Full text data of HTATIP2
HTATIP2
(CC3, TIP30)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Oxidoreductase HTATIP2; 1.1.1.- (30 kDa HIV-1 TAT-interacting protein; HIV-1 TAT-interactive protein 2)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Oxidoreductase HTATIP2; 1.1.1.- (30 kDa HIV-1 TAT-interacting protein; HIV-1 TAT-interactive protein 2)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9BUP3
ID HTAI2_HUMAN Reviewed; 242 AA.
AC Q9BUP3; A8K7S7; D3DQY8; O15383; O60520; O95345; Q53GC1; Q53GG2;
read moreAC Q6IBI3;
DT 25-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 2.
DT 22-JAN-2014, entry version 105.
DE RecName: Full=Oxidoreductase HTATIP2;
DE EC=1.1.1.-;
DE AltName: Full=30 kDa HIV-1 TAT-interacting protein;
DE AltName: Full=HIV-1 TAT-interactive protein 2;
GN Name=HTATIP2; Synonyms=CC3, TIP30;
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 1), FUNCTION, TISSUE SPECIFICITY,
RP AND VARIANT ARG-197.
RC TISSUE=Lung cancer;
RX PubMed=9174052; DOI=10.1038/sj.onc.1201059;
RA Shtivelman E.;
RT "A link between metastasis and resistance to apoptosis of variant
RT small cell lung carcinoma.";
RL Oncogene 14:2167-2173(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INTERACTION WITH HIV-1
RP TAT.
RC TISSUE=Pancreatic islet;
RX PubMed=9482853; DOI=10.1073/pnas.95.5.2146;
RA Xiao H., Tao Y., Greenblatt J., Roeder R.G.;
RT "A cofactor, TIP30, specifically enhances HIV-1 Tat-activated
RT transcription.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:2146-2151(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, AND INTERACTION WITH
RP PSMD4.
RC TISSUE=Placenta;
RX PubMed=10611237; DOI=10.1128/MCB.20.2.583-593.2000;
RA Whitman S., Wang X., Shalaby R., Shtivelman E.;
RT "Alternatively spliced products CC3 and TC3 have opposing effects on
RT apoptosis.";
RL Mol. Cell. Biol. 20:583-593(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Synovium;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Small intestine;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F.,
RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E.,
RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S.,
RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W.,
RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S.,
RA Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANT
RP ARG-197.
RC TISSUE=Cervix, and Skin;
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 [10]
RP MUTAGENESIS OF 28-GLY--GLY-31.
RX PubMed=10698937; DOI=10.1093/emboj/19.5.956;
RA Xiao H., Palhan V., Yang Y., Roeder R.G.;
RT "TIP30 has an intrinsic kinase activity required for up-regulation of
RT a subset of apoptotic genes.";
RL EMBO J. 19:956-963(2000).
RN [11]
RP FUNCTION.
RX PubMed=11313954; DOI=10.1038/sj.onc.1204075;
RA NicAmhlaoibh R., Shtivelman E.;
RT "Metastasis suppressor CC3 inhibits angiogenic properties of tumor
RT cells in vitro.";
RL Oncogene 20:270-275(2001).
RN [12]
RP TISSUE SPECIFICITY, VARIANTS SER-106; TYR-108; THR-116; VAL-134 AND
RP ILE-144, MUTAGENESIS OF ARG-106, AND CHARACTERIZATION OF VARIANT
RP VAL-134.
RX PubMed=14695192;
RA Ito M., Jiang C., Krumm K., Zhang X., Pecha J., Zhao J., Guo Y.,
RA Roeder R.G., Xiao H.;
RT "TIP30 deficiency increases susceptibility to tumorigenesis.";
RL Cancer Res. 63:8763-8767(2003).
RN [13]
RP INTERACTION WITH NCOA5.
RX PubMed=15073177; DOI=10.1074/jbc.M401809200;
RA Jiang C., Ito M., Piening V., Bruck K., Roeder R.G., Xiao H.;
RT "TIP30 interacts with an estrogen receptor alpha-interacting
RT coactivator CIA and regulates c-myc transcription.";
RL J. Biol. Chem. 279:27781-27789(2004).
RN [14]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH XPO4; IPO5; IPO7;
RP IPO9; KPNB1; GCN1L1 AND LRPPRC.
RX PubMed=15282309; DOI=10.1128/MCB.24.16.7091-7101.2004;
RA King F.W., Shtivelman E.;
RT "Inhibition of nuclear import by the proapoptotic protein CC3.";
RL Mol. Cell. Biol. 24:7091-7101(2004).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS).
RX PubMed=15728189; DOI=10.1074/jbc.M501113200;
RA El Omari K., Bird L.E., Nichols C.E., Ren J., Stammers D.K.;
RT "Crystal structure of CC3 (TIP30): implications for its role as a
RT tumor suppressor.";
RL J. Biol. Chem. 280:18229-18236(2005).
