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HTATIP2 (HIV-1 Tat interactive protein 2, 30kDa)

Written2009-03Jian Zhao
International Joint Cancer Institute, The Second Military Medical University, Shanghai, People's Republic of China

(Note : for Links provided by Atlas : click)


Alias (NCBI)CC3
HGNC Alias symbTIP30
HGNC Alias nameTat-interacting protein (30kD)
 short chain dehydrogenase/reductase family 44U, member 1
HGNC Previous nameHIV-1 Tat interactive protein 2, 30 kDa
 HIV-1 Tat interactive protein 2, 30kDa
LocusID (NCBI) 10553
Atlas_Id 40894
Location 11p15.1  [Link to chromosome band 11p15]
Location_base_pair Starts at 20363685 and ends at 20383783 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping HTATIP2.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
HTATIP2 (11p15.1)::CA1 (8q21.2)HTATIP2 (11p15.1)::SUPT20H (13q13.3)
Note HTATIP2, also called TIP30, is a transcriptional cofactor that enhances Tat-mediated transcription.


  Genomic structure of published HTATIP2 alternatively spliced transcripts. Boxes indicate exons with coding regions in green. Red boxes indicate UTRs.
Description The human HTATIP2 gene has 6 exons that span more than 2.5 kb of genomic sequence located on chromosome 11p15.1.
Transcription HTATIP2 has four types of transcripts with 1.5 kb, 1.4 kb, 1.7 kb and 1.4 kb and they encode the same protein, 242aa, as a result of alternative splicing. And a small type of HTATIP2 isoform is 0.78 kb composed of 2 exons coding a 133aa protein.
Pseudogene None.


  Structure model of HTATIP2/TIP30. Serine-132, tyrosine-143 and lysine-147, which correspond to the catalytically active residues in SDRs and NADPH are shown. The a-helices E and F normally involved in a dimer interface are labelled (Baker et al., 2000).
Description HTATIP2 includes isoform a and isoform b, both of which contain 242aa, and isoform c, 131aa. HTATIP2 can interact with the N-terminal trans-activation domain of HIV-tat directly as 30kDa Tat-interacting protein, to activate the HIV-1 promoter (Xiao et al., 1998), and with an ERa-interacting coactivator CIA to repress the expression of c-myc (Jiang et al., 2004). It is a member of the short-chain dehydrogenases/reductases (SDR) family (Baker et al., 2000) and have a cavity of NADPH binding site in its structure (El Omari et al., 2005). HTATIP2 has Ser/Thr protein kinase activity, which can undergo autophosphorylation, and phosphorylates the heptapeptide repeats of the C-terminal domain of the largest RNA polymerase II subunit in a tat-dependent manner. HTATIP2 binds directly to the karyopherins of the importin beta family in a RanGTP-insensitive manner and associates with nucleoporins in vivo (King and Shtivelman, 2004).
Expression HTATIP2 is an evolutionary conserved gene that is expressed ubiquitously in human tissues, while it is down-expressed in many tumors tissues, such as prostate, colon, liver, lung and breast cancers (Hewitt et al., 2000; Jiang et al., 2007; Lee et al., 2004; Varambally et al., 2002).
Localisation HTATIP2 protein was found predominantly in the membrane and nuclear fractions but not in the particulate free cytoplasmic fraction (Whitman et al., 2000).
Function The HTATIP2 gene is a tumor susceptibility gene, which is associated with the suppression of metastasis in small cell lung cancer (SCLC) (Shtivelman, 1997), hepatocarcinoma (Ito et al., 2003). HTATIP2 interacts with an Estrogen Receptor alpha-interacting coactivator CIA (coactivator independent of AF-2 function), to repress the expression of c-myc gene, and also associated with ets-1 to inhibit osteopontin transcription in human hepatocellular carcinoma (Zhao et al., 2008b). HTATIP2 forms a RanGTP-resistant complex with importins to inhibit nuclear import and induce apoptosis (King and Shtivelman, 2004). HTATIP2 also induces apoptosis under oxidative stress through stabilization of p53 mRNA (Zhao et al., 2008a).
Homology HTATIP2 encodes a protein whose sequence is highly conserved in evolution, with homologous genes being present in Caenorhabditis elegans, Saccharomyces cerevisiae, Escherichia coli (Whitman et al., 2000), Branchiostoma belcheri (Wang et al., 2008), and Mus musculus.


Note HTATIP2 mutant derived from hepatocellular carcinoma specimens promotes growth of HepG2 cells (Jiang et al., 2007).
  The red amino acids are mutated into other one, as schematic representation (Jiang et al., 2007).
Somatic There are two types of HTATIP2 mutation, G134V and R106H, in hepatocellular carcinoma specimens (Jiang et al., 2007).

Implicated in

Entity Various carcinomas
Disease HTATIP2 reported to be down-regulated in some kinds of cancers, such as lung cancer (NicAmhlaoibh and Shtivelman, 2001), hepatocellular carcinoma (Zhao et al., 2008), gastric cancer (Li et al., 2009), prostate cancer (Zhang et al., 2008), breast carcinoma (Zhang et al., 2005; Zhao et al., 2007).
Entity Multiple sclerosis (MS)
Disease Oligodendrocyte precursor cells (OPCs) presist near the demyelinated axons arising in MS but inefficiently differentiate into oligodendrocytes and remyelinate these axons. Abnormal expression of HTATIP2, a direct inhibitor of Importin, is observed in these OPCs. Overexpression of HTATIP2 in a rat OPC cell line resulted in cytoplasmic entrapment of NICD and arrest of differentiation upon stimulation with Contactin- Fc.


Three-dimensional model of human TIP30, a coactivator for HIV-1 Tat-activated transcription, and CC3, a protein associated with metastasis suppression.
Baker ME, Yan L, Pear MR.
Cell Mol Life Sci. 2000 May;57(5):851-8.
PMID 10892349
Crystal structure of CC3 (TIP30): implications for its role as a tumor suppressor.
El Omari K, Bird LE, Nichols CE, Ren J, Stammers DK.
J Biol Chem. 2005 May 6;280(18):18229-36. Epub 2005 Feb 22.
PMID 15728189
Increased expression of tissue inhibitor of metalloproteinases type 1 (TIMP-1) in a more tumourigenic colon cancer cell line.
Hewitt RE, Brown KE, Corcoran M, Stetler-Stevenson WG.
J Pathol. 2000 Dec;192(4):455-9.
PMID 11113862
TIP30 deficiency increases susceptibility to tumorigenesis.
Ito M, Jiang C, Krumm K, Zhang X, Pecha J, Zhao J, Guo Y, Roeder RG, Xiao H.
Cancer Res. 2003 Dec 15;63(24):8763-7.
PMID 14695192
TIP30 interacts with an estrogen receptor alpha-interacting coactivator CIA and regulates c-myc transcription.
Jiang C, Ito M, Piening V, Bruck K, Roeder RG, Xiao H.
J Biol Chem. 2004 Jun 25;279(26):27781-9. Epub 2004 Apr 8.
PMID 15073177
TIP30 mutant derived from hepatocellular carcinoma specimens promotes growth of HepG2 cells through up-regulation of N-cadherin.
Jiang C, Pecha J, Hoshino I, Ankrapp D, Xiao H.
Cancer Res. 2007 Apr 15;67(8):3574-82.
PMID 17440068
Inhibition of nuclear import by the proapoptotic protein CC3.
King FW, Shtivelman E.
Mol Cell Biol. 2004 Aug;24(16):7091-101.
PMID 15282309
CC3/TIP30 expression was strongly associated with HER-2/NEU status in breast cancer.
Lee LW, Zhang DH, Lee KT, Koay ES, Hewitt RE.
Ann Acad Med Singapore. 2004 Sep;33(5 Suppl):S30-2.
PMID 15651195
Reduction of TIP30 correlates with poor prognosis of gastric cancer patients and its restoration drastically inhibits tumor growth and metastasis.
Li X, Zhang Y, Cao S, Chen X, Lu Y, Jin H, Sun S, Chen B, Liu J, Ding J, Wu K, Fan D.
Int J Cancer. 2009 Feb 1;124(3):713-21.
PMID 18972434
Methylation of Tip30 promoter is associated with poor prognosis in human hepatocellular carcinoma.
Lu B, Ma Y, Wu G, Tong X, Guo H, Liang A, Cong W, Liu C, Wang H, Wu M, Zhao J, Guo Y.
Clin Cancer Res. 2008 Nov 15;14(22):7405-12.
PMID 19010857
Abnormal expression of TIP30 and arrested nucleocytoplasmic transport within oligodendrocyte precursor cells in multiple sclerosis.
Nakahara J, Kanekura K, Nawa M, Aiso S, Suzuki N.
J Clin Invest. 2009 Jan;119(1):169-81.
PMID 19104151
Metastasis suppressor CC3 inhibits angiogenic properties of tumor cells in vitro.
NicAmhlaoibh R, Shtivelman E.
Oncogene. 2001 Jan 11;20(2):270-5.
PMID 11313954
A link between metastasis and resistance to apoptosis of variant small cell lung carcinoma.
Shtivelman E.
Oncogene. 1997 May 8;14(18):2167-73.
PMID 9174052
The polycomb group protein EZH2 is involved in progression of prostate cancer.
Varambally S, Dhanasekaran SM, Zhou M, Barrette TR, Kumar-Sinha C, Sanda MG, Ghosh D, Pienta KJ, Sewalt RG, Otte AP, Rubin MA, Chinnaiyan AM.
Nature. 2002 Oct 10;419(6907):624-9.
PMID 12374981
Cloning, expression, purification, and characterization of AmphiTip30, a member of short-chain dehydrogenases/reductases family from the amphioxus Branchiostoma belcheri tsingtauense.
Wang S, Zhao B, Zhang S, Ji H.
Protein Expr Purif. 2008 Jan;57(1):63-71. Epub 2007 Sep 14.
PMID 17950618
Alternatively spliced products CC3 and TC3 have opposing effects on apoptosis.
Whitman S, Wang X, Shalaby R, Shtivelman E.
Mol Cell Biol. 2000 Jan;20(2):583-93.
PMID 10611237
A cofactor, TIP30, specifically enhances HIV-1 Tat-activated transcription.
Xiao H, Tao Y, Greenblatt J, Roeder RG.
Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2146-51.
PMID 9482853
Overexpression of CC3/TIP30 is associated with HER-2/neu status in breast cancer.
Zhang DH, Wong LL, Tai LK, Koay ES, Hewitt RE.
J Cancer Res Clin Oncol. 2005 Sep;131(9):603-8. Epub 2005 Oct 20.
PMID 15931508
TIP30 is associated with progression and metastasis of prostate cancer.
Zhang H, Zhang Y, Duan HO, Kirley SD, Lin SX, McDougal WS, Xiao H, Wu CL.
Int J Cancer. 2008 Aug 15;123(4):810-6.
PMID 18528861
TIP30 induces apoptosis under oxidative stress through stabilization of p53 messenger RNA in human hepatocellular carcinoma.
Zhao J, Chen J, Lu B, Dong L, Wang H, Bi C, Wu G, Guo H, Wu M, Guo Y.
Cancer Res. 2008 Jun 1;68(11):4133-41.
PMID 18519672
Thirty-kilodalton Tat-interacting protein suppresses tumor metastasis by inhibition of osteopontin transcription in human hepatocellular carcinoma.
Zhao J, Lu B, Xu H, Tong X, Wu G, Zhang X, Liang A, Cong W, Dai J, Wang H, Wu M, Guo Y.
Hepatology. 2008 Jul;48(1):265-75.
PMID 18537194
TIP30/CC3 expression in breast carcinoma: relation to metastasis, clinicopathologic parameters, and P53 expression.
Zhao J, Ni H, Ma Y, Dong L, Dai J, Zhao F, Yan X, Lu B, Xu H, Guo Y.
Hum Pathol. 2007 Feb;38(2):293-8. Epub 2006 Nov 13.
PMID 17097132


This paper should be referenced as such :
Zhao, J
HTATIP2 (HIV-1 Tat interactive protein 2, 30kDa)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(2):137-140.
Free journal version : [ pdf ]   [ DOI ]

