSM00292. BRCT. 6 hits.
[Graphical view]
SUPFAMiSSF52113. SSF52113. 5 hits.
PROSITEiPS50172. BRCT. 5 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q6NZQ4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSEPAPEVPE ELFREVKYYA VGDIDPQVIQ LLKAGKAKEV SYNALASHII
60 70 80 90 100
SEDGDNPEVG EAREVFDLPV VKPSWVTLSV QCGALLPVNG FSPESCQIFF
110 120 130 140 150
GLTACLSQVS SEDRSALWAL VTFHGGSCQL NLNKKCTHLI VPEPKGEKYE
160 170 180 190 200
RAVKRTSIKI VTPDWVLDCV SEKRRKDEAF YHPRLIIYEE EEEEEEEGDN
210 220 230 240 250
EEQDSQNEGS TEKSSVASSA VASPAEQPCS PKPRAEVSKG ELMFDDSSDS
260 270 280 290 300
SPEKQERSLN WAPAEAPPLN TAQRRLPQGK GPGLINLCAN VPPVPGDILP
310 320 330 340 350
PDMRGNLMAP GQNLQNSERS EILGTWSPAV RTLRNITNNA DIQQINRPSN
360 370 380 390 400
VAHILQSLSA PTKSLEQQVA RGQQGHPNAS AVLFGQAKGA PETHVLQQHH
410 420 430 440 450
PPQQPQQQHP ALHLQPQIMQ LQQQQQQQQQ QQQQPQPYPQ PPSHQFPQQV
460 470 480 490 500
HQHQFSQQQL QFPQQPLHPQ QQLHRPQQQL QPFQQQHALQ QQLHQLQQQQ
510 520 530 540 550
LQHHQLAQLQ QQQQQQHNLL QQQQQQQQLQ RLQQQQQMQN QAAHLSQASQ
560 570 580 590 600
ALQHQVLPQQ PLQLSLQPPP QQQQQQQLFG HDPAVEIPEE SFLLGCVFAI
610 620 630 640 650
ADYPEQMSDK QLLATWKRII QAHGGTVDPT FTSRCTHLLC ASQVSSMYTQ
660 670 680 690 700
ALRERKRCVT AHWLNTVLKK KKLMPPHRAL HFPVAFPPGG KPCSQHIISV
710 720 730 740 750
TGFVDNDRDD LKLMAYLAGA KYTGYLCRSN TVLICKEPSG LKYEKAKEWR
760 770 780 790 800
IPCVNAQWLG DILLGNFEAL RQVQYSRYTA FNMPDPFVPT PHLVLGLLDA
810 820 830 840 850
WRTPVKVTAE LLMGVRLPPK LKPNEVANIQ PSSKRARIED LPPPTKKLTP
860 870 880 890 900
ELTPLVLFTG FEPVQVQQYI KKLYILGGEV AECTKKCTHL IASKVTRTVK
910 920 930 940 950
FLTAISVVKH IVTPDWLEEC FKRQTFIDEQ NYILRDAEAE VLFSFSLEES
960 970 980 990 1000
LKRAHVSPLF KTKYFYITPG ICPSLATMKA IVECAGGKVL AKQPSFRKLM
1010 1020 1030 1040 1050
EHKQNKSLSE IILISCENDL HLCREYFARG IDVHNAEFVL TGVLTQTLDY

ESYKFN
Length:1,056
Mass (Da):119,269
Last modified:July 5, 2004 - v1
Checksum:i86762841515A07AB
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF104261 mRNA. Translation: AAD17923.1.
AK144606 mRNA. Translation: BAE25965.1.
BC066014 mRNA. Translation: AAH66014.1.
CCDSiCCDS39039.1.
RefSeqiNP_061366.2. NM_018878.3.
UniGeneiMm.277190.
Mm.444095.

Genome annotation databases

EnsembliENSMUST00000002291; ENSMUSP00000002291; ENSMUSG00000002221.
GeneIDi55982.
KEGGimmu:55982.
UCSCiuc033iid.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF104261 mRNA. Translation: AAD17923.1.
AK144606 mRNA. Translation: BAE25965.1.
BC066014 mRNA. Translation: AAH66014.1.
CCDSiCCDS39039.1.
RefSeqiNP_061366.2. NM_018878.3.
UniGeneiMm.277190.
Mm.444095.

3D structure databases

ProteinModelPortaliQ6NZQ4.
SMRiQ6NZQ4. Positions 847-1056.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi207754. 3 interactions.
IntActiQ6NZQ4. 41 interactions.
MINTiMINT-4131297.
STRINGi10090.ENSMUSP00000002291.

PTM databases

iPTMnetiQ6NZQ4.
PhosphoSiteiQ6NZQ4.

Proteomic databases

EPDiQ6NZQ4.
MaxQBiQ6NZQ4.
PaxDbiQ6NZQ4.
PeptideAtlasiQ6NZQ4.
PRIDEiQ6NZQ4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000002291; ENSMUSP00000002291; ENSMUSG00000002221.
GeneIDi55982.
KEGGimmu:55982.
UCSCiuc033iid.1. mouse.

Organism-specific databases

CTDi22976.
MGIiMGI:1890430. Paxip1.

Phylogenomic databases

eggNOGiKOG2043. Eukaryota.
ENOG410XSGS. LUCA.
GeneTreeiENSGT00600000084454.
HOGENOMiHOG000115463.
HOVERGENiHBG061191.
InParanoidiQ6NZQ4.
KOiK14972.
OMAiMEHKQNS.
OrthoDBiEOG091G0YK0.
PhylomeDBiQ6NZQ4.
TreeFamiTF329580.

Enzyme and pathway databases

ReactomeiR-MMU-5617472. Activation of anterior HOX genes in hindbrain development during early embryogenesis.
R-MMU-5693571. Nonhomologous End-Joining (NHEJ).

Miscellaneous databases

ChiTaRSiPaxip1. mouse.
PROiQ6NZQ4.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000002221.
ExpressionAtlasiQ6NZQ4. baseline and differential.
GenevisibleiQ6NZQ4. MM.

Family and domain databases

Gene3Di3.40.50.10190. 4 hits.
InterProiIPR001357. BRCT_dom.
[Graphical view]
PfamiPF00533. BRCT. 1 hit.
PF12738. PTCB-BRCT. 2 hits.
PF16770. RTT107_BRCT_5. 1 hit.
[Graphical view]
SMARTiSM00292. BRCT. 6 hits.
[Graphical view]
SUPFAMiSSF52113. SSF52113. 5 hits.
PROSITEiPS50172. BRCT. 5 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPAXI1_MOUSE
AccessioniPrimary (citable) accession number: Q6NZQ4
Secondary accession number(s): Q9Z0W6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 24, 2007
Last sequence update: July 5, 2004
Last modified: September 7, 2016
This is version 116 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.