ID   ASPP2_HUMAN             Reviewed;        1128 AA.
AC   Q13625; Q12892; Q86X75; Q96KQ3;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   15-AUG-2003, sequence version 2.
DT   15-JAN-2008, entry version 85.
DE   Apoptosis-stimulating of p53 protein 2 (Tumor suppressor p53-binding
DE   protein 2) (p53-binding protein 2) (p53BP2) (53BP2) (Bcl2-binding
DE   protein) (Bbp) (Renal carcinoma antigen NY-REN-51).
GN   Name=TP53BP2; Synonyms=ASPP2, BBP;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND INTERACTION WITH BCL2.
RX   MEDLINE=96251339; PubMed=8668206;
RA   Naumovski L., Cleary M.L.;
RT   "The p53-binding protein 53BP2 also interacts with Bcl2 and impedes
RT   cell cycle progression at G2/M.";
RL   Mol. Cell. Biol. 16:3884-3892(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, DISEASE, AND
RP   INTERACTION WITH TP53.
RX   MEDLINE=21541920; PubMed=11684014; DOI=10.1016/S1097-2765(01)00367-7;
RA   Samuels-Lev Y., O'Connor D.J., Bergamaschi D., Trigiante G.,
RA   Hsieh J.-K., Zhong S., Campargue I., Naumovski L., Crook T., Lu X.;
RT   "ASPP proteins specifically stimulate the apoptotic function of p53.";
RL   Mol. Cell 8:781-794(2001).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Testis, and Uterus;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 600-1128, AND INTERACTION WITH TP53.
RX   MEDLINE=94286584; PubMed=8016121;
RA   Iwabuchi K., Bartel P.L., Li B., Marraccino R., Fields S.;
RT   "Two cellular proteins that bind to wild-type but not mutant p53.";
RL   Proc. Natl. Acad. Sci. U.S.A. 91:6098-6102(1994).
RN   [5]
RP   IDENTIFICATION AS A RENAL CANCER ANTIGEN.
RC   TISSUE=Renal cell carcinoma;
RX   MEDLINE=99438124; PubMed=10508479;
RX   DOI=10.1002/(SICI)1097-0215(19991112)83:4<456::AID-IJC4>3.0.CO;2-5;
RA   Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H.,
RA   Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T.,
RA   Old L.J.;
RT   "Antigens recognized by autologous antibody in patients with renal-
RT   cell carcinoma.";
RL   Int. J. Cancer 83:456-464(1999).
RN   [6]
RP   TISSUE SPECIFICITY, AND INTERACTION WITH RELA.
RX   MEDLINE=99430097; PubMed=10498867; DOI=10.1038/sj.onc.1202904;
RA   Yang J.-P., Hori M., Takahashi N., Kawabe T., Kato H., Okamoto T.;
RT   "NF-kappaB subunit p65 binds to 53BP2 and inhibits cell death induced
RT   by 53BP2.";
RL   Oncogene 18:5177-5186(1999).
RN   [7]
RP   INTERACTION WITH APC2, MUTAGENESIS OF TRP-1098, AND SUBCELLULAR
RP   LOCATION.
RX   PubMed=10646860;
RA   Nakagawa H., Koyama K., Murata Y., Morito M., Akiyama T., Nakamura Y.;
RT   "APCL, a central nervous system-specific homologue of adenomatous
RT   polyposis coli tumor suppressor, binds to p53-binding protein 2 and
RT   translocates it to the perinucleus.";
RL   Cancer Res. 60:101-105(2000).
RN   [8]
RP   INDUCTION.
RX   MEDLINE=20481761; PubMed=11027272;
RX   DOI=10.1128/MCB.20.21.8018-8025.2000;
RA   Lopez C.D., Ao Y., Rohde L.H., Perez T.D., O'Connor D.J., Lu X.,
RA   Ford J.M., Naumovski L.;
RT   "Proapoptotic p53-interacting protein 53BP2 is induced by UV
RT   irradiation but suppressed by p53.";
RL   Mol. Cell. Biol. 20:8018-8025(2000).
RN   [9]
RP   DISEASE.
RX   MEDLINE=20123886; PubMed=10631318; DOI=10.1016/S0014-5793(99)01726-3;
RA   Mori T., Okamoto H., Takahashi N., Ueda R., Okamoto T.;
RT   "Aberrant overexpression of 53BP2 mRNA in lung cancer cell lines.";
RL   FEBS Lett. 465:124-128(2000).
RN   [10]
RP   FUNCTION, AND INTERACTION WITH APPBP1.
RX   MEDLINE=22581840; PubMed=12694406;
RA   Chen Y., Liu W., Naumovski L., Neve R.L.;
RT   "ASPP2 inhibits APP-BP1-mediated NEDD8 conjugation to cullin-1 and
RT   decreases APP-BP1-induced cell proliferation and neuronal apoptosis.";
RL   J. Neurochem. 85:801-809(2003).
RN   [11]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-698, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Epithelium;
RX   PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA   Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA   Mann M.;
RT   "Global, in vivo, and site-specific phosphorylation dynamics in
RT   signaling networks.";
RL   Cell 127:635-648(2006).