RN [17]
RP VARIANT [LARGE SCALE ANALYSIS] ARG-197, AND MASS SPECTROMETRY.
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Oxidoreductase required for tumor suppression. NAPDH-
CC bound form inhibits nuclear import by competing with nuclear
CC import substrates for binding to a subset of nuclear transport
CC receptors. May act as a redox sensor linked to transcription
CC through regulation of nuclear import. Isoform 1 is a metastasis
CC suppressor with proapoptotic as well as antiangiogenic properties.
CC Isoform 2 has an antiapoptotic effect.
CC -!- SUBUNIT: Monomer. Binds nuclear transport receptors XPO4,
CC IPO5/RANBP5, IPO7, IPO9 and KPNB1 as well as GCN1L1/GCN1 and
CC LRPPRC probably through their HEAT repeats. Binds NCOA5/CIA.
CC Isoform 2 binds the proteasome subunit PSMD4/s5a through its N-
CC terminus. Binds the activation domain of HIV-1 Tat.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus envelope.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=CC3;
CC IsoId=Q9BUP3-1; Sequence=Displayed;
CC Name=2; Synonyms=TC3;
CC IsoId=Q9BUP3-2; Sequence=VSP_051864, VSP_051865;
CC Note=Mutagenesis of Leu-154 and Leu-157 or Cys-158, Cys-160 and
CC Cys-161 abolishes antiapoptotic effect;
CC Name=3;
CC IsoId=Q9BUP3-3; Sequence=VSP_038339;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Highest level in liver. High
CC levels in lung, skeletal muscle, pancreas and placenta. Moderate
CC levels in heart and kidney. Low levels in brain. Not expressed or
CC low levels in variant small cell lung carcinomas, 33% of
CC hepatocellular carcinomas and neuroblastomas.
CC -!- DOMAIN: Unique C-terminus confers high proteasome-dependent
CC instability to isoform 2.
CC -!- CAUTION: Was originally (PubMed:9482853 and PubMed:10698937)
CC thought to be a transcriptional coregulator with protein kinase
CC activity. However, crystal structure reveals a short chain
CC dehydrogenase/reductase fold binding NADPH rather than ATP.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/HTATIP2ID40894ch11p15.html";
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DR EMBL; U69161; AAB84360.1; -; mRNA.
DR EMBL; AF039103; AAC39694.1; -; mRNA.
DR EMBL; AF092095; AAC78331.1; -; mRNA.
DR EMBL; AK292092; BAF84781.1; -; mRNA.
DR EMBL; CR456821; CAG33102.1; -; mRNA.
DR EMBL; AK223010; BAD96730.1; -; mRNA.
DR EMBL; AK222969; BAD96689.1; -; mRNA.
DR EMBL; AC025972; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471064; EAW68338.1; -; Genomic_DNA.
DR EMBL; CH471064; EAW68339.1; -; Genomic_DNA.
DR EMBL; BC002439; AAH02439.2; -; mRNA.
DR EMBL; BC015358; AAH15358.1; -; mRNA.
DR RefSeq; NP_001091990.1; NM_001098520.1.
DR RefSeq; NP_001091991.1; NM_001098521.1.
DR RefSeq; NP_001091992.1; NM_001098522.1.
DR RefSeq; NP_001091993.1; NM_001098523.1.
DR RefSeq; NP_006401.3; NM_006410.4.
DR UniGene; Hs.90753; -.
DR PDB; 2BKA; X-ray; 1.70 A; A=1-242.
DR PDBsum; 2BKA; -.
DR ProteinModelPortal; Q9BUP3; -.
DR SMR; Q9BUP3; 5-235.
DR MINT; MINT-5003508; -.
DR STRING; 9606.ENSP00000392985; -.
DR PhosphoSite; Q9BUP3; -.
DR DMDM; 74733240; -.
DR PaxDb; Q9BUP3; -.
DR PRIDE; Q9BUP3; -.
DR DNASU; 10553; -.
DR Ensembl; ENST00000419348; ENSP00000392985; ENSG00000109854.
DR Ensembl; ENST00000421577; ENSP00000397752; ENSG00000109854.
DR Ensembl; ENST00000443524; ENSP00000387876; ENSG00000109854.
DR Ensembl; ENST00000451739; ENSP00000394259; ENSG00000109854.
DR Ensembl; ENST00000530266; ENSP00000436548; ENSG00000109854.
DR Ensembl; ENST00000532081; ENSP00000432107; ENSG00000109854.
DR Ensembl; ENST00000532505; ENSP00000432338; ENSG00000109854.
DR GeneID; 10553; -.
DR KEGG; hsa:10553; -.
DR UCSC; uc001mpz.2; human.
DR CTD; 10553; -.
DR GeneCards; GC11P020341; -.
DR HGNC; HGNC:16637; HTATIP2.
DR HPA; HPA006417; -.
DR HPA; HPA024321; -.
DR MIM; 605628; gene.
DR neXtProt; NX_Q9BUP3; -.
DR PharmGKB; PA29539; -.
DR eggNOG; COG0702; -.
DR HOVERGEN; HBG052833; -.
DR InParanoid; Q9BUP3; -.
DR KO; K17290; -.
DR OMA; PRDKQME; -.
DR OrthoDB; EOG7GJ6GJ; -.
DR PhylomeDB; Q9BUP3; -.
DR EvolutionaryTrace; Q9BUP3; -.
DR GeneWiki; HTATIP2; -.
DR GenomeRNAi; 10553; -.
DR NextBio; 40029; -.
DR PRO; PR:Q9BUP3; -.
DR ArrayExpress; Q9BUP3; -.
DR Bgee; Q9BUP3; -.
DR CleanEx; HS_HTATIP2; -.
DR Genevestigator; Q9BUP3; -.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005635; C:nuclear envelope; IDA:UniProtKB.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0003713; F:transcription coactivator activity; TAS:ProtInc.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:UniProtKB.
DR GO; GO:0051170; P:nuclear import; IDA:UniProtKB.
DR GO; GO:0045765; P:regulation of angiogenesis; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; TAS:ProtInc.
DR Gene3D; 3.40.50.720; -; 1.
DR InterPro; IPR016040; NAD(P)-bd_dom.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Angiogenesis;
KW Apoptosis; Complete proteome; Cytoplasm; Developmental protein;
KW Differentiation; Host-virus interaction; NADP; Nucleus;
KW Oxidoreductase; Polymorphism; Reference proteome; Tumor suppressor.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 242 Oxidoreductase HTATIP2.
FT /FTId=PRO_0000072544.
FT NP_BIND 19 52 NADP.
FT ACT_SITE 143 143 Proton acceptor (Probable).
FT ACT_SITE 147 147 Probable.
FT BINDING 131 131 Substrate (Probable).
FT MOD_RES 2 2 N-acetylalanine.
FT VAR_SEQ 1 1 M -> MAGPAALSAAAAAALAAALLLLRREDPGPGAGPSM
FT (in isoform 3).
FT /FTId=VSP_038339.
FT VAR_SEQ 102 133 EGFVRVDRDYVLKSAELAKAGGCKHFNLLSSK -> VRKAY
FT ALFPFCWPVISRILFLLTLFLCACCNA (in isoform
FT 2).
FT /FTId=VSP_051864.
FT VAR_SEQ 134 242 Missing (in isoform 2).
FT /FTId=VSP_051865.
FT VARIANT 106 106 R -> S (in a hepatocellular carcinoma
FT sample).
FT /FTId=VAR_023713.
FT VARIANT 108 108 D -> Y (in a hepatocellular carcinoma
FT sample).
FT /FTId=VAR_023714.
FT VARIANT 116 116 A -> T (in a hepatocellular carcinoma
FT sample).
FT /FTId=VAR_023715.
FT VARIANT 134 134 G -> V (in a hepatocellular carcinoma
FT sample; reduces protein stability).
FT /FTId=VAR_023716.
FT VARIANT 144 144 L -> I (in a hepatocellular carcinoma
FT sample).
FT /FTId=VAR_023717.
FT VARIANT 197 197 S -> R (in dbSNP:rs3824886).
FT /FTId=VAR_023718.
FT MUTAGEN 28 31 GETG->VETA: Loss of proapoptotic and
FT metastatis-inhibiting effect.
FT MUTAGEN 106 106 R->H: Loss of association with nucleus.
FT CONFLICT 87 87 V -> F (in Ref. 5; CAG33102).
FT CONFLICT 170 170 L -> P (in Ref. 6; BAD96730).
FT CONFLICT 182 182 W -> R (in Ref. 2; AAC39694).
FT CONFLICT 187 187 F -> L (in Ref. 1; AAB84360).
FT HELIX 6 16
FT STRAND 20 24
FT HELIX 29 41
FT STRAND 45 53
FT HELIX 60 64
FT STRAND 66 69
FT HELIX 72 82
FT STRAND 86 90
FT HELIX 96 108
FT HELIX 110 121
FT STRAND 126 130
FT HELIX 142 155
FT STRAND 160 166
FT STRAND 169 171
FT HELIX 175 177
FT HELIX 179 188
FT HELIX 195 198
FT STRAND 200 202
FT HELIX 203 214
FT STRAND 220 226
FT HELIX 227 233
SQ SEQUENCE 242 AA; 27049 MW; 6A26E4A095243678 CRC64;
MAETEALSKL REDFRMQNKS VFILGASGET GRVLLKEILE QGLFSKVTLI GRRKLTFDEE
AYKNVNQEVV DFEKLDDYAS AFQGHDVGFC CLGTTRGKAG AEGFVRVDRD YVLKSAELAK
AGGCKHFNLL SSKGADKSSN FLYLQVKGEV EAKVEELKFD RYSVFRPGVL LCDRQESRPG
EWLVRKFFGS LPDSWASGHS VPVVTVVRAM LNNVVRPRDK QMELLENKAI HDLGKAHGSL
KP
//
ID HTAI2_HUMAN Reviewed; 242 AA.
AC Q9BUP3; A8K7S7; D3DQY8; O15383; O60520; O95345; Q53GC1; Q53GG2;
read moreAC Q6IBI3;
DT 25-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 2.
DT 22-JAN-2014, entry version 105.
DE RecName: Full=Oxidoreductase HTATIP2;
DE EC=1.1.1.-;
DE AltName: Full=30 kDa HIV-1 TAT-interacting protein;
DE AltName: Full=HIV-1 TAT-interactive protein 2;
GN Name=HTATIP2; Synonyms=CC3, TIP30;
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 1), FUNCTION, TISSUE SPECIFICITY,
RP AND VARIANT ARG-197.
RC TISSUE=Lung cancer;
RX PubMed=9174052; DOI=10.1038/sj.onc.1201059;
RA Shtivelman E.;
RT "A link between metastasis and resistance to apoptosis of variant
RT small cell lung carcinoma.";
RL Oncogene 14:2167-2173(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INTERACTION WITH HIV-1
RP TAT.
RC TISSUE=Pancreatic islet;
RX PubMed=9482853; DOI=10.1073/pnas.95.5.2146;
RA Xiao H., Tao Y., Greenblatt J., Roeder R.G.;
RT "A cofactor, TIP30, specifically enhances HIV-1 Tat-activated
RT transcription.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:2146-2151(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, AND INTERACTION WITH
RP PSMD4.
RC TISSUE=Placenta;
RX PubMed=10611237; DOI=10.1128/MCB.20.2.583-593.2000;
RA Whitman S., Wang X., Shalaby R., Shtivelman E.;
RT "Alternatively spliced products CC3 and TC3 have opposing effects on
RT apoptosis.";
RL Mol. Cell. Biol. 20:583-593(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Synovium;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Small intestine;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F.,
RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E.,
RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S.,
RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W.,
RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S.,
RA Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANT
RP ARG-197.
RC TISSUE=Cervix, and Skin;
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 [10]
RP MUTAGENESIS OF 28-GLY--GLY-31.
RX PubMed=10698937; DOI=10.1093/emboj/19.5.956;
RA Xiao H., Palhan V., Yang Y., Roeder R.G.;
RT "TIP30 has an intrinsic kinase activity required for up-regulation of
RT a subset of apoptotic genes.";
RL EMBO J. 19:956-963(2000).
RN [11]
RP FUNCTION.
RX PubMed=11313954; DOI=10.1038/sj.onc.1204075;
RA NicAmhlaoibh R., Shtivelman E.;
RT "Metastasis suppressor CC3 inhibits angiogenic properties of tumor
RT cells in vitro.";
RL Oncogene 20:270-275(2001).
RN [12]
RP TISSUE SPECIFICITY, VARIANTS SER-106; TYR-108; THR-116; VAL-134 AND
RP ILE-144, MUTAGENESIS OF ARG-106, AND CHARACTERIZATION OF VARIANT
RP VAL-134.
RX PubMed=14695192;
RA Ito M., Jiang C., Krumm K., Zhang X., Pecha J., Zhao J., Guo Y.,
RA Roeder R.G., Xiao H.;
RT "TIP30 deficiency increases susceptibility to tumorigenesis.";
RL Cancer Res. 63:8763-8767(2003).
RN [13]
RP INTERACTION WITH NCOA5.
RX PubMed=15073177; DOI=10.1074/jbc.M401809200;
RA Jiang C., Ito M., Piening V., Bruck K., Roeder R.G., Xiao H.;
RT "TIP30 interacts with an estrogen receptor alpha-interacting
RT coactivator CIA and regulates c-myc transcription.";
RL J. Biol. Chem. 279:27781-27789(2004).
RN [14]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH XPO4; IPO5; IPO7;
RP IPO9; KPNB1; GCN1L1 AND LRPPRC.
RX PubMed=15282309; DOI=10.1128/MCB.24.16.7091-7101.2004;
RA King F.W., Shtivelman E.;
RT "Inhibition of nuclear import by the proapoptotic protein CC3.";
RL Mol. Cell. Biol. 24:7091-7101(2004).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS).
