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Q9BUP3 (HTAI2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 108. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Oxidoreductase HTATIP2

EC=1.1.1.-
Alternative name(s):
30 kDa HIV-1 TAT-interacting protein
HIV-1 TAT-interactive protein 2
Gene names
Name:HTATIP2
Synonyms:CC3, TIP30
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length242 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Oxidoreductase required for tumor suppression. NAPDH-bound form inhibits nuclear import by competing with nuclear import substrates for binding to a subset of nuclear transport receptors. May act as a redox sensor linked to transcription through regulation of nuclear import. Isoform 1 is a metastasis suppressor with proapoptotic as well as antiangiogenic properties. Isoform 2 has an antiapoptotic effect. Ref.1 Ref.3 Ref.11 Ref.14

Subunit structure

Monomer. Binds nuclear transport receptors XPO4, IPO5/RANBP5, IPO7, IPO9 and KPNB1 as well as GCN1L1/GCN1 and LRPPRC probably through their HEAT repeats. Binds NCOA5/CIA. Isoform 2 binds the proteasome subunit PSMD4/s5a through its N-terminus. Binds the activation domain of HIV-1 Tat. Ref.2 Ref.3 Ref.13 Ref.14 Ref.16

Subcellular location

Cytoplasm. Nucleus envelope Ref.14.

Tissue specificity

Ubiquitous. Highest level in liver. High levels in lung, skeletal muscle, pancreas and placenta. Moderate levels in heart and kidney. Low levels in brain. Not expressed or low levels in variant small cell lung carcinomas, 33% of hepatocellular carcinomas and neuroblastomas. Ref.1 Ref.12

Domain

Unique C-terminus confers high proteasome-dependent instability to isoform 2. Ref.3

Caution

Was originally (Ref.2 and Ref.10) thought to be a transcriptional coregulator with protein kinase activity. However, crystal structure reveals a short chain dehydrogenase/reductase fold binding NADPH rather than ATP.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 Ref.1 (identifier: Q9BUP3-1)

Also known as: CC3;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 Ref.3 (identifier: Q9BUP3-2)

Also known as: TC3;

The sequence of this isoform differs from the canonical sequence as follows:
     102-133: EGFVRVDRDYVLKSAELAKAGGCKHFNLLSSK → VRKAYALFPFCWPVISRILFLLTLFLCACCNA
     134-242: Missing.
Note: Mutagenesis of Leu-154 and Leu-157 or Cys-158, Cys-160 and Cys-161 abolishes antiapoptotic effect.
Isoform 3 (identifier: Q9BUP3-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MAGPAALSAAAAAALAAALLLLRREDPGPGAGPSM

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.15
Chain2 – 242241Oxidoreductase HTATIP2
PRO_0000072544

Regions

Nucleotide binding19 – 5234NADP Ref.16

Sites

Active site1431Proton acceptor Probable Ref.16
Active site1471 Probable Ref.16
Binding site1311Substrate Probable Ref.16

Amino acid modifications

Modified residue21N-acetylalanine Ref.15

Natural variations

Alternative sequence11M → MAGPAALSAAAAAALAAALL LLRREDPGPGAGPSM in isoform 3.
VSP_038339
Alternative sequence102 – 13332EGFVR…LLSSK → VRKAYALFPFCWPVISRILF LLTLFLCACCNA in isoform 2.
VSP_051864
Alternative sequence134 – 242109Missing in isoform 2.
VSP_051865
Natural variant1061R → S in a hepatocellular carcinoma sample. Ref.12
VAR_023713
Natural variant1081D → Y in a hepatocellular carcinoma sample. Ref.12
VAR_023714
Natural variant1161A → T in a hepatocellular carcinoma sample. Ref.12
VAR_023715
Natural variant1341G → V in a hepatocellular carcinoma sample; reduces protein stability. Ref.12
VAR_023716
Natural variant1441L → I in a hepatocellular carcinoma sample. Ref.12
VAR_023717
Natural variant1971S → R Highly associated with hepatocellular carcinoma (HCC) progression. Ref.1 Ref.9 Ref.17 Ref.18
Corresponds to variant rs3824886 [ dbSNP | Ensembl ].
VAR_023718

Experimental info

Mutagenesis28 – 314GETG → VETA: Loss of proapoptotic and metastatis-inhibiting effect. Ref.10
Mutagenesis1061R → H: Loss of association with nucleus. Ref.12
Sequence conflict871V → F in CAG33102. Ref.5
Sequence conflict1701L → P in BAD96730. Ref.6
Sequence conflict1821W → R in AAC39694. Ref.2
Sequence conflict1871F → L in AAB84360. Ref.1

Secondary structure

......................................... 242
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (CC3) [UniParc].