RN   [12]
RP   X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 892-1128.
RX   MEDLINE=97035414; PubMed=8875926; DOI=10.1126/science.274.5289.1001;
RA   Gorina S., Pavletich N.P.;
RT   "Structure of the p53 tumor suppressor bound to the ankyrin and SH3
RT   domains of 53BP2.";
RL   Science 274:1001-1005(1996).
CC   -!- FUNCTION: Regulator that plays a central role in regulation of
CC       apoptosis and cell growth via its interactions. Regulates TP53 by
CC       enhancing the DNA binding and transactivation function of TP53 on
CC       the promoters of proapoptotic genes in vivo. Inhibits the ability
CC       of APPBP1 to conjugate NEDD8 to CUL1, and thereby decreases APPBP1
CC       ability to induce apoptosis. Impedes cell cycle progression at
CC       G2/M.
CC   -!- SUBUNIT: Binds to the central domain of TP53 as well as to BCL2.
CC       Interacts with protein phosphatase 1. Interacts with RELA NF-
CC       kappa-B subunit. This interaction probably prevents the activation
CC       of apoptosis, possibly by preventing its interaction with TP53.
CC       Interacts with APC2 and APPBP1.
CC   -!- INTERACTION:
CC       P05067:APP; NbExp=2; IntAct=EBI-77642, EBI-77613;
CC       P04637:TP53; NbExp=1; IntAct=EBI-77642, EBI-366083;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region. Nucleus.
CC       Note=Predominantly found in the perinuclear region. Some small
CC       fraction is nuclear.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q13625-1; Sequence=Displayed;
CC       Name=2; Synonyms=Bbp;
CC         IsoId=Q13625-2; Sequence=VSP_008010;
CC         Note=Due to Alu sequence insertion that creates a shorter but
CC         existing form that may have an alternative function;
CC   -!- TISSUE SPECIFICITY: Widely expressed. Expressed in spleen, thymus,
CC       prostate, testis, ovary, small intestine, colon and peripheral
CC       blood leukocyte.
CC   -!- INDUCTION: Following DNA damage induced by UV irradiation. Down-
CC       regulated by wild-type, but not mutant, TP53.
CC   -!- DOMAIN: The ankyrin repeats and the SH3 domain are required for a
CC       specific interactions with TP53.
CC   -!- DISEASE: Defects in TP53BP2 may be involved in breast cancer.
CC       TP53BP2 is down-regulated in many patients suffering from breast
CC       carcinomas and expressing a wild-type TP53 protein. Overexpressed
CC       in lung cancer cell lines.
CC   -!- SIMILARITY: Belongs to the ASPP family.
CC   -!- SIMILARITY: Contains 2 ANK repeats.
CC   -!- SIMILARITY: Contains 1 SH3 domain.
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DR   EMBL; U58334; AAC50557.1; -; mRNA.
DR   EMBL; AJ318888; CAC83012.1; -; mRNA.
DR   EMBL; BC046150; AAH46150.1; -; mRNA.
DR   EMBL; BC058918; AAH58918.1; -; mRNA.
DR   EMBL; U09582; AAA21597.1; -; mRNA.
DR   PIR; I38607; I38607.
DR   RefSeq; NP_005417.1; -.
DR   UniGene; Hs.523968; -.
DR   PDB; 1YCS; X-ray; 2.20 A; B=892-1128.
DR   PDB; 2UWQ; NMR; -; A=1-83.
DR   PDBsum; 1YCS; -.
DR   PDBsum; 2UWQ; -.
DR   DIP; DIP:24266N; -.
DR   DIP; DIP:426N; -.
DR   IntAct; Q13625; -.
DR   Ensembl; ENSG00000143514; Homo sapiens.
DR   GeneID; 7159; -.
DR   KEGG; hsa:7159; -.
DR   H-InvDB; HIX0028630; -.
DR   HGNC; HGNC:12000; TP53BP2.
DR   MIM; 602143; gene.
DR   PharmGKB; PA36681; -.
DR   LinkHub; Q13625; -.
DR   ArrayExpress; Q13625; -.
DR   CleanEx; HS_TP53BP2; -.
DR   GermOnline; ENSG00000143514; Homo sapiens.
DR   GO; GO:0005737; C:cytoplasm; TAS:UniProtKB.
DR   GO; GO:0051059; F:NF-kappaB binding; IPI:UniProtKB.
DR   GO; GO:0005070; F:SH3/SH2 adaptor activity; TAS:ProtInc.
DR   GO; GO:0006917; P:induction of apoptosis; IDA:UniProtKB.
DR   GO; GO:0045786; P:negative regulation of progression through ...; TAS:UniProtKB.
DR   GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR   InterPro; IPR002110; ANK.
DR   InterPro; IPR001452; SH3.
DR   Gene3D; G3DSA:1.25.40.20; ANK; 1.
DR   Pfam; PF00023; Ank; 2.
DR   Pfam; PF00018; SH3_1; 1.
DR   PRINTS; PR01415; ANKYRIN.
DR   PRINTS; PR00452; SH3DOMAIN.
DR   ProDom; PD000066; SH3; 1.
DR   SMART; SM00248; ANK; 2.
DR   SMART; SM00326; SH3; 1.
DR   PROSITE; PS50297; ANK_REP_REGION; 1.
DR   PROSITE; PS50088; ANK_REPEAT; 2.
DR   PROSITE; PS50002; SH3; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; ANK repeat; Apoptosis; Cell cycle;
KW   Cytoplasm; Nucleus; Phosphoprotein; Repeat; SH3 domain; SH3-binding.
FT   CHAIN         1   1128       Apoptosis-stimulating of p53 protein 2.
FT                                /FTId=PRO_0000066964.
FT   REPEAT      958    990       ANK 1.
FT   REPEAT      991   1023       ANK 2.
FT   DOMAIN     1057   1119       SH3.
FT   REGION      332    348       Interaction with APPBP1.
FT   REGION      876   1128       Mediates interaction with APC2.
FT   MOTIF       866    875       SH3-binding (Potential).
FT   COMPBIAS    132    173       Gln-rich.
FT   COMPBIAS    824    902       Pro-rich.
FT   MOD_RES     480    480       Phosphoserine (By similarity).
FT   MOD_RES     698    698       Phosphoserine.
FT   VAR_SEQ       1    123       Missing (in isoform 2).
FT                                /FTId=VSP_008010.
FT   MUTAGEN    1098   1098       W->K: Loss of interaction with APC2.
FT   HELIX       927    936
FT   HELIX       939    945
FT   HELIX       962    969
FT   HELIX       972    981
FT   HELIX       995   1001
FT   HELIX      1005   1013
FT   STRAND     1023   1025
FT   HELIX      1029   1032
FT   STRAND     1035   1037
FT   HELIX      1043   1053
FT   TURN       1054   1057
FT   HELIX      1058   1060
FT   STRAND     1061   1066
FT   STRAND     1083   1086
FT   STRAND     1095   1102
FT   STRAND     1105   1110
FT   HELIX      1111   1113
SQ   SEQUENCE   1128 AA;  125616 MW;  C75D056FBC1DAD75 CRC64;
     MMPMFLTVYL SNNEQHFTEV PVTPETICRD VVDLCKEPGE SDCHLAEVWC GSERPVADNE
     RMFDVLQRFG SQRNEVRFFL RHERPPGRDI VSGPRSQDPS LKRNGVKVPG EYRRKENGVN
     SPRMDLTLAE LQEMASRQQQ QIEAQQQLLA TKEQRLKFLK QQDQRQQQQV AEQEKLKRLK
     EIAENQEAKL KKVRALKGHV EQKRLSNGKL VEEIEQMNNL FQQKQRELVL AVSKVEELTR
     QLEMLKNGRI DSHHDNQSAV AELDRLYKEL QLRNKLNQEQ NAKLQQQREC LNKRNSEVAV
     MDKRVNELRD RLWKKKAALQ QKENLPVSSD GNLPQQAASA PSRVAAVGPY IQSSTMPRMP
     SRPELLVKPA LPDGSLVIQA SEGPMKIQTL PNMRSGAASQ TKGSKIHPVG PDWSPSNADL
     FPSQGSASVP QSTGNALDQV DDGEVPLREK EKKVRPFSMF DAVDQSNAPP SFGTLRKNQS
     SEDILRDAQV ANKNVAKVPP PVPTKPKQIN LPYFGQTNQP PSDIKPDGSS QQLSTVVPSM
     GTKPKPAGQQ PRVLLSPSIP SVGQDQTLSP GSKQESPPAA AVRPFTPQPS KDTLLPPFRK
     PQTVAASSIY SMYTQQQAPG KNFQQAVQSA LTKTHTRGPH FSSVYGKPVI AAAQNQQQHP
     ENIYSNSQGK PGSPEPETEP VSSVQENHEN ERIPRPLSPT KLLPFLSNPY RNQSDADLEA
     LRKKLSNAPR PLKKRSSITE PEGPNGPNIQ KLLYQRTTIA AMETISVPSY PSKSASVTAS
     SESPVEIQNP YLHVEPEKEV VSLVPESLSP EDVGNASTEN SDMPAPSPGL DYEPEGVPDN
     SPNLQNNPEE PNPEAPHVLD VYLEEYPPYP PPPYPSGEPE GPGEDSVSMR PPEITGQVSL
     PPGKRTNLRK TGSERIAHGM RVKFNPLALL LDSSLEGEFD LVQRIIYEVD DPSLPNDEGI
     TALHNAVCAG HTEIVKFLVQ FGVNVNAADS DGWTPLHCAA SCNNVQVCKF LVESGAAVFA
     MTYSDMQTAA DKCEEMEEGY TQCSQFLYGV QEKMGIMNKG VIYALWDYEP QNDDELPMKE
     GDCMTIIHRE DEDEIEWWWA RLNDKEGYVP RNLLGLYPRI KPRQRSLA
//