Q9BUP3 (HTAI2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	242 AA.
Sequence status	Complete.
Protein existence	Evidence 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.15
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.

Ontologies

Keywords
Biological process	Angiogenesis Apoptosis Differentiation Host-virus interaction
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Tumor suppressor
Ligand	NADP
Molecular function	Developmental protein Oxidoreductase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis Inferred from electronic annotation. Source: UniProtKB-KW apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW induction of apoptosis Traceable author statement Ref.1. Source: ProtInc negative regulation of apoptotic process Traceable author statement Ref.3. Source: UniProtKB nuclear import Inferred from direct assay Ref.14. Source: UniProtKB regulation of angiogenesis Inferred from direct assay Ref.11. Source: UniProtKB regulation of transcription from RNA polymerase II promoter Traceable author statement Ref.2. Source: ProtInc virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from direct assay Ref.14. Source: UniProtKB nuclear envelope Inferred from direct assay Ref.14. Source: UniProtKB
Molecular_function	nucleotide binding Inferred from electronic annotation. Source: InterPro oxidoreductase activity Inferred from electronic annotation. Source: UniProtKB-KW transcription coactivator activity Traceable author statement Ref.2. Source: ProtInc
Complete GO annotation...

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 242

242

Oxidoreductase HTATIP2

PRO_0000072544

Regions

Nucleotide binding

19 – 52

34

NADP Ref.15

Sites

Active site

143

1

Proton acceptor Probable Ref.15

Active site

147

1

Probable Ref.15

Binding site

131

1

Substrate Probable Ref.15

Amino acid modifications

Modified residue

45

1

Phosphoserine By similarity

Natural variations

Alternative sequence

1

1

M → MAGPAALSAAAAAALAAALL LLRREDPGPGAGPSM in isoform 3.

VSP_038339

Alternative sequence

102 – 133

32

EGFVR…LLSSK → VRKAYALFPFCWPVISRILF LLTLFLCACCNA in isoform 2.

VSP_051864

Alternative sequence

134 – 242

109

Missing in isoform 2.

VSP_051865

Natural variant

106

1

R → S in a hepatocellular carcinoma sample. Ref.12

VAR_023713

Natural variant

108

1

D → Y in a hepatocellular carcinoma sample. Ref.12

VAR_023714

Natural variant

116

1

A → T in a hepatocellular carcinoma sample. Ref.12

VAR_023715

Natural variant

134

1

G → V in a hepatocellular carcinoma sample; reduces protein stability. Ref.12

VAR_023716

Natural variant

144

1

L → I in a hepatocellular carcinoma sample. Ref.12

VAR_023717

Natural variant

197

1

S → R. Ref.1 Ref.9 Ref.16
Corresponds to variant rs3824886 [ dbSNP | Ensembl ].

VAR_023718

Experimental info

Mutagenesis

28 – 31

4

GETG → VETA: Loss of proapoptotic and metastatis-inhibiting effect. Ref.10

Mutagenesis

106

1

R → H: Loss of association with nucleus. Ref.12

Sequence conflict

87

1

V → F in CAG33102. Ref.5

Sequence conflict

170

1

L → P in BAD96730. Ref.6

Sequence conflict

182

1

W → R in AAC39694. Ref.2

Sequence conflict

187

1

F → L in AAB84360. Ref.1

Secondary structure

1

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242

Helix Strand Turn

Details...