Last modified January 11, 2011. Version 2.
Checksum: 6A26E4A095243678

FASTA24227,049
        10         20         30         40         50         60 
MAETEALSKL REDFRMQNKS VFILGASGET GRVLLKEILE QGLFSKVTLI GRRKLTFDEE 

        70         80         90        100        110        120 
AYKNVNQEVV DFEKLDDYAS AFQGHDVGFC CLGTTRGKAG AEGFVRVDRD YVLKSAELAK 

       130        140        150        160        170        180 
AGGCKHFNLL SSKGADKSSN FLYLQVKGEV EAKVEELKFD RYSVFRPGVL LCDRQESRPG 

       190        200        210        220        230        240 
EWLVRKFFGS LPDSWASGHS VPVVTVVRAM LNNVVRPRDK QMELLENKAI HDLGKAHGSL 


KP 

« Hide

Isoform 2 (TC3) [UniParc].

Checksum: D5C06E44FAE16E82
Show »

FASTA13314,914
Isoform 3 [UniParc].

Checksum: 655FB91EC4F33B34
Show »

FASTA27630,131

References

« Hide 'large scale' references
[1]"A link between metastasis and resistance to apoptosis of variant small cell lung carcinoma."
Shtivelman E.
Oncogene 14:2167-2173(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, VARIANT ARG-197.
Tissue: Lung cancer.
[2]"A cofactor, TIP30, specifically enhances HIV-1 Tat-activated transcription."
Xiao H., Tao Y., Greenblatt J., Roeder R.G.
Proc. Natl. Acad. Sci. U.S.A. 95:2146-2151(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH HIV-1 TAT.
Tissue: Pancreatic islet.
[3]"Alternatively spliced products CC3 and TC3 have opposing effects on apoptosis."
Whitman S., Wang X., Shalaby R., Shtivelman E.
Mol. Cell. Biol. 20:583-593(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, INTERACTION WITH PSMD4.
Tissue: Placenta.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Synovium.
[5]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[6]Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Small intestine.
[7]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"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] (ISOFORMS 1 AND 3), VARIANT ARG-197.
Tissue: Cervix and Skin.
[10]"TIP30 has an intrinsic kinase activity required for up-regulation of a subset of apoptotic genes."
Xiao H., Palhan V., Yang Y., Roeder R.G.
EMBO J. 19:956-963(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF 28-GLY--GLY-31.
[11]"Metastasis suppressor CC3 inhibits angiogenic properties of tumor cells in vitro."
NicAmhlaoibh R., Shtivelman E.
Oncogene 20:270-275(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[12]"TIP30 deficiency increases susceptibility to tumorigenesis."
Ito M., Jiang C., Krumm K., Zhang X., Pecha J., Zhao J., Guo Y., Roeder R.G., Xiao H.
Cancer Res. 63:8763-8767(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, VARIANTS SER-106; TYR-108; THR-116; VAL-134 AND ILE-144, MUTAGENESIS OF ARG-106, CHARACTERIZATION OF VARIANT VAL-134.
[13]"TIP30 interacts with an estrogen receptor alpha-interacting coactivator CIA and regulates c-myc transcription."
Jiang C., Ito M., Piening V., Bruck K., Roeder R.G., Xiao H.
J. Biol. Chem. 279:27781-27789(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NCOA5.
[14]"Inhibition of nuclear import by the proapoptotic protein CC3."
King F.W., Shtivelman E.
Mol. Cell. Biol. 24:7091-7101(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH XPO4; IPO5; IPO7; IPO9; KPNB1; GCN1L1 AND LRPPRC.
[15]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[16]"Crystal structure of CC3 (TIP30): implications for its role as a tumor suppressor."
El Omari K., Bird L.E., Nichols C.E., Ren J., Stammers D.K.
J. Biol. Chem. 280:18229-18236(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS).
[17]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] ARG-197, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]"Large-scale quantification of single amino-acid variations by a variation-associated database search strategy."
Song C., Wang F., Cheng K., Wei X., Bian Y., Wang K., Tan Y., Wang H., Ye M., Zou H.
J. Proteome Res. 13:241-248(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ARG-197.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U69161 mRNA. Translation: AAB84360.1.
AF039103 mRNA. Translation: AAC39694.1.
AF092095 mRNA. Translation: AAC78331.1.
AK292092 mRNA. Translation: BAF84781.1.
CR456821 mRNA. Translation: CAG33102.1.
AK223010 mRNA. Translation: BAD96730.1.
AK222969 mRNA. Translation: BAD96689.1.
AC025972 Genomic DNA. No translation available.
CH471064 Genomic DNA. Translation: EAW68338.1.
CH471064 Genomic DNA. Translation: EAW68339.1.
BC002439 mRNA. Translation: AAH02439.2.
BC015358 mRNA. Translation: AAH15358.1.
RefSeqNP_001091990.1. NM_001098520.1.
NP_001091991.1. NM_001098521.1.
NP_001091992.1. NM_001098522.1.
NP_001091993.1. NM_001098523.1.
NP_006401.3. NM_006410.4.
UniGeneHs.90753.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2BKAX-ray1.70A1-242[»]
ProteinModelPortalQ9BUP3.
SMRQ9BUP3. Positions 5-235.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115804. 3 interactions.
MINTMINT-5003508.
STRING9606.ENSP00000392985.

PTM databases

PhosphoSiteQ9BUP3.

Polymorphism databases

DMDM317373366.

Proteomic databases

PaxDbQ9BUP3.
PRIDEQ9BUP3.

Protocols and materials databases

DNASU10553.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000419348; ENSP00000392985; ENSG00000109854. [Q9BUP3-3]
ENST00000421577; ENSP00000397752; ENSG00000109854. [Q9BUP3-1]
ENST00000443524; ENSP00000387876; ENSG00000109854. [Q9BUP3-1]
ENST00000451739; ENSP00000394259; ENSG00000109854. [Q9BUP3-1]
ENST00000530266; ENSP00000436548; ENSG00000109854. [Q9BUP3-2]
ENST00000532081; ENSP00000432107; ENSG00000109854. [Q9BUP3-2]
ENST00000532505; ENSP00000432338; ENSG00000109854. [Q9BUP3-2]
GeneID10553.
KEGGhsa:10553.
UCSCuc001mpx.2. human. [Q9BUP3-3]
uc001mpy.4. human. [Q9BUP3-2]
uc001mpz.2. human. [Q9BUP3-1]

Organism-specific databases

CTD10553.
GeneCardsGC11P020341.
HGNCHGNC:16637. HTATIP2.
HPAHPA006417.
HPA024321.
MIM605628. gene.
neXtProtNX_Q9BUP3.
PharmGKBPA29539.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0702.
HOVERGENHBG052833.
InParanoidQ9BUP3.
KOK17290.
OMAPRDKQME.
OrthoDBEOG7GJ6GJ.
PhylomeDBQ9BUP3.
TreeFamTF312849.

Gene expression databases

ArrayExpressQ9BUP3.
BgeeQ9BUP3.
CleanExHS_HTATIP2.
GenevestigatorQ9BUP3.

Family and domain databases

Gene3D3.40.50.720. 1 hit.
InterProIPR016040. NAD(P)-bd_dom.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9BUP3.
GeneWikiHTATIP2.
GenomeRNAi10553.
NextBio40029.
PROQ9BUP3.
SOURCESearch...

Entry information

Entry nameHTAI2_HUMAN
AccessionPrimary (citable) accession number: Q9BUP3
Secondary accession number(s): A8K7S7 expand/collapse secondary AC list , D3DQY8, O15383, O60520, O95345, Q53GC1, Q53GG2, Q6IBI3
Entry history
Integrated into UniProtKB/Swiss-Prot: October 25, 2005
Last sequence update: January 11, 2011
Last modified: April 16, 2014
This is version 108 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM