Tchem PAM Peptidyl-glycine alpha-amidating monooxygenase

Protein Summary

Description

Bifunctional enzyme that catalyzes 2 sequential steps in C-terminal alpha-amidation of peptides. The monooxygenase part produces an unstable peptidyl(2-hydroxyglycine) intermediate that is dismutated to glyoxylate and the corresponding desglycine peptide amide by the lyase part. C-terminal amidation of peptides such as neuropeptides is essential for full biological activity. This gene encodes a multifunctional protein. The encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme includes two domains with distinct catalytic activities, a peptidylglycine alpha-hydroxylating monooxygenase (PHM) domain and a peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL) domain. These catalytic domains work sequentially to catalyze the conversion of neuroendocrine peptides to active alpha-amidated products. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]

Uniprot Accession IDs

• P19021
• A6NMR0
• A8K293
• O43211
• O95080
• Q16252
• Q16253
• Q54A45
• Q86U53
• Q8WVC7
• Q9UCG0
• PAM

Gene Name

• PAM

Ensembl ID

• ENST00000304400
• ENSP00000306100
• ENSG00000145730
• ENST00000346918
• ENSP00000282992
• ENST00000348126
• ENSP00000314638
• ENST00000438793
• ENSP00000396493
• ENST00000455264
• ENSP00000403461

Symbol

• PAL
• PHM

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
protein domain	0.99
transcription factor perturbation	0.91
molecular function	0.88
virus perturbation	0.85
ligand (protein) perturbation	0.83

Protein Classes

PANTHER Classes

Protein / Oxidoreductase / Oxygenase / Peptidyl-glycine Alpha-amidating Monooxygenase

DTO Classes

Protein / Enzyme / Oxidoreductase / Oxygenase / Peptidyl-glycine Alpha-amidating Monooxygenase

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 244.42   (req: < 5)

Gene RIFs: 12   (req: <= 3)

Antibodies: 131   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 244.42   (req: >= 5)

Gene RIFs: 12   (req: > 3)

Antibodies: 131   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 28

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 5

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Expression Data (0 Tissues)

tutorial

No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (4)

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (5)

Explore Active Ligands

1 – 5 of 5

((E)-Styrylsulfanyl)-acetic acid

PAMTchem Enzyme

pKi : 10

Phenylethynylsulfanyl-acetic acid

PAMTchem Enzyme

pKi : 9.72

alpha-O-Decanoylglycolic acid

PAMTchem Enzyme

pIC50 : 7.4

alpha-O-Dodecanoylglycolic acid

PAMTchem Enzyme

pIC50 : 7.22

Trans-4-Phenylbut-3-enoic acid

PAMTchem Enzyme

pKi : 7.02

Protein-Protein Interactions (60)

Explore Interacting Targets

1 – 10 of 60

• See Interactions on String-DB

FAM19A2

Tbio

Novelty:  0.28999346

p_int:  0.999558303

p_ni:  0.000441697

Data Source:  BioPlex

RALB

Tbio

Family:  Enzyme

Novelty:  0.01605746

p_int:  0.999069217

p_ni:  0.000930779

p_wrong:  4e-9

Score:  0.19

Data Source:  BioPlex,STRINGDB

TMEM25

Tdark

Novelty:  0.35505784

p_int:  0.995449832

p_ni:  0.004550167

Data Source:  BioPlex

DKKL1

Tbio

Novelty:  0.00544618

p_int:  0.98382012

p_ni:  0.01617988

Data Source:  BioPlex

UBR2

Tbio

Family:  Enzyme

Novelty:  0.03126228

p_int:  0.971681938

p_ni:  0.02831806

p_wrong:  2e-9

Data Source:  BioPlex

PTCH1

Tbio

Novelty:  0.00077635

p_int:  0.949417874

p_ni:  0.050582124

p_wrong:  2e-9

Data Source:  BioPlex

TAZ

Tbio

Novelty:  0.00372301

p_int:  0.902562978

p_ni:  0.097437022

Score:  0.202

Data Source:  BioPlex,STRINGDB

SERPINA6

Tchem

Novelty:  0.00055116

p_int:  0.799880681

p_ni:  0.200109358

p_wrong:  0.000009961

Score:  0.345

Data Source:  BioPlex,STRINGDB

B3GNT2

Tbio

Family:  Enzyme

Novelty:  0.02724566

p_int:  0.772537966

p_ni:  0.227462033

Data Source:  BioPlex

ART3

Tbio

Family:  Enzyme

Novelty:  0.02783085

p_int:  0.759011932

p_ni:  0.240988048

p_wrong:  2e-8

Score:  0.188

Data Source:  BioPlex,STRINGDB

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (1)

PathwayCommons (1)

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5

1 – 1 of 1

Data Source	Name	Explore in Pharos	Explore in Source
PathwayCommons: panther	Vasopressin synthesis	11 targets	PathwayCommons: panther

Name	Explore in Pharos	Explore in Source
Vasopressin synthesis	11 targets	PathwayCommons: panther

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (39)

Functions (7)

Components (11)

Processes (21)

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10

1 – 7 of 7

GO Term	Evidence	Assigned by
peptidylamidoglycolate lyase activity	Inferred from Direct Assay (IDA)	UniProtKB
peptidylglycine monooxygenase activity	Inferred from Direct Assay (IDA)	UniProtKB
zinc ion binding	Inferred from Direct Assay (IDA)	UniProtKB
calcium ion binding	Inferred from Electronic Annotation (IEA)	Ensembl
copper ion binding	Inferred from Electronic Annotation (IEA)	Ensembl
L-ascorbic acid binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW
protein kinase binding	Inferred from Electronic Annotation (IEA)	Ensembl

Disease Associations (null)

No disease associations found

GWAS Traits (18)

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 18

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
type II diabetes mellitus	EