PAXI1_HUMAN
ID PAXI1_HUMAN Reviewed; 1069 AA.
AC Q6ZW49; O15404; Q6N099; Q6ZWH9; Q7Z315; Q86UN0; Q8N4P9; Q96HP2;
DT 24-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 2.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=PAX-interacting protein 1;
DE AltName: Full=PAX transactivation activation domain-interacting protein;
GN Name=PAXIP1; Synonyms=PAXIP1L, PTIP; ORFNames=CAGF28;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 1-680 (ISOFORM 1).
RC TISSUE=Adrenal gland, Prostate, and Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT VAL-1013.
RC TISSUE=Rectum tumor, and Uterus;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 202-1069.
RC TISSUE=Fetal brain;
RX PubMed=9225980; DOI=10.1007/s004390050476;
RA Margolis R.L., Abraham M.R., Gatchell S.B., Li S.-H., Kidwai A.S.,
RA Breschel T.S., Stine O.C., Callahan C., McInnis M.G., Ross C.A.;
RT "cDNAs with long CAG trinucleotide repeats from human brain.";
RL Hum. Genet. 100:114-122(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 244-1069.
RC TISSUE=Brain, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP INTERACTION WITH NUPR1.
RX PubMed=11940591; DOI=10.1074/jbc.m201657200;
RA Hoffmeister A., Ropolo A., Vasseur S., Mallo G.V., Bodeker H.,
RA Ritz-Laser B., Dressler G.R., Vaccaro M.I., Dagorn J.C., Moreno S.,
RA Iovanna J.L.;
RT "The HMG-I/Y-related protein p8 binds to p300 and Pax2 trans-activation
RT domain-interacting protein to regulate the trans-activation activity of the
RT Pax2A and Pax2B transcription factors on the glucagon gene promoter.";
RL J. Biol. Chem. 277:22314-22319(2002).
RN [7]
RP FUNCTION.
RX PubMed=14576432; DOI=10.1126/science.1088877;
RA Manke I.A., Lowery D.M., Nguyen A., Yaffe M.B.;
RT "BRCT repeats as phosphopeptide-binding modules involved in protein
RT targeting.";
RL Science 302:636-639(2003).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH TP53BP1.
RX PubMed=15456759; DOI=10.1074/jbc.m411021200;
RA Jowsey P.A., Doherty A.J., Rouse J.;
RT "Human PTIP facilitates ATM-mediated activation of p53 and promotes
RT cellular resistance to ionizing radiation.";
RL J. Biol. Chem. 279:55562-55569(2004).
RN [9]
RP FUNCTION IN MLL2 COMPLEX ASSEMBLY, AND IDENTIFICATION IN THE MLL2/3
RP COMPLEX.
RX PubMed=17925232; DOI=10.1016/j.devcel.2007.09.004;
RA Patel S.R., Kim D., Levitan I., Dressler G.R.;
RT "The BRCT-domain containing protein PTIP links PAX2 to a histone H3, lysine
RT 4 methyltransferase complex.";
RL Dev. Cell 13:580-592(2007).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE MLL2/3
RP COMPLEX.
RX PubMed=17500065; DOI=10.1074/jbc.m701574200;
RA Cho Y.-W., Hong T., Hong S., Guo H., Yu H., Kim D., Guszczynski T.,
RA Dressler G.R., Copeland T.D., Kalkum M., Ge K.;
RT "PTIP associates with MLL3- and MLL4-containing histone H3 lysine 4
RT methyltransferase complex.";
RL J. Biol. Chem. 282:20395-20406(2007).
RN [11]
RP IDENTIFICATION IN THE MLL2 COMPLEX, AND ASSOCIATION WITH KMT2D-REGULATED
RP GENE PROMOTERS.
RX PubMed=17178841; DOI=10.1128/mcb.01506-06;
RA Issaeva I., Zonis Y., Rozovskaia T., Orlovsky K., Croce C.M., Nakamura T.,
RA Mazo A., Eisenbach L., Canaani E.;
RT "Knockdown of ALR (MLL2) reveals ALR target genes and leads to alterations
RT in cell adhesion and growth.";
RL Mol. Cell. Biol. 27:1889-1903(2007).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH TP53BP1, AND MUTAGENESIS
RP OF TRP-676; ARG-910 AND TRP-929.
RX PubMed=17690115; DOI=10.1093/nar/gkm493;
RA Munoz I.M., Jowsey P.A., Toth R., Rouse J.;
RT "Phospho-epitope binding by the BRCT domains of hPTIP controls multiple
RT aspects of the cellular response to DNA damage.";
RL Nucleic Acids Res. 35:5312-5322(2007).
RN [13]
RP IDENTIFICATION IN THE MLL2/3 COMPLEX.
RX PubMed=17761849; DOI=10.1126/science.1149042;
RA Lee M.G., Villa R., Trojer P., Norman J., Yan K.P., Reinberg D.,
RA Di Croce L., Shiekhattar R.;
RT "Demethylation of H3K27 regulates polycomb recruitment and H2A
RT ubiquitination.";
RL Science 318:447-450(2007).
RN [14]
RP FUNCTION.
RX PubMed=18353733; DOI=10.1016/j.dnarep.2008.02.001;
RA Gohler T., Munoz I.M., Rouse J., Blow J.J.;
RT "PTIP/Swift is required for efficient PCNA ubiquitination in response to
RT DNA damage.";
RL DNA Repair 7:775-787(2008).
RN [15]
RP INTERACTION WITH HLTF.
RX PubMed=19723507; DOI=10.1016/j.bbrc.2009.08.151;
RA MacKay C., Toth R., Rouse J.;
RT "Biochemical characterisation of the SWI/SNF family member HLTF.";
RL Biochem. Biophys. Res. Commun. 390:187-191(2009).
RN [16]
RP FUNCTION.
RX PubMed=20088963; DOI=10.1111/j.1365-2443.2009.01379.x;
RA Wang X., Takenaka K., Takeda S.;
RT "PTIP promotes DNA double-strand break repair through homologous
RT recombination.";
RL Genes Cells 15:243-254(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP FUNCTION, AND INTERACTION WITH TP53BP1.
RX PubMed=23727112; DOI=10.1016/j.cell.2013.05.023;
RA Callen E., Di Virgilio M., Kruhlak M.J., Nieto-Soler M., Wong N.,
RA Chen H.T., Faryabi R.B., Polato F., Santos M., Starnes L.M., Wesemann D.R.,
RA Lee J.E., Tubbs A., Sleckman B.P., Daniel J.A., Ge K., Alt F.W.,
RA Fernandez-Capetillo O., Nussenzweig M.C., Nussenzweig A.;
RT "53BP1 mediates productive and mutagenic DNA repair through distinct
RT phosphoprotein interactions.";
RL Cell 153:1266-1280(2013).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-235, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
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:0000269|PubMed:14576432, ECO:0000269|PubMed:15456759,
CC ECO:0000269|PubMed:17690115, ECO:0000269|PubMed:17925232,
CC ECO:0000269|PubMed:18353733, ECO:0000269|PubMed:20088963,
CC ECO:0000269|PubMed:23727112}.
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 (By similarity). Interacts with TP53BP1 (when
CC phosphorylated at the N-terminus by ATM) (PubMed:15456759,
CC PubMed:17690115, PubMed:23727112). Interacts with HLTF
CC (PubMed:19723507). Component of the KMT2 family MLL2/MLL3 complex (also
CC named ASCOM complex), at least composed of the HMTs KMT2D and/or KMT2C,
CC the common subunits ASH2L, RBBP5, WDR5 and DPY30, and the complex type-
CC specific subunits PAXIP1/PTIP, PAGR1, NCOA6 and KDM6A; required for the
CC association of PAGR1 with the MLL2/MLL3 complex (PubMed:17178841,
CC PubMed:17500065, PubMed:17761849, PubMed:17925232). Interacts with
CC NUPR1; this interaction prevents PAXIP1 inhibition of PAX2
CC transcription factor activity (PubMed:11940591).
CC {ECO:0000250|UniProtKB:Q6NZQ4, ECO:0000269|PubMed:11940591,
CC ECO:0000269|PubMed:15456759, ECO:0000269|PubMed:17178841,
CC ECO:0000269|PubMed:17500065, ECO:0000269|PubMed:17690115,
CC ECO:0000269|PubMed:17761849, ECO:0000269|PubMed:17925232,
CC ECO:0000269|PubMed:19723507, ECO:0000269|PubMed:23727112}.