RX PubMed=15728189; DOI=10.1074/jbc.M501113200;
RA El Omari K., Bird L.E., Nichols C.E., Ren J., Stammers D.K.;
RT "Crystal structure of CC3 (TIP30): implications for its role as a
RT tumor suppressor.";
RL J. Biol. Chem. 280:18229-18236(2005).
RN [17]
RP VARIANT [LARGE SCALE ANALYSIS] ARG-197, AND MASS SPECTROMETRY.
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Oxidoreductase required for tumor suppression. NAPDH-
CC bound form inhibits nuclear import by competing with nuclear
CC import substrates for binding to a subset of nuclear transport
CC receptors. May act as a redox sensor linked to transcription
CC through regulation of nuclear import. Isoform 1 is a metastasis
CC suppressor with proapoptotic as well as antiangiogenic properties.
CC Isoform 2 has an antiapoptotic effect.
CC -!- SUBUNIT: Monomer. Binds nuclear transport receptors XPO4,
CC IPO5/RANBP5, IPO7, IPO9 and KPNB1 as well as GCN1L1/GCN1 and
CC LRPPRC probably through their HEAT repeats. Binds NCOA5/CIA.
CC Isoform 2 binds the proteasome subunit PSMD4/s5a through its N-
CC terminus. Binds the activation domain of HIV-1 Tat.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus envelope.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=CC3;
CC IsoId=Q9BUP3-1; Sequence=Displayed;
CC Name=2; Synonyms=TC3;
CC IsoId=Q9BUP3-2; Sequence=VSP_051864, VSP_051865;
CC Note=Mutagenesis of Leu-154 and Leu-157 or Cys-158, Cys-160 and
CC Cys-161 abolishes antiapoptotic effect;
CC Name=3;
CC IsoId=Q9BUP3-3; Sequence=VSP_038339;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Highest level in liver. High
CC levels in lung, skeletal muscle, pancreas and placenta. Moderate
CC levels in heart and kidney. Low levels in brain. Not expressed or
CC low levels in variant small cell lung carcinomas, 33% of
CC hepatocellular carcinomas and neuroblastomas.
CC -!- DOMAIN: Unique C-terminus confers high proteasome-dependent
CC instability to isoform 2.
CC -!- CAUTION: Was originally (PubMed:9482853 and PubMed:10698937)
CC thought to be a transcriptional coregulator with protein kinase
CC activity. However, crystal structure reveals a short chain
CC dehydrogenase/reductase fold binding NADPH rather than ATP.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/HTATIP2ID40894ch11p15.html";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; U69161; AAB84360.1; -; mRNA.
DR EMBL; AF039103; AAC39694.1; -; mRNA.
DR EMBL; AF092095; AAC78331.1; -; mRNA.
DR EMBL; AK292092; BAF84781.1; -; mRNA.
DR EMBL; CR456821; CAG33102.1; -; mRNA.
DR EMBL; AK223010; BAD96730.1; -; mRNA.
DR EMBL; AK222969; BAD96689.1; -; mRNA.
DR EMBL; AC025972; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471064; EAW68338.1; -; Genomic_DNA.
DR EMBL; CH471064; EAW68339.1; -; Genomic_DNA.
DR EMBL; BC002439; AAH02439.2; -; mRNA.
DR EMBL; BC015358; AAH15358.1; -; mRNA.
DR RefSeq; NP_001091990.1; NM_001098520.1.
DR RefSeq; NP_001091991.1; NM_001098521.1.
DR RefSeq; NP_001091992.1; NM_001098522.1.
DR RefSeq; NP_001091993.1; NM_001098523.1.
DR RefSeq; NP_006401.3; NM_006410.4.
DR UniGene; Hs.90753; -.
DR PDB; 2BKA; X-ray; 1.70 A; A=1-242.
DR PDBsum; 2BKA; -.
DR ProteinModelPortal; Q9BUP3; -.
DR SMR; Q9BUP3; 5-235.
DR MINT; MINT-5003508; -.
DR STRING; 9606.ENSP00000392985; -.
DR PhosphoSite; Q9BUP3; -.
DR DMDM; 74733240; -.
DR PaxDb; Q9BUP3; -.
DR PRIDE; Q9BUP3; -.
DR DNASU; 10553; -.
DR Ensembl; ENST00000419348; ENSP00000392985; ENSG00000109854.
DR Ensembl; ENST00000421577; ENSP00000397752; ENSG00000109854.
DR Ensembl; ENST00000443524; ENSP00000387876; ENSG00000109854.
DR Ensembl; ENST00000451739; ENSP00000394259; ENSG00000109854.
DR Ensembl; ENST00000530266; ENSP00000436548; ENSG00000109854.
DR Ensembl; ENST00000532081; ENSP00000432107; ENSG00000109854.
DR Ensembl; ENST00000532505; ENSP00000432338; ENSG00000109854.
DR GeneID; 10553; -.
DR KEGG; hsa:10553; -.
DR UCSC; uc001mpz.2; human.
DR CTD; 10553; -.
DR GeneCards; GC11P020341; -.
DR HGNC; HGNC:16637; HTATIP2.
DR HPA; HPA006417; -.
DR HPA; HPA024321; -.
DR MIM; 605628; gene.
DR neXtProt; NX_Q9BUP3; -.
DR PharmGKB; PA29539; -.
DR eggNOG; COG0702; -.
DR HOVERGEN; HBG052833; -.
DR InParanoid; Q9BUP3; -.
DR KO; K17290; -.
DR OMA; PRDKQME; -.
DR OrthoDB; EOG7GJ6GJ; -.
DR PhylomeDB; Q9BUP3; -.
DR EvolutionaryTrace; Q9BUP3; -.
DR GeneWiki; HTATIP2; -.
DR GenomeRNAi; 10553; -.
DR NextBio; 40029; -.
DR PRO; PR:Q9BUP3; -.
DR ArrayExpress; Q9BUP3; -.
DR Bgee; Q9BUP3; -.
DR CleanEx; HS_HTATIP2; -.
DR Genevestigator; Q9BUP3; -.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005635; C:nuclear envelope; IDA:UniProtKB.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0003713; F:transcription coactivator activity; TAS:ProtInc.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:UniProtKB.
DR GO; GO:0051170; P:nuclear import; IDA:UniProtKB.
DR GO; GO:0045765; P:regulation of angiogenesis; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; TAS:ProtInc.
DR Gene3D; 3.40.50.720; -; 1.
DR InterPro; IPR016040; NAD(P)-bd_dom.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Angiogenesis;
KW Apoptosis; Complete proteome; Cytoplasm; Developmental protein;
KW Differentiation; Host-virus interaction; NADP; Nucleus;
KW Oxidoreductase; Polymorphism; Reference proteome; Tumor suppressor.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 242 Oxidoreductase HTATIP2.
FT /FTId=PRO_0000072544.
FT NP_BIND 19 52 NADP.
FT ACT_SITE 143 143 Proton acceptor (Probable).
FT ACT_SITE 147 147 Probable.
FT BINDING 131 131 Substrate (Probable).
FT MOD_RES 2 2 N-acetylalanine.
FT VAR_SEQ 1 1 M -> MAGPAALSAAAAAALAAALLLLRREDPGPGAGPSM
FT (in isoform 3).
FT /FTId=VSP_038339.
FT VAR_SEQ 102 133 EGFVRVDRDYVLKSAELAKAGGCKHFNLLSSK -> VRKAY
FT ALFPFCWPVISRILFLLTLFLCACCNA (in isoform
FT 2).
FT /FTId=VSP_051864.
FT VAR_SEQ 134 242 Missing (in isoform 2).
FT /FTId=VSP_051865.
FT VARIANT 106 106 R -> S (in a hepatocellular carcinoma
FT sample).
FT /FTId=VAR_023713.
FT VARIANT 108 108 D -> Y (in a hepatocellular carcinoma
FT sample).
FT /FTId=VAR_023714.
FT VARIANT 116 116 A -> T (in a hepatocellular carcinoma
FT sample).
FT /FTId=VAR_023715.
FT VARIANT 134 134 G -> V (in a hepatocellular carcinoma
FT sample; reduces protein stability).
FT /FTId=VAR_023716.
FT VARIANT 144 144 L -> I (in a hepatocellular carcinoma
FT sample).
FT /FTId=VAR_023717.
FT VARIANT 197 197 S -> R (in dbSNP:rs3824886).
FT /FTId=VAR_023718.
FT MUTAGEN 28 31 GETG->VETA: Loss of proapoptotic and
FT metastatis-inhibiting effect.
FT MUTAGEN 106 106 R->H: Loss of association with nucleus.
FT CONFLICT 87 87 V -> F (in Ref. 5; CAG33102).
FT CONFLICT 170 170 L -> P (in Ref. 6; BAD96730).
FT CONFLICT 182 182 W -> R (in Ref. 2; AAC39694).
FT CONFLICT 187 187 F -> L (in Ref. 1; AAB84360).
