Target Information

Target General Information

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Target ID

T92639

Target Name

Alpha-tubulin N-acetyltransferase 1 (ATAT1)

Synonyms

MEC17; C6orf134; Alpha-TAT; Acetyltransferase mec-17 homolog

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Gene Name

ATAT1

Target Type

Literature-reported target

[1]

Function

Specifically acetylates 'Lys-40' in alpha-tubulin on the lumenal side of microtubules. Promotes microtubule destabilization and accelerates microtubule dynamics; this activity may be independent of acetylation activity. Acetylates alpha-tubulin with a slow enzymatic rate, due to a catalytic site that is not optimized for acetyl transfer. Enters the microtubule through each end and diffuses quickly throughout the lumen of microtubules. Acetylates only long/old microtubules because of its slow acetylation rate since it does not have time to act on dynamically unstable microtubules before the enzyme is released. Required for normal sperm flagellar function. Promotes directional cell locomotion and chemotaxis, through AP2A2-dependent acetylation of alpha-tubulin at clathrin-coated pits that are concentrated at the leading edge of migrating cells. May facilitate primary cilium assembly.

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BioChemical Class

Acetyltransferase ATAT1 family

UniProt ID

ATAT_HUMAN

EC Number

EC 2.3.1.108

Sequence

MEFPFDVDALFPERITVLDQHLRPPARRPGTTTPARVDLQQQIMTIIDELGKASAKAQNL
SAPITSASRMQSNRHVVYILKDSSARPAGKGAIIGFIKVGYKKLFVLDDREAHNEVEPLC
ILDFYIHESVQRHGHGRELFQYMLQKERVEPHQLAIDRPSQKLLKFLNKHYNLETTVPQV
NNFVIFEGFFAHQHRPPAPSLRATRHSRAAAVDPTPAAPARKLPPKRAEGDIKPYSSSDR
EFLKVAVEPPWPLNRAPRRATPPAHPPPRSSSLGNSPERGPLRPFVPEQELLRSLRLCPP
HPTARLLLAADPGGSPAQRRRTRGTPPGLVAQSCCYSRHGGVNSSSPNTGNQDSKQGEQE
TKNRSASEEQALSQDGSGEKPMHTAPPQAPAPPAQSWTVGGDILNARFIRNLQERRSTRP
W

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3D Structure

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AlphaFold

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Drug Binding Sites of Target

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Ligand Name: Acetyl CoA

Ligand Info

Structure Description

Crystal structure of human alpha tubulin acetyltransferase catalytic domain

PDB:4B5O

Method

X-ray diffraction

Resolution

1.05 Å

Mutation

[2]

PDB Sequence

SMEFPFDVDA

⁹

LFPERITVLD

¹⁹

QHLRPPARRP

²⁹

GTTTPARVDL

³⁹

QQQIMTIIDE

⁴⁹

LGKASAKAQN

⁵⁹

LSAPITSASR

⁶⁹

MQSNRHVVYI

⁷⁹

LKDSSARPAI

⁹³

IGFIKVGYKK

¹⁰³

LFVLDDREAH

¹¹³

NEVEPLCILD

¹²³

FYIHESVQRH

¹³³

GHGRELFQYM

¹⁴³

LQKERVEPHQ

¹⁵³

LAIDRPSQKL

¹⁶³

LKFLNKHYNL

¹⁷³

ETTVPQVNNF

¹⁸³

VIFEGFFAHQ

¹⁹³

Residue

Distance (Å)

SER54

4.612

ALA57

2.854

GLN58

2.821

ILE64

4.836

ILE121

2.664

LEU122

3.204

ASP123

2.606

PHE124

1.903

TYR125

2.491

ILE126

2.089

GLU128

4.782

VAL130

4.674

GLN131

2.384

ARG132

1.948

HIS133

3.006

GLY134

2.011

Residue

Distance (Å)

HIS135

3.486

GLY136

2.057

ARG137

2.111

GLU138

4.722

ILE156

2.495

ASP157

2.297

ARG158

3.629

PRO159

2.973

SER160

1.956

LYS162

2.376

LEU163

2.458

LYS165

2.774

PHE166

2.577

LYS169

1.850

HIS170

2.195

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Ligand Name: Coenzyme A

Ligand Info

Structure Description

tubulin acetyltransferase complex with bisubstrate analog

PDB:4PK2

Method

X-ray diffraction

Resolution

1.35 Å

Mutation

[3]

PDB Sequence

FTMEFPFDVD

⁸

ALFPERITVL

¹⁸

DQHLRPPAVD

³⁸

LQQQIMTIID

⁴⁸

ELGKASAKAQ

⁵⁸

NLSAPITSAS

⁶⁸

RMQSNRHVVY

⁷⁸

ILKDSSARPA

⁸⁸

GKGAIIGFIK

⁹⁸

VGYKKLFVLD

¹⁰⁸

DREAHNEVEP

¹¹⁸

LCILDFYIHE

¹²⁸

SVQRHGHGRE

¹³⁸

LFQYMLQKER

¹⁴⁸

VEPHQLAIDR

¹⁵⁸

PSQKLLKFLN

¹⁶⁸

KHYNLETTVP

¹⁷⁸

QVNNFVIFEG

¹⁸⁸

FFAHQHPP

Residue

Distance (Å)

SER54

4.798

ALA57

3.404

GLN58

3.449

ASP123

4.794

PHE124

2.810

TYR125

2.515

ILE126

2.125

VAL130

4.647

GLN131

3.000

ARG132

1.916

HIS133

3.239

GLY134

2.062

HIS135

3.378

GLY136

2.060

Residue

Distance (Å)

ARG137

2.196

GLU138

4.694

ILE156

4.395

ASP157

4.598

ARG158

4.220

PRO159

2.791

SER160

2.090

LYS162

2.729

LEU163

3.113

LYS165

3.149

PHE166

2.708

LYS169

1.744

HIS170

2.227

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Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues. The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021). Human Similarity Proteins Human Tissue Distribution

Different Human System Profiles of Target

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Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.

The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021).

Human Similarity Proteins

Human Tissue Distribution

There is no similarity protein (E value < 0.005) for this target


Note: If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.

References

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REF 1

Alpha-tubulin acetyltransferase/MEC-17 regulates cancer cell migration and invasion through epithelial-mesenchymal transition suppression and cell ... Sci Rep. 2018 Nov 30;8(1):17477.

REF 2

Atomic resolution structure of human Alpha-tubulin acetyltransferase bound to acetyl-CoA. Proc Natl Acad Sci U S A. 2012 Nov 27;109(48):19649-54.

REF 3

Molecular basis for age-dependent microtubule acetylation by tubulin acetyltransferase. Cell. 2014 Jun 5;157(6):1405-1415.

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