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Protein

Oxidoreductase HTATIP2

Gene

HTATIP2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei131Substrate1 Publication1
Active sitei143Proton acceptor1 Publication1
Active sitei1471 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi19 – 52NADP1 PublicationAdd BLAST34

GO - Molecular functioni

  • oxidoreductase activity Source: UniProtKB-KW
  • transcription coactivator activity Source: ProtInc

GO - Biological processi

  • angiogenesis Source: UniProtKB-KW
  • apoptotic process Source: UniProtKB-KW
  • cell differentiation Source: UniProtKB-KW
  • negative regulation of apoptotic process Source: UniProtKB
  • nuclear import Source: UniProtKB
  • regulation of angiogenesis Source: UniProtKB
  • regulation of transcription from RNA polymerase II promoter Source: ProtInc
  • viral process Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Oxidoreductase

Keywords - Biological processi

Angiogenesis, Apoptosis, Differentiation, Host-virus interaction

Keywords - Ligandi

NADP

Enzyme and pathway databases

BioCyciZFISH:ENSG00000109854-MONOMER.

Names & Taxonomyi

Protein namesi
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 namesi
Name:HTATIP2Imported
Synonyms:CC3Imported, TIP301 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:16637. HTATIP2.

Subcellular locationi

  • Cytoplasm 1 Publication
  • Nucleus envelope 1 Publication

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • membrane Source: UniProtKB
  • nuclear envelope Source: UniProtKB
  • nucleoplasm Source: HPA
  • nucleus Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi28 – 31GETG → VETA: Loss of proapoptotic and metastatis-inhibiting effect. 1 Publication4
Mutagenesisi106R → H: Loss of association with nucleus. 1 Publication1

Keywords - Diseasei

Tumor suppressor

Organism-specific databases

DisGeNETi10553.
OpenTargetsiENSG00000109854.
PharmGKBiPA29539.

Polymorphism and mutation databases

BioMutaiHTATIP2.
DMDMi317373366.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000725442 – 242Oxidoreductase HTATIP2Add BLAST241

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiQ9BUP3.
MaxQBiQ9BUP3.
PaxDbiQ9BUP3.
PeptideAtlasiQ9BUP3.
PRIDEiQ9BUP3.

PTM databases

iPTMnetiQ9BUP3.
PhosphoSitePlusiQ9BUP3.
SwissPalmiQ9BUP3.

Expressioni

Tissue specificityi

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.2 Publications

Gene expression databases

BgeeiENSG00000109854.
CleanExiHS_HTATIP2.
ExpressionAtlasiQ9BUP3. baseline and differential.
GenevisibleiQ9BUP3. HS.

Organism-specific databases

HPAiHPA006417.
HPA024321.

Interactioni

Subunit structurei

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.

Protein-protein interaction databases

BioGridi115804. 7 interactors.
MINTiMINT-5003508.
STRINGi9606.ENSP00000392985.

Structurei

Secondary structure

1242
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi6 – 16Combined sources11
Beta strandi20 – 24Combined sources5
Helixi29 – 41Combined sources13
Beta strandi45 – 53Combined sources9
Helixi60 – 64Combined sources5
Beta strandi66 – 69Combined sources4
Helixi72 – 82Combined sources11
Beta strandi86 – 90Combined sources5
Helixi96 – 108Combined sources13
Helixi110 – 121Combined sources12
Beta strandi126 – 130Combined sources5
Helixi142 – 155Combined sources14
Beta strandi160 – 166Combined sources7
Beta strandi169 – 171Combined sources3
Helixi175 – 177Combined sources3
Helixi179 – 188Combined sources10
Helixi195 – 198Combined sources4
Beta strandi200 – 202Combined sources3
Helixi203 – 214Combined sources12
Beta strandi220 – 226Combined sources7
Helixi227 – 233Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2BKAX-ray1.70A1-242[»]
ProteinModelPortaliQ9BUP3.
SMRiQ9BUP3.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9BUP3.

Family & Domainsi

Domaini

Unique C-terminus confers high proteasome-dependent instability to isoform 2.1 Publication

Phylogenomic databases

eggNOGiKOG4039. Eukaryota.
COG0702. LUCA.
GeneTreeiENSGT00390000008184.
HOVERGENiHBG052833.
InParanoidiQ9BUP3.
KOiK17290.
OMAiGEWLARK.
OrthoDBiEOG091G0S5T.
PhylomeDBiQ9BUP3.
TreeFamiTF312849.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
InterProiIPR016040. NAD(P)-bd_dom.
[Graphical view]
PfamiPF13460. NAD_binding_10. 1 hit.
[Graphical view]
SUPFAMiSSF51735. SSF51735. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 11 Publication (identifier: Q9BUP3-1) [UniParc]FASTAAdd to basket
Also known as: CC31 Publication

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.

« Hide

        10         20         30         40         50
MAETEALSKL REDFRMQNKS VFILGASGET GRVLLKEILE QGLFSKVTLI
60 70 80 90 100
GRRKLTFDEE AYKNVNQEVV DFEKLDDYAS AFQGHDVGFC CLGTTRGKAG
110 120 130 140 150
AEGFVRVDRD YVLKSAELAK AGGCKHFNLL SSKGADKSSN FLYLQVKGEV
160 170 180 190 200
EAKVEELKFD RYSVFRPGVL LCDRQESRPG EWLVRKFFGS LPDSWASGHS
210 220 230 240
VPVVTVVRAM LNNVVRPRDK QMELLENKAI HDLGKAHGSL KP
Length:242
Mass (Da):27,049
Last modified:January 11, 2011 - v2
Checksum:i6A26E4A095243678
GO
Isoform 2Curated1 Publication (identifier: Q9BUP3-2) [UniParc]FASTAAdd to basket
Also known as: TC31 Publication

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.
Show »
Length:133
Mass (Da):14,914
Checksum:iD5C06E44FAE16E82
GO
Isoform 3 (identifier: Q9BUP3-3) [UniParc]FASTAAdd to basket

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

Show »
Length:276
Mass (Da):30,131
Checksum:i655FB91EC4F33B34
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti87V → F in CAG33102 (Ref. 5) Curated1
Sequence conflicti170L → P in BAD96730 (Ref. 6) Curated1
Sequence conflicti182W → R in AAC39694 (PubMed:9482853).Curated1
Sequence conflicti187F → L in AAB84360 (PubMed:9174052).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_023713106R → S in a hepatocellular carcinoma sample. 1 Publication1
Natural variantiVAR_023714108D → Y in a hepatocellular carcinoma sample. 1 Publication1
Natural variantiVAR_023715116A → T in a hepatocellular carcinoma sample. 1 PublicationCorresponds to variant rs761113892dbSNPEnsembl.1
Natural variantiVAR_023716134G → V in a hepatocellular carcinoma sample; reduces protein stability. 1 Publication1
Natural variantiVAR_023717144L → I in a hepatocellular carcinoma sample. 1 Publication1
Natural variantiVAR_023718197S → R Highly associated with hepatocellular carcinoma (HCC) progression. Combined sources3 PublicationsCorresponds to variant rs3824886dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0383391M → MAGPAALSAAAAAALAAALL LLRREDPGPGAGPSM in isoform 3. 1 Publication1
Alternative sequenceiVSP_051864102 – 133EGFVR…LLSSK → VRKAYALFPFCWPVISRILF LLTLFLCACCNA in isoform 2. 2 PublicationsAdd BLAST32
Alternative sequenceiVSP_051865134 – 242Missing in isoform 2. 2 PublicationsAdd BLAST109

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS44553.1. [Q9BUP3-3]
CCDS53613.1. [Q9BUP3-2]
CCDS7852.1. [Q9BUP3-1]
RefSeqiNP_001091990.1. NM_001098520.1. [Q9BUP3-3]
NP_001091991.1. NM_001098521.1. [Q9BUP3-1]
NP_001091992.1. NM_001098522.1. [Q9BUP3-1]
NP_001091993.1. NM_001098523.1. [Q9BUP3-2]
NP_006401.3. NM_006410.4. [Q9BUP3-1]
UniGeneiHs.90753.

Genome annotation databases

EnsembliENST00000419348; 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]
GeneIDi10553.
KEGGihsa:10553.
UCSCiuc001mpx.3. human. [Q9BUP3-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS44553.1. [Q9BUP3-3]
CCDS53613.1. [Q9BUP3-2]
CCDS7852.1. [Q9BUP3-1]
RefSeqiNP_001091990.1. NM_001098520.1. [Q9BUP3-3]
NP_001091991.1. NM_001098521.1. [Q9BUP3-1]
NP_001091992.1. NM_001098522.1. [Q9BUP3-1]
NP_001091993.1. NM_001098523.1. [Q9BUP3-2]
NP_006401.3. NM_006410.4. [Q9BUP3-1]
UniGeneiHs.90753.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2BKAX-ray1.70A1-242[»]
ProteinModelPortaliQ9BUP3.
SMRiQ9BUP3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115804. 7 interactors.
MINTiMINT-5003508.
STRINGi9606.ENSP00000392985.

PTM databases

iPTMnetiQ9BUP3.
PhosphoSitePlusiQ9BUP3.
SwissPalmiQ9BUP3.

Polymorphism and mutation databases

BioMutaiHTATIP2.
DMDMi317373366.

Proteomic databases

EPDiQ9BUP3.
MaxQBiQ9BUP3.
PaxDbiQ9BUP3.
PeptideAtlasiQ9BUP3.
PRIDEiQ9BUP3.

Protocols and materials databases

DNASUi10553.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000419348; 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]
GeneIDi10553.
KEGGihsa:10553.
UCSCiuc001mpx.3. human. [Q9BUP3-1]

Organism-specific databases

CTDi10553.
DisGeNETi10553.
GeneCardsiHTATIP2.
HGNCiHGNC:16637. HTATIP2.
HPAiHPA006417.
HPA024321.
MIMi605628. gene.
neXtProtiNX_Q9BUP3.
OpenTargetsiENSG00000109854.
PharmGKBiPA29539.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4039. Eukaryota.
COG0702. LUCA.
GeneTreeiENSGT00390000008184.
HOVERGENiHBG052833.
InParanoidiQ9BUP3.
KOiK17290.
OMAiGEWLARK.
OrthoDBiEOG091G0S5T.
PhylomeDBiQ9BUP3.
TreeFamiTF312849.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000109854-MONOMER.

Miscellaneous databases

EvolutionaryTraceiQ9BUP3.
GeneWikiiHTATIP2.
GenomeRNAii10553.
PROiQ9BUP3.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000109854.
CleanExiHS_HTATIP2.
ExpressionAtlasiQ9BUP3. baseline and differential.
GenevisibleiQ9BUP3. HS.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
InterProiIPR016040. NAD(P)-bd_dom.
[Graphical view]
PfamiPF13460. NAD_binding_10. 1 hit.
[Graphical view]
SUPFAMiSSF51735. SSF51735. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiHTAI2_HUMAN
AccessioniPrimary (citable) accession number: Q9BUP3
Secondary accession number(s): A8K7S7
, D3DQY8, O15383, O60520, O95345, Q53GC1, Q53GG2, Q6IBI3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 25, 2005
Last sequence update: January 11, 2011
Last modified: November 2, 2016
This is version 130 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Caution

Was originally (PubMed:9482853 and PubMed:10698937) 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.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.