External links


HGNC (Hugo)HTATIP2   16637
Entrez_Gene (NCBI)HTATIP2    HIV-1 Tat interactive protein 2
AliasesCC3; SDR44U1; TIP30
GeneCards (Weizmann)HTATIP2
Ensembl hg19 (Hinxton)ENSG00000109854 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000109854 [Gene_View]  ENSG00000109854 [Sequence]  chr11:20363685-20383783 [Contig_View]  HTATIP2 [Vega]
ICGC DataPortalENSG00000109854
Genatlas (Paris)HTATIP2
Genetics Home Reference (NIH)HTATIP2
Genomic and cartography
GoldenPath hg38 (UCSC)HTATIP2  -     chr11:20363685-20383783 +  11p15.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)HTATIP2  -     11p15.1   [Description]    (hg19-Feb_2009)
GoldenPathHTATIP2 - 11p15.1 [CytoView hg19]  HTATIP2 - 11p15.1 [CytoView hg38]
Genome Data Viewer NCBIHTATIP2 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AF039103 AF092095 AI193677 AK130473 AK222969
RefSeq transcript (Entrez)NM_001098520 NM_001098521 NM_001098522 NM_001098523 NM_006410
Consensus coding sequences : CCDS (NCBI)HTATIP2
Gene Expression Viewer (FireBrowse)HTATIP2 [ Firebrowse - Broad ]
GenevisibleExpression of HTATIP2 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)10553
GTEX Portal (Tissue expression)HTATIP2
Human Protein AtlasENSG00000109854-HTATIP2 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9BUP3   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9BUP3  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9BUP3
Catalytic activity : Enzyme1.1.1.- [ Enzyme-Expasy ]   1.1.1.-1.1.1.- [ IntEnz-EBI ]   1.1.1.- [ BRENDA ]   1.1.1.- [ KEGG ]   [ MEROPS ]
Domains : Interpro (EBI)NAD(P)-bd_dom    NAD(P)-bd_dom_sf   
Domain families : Pfam (Sanger)NAD_binding_10 (PF13460)   
Domain families : Pfam (NCBI)pfam13460   
Conserved Domain (NCBI)HTATIP2
PDB Europe2BKA   
Structural Biology KnowledgeBase2BKA   
SCOP (Structural Classification of Proteins)2BKA   
CATH (Classification of proteins structures)2BKA   
AlphaFold pdb e-kbQ9BUP3   
Human Protein Atlas [tissue]ENSG00000109854-HTATIP2 [tissue]
Protein Interaction databases
IntAct (EBI)Q9BUP3
Ontologies - Pathways
Ontology : AmiGOangiogenesis  transcription coactivator activity  protein serine/threonine kinase activity  protein binding  nucleus  nuclear envelope  cytoplasm  cytoplasm  cytosol  regulation of transcription by RNA polymerase II  apoptotic process  membrane  oxidoreductase activity  cell differentiation  negative regulation of apoptotic process  positive regulation of programmed cell death  regulation of angiogenesis  positive regulation of transcription by RNA polymerase II  protein autophosphorylation  import into nucleus  import into nucleus  
Ontology : EGO-EBIangiogenesis  transcription coactivator activity  protein serine/threonine kinase activity  protein binding  nucleus  nuclear envelope  cytoplasm  cytoplasm  cytosol  regulation of transcription by RNA polymerase II  apoptotic process  membrane  oxidoreductase activity  cell differentiation  negative regulation of apoptotic process  positive regulation of programmed cell death  regulation of angiogenesis  positive regulation of transcription by RNA polymerase II  protein autophosphorylation  import into nucleus  import into nucleus  
Atlas of Cancer Signalling NetworkHTATIP2
Wikipedia pathwaysHTATIP2
Orthology - Evolution
GeneTree (enSembl)ENSG00000109854
Phylogenetic Trees/Animal Genes : TreeFamHTATIP2
Homologs : HomoloGeneHTATIP2
Homology/Alignments : Family Browser (UCSC)HTATIP2
Gene fusions - Rearrangements
Fusion : MitelmanHTATIP2::CA1 [11p15.1/8q21.2]  
Fusion : FusionGDB1.1.1.-   
Fusion : QuiverHTATIP2
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerHTATIP2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)HTATIP2
Exome Variant ServerHTATIP2
GNOMAD BrowserENSG00000109854
Varsome BrowserHTATIP2
ACMGHTATIP2 variants
Genomic Variants (DGV)HTATIP2 [DGVbeta]
DECIPHERHTATIP2 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisHTATIP2 
ICGC Data PortalHTATIP2 
TCGA Data PortalHTATIP2 
Broad Tumor PortalHTATIP2
OASIS PortalHTATIP2 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICHTATIP2  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DHTATIP2
Mutations and Diseases : HGMDHTATIP2
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)HTATIP2
DoCM (Curated mutations)HTATIP2
CIViC (Clinical Interpretations of Variants in Cancer)HTATIP2
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry HTATIP2
NextProtQ9BUP3 [Medical]
Target ValidationHTATIP2
Huge Navigator HTATIP2 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDHTATIP2
Pharm GKB GenePA29539
Clinical trialHTATIP2
DataMed IndexHTATIP2
PubMed75 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Oct 8 21:19:51 CEST 2021

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