CC -!- INTERACTION:
CC Q6ZW49; P05067: APP; NbExp=3; IntAct=EBI-743225, EBI-77613;
CC Q6ZW49; Q9UBL3: ASH2L; NbExp=12; IntAct=EBI-743225, EBI-540797;
CC Q6ZW49; P48730-2: CSNK1D; NbExp=3; IntAct=EBI-743225, EBI-9087876;
CC Q6ZW49; Q9BTK6: PAGR1; NbExp=8; IntAct=EBI-743225, EBI-2372223;
CC Q6ZW49; Q15291: RBBP5; NbExp=11; IntAct=EBI-743225, EBI-592823;
CC Q6ZW49; Q12888: TP53BP1; NbExp=4; IntAct=EBI-743225, EBI-396540;
CC Q6ZW49; P61964: WDR5; NbExp=10; IntAct=EBI-743225, EBI-540834;
CC Q6ZW49-1; P16104: H2AX; NbExp=7; IntAct=EBI-7521368, EBI-494830;
CC Q6ZW49-2; Q15555: MAPRE2; NbExp=3; IntAct=EBI-10236271, EBI-739717;
CC Q6ZW49-2; Q9UKK6: NXT1; NbExp=3; IntAct=EBI-10236271, EBI-301889;
CC Q6ZW49-2; Q96HA1: POM121; NbExp=3; IntAct=EBI-10236271, EBI-739990;
CC -!- SUBCELLULAR LOCATION: Nucleus matrix {ECO:0000250|UniProtKB:Q6NZQ4}.
CC Chromosome {ECO:0000269|PubMed:15456759, ECO:0000269|PubMed:17690115}.
CC Note=Localizes to DNA damage foci upon ionizing radiation.
CC {ECO:0000269|PubMed:15456759, ECO:0000269|PubMed:17690115}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q6ZW49-6; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6ZW49-1; Sequence=VSP_040300;
CC Name=3;
CC IsoId=Q6ZW49-2; Sequence=VSP_040303;
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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB91434.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAH33781.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH33781.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence.; Evidence={ECO:0000305};
CC Sequence=AAP21865.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=BAC85523.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
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DR EMBL; AK123044; BAC85523.1; ALT_SEQ; mRNA.
DR EMBL; AK123600; BAC85657.1; -; mRNA.
DR EMBL; AK307417; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BX538201; CAD98066.1; -; mRNA.
DR EMBL; BX640616; CAE45762.1; -; mRNA.
DR EMBL; AC093726; AAP21865.1; ALT_SEQ; Genomic_DNA.
DR EMBL; U80735; AAB91434.1; ALT_FRAME; mRNA.
DR EMBL; BC008328; AAH08328.1; -; mRNA.
DR EMBL; BC033781; AAH33781.1; ALT_SEQ; mRNA.
DR CCDS; CCDS47753.1; -. [Q6ZW49-6]
DR RefSeq; NP_031375.3; NM_007349.3. [Q6ZW49-6]
DR RefSeq; XP_005249596.1; XM_005249539.1. [Q6ZW49-1]
DR RefSeq; XP_016867370.1; XM_017011881.1. [Q6ZW49-1]
DR PDB; 3SQD; X-ray; 2.15 A; A/B=860-1069.
DR PDBsum; 3SQD; -.
DR AlphaFoldDB; Q6ZW49; -.
DR SMR; Q6ZW49; -.
DR BioGRID; 116625; 340.
DR ComplexPortal; CPX-7091; Histone-lysine N-methyltransferase complex, KMT2C variant.
DR ComplexPortal; CPX-7104; Histone-lysine N-methyltransferase complex, KMT2D variant.
DR CORUM; Q6ZW49; -.
DR DIP; DIP-41786N; -.
DR IntAct; Q6ZW49; 86.
DR MINT; Q6ZW49; -.
DR STRING; 9606.ENSP00000384048; -.
DR iPTMnet; Q6ZW49; -.
DR PhosphoSitePlus; Q6ZW49; -.
DR BioMuta; PAXIP1; -.
DR DMDM; 317373316; -.
DR EPD; Q6ZW49; -.
DR jPOST; Q6ZW49; -.
DR MassIVE; Q6ZW49; -.
DR MaxQB; Q6ZW49; -.
DR PaxDb; Q6ZW49; -.
DR PeptideAtlas; Q6ZW49; -.
DR PRIDE; Q6ZW49; -.
DR ProteomicsDB; 68459; -. [Q6ZW49-6]
DR ProteomicsDB; 68460; -. [Q6ZW49-1]
DR ProteomicsDB; 68461; -. [Q6ZW49-2]
DR Antibodypedia; 1874; 130 antibodies from 25 providers.
DR DNASU; 22976; -.
DR Ensembl; ENST00000397192.5; ENSP00000380376.1; ENSG00000157212.19. [Q6ZW49-6]
DR Ensembl; ENST00000404141.6; ENSP00000384048.1; ENSG00000157212.19. [Q6ZW49-6]
DR GeneID; 22976; -.
DR KEGG; hsa:22976; -.
DR MANE-Select; ENST00000404141.6; ENSP00000384048.1; NM_007349.4; NP_031375.3.
DR UCSC; uc033aqm.2; human. [Q6ZW49-6]
DR CTD; 22976; -.
DR DisGeNET; 22976; -.
DR GeneCards; PAXIP1; -.
DR HGNC; HGNC:8624; PAXIP1.
DR HPA; ENSG00000157212; Tissue enhanced (lymphoid).
DR MIM; 608254; gene.
DR neXtProt; NX_Q6ZW49; -.
DR OpenTargets; ENSG00000157212; -.
DR PharmGKB; PA32964; -.
DR VEuPathDB; HostDB:ENSG00000157212; -.
DR eggNOG; KOG2043; Eukaryota.
DR GeneTree; ENSGT00940000155757; -.
DR HOGENOM; CLU_009382_0_0_1; -.
DR InParanoid; Q6ZW49; -.
DR OMA; QGPNSIR; -.
DR OrthoDB; 840249at2759; -.
DR PhylomeDB; Q6ZW49; -.
DR TreeFam; TF329580; -.
DR PathwayCommons; Q6ZW49; -.
DR Reactome; R-HSA-5617472; Activation of anterior HOX genes in hindbrain development during early embryogenesis.
DR Reactome; R-HSA-5693571; Nonhomologous End-Joining (NHEJ).
DR SignaLink; Q6ZW49; -.
DR SIGNOR; Q6ZW49; -.
DR BioGRID-ORCS; 22976; 157 hits in 1087 CRISPR screens.
DR ChiTaRS; PAXIP1; human.
DR GeneWiki; PAXIP1; -.
DR GenomeRNAi; 22976; -.
DR Pharos; Q6ZW49; Tbio.
DR PRO; PR:Q6ZW49; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q6ZW49; protein.
DR Bgee; ENSG00000157212; Expressed in secondary oocyte and 182 other tissues.
DR ExpressionAtlas; Q6ZW49; baseline and differential.
DR Genevisible; Q6ZW49; HS.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0035097; C:histone methyltransferase complex; IDA:UniProtKB.
DR GO; GO:0044666; C:MLL3/4 complex; IDA:UniProtKB.
DR GO; GO:0016363; C:nuclear matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0060612; P:adipose tissue development; IEA:Ensembl.
DR GO; GO:0060717; P:chorion development; IEA:Ensembl.
DR GO; GO:0030330; P:DNA damage response, signal transduction by p53 class mediator; IMP:UniProtKB.
DR GO; GO:0006310; P:DNA recombination; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0043542; P:endothelial cell migration; IEA:Ensembl.
DR GO; GO:0051568; P:histone H3-K4 methylation; IDA:UniProtKB.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IMP:UniProtKB.
DR GO; GO:0035066; P:positive regulation of histone acetylation; ISS:UniProtKB.
DR GO; GO:0000416; P:positive regulation of histone H3-K36 methylation; ISS:UniProtKB.
DR GO; GO:0051571; P:positive regulation of histone H3-K4 methylation; ISS:UniProtKB.
DR GO; GO:0045830; P:positive regulation of isotype switching; ISS:UniProtKB.
DR GO; GO:0048304; P:positive regulation of isotype switching to IgG isotypes; IEA:Ensembl.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; ISS:UniProtKB.
DR GO; GO:2001022; P:positive regulation of response to DNA damage stimulus; IEA:Ensembl.
DR GO; GO:0060261; P:positive regulation of transcription initiation from RNA polymerase II promoter; IMP:UniProtKB.
DR GO; GO:1902749; P:regulation of cell cycle G2/M phase transition; IEA:Ensembl.
DR GO; GO:0010212; P:response to ionizing radiation; IDA:UniProtKB.
DR GO; GO:0001570; P:vasculogenesis; IEA:Ensembl.
DR Gene3D; 3.40.50.10190; -; 5.
DR IDEAL; IID00483; -.
DR InterPro; IPR001357; BRCT_dom.
DR InterPro; IPR036420; BRCT_dom_sf.
DR InterPro; IPR037886; Paxip1.
DR PANTHER; PTHR23196:SF31; PTHR23196:SF31; 1.
DR Pfam; PF00533; BRCT; 1.
DR Pfam; PF12738; PTCB-BRCT; 2.
DR Pfam; PF16770; RTT107_BRCT_5; 1.
DR SMART; SM00292; BRCT; 5.
DR SUPFAM; SSF52113; SSF52113; 5.
DR PROSITE; PS50172; BRCT; 5.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chromosome; DNA damage;
KW DNA recombination; DNA repair; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat; Transcription; Transcription regulation.
FT CHAIN 1..1069
FT /note="PAX-interacting protein 1"
FT /id="PRO_0000296262"
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 601..694
FT /note="BRCT 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 703..779
FT /note="BRCT 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 866..947
FT /note="BRCT 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 970..1059
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 188..271
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 428..494
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 543..592
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 590..1069
FT /note="Interaction with TP53BP1"
FT MOTIF 702..719
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 189..209
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 213..242
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 447..494
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 543..574
FT /note="Polar 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:0007744|PubMed:23186163"
FT VAR_SEQ 1..247
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_040303"
FT VAR_SEQ 1..108
FT /note="MSDQAPKVPEEMFREVKYYAVGDIDPQVIQLLKAGKAKEVSYNALASHIISE
FT DGDNPEVGEAREVFDLPVVKPSWVILSVQCGTLLPVNGFSPESCQIFFGITACLSQ ->
FT MVFLQNHVRFFLESLPAFLRVLIQAGALCWSLPELSQGEVGKGACPAEVGKHRDHLPSS
FT DPVLMQAEASVVMCW (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_040300"
FT VARIANT 1013
FT /note="M -> V (in dbSNP:rs3501)"
FT /evidence="ECO:0000269|PubMed:17974005"
FT /id="VAR_034627"
FT MUTAGEN 676
FT /note="W->A: Abolishes interaction with TP53BP1; prevents
FT recruitment to DNA damage foci."
FT /evidence="ECO:0000269|PubMed:17690115"
FT MUTAGEN 910
FT /note="R->Q: Abolishes interaction with TP53BP1; impairs
FT intact cellular response to DNA damage."
FT /evidence="ECO:0000269|PubMed:17690115"
FT MUTAGEN 929
FT /note="W->A: Abolishes interaction with TP53BP1; prevents
FT recruitment to DNA damage foci."
FT /evidence="ECO:0000269|PubMed:17690115"
FT CONFLICT 121
FT /note="V -> D (in Ref. 1; AK307417)"
FT /evidence="ECO:0000305"
FT CONFLICT 154
FT /note="K -> R (in Ref. 2; CAE45762)"
FT /evidence="ECO:0000305"
FT CONFLICT 260
FT /note="Q -> H (in Ref. 2; CAE45762)"
FT /evidence="ECO:0000305"
FT CONFLICT 406
FT /note="Missing (in Ref. 1; AK307417)"
FT /evidence="ECO:0000305"
FT CONFLICT 458..581
FT /note="Missing (in Ref. 4; AAB91434)"
FT /evidence="ECO:0000305"
FT CONFLICT 847
FT /note="K -> Q (in Ref. 4; AAB91434)"
FT /evidence="ECO:0000305"
FT CONFLICT 912
FT /note="V -> L (in Ref. 4; AAB91434)"
FT /evidence="ECO:0000305"
FT CONFLICT 916
FT /note="T -> A (in Ref. 4; AAB91434)"
FT /evidence="ECO:0000305"
FT HELIX 863..865
FT /evidence="ECO:0007829|PDB:3SQD"
FT STRAND 868..871
FT /evidence="ECO:0007829|PDB:3SQD"
FT HELIX 876..888
FT /evidence="ECO:0007829|PDB:3SQD"
FT HELIX 897..899
FT /evidence="ECO:0007829|PDB:3SQD"
FT STRAND 901..904
FT /evidence="ECO:0007829|PDB:3SQD"
FT HELIX 912..917
FT /evidence="ECO:0007829|PDB:3SQD"
FT TURN 918..920
FT /evidence="ECO:0007829|PDB:3SQD"
FT STRAND 922..925
FT /evidence="ECO:0007829|PDB:3SQD"
FT HELIX 927..936
FT /evidence="ECO:0007829|PDB:3SQD"
FT HELIX 943..945
FT /evidence="ECO:0007829|PDB:3SQD"
FT HELIX 950..955
FT /evidence="ECO:0007829|PDB:3SQD"
FT HELIX 960..969
FT /evidence="ECO:0007829|PDB:3SQD"
FT TURN 972..975
FT /evidence="ECO:0007829|PDB:3SQD"
FT STRAND 976..980
FT /evidence="ECO:0007829|PDB:3SQD"
FT HELIX 988..997
FT /evidence="ECO:0007829|PDB:3SQD"
FT STRAND 1001..1005
FT /evidence="ECO:0007829|PDB:3SQD"
FT HELIX 1009..1017
FT /evidence="ECO:0007829|PDB:3SQD"
FT STRAND 1023..1028
FT /evidence="ECO:0007829|PDB:3SQD"
FT HELIX 1030..1036
FT /evidence="ECO:0007829|PDB:3SQD"
FT HELIX 1037..1041
FT /evidence="ECO:0007829|PDB:3SQD"
FT HELIX 1050..1058
FT /evidence="ECO:0007829|PDB:3SQD"
FT TURN 1063..1065
FT /evidence="ECO:0007829|PDB:3SQD"
SQ SEQUENCE 1069 AA; 121341 MW; 78CD535A150E1FC1 CRC64;
MSDQAPKVPE EMFREVKYYA VGDIDPQVIQ LLKAGKAKEV SYNALASHII SEDGDNPEVG
EAREVFDLPV VKPSWVILSV QCGTLLPVNG FSPESCQIFF GITACLSQVS SEDRSALWAL
VTFYGGDCQL TLNKKCTHLI VPEPKGEKYE CALKRASIKI VTPDWVLDCV SEKTKKDEAF
YHPRLIIYEE EEEEEEEEEE VENEEQDSQN EGSTDEKSSP ASSQEGSPSG DQQFSPKSNT
EKSKGELMFD DSSDSSPEKQ ERNLNWTPAE VPQLAAAKRR LPQGKEPGLI NLCANVPPVP
GNILPPEVRG NLMAAGQNLQ SSERSEMIAT WSPAVRTLRN ITNNADIQQM NRPSNVAHIL
QTLSAPTKNL EQQVNHSQQG HTNANAVLFS QVKVTPETHM LQQQQQAQQQ QQQHPVLHLQ
PQQIMQLQQQ QQQQISQQPY PQQPPHPFSQ QQQQQQQAHP HQFSQQQLQF PQQQLHPPQQ
LHRPQQQLQP FQQQHALQQQ FHQLQQHQLQ QQQLAQLQQQ HSLLQQQQQQ QIQQQQLQRM
HQQQQQQQMQ SQTAPHLSQT SQALQHQVPP QQPPQQQQQQ QPPPSPQQHQ LFGHDPAVEI
PEEGFLLGCV FAIADYPEQM SDKQLLATWK RIIQAHGGTV DPTFTSRCTH LLCESQVSSA
YAQAIRERKR CVTAHWLNTV LKKKKMVPPH RALHFPVAFP PGGKPCSQHI ISVTGFVDSD
RDDLKLMAYL AGAKYTGYLC RSNTVLICKE PTGLKYEKAK EWRIPCVNAQ WLGDILLGNF
EALRQIQYSR YTAFSLQDPF APTQHLVLNL LDAWRVPLKV SAELLMSIRL PPKLKQNEVA
NVQPSSKRAR IEDVPPPTKK LTPELTPFVL FTGFEPVQVQ QYIKKLYILG GEVAESAQKC
THLIASKVTR TVKFLTAISV VKHIVTPEWL EECFRCQKFI DEQNYILRDA EAEVLFSFSL
EESLKRAHVS PLFKAKYFYI TPGICPSLST MKAIVECAGG KVLSKQPSFR KLMEHKQNSS
LSEIILISCE NDLHLCREYF ARGIDVHNAE FVLTGVLTQT LDYESYKFN