Helix

6 – 16

11

Beta strand

20 – 24

5

Helix

29 – 41

13

Beta strand

45 – 53

9

Helix

60 – 64

5

Beta strand

66 – 69

4

Helix

72 – 82

11

Beta strand

86 – 90

5

Helix

96 – 108

13

Helix

110 – 121

12

Beta strand

126 – 130

5

Helix

142 – 155

14

Beta strand

160 – 166

7

Beta strand

169 – 171

3

Helix

175 – 177

3

Helix

179 – 188

10

Helix

195 – 198

4

Beta strand

200 – 202

3

Helix

203 – 214

12

Beta strand

220 – 226

7

Helix

227 – 233

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (CC3) [UniParc]. Last modified January 11, 2011. Version 2. Checksum: 6A26E4A095243678	FASTA	242	27,049
	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
	Isoform 2 (TC3) [UniParc]. Checksum: D5C06E44FAE16E82	FASTA	133	14,914
	10 20 30 40 50 60 MAETEALSKL REDFRMQNKS VFILGASGET GRVLLKEILE QGLFSKVTLI GRRKLTFDEE 70 80 90 100 110 120 AYKNVNQEVV DFEKLDDYAS AFQGHDVGFC CLGTTRGKAG AVRKAYALFP FCWPVISRIL 130 FLLTLFLCAC CNA
	Isoform 3 [UniParc]. Checksum: 655FB91EC4F33B34	FASTA	276	30,131
	10 20 30 40 50 60 MAGPAALSAA AAAALAAALL LLRREDPGPG AGPSMAETEA LSKLREDFRM QNKSVFILGA 70 80 90 100 110 120 SGETGRVLLK EILEQGLFSK VTLIGRRKLT FDEEAYKNVN QEVVDFEKLD DYASAFQGHD 130 140 150 160 170 180 VGFCCLGTTR GKAGAEGFVR VDRDYVLKSA ELAKAGGCKH FNLLSSKGAD KSSNFLYLQV 190 200 210 220 230 240 KGEVEAKVEE LKFDRYSVFR PGVLLCDRQE SRPGEWLVRK FFGSLPDSWA SGHSVPVVTV 250 260 270 VRAMLNNVVR PRDKQMELLE NKAIHDLGKA HGSLKP

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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]	"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).
[16]	"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, MASS SPECTROMETRY.
+	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.

IPI

IPI00383665.
IPI00784029.
IPI00847689.

RefSeq

NP_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.

UniGene

Hs.90753.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2BKA	X-ray	1.70	A	1-242	[»]

ProteinModelPortal

Q9BUP3.

SMR

Q9BUP3. Positions 5-235.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000392985.

PTM databases

PhosphoSite

Q9BUP3.

Polymorphism databases

DMDM

74733240.

Proteomic databases

PaxDb

Q9BUP3.

PRIDE

Q9BUP3.

Protocols and materials databases

DNASU

10553.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000419348; ENSP00000392985; ENSG00000109854.
ENST00000421577; ENSP00000397752; ENSG00000109854.
ENST00000443524; ENSP00000387876; ENSG00000109854.
ENST00000451739; ENSP00000394259; ENSG00000109854.
ENST00000530266; ENSP00000436548; ENSG00000109854.
ENST00000532081; ENSP00000432107; ENSG00000109854.
ENST00000532505; ENSP00000432338; ENSG00000109854.

GeneID

10553.

KEGG

hsa:10553.

UCSC

uc001mpx.2. human.
uc001mpy.4. human.
uc001mpz.2. human.

Organism-specific databases

CTD

10553.

GeneCards

GC11P020341.

HGNC

HGNC:16637. HTATIP2.

HPA

HPA006417.
HPA024321.

MIM

605628. gene.

neXtProt

NX_Q9BUP3.

PharmGKB

PA29539.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0702.

HOVERGEN

HBG052833.

InParanoid

Q9BUP3.

OMA

HLENPVG.

OrthoDB

EOG43JC5K.

PhylomeDB

Q9BUP3.

Gene expression databases

ArrayExpress

Q9BUP3.

Bgee

Q9BUP3.

CleanEx

HS_HTATIP2.

Genevestigator

Q9BUP3.

GermOnline

ENSG00000109854. Homo sapiens.

Family and domain databases

Gene3D

3.40.50.720. 1 hit.

InterPro

IPR016040. NAD(P)-bd_dom.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9BUP3.

GenomeRNAi

10553.

NextBio

40029.

SOURCE

Search...

Entry information

Entry name

HTAI2_HUMAN

Accession

Primary (citable) accession number: Q9BUP3
Secondary accession number(s): A8K7S7 , 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 3, 2013
This is version 100 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.