FT HELIX 6 16
FT STRAND 20 24
FT HELIX 29 41
FT STRAND 45 53
FT HELIX 60 64
FT STRAND 66 69
FT HELIX 72 82
FT STRAND 86 90
FT HELIX 96 108
FT HELIX 110 121
FT STRAND 126 130
FT HELIX 142 155
FT STRAND 160 166
FT STRAND 169 171
FT HELIX 175 177
FT HELIX 179 188
FT HELIX 195 198
FT STRAND 200 202
FT HELIX 203 214
FT STRAND 220 226
FT HELIX 227 233
SQ SEQUENCE 242 AA; 27049 MW; 6A26E4A095243678 CRC64;
MAETEALSKL REDFRMQNKS VFILGASGET GRVLLKEILE QGLFSKVTLI GRRKLTFDEE
AYKNVNQEVV DFEKLDDYAS AFQGHDVGFC CLGTTRGKAG AEGFVRVDRD YVLKSAELAK
AGGCKHFNLL SSKGADKSSN FLYLQVKGEV EAKVEELKFD RYSVFRPGVL LCDRQESRPG
EWLVRKFFGS LPDSWASGHS VPVVTVVRAM LNNVVRPRDK QMELLENKAI HDLGKAHGSL
KP
//
MIM
605628
*RECORD*
*FIELD* NO
605628
*FIELD* TI
*605628 HIV-1 TAT-INTERACTING PROTEIN 2, 30-KD; HTATIP2
;;TIP30;;
CC3
*FIELD* TX
CLONING
read more
Small cell lung carcinoma (SCLC), which accounts for 25% of all lung
cancers, has the poorest survival rate of all histologic types of lung
cancer. Relapses and aggressive metastasis commonly occur after
favorable initial responses to therapy. By differential display of mRNA
from classic SCLC (c-SCLC) and variant SCLC (v-SCLC) cell lines,
followed by EST database searching, cDNA library screening, and 5-prime
RACE, Shtivelman (1997) identified a cDNA encoding CC3. The deduced
242-amino acid protein is evolutionarily conserved and lacks known
protein domains. Northern blot analysis revealed ubiquitous expression
of a 1.6-kb transcript in normal tissues and tumor cell lines except for
v-SCLC and neuroblastoma. Introduction of CC3 into v-SCLC cells resulted
in a significant suppression of metastasis in a SCID-hu mouse model, as
well as massive and rapid cell death in vitro through apoptosis. The
author suggested that loss of CC3 in SCLC cells might render them
resistant to death-inducing signals.
Using affinity chromatography with the human immunodeficiency virus-1
(HIV-1) Tat protein (see 601409) to screen HeLa cell extracts, followed
by SDS-PAGE analysis, Xiao et al. (1998) identified 2 Tat-interacting
proteins, TIP30 and TIP56. By micropeptide sequence analysis and EST
database searching, Xiao et al. (1998) identified a cDNA encoding TIP30.
Western blot analysis determined that the translated 242-amino acid
protein and the native protein have a molecular mass of 30 kD.
Coexpression of TIP30 specifically enhanced transcription of Tat in
transfected cells. Immunodepletion of TIP30 from nuclear extracts
abolished Tat-activated transcription while leaving Tat-independent
transcription unimpaired.
GENE FUNCTION
Whitman et al. (2000) identified a splice variant of CC3, which they
termed TC3, that encodes a 133-amino acid protein. TC3 shares its
N-terminal domain with CC3 but has a short, unique C terminus. Northern
blot analysis detected a 0.8-kb TC3 transcript in some but not all tumor
cell lines. Western blot analysis detected CC3 predominantly in membrane
and nuclear fractions but not in the cytoplasm, whereas TC3 was
predominantly in membrane fractions. The authors determined that the
potent proapoptotic activity of CC3 resides in the N-terminal domain;
however, the short C terminus of TC3 confers upon it antiapoptotic
properties capable of inhibiting apoptosis induced by CC3 and other
death stimuli.
BIOCHEMICAL FEATURES
Baker et al. (2000) pointed out that the sequences of CC3 and TIP30 are
identical. Sequence analysis indicated that TIP30/CC3 is a member of the
short-chain dehydrogenase/reductase (SDR) family. The authors created a
3-dimensional model of the TIP30/CC3 protein, which showed that like
other SDR proteins, TIP30/CC3 contains several well-conserved features.
These include a beta-alpha-beta fold at the N terminus, which Baker et
al. (2000) predicted binds to NADP(H). The N terminus also contains a
unique 20-amino acid alpha-helical stretch that may enable docking to
other proteins.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the HTATIP2
gene to chromosome 11 (TMAP SGC34227).
*FIELD* RF
1. Baker, M. E.; Yan, L.; Pear, M. R.: Three-dimensional model of
human TIP30, a coactivator for HIV-1 Tat-activated transcription,
and CC3, a protein associated with metastasis suppression. Cell.
Molec. Life Sci. 57: 851-858, 2000.
2. Shtivelman, E.: A link between metastasis and resistance to apoptosis
of variant small cell lung carcinoma. Oncogene 14: 2167-2173, 1997.
3. Whitman, S.; Wang, X.; Shalaby, R.; Shtivelman, E.: Alternatively
spliced products CC3 and TC3 have opposing effects on apoptosis. Molec.
Cell. Biol. 20: 583-593, 2000.
