Q6NZQ4 (PAXI1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
PAX-interacting protein 1

Alternative name(s):
PAX transactivation activation domain-interacting protein

Gene names

Name:	Paxip1
Synonyms:	Ptip

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1056 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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. 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 By similarity. Ref.1 Ref.4 Ref.5 Ref.6 Ref.7 Ref.8
Subunit structure	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 By similarity. Ref.1 Ref.6
Subcellular location	Nucleus matrix Ref.1 Ref.6.
Tissue specificity	Expression detected in all tissues examined, including brain stem, cerebellum, cortex, heart, spleen, kidney, liver, thymus and lung.,. Ref.1
Developmental stage	Highly expressed in embryonic kidney and brain. Ref.1
Disruption phenotype	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. Ref.4 Ref.5
Sequence similarities	Contains 6 BRCT domains.

Ontologies

Keywords
Biological process	DNA damage DNA recombination DNA repair Transcription Transcription regulation
Cellular component	Nucleus
Domain	Repeat
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA damage response, signal transduction by p53 class mediator Inferred from electronic annotation. Source: Compara DNA recombination Inferred from electronic annotation. Source: UniProtKB-KW DNA repair Inferred from electronic annotation. Source: UniProtKB-KW adipose tissue development Inferred from mutant phenotype PubMed 19583951. Source: UniProtKB chorion development Inferred from mutant phenotype PubMed 18710940. Source: UniProtKB endothelial cell migration Inferred from mutant phenotype PubMed 18710940. Source: UniProtKB histone H3-K4 methylation Inferred from electronic annotation. Source: Compara positive regulation of histone H3-K36 methylation Inferred from mutant phenotype Ref.8. Source: UniProtKB positive regulation of histone H3-K4 methylation Inferred from mutant phenotype PubMed 19583951Ref.8. Source: UniProtKB positive regulation of histone acetylation Inferred from mutant phenotype Ref.8. Source: UniProtKB positive regulation of isotype switching Inferred from mutant phenotype Ref.8. Source: UniProtKB positive regulation of protein ubiquitination Inferred from mutant phenotype PubMed 18353733. Source: UniProtKB positive regulation of transcription initiation from RNA polymerase II promoter Inferred from mutant phenotype PubMed 19583951Ref.8. Source: UniProtKB response to DNA damage stimulus Inferred from direct assay PubMed 17500065. Source: MGI response to ionizing radiation Inferred from electronic annotation. Source: Compara transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW vasculogenesis Inferred from mutant phenotype PubMed 18710940. Source: UniProtKB
Cellular_component	histone methyltransferase complex Inferred from direct assay PubMed 17500065. Source: MGI nuclear matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Pax2	P32114	3	EBI-1395317,EBI-1395232
Pax2	P32114-2	2	EBI-1395317,EBI-1395250
TP53BP1	Q12888	2	EBI-1395317,EBI-396540	From a different organism.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1056	1056	PAX-interacting protein 1		PRO_0000296263
Regions
	Domain	8 – 93	86	BRCT 1
	Domain	94 – 183	90	BRCT 2
	Domain	588 – 681	94	BRCT 3
	Domain	688 – 776	89	BRCT 4
	Domain	853 – 934	82	BRCT 5
	Domain	955 – 989	35	BRCT 6
	Region	94 – 183	90	Interaction with PAGR1
	Region	577 – 1056	480	Interaction with TP53BP1 By similarity
	Motif	655 – 672	18	Nuclear localization signal Potential
	Compositional bias	189 – 197	9	Poly-Glu
	Compositional bias	367 – 577	211	Gln-rich

Sequences

	Sequence		Length	Mass (Da)
	Q6NZQ4 [UniParc]. Last modified July 5, 2004. Version 1. Checksum: 86762841515A07AB	FASTA	1,056	119,269
	10 20 30 40 50 60 MSEPAPEVPE ELFREVKYYA VGDIDPQVIQ LLKAGKAKEV SYNALASHII SEDGDNPEVG 70 80 90 100 110 120 EAREVFDLPV VKPSWVTLSV QCGALLPVNG FSPESCQIFF GLTACLSQVS SEDRSALWAL 130 140 150 160 170 180 VTFHGGSCQL NLNKKCTHLI VPEPKGEKYE RAVKRTSIKI VTPDWVLDCV SEKRRKDEAF 190 200 210 220 230 240 YHPRLIIYEE EEEEEEEGDN EEQDSQNEGS TEKSSVASSA VASPAEQPCS PKPRAEVSKG 250 260 270 280 290 300 ELMFDDSSDS SPEKQERSLN WAPAEAPPLN TAQRRLPQGK GPGLINLCAN VPPVPGDILP 310 320 330 340 350 360 PDMRGNLMAP GQNLQNSERS EILGTWSPAV RTLRNITNNA DIQQINRPSN VAHILQSLSA 370 380 390 400 410 420 PTKSLEQQVA RGQQGHPNAS AVLFGQAKGA PETHVLQQHH PPQQPQQQHP ALHLQPQIMQ 430 440 450 460 470 480 LQQQQQQQQQ QQQQPQPYPQ PPSHQFPQQV HQHQFSQQQL QFPQQPLHPQ QQLHRPQQQL 490 500 510 520 530 540 QPFQQQHALQ QQLHQLQQQQ LQHHQLAQLQ QQQQQQHNLL QQQQQQQQLQ RLQQQQQMQN 550 560 570 580 590 600 QAAHLSQASQ ALQHQVLPQQ PLQLSLQPPP QQQQQQQLFG HDPAVEIPEE SFLLGCVFAI 610 620 630 640 650 660 ADYPEQMSDK QLLATWKRII QAHGGTVDPT FTSRCTHLLC ASQVSSMYTQ ALRERKRCVT 670 680 690 700 710 720 AHWLNTVLKK KKLMPPHRAL HFPVAFPPGG KPCSQHIISV TGFVDNDRDD LKLMAYLAGA 730 740 750 760 770 780 KYTGYLCRSN TVLICKEPSG LKYEKAKEWR IPCVNAQWLG DILLGNFEAL RQVQYSRYTA 790 800 810 820 830 840 FNMPDPFVPT PHLVLGLLDA WRTPVKVTAE LLMGVRLPPK LKPNEVANIQ PSSKRARIED 850 860 870 880 890 900 LPPPTKKLTP ELTPLVLFTG FEPVQVQQYI KKLYILGGEV AECTKKCTHL IASKVTRTVK 910 920 930 940 950 960 FLTAISVVKH IVTPDWLEEC FKRQTFIDEQ NYILRDAEAE VLFSFSLEES LKRAHVSPLF 970 980 990 1000 1010 1020 KTKYFYITPG ICPSLATMKA IVECAGGKVL AKQPSFRKLM EHKQNKSLSE IILISCENDL 1030 1040 1050 HLCREYFARG IDVHNAEFVL TGVLTQTLDY ESYKFN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"PTIP, a novel BRCT domain-containing protein interacts with Pax2 and is associated with active chromatin." Lechner M.S., Levitan I., Dressler G.R. Nucleic Acids Res. 28:2741-2751(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INTERACTION WITH PAX2. Strain: FVB.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6. Tissue: Brain.
[4]	"BRCT domain-containing protein PTIP is essential for progression through mitosis." Cho E.A., Prindle M.J., Dressler G.R. Mol. Cell. Biol. 23:1666-1673(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[5]	"The BRCT-domain containing protein PTIP links PAX2 to a histone H3, lysine 4 methyltransferase complex." Patel S.R., Kim D., Levitan I., Dressler G.R. Dev. Cell 13:580-592(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[6]	"Accumulation of Pax2 transactivation domain interaction protein (PTIP) at sites of DNA breaks via RNF8-dependent pathway is required for cell survival after DNA damage." Gong Z., Cho Y.-W., Kim J.-E., Ge K., Chen J. J. Biol. Chem. 284:7284-7293(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PAGR1.
[7]	"PTIP regulates 53BP1 and SMC1 at the DNA damage sites." Wu J., Prindle M.J., Dressler G.R., Yu X. J. Biol. Chem. 284:18078-18084(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"PTIP promotes chromatin changes critical for immunoglobulin class switch recombination." Daniel J.A., Santos M.A., Wang Z., Zang C., Schwab K.R., Jankovic M., Filsuf D., Chen H.T., Gazumyan A., Yamane A., Cho Y.W., Sun H.W., Ge K., Peng W., Nussenzweig M.C., Casellas R., Dressler G.R., Zhao K., Nussenzweig A. Science 329:917-923(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF104261 mRNA. Translation: AAD17923.1. AK144606 mRNA. Translation: BAE25965.1. BC066014 mRNA. Translation: AAH66014.1.
IPI	IPI00421197.
RefSeq	NP_061366.2. NM_018878.2.
UniGene	Mm.277190. Mm.409895.
3D structure databases
HSSP	HSSP built from PDB template 2ETX based on UniProtKB Q14676.
ProteinModelPortal	Q6NZQ4.
SMR	Q6NZQ4. Positions 11-181, 618-767, 847-1056.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q6NZQ4. 16 interactions.
STRING	10090.ENSMUSP00000002291.
PTM databases
PhosphoSite	Q6NZQ4.
Proteomic databases
PaxDb	Q6NZQ4.
PRIDE	Q6NZQ4.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000002291; ENSMUSP00000002291; ENSMUSG00000002221.
GeneID	55982.
KEGG	mmu:55982.
UCSC	uc008wtr.1. mouse.
Organism-specific databases
CTD	22976.
MGI	MGI:1890430. Paxip1.
Phylogenomic databases
eggNOG	NOG310206.
GeneTree	ENSGT00600000084454.
HOGENOM	HOG000115463.
HOVERGEN	HBG061191.
InParanoid	Q6NZQ4.
KO	K14972.
OMA	DIQQINR.
OrthoDB	EOG4CRKZF.
Gene expression databases
Bgee	Q6NZQ4.
Genevestigator	Q6NZQ4.
Family and domain databases
InterPro	IPR001357. BRCT_dom. [Graphical view]
Pfam	PF00533. BRCT. 3 hits. [Graphical view]
SMART	SM00292. BRCT. 6 hits. [Graphical view]
SUPFAM	SSF52113. BRCT. 4 hits.
PROSITE	PS50172. BRCT. 5 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	PAXIP1. mouse.
NextBio	311686.
SOURCE	Search...

Entry information

Entry name

PAXI1_MOUSE

Accession

Primary (citable) accession number: Q6NZQ4
Secondary accession number(s): Q9Z0W6

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 24, 2007
Last sequence update:	July 5, 2004
Last modified:	May 1, 2013
This is version 87 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program