Target Information

Target General Information

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Target ID

T91286 (Former ID: TTDNC00499)

Target Name

Metalloreductase STEAP1 (STEAP1)

Synonyms

Sixtransmembrane epithelial antigen of prostate 1; STEAP1

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Gene Name

STEAP1

Target Type

Clinical trial target

[1]

Disease

[+] 1 Target-related Diseases

Prostate cancer [ICD-11: 2C82]

Function

Metalloreductase that has the ability to reduce both Fe(3+) to Fe(2+) and Cu(2+) to Cu(1+). Uses NAD(+) as acceptor.

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BioChemical Class

Metal ion oxidoreductase

UniProt ID

STEA1_HUMAN

EC Number

EC 1.16.1.-

Sequence

MESRKDITNQEELWKMKPRRNLEEDDYLHKDTGETSMLKRPVLLHLHQTAHADEFDCPSE
LQHTQELFPQWHLPIKIAAIIASLTFLYTLLREVIHPLATSHQQYFYKIPILVINKVLPM
VSITLLALVYLPGVIAAIVQLHNGTKYKKFPHWLDKWMLTRKQFGLLSFFFAVLHAIYSL
SYPMRRSYRYKLLNWAYQQVQQNKEDAWIEHDVWRMEIYVSLGIVGLAILALLAVTSIPS
VSDSLTWREFHYIQSKLGIVSLLLGTIHALIFAWNKWIDIKQFVWYTPPTFMIAVFLPIV
VLIFKSILFLPCLRKKILKIRHGWEDVTKINKTEICSQL

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3D Structure

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PDB

Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 2 Clinical Trial Drugs

AMG 509

Drug Info

Phase 1

Prostate cancer

[2]

RG7450

Drug Info

Phase 1

Prostate cancer

[3]

Mode of Action

[+] 2 Modes of Action

Inhibitor

[+] 1 Inhibitor drugs

AMG 509

Drug Info

[4]

Modulator

[+] 1 Modulator drugs

RG7450

Drug Info

[1]

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: 1,2-Dimyristoyl-Sn-Glycero-3-Phosphate

Ligand Info

Structure Description

Cryo-EM structure of trimeric human STEAP1 bound to three Fab120.545 fragments

PDB:6Y9B

Method

Electron microscopy

Resolution

2.97 Å

Mutation

[5]

PDB Sequence

LFPQWHLPIK

⁷⁶

IAAIIASLTF

⁸⁶

LYTLLREVIH

⁹⁶

PLATSHQQYF

¹⁰⁶

YKIPILVINK

¹¹⁶

VLPMVSITLL

¹²⁶

ALVYLPGVIA

¹³⁶

AIVQLHNGTK

¹⁴⁸

KFPHWLDKWM

¹⁵⁸

LTRKQFGLLS

¹⁶⁸

FFFAVLHAIY

¹⁷⁸

SLSYPMRRSY

¹⁸⁸

RYKLLNWAYQ

¹⁹⁸

QVQQNKEDAW

²⁰⁸

IEHDVWRMEI

²¹⁸

YVSLGIVGLA

²²⁸

ILALLAVTSI

²³⁸

PSVSDSLTWR

²⁴⁸

EFHYIQSKLG

²⁵⁸

IVSLLLGTIH

²⁶⁸

ALIFAWNKWI

²⁷⁸

DIKQFVWYTP

²⁸⁸

PTFMIAVFLP

²⁹⁸

IVVLIFKSIL

³⁰⁸

FLPC

Residue

Distance (Å)

PHE68

3.279

GLN70

2.897

TRP71

3.408

LYS162

3.772

GLN163

4.248

LEU166

4.085

PHE169

3.802

PHE170

3.589

VAL173

3.551

Residue

Distance (Å)

LEU174

4.971

ILE177

4.707

ALA231

4.770

ALA234

3.477

VAL235

4.435

SER237

2.896

ILE238

3.981

PRO239

3.525

Click to View More Binding Site Information of This Target with Different Ligands

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 Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function. Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006). Human Similarity Proteins Human Tissue Distribution Human Pathway Affiliation

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 Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.

Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).

Human Similarity Proteins

Human Tissue Distribution

Human Pathway Affiliation

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.

KEGG Pathway	Pathway ID	Affiliated Target	Pathway Map
Mineral absorption	hsa04978	Affiliated Target
Class: Organismal Systems => Digestive system	Pathway Hierarchy

Target Profiles in Patients

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Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways

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KEGG Pathway

[+] 1 KEGG Pathways

Mineral absorption

WikiPathways

[+] 1 WikiPathways

Copper homeostasis

References

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REF 1

Marine-Sourced Anti-Cancer and Cancer Pain Control Agents in Clinical and Late Preclinical Development. Mar Drugs. 2014 January; 12(1): 255-278.

REF 2

ClinicalTrials.gov (NCT04221542) Study of AMG 509 in Subjects With Metastatic Castration-Resistant Prostate Cancer. U.S. National Institutes of Health.

REF 3

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800033873)

REF 4

Clinical pipeline report, company report or official report of Amgen.

REF 5

Cryo-electron microscopy structure and potential enzymatic function of human six-transmembrane epithelial antigen of the prostate 1 (STEAP1). J Biol Chem. 2020 Jul 10;295(28):9502-9512.

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