4. Xiao, H.; Tao, Y.; Greenblatt, J.; Roeder, R. G.: A cofactor,
TIP30, specifically enhances HIV-1 Tat-activated transcription. Proc.
Nat. Acad. Sci. 95: 2146-2151, 1998.
*FIELD* CD
Paul J. Converse: 2/8/2001
*FIELD* ED
alopez: 05/28/2004
mgross: 2/8/2001
*RECORD*
*FIELD* NO
605628
*FIELD* TI
*605628 HIV-1 TAT-INTERACTING PROTEIN 2, 30-KD; HTATIP2
;;TIP30;;
CC3
*FIELD* TX
CLONING
read more
Small cell lung carcinoma (SCLC), which accounts for 25% of all lung
cancers, has the poorest survival rate of all histologic types of lung
cancer. Relapses and aggressive metastasis commonly occur after
favorable initial responses to therapy. By differential display of mRNA
from classic SCLC (c-SCLC) and variant SCLC (v-SCLC) cell lines,
followed by EST database searching, cDNA library screening, and 5-prime
RACE, Shtivelman (1997) identified a cDNA encoding CC3. The deduced
242-amino acid protein is evolutionarily conserved and lacks known
protein domains. Northern blot analysis revealed ubiquitous expression
of a 1.6-kb transcript in normal tissues and tumor cell lines except for
v-SCLC and neuroblastoma. Introduction of CC3 into v-SCLC cells resulted
in a significant suppression of metastasis in a SCID-hu mouse model, as
well as massive and rapid cell death in vitro through apoptosis. The
author suggested that loss of CC3 in SCLC cells might render them
resistant to death-inducing signals.
Using affinity chromatography with the human immunodeficiency virus-1
(HIV-1) Tat protein (see 601409) to screen HeLa cell extracts, followed
by SDS-PAGE analysis, Xiao et al. (1998) identified 2 Tat-interacting
proteins, TIP30 and TIP56. By micropeptide sequence analysis and EST
database searching, Xiao et al. (1998) identified a cDNA encoding TIP30.
Western blot analysis determined that the translated 242-amino acid
protein and the native protein have a molecular mass of 30 kD.
Coexpression of TIP30 specifically enhanced transcription of Tat in
transfected cells. Immunodepletion of TIP30 from nuclear extracts
abolished Tat-activated transcription while leaving Tat-independent
transcription unimpaired.
GENE FUNCTION
Whitman et al. (2000) identified a splice variant of CC3, which they
termed TC3, that encodes a 133-amino acid protein. TC3 shares its
N-terminal domain with CC3 but has a short, unique C terminus. Northern
blot analysis detected a 0.8-kb TC3 transcript in some but not all tumor
cell lines. Western blot analysis detected CC3 predominantly in membrane
and nuclear fractions but not in the cytoplasm, whereas TC3 was
predominantly in membrane fractions. The authors determined that the
potent proapoptotic activity of CC3 resides in the N-terminal domain;
however, the short C terminus of TC3 confers upon it antiapoptotic
properties capable of inhibiting apoptosis induced by CC3 and other
death stimuli.
BIOCHEMICAL FEATURES
Baker et al. (2000) pointed out that the sequences of CC3 and TIP30 are
identical. Sequence analysis indicated that TIP30/CC3 is a member of the
short-chain dehydrogenase/reductase (SDR) family. The authors created a
3-dimensional model of the TIP30/CC3 protein, which showed that like
other SDR proteins, TIP30/CC3 contains several well-conserved features.
These include a beta-alpha-beta fold at the N terminus, which Baker et
al. (2000) predicted binds to NADP(H). The N terminus also contains a
unique 20-amino acid alpha-helical stretch that may enable docking to
other proteins.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the HTATIP2
gene to chromosome 11 (TMAP SGC34227).
*FIELD* RF
1. Baker, M. E.; Yan, L.; Pear, M. R.: Three-dimensional model of
human TIP30, a coactivator for HIV-1 Tat-activated transcription,
and CC3, a protein associated with metastasis suppression. Cell.
Molec. Life Sci. 57: 851-858, 2000.
2. Shtivelman, E.: A link between metastasis and resistance to apoptosis
of variant small cell lung carcinoma. Oncogene 14: 2167-2173, 1997.
3. Whitman, S.; Wang, X.; Shalaby, R.; Shtivelman, E.: Alternatively
spliced products CC3 and TC3 have opposing effects on apoptosis. Molec.
Cell. Biol. 20: 583-593, 2000.
4. Xiao, H.; Tao, Y.; Greenblatt, J.; Roeder, R. G.: A cofactor,
TIP30, specifically enhances HIV-1 Tat-activated transcription. Proc.
Nat. Acad. Sci. 95: 2146-2151, 1998.
*FIELD* CD
Paul J. Converse: 2/8/2001
*FIELD* ED
alopez: 05/28/2004
mgross: 2/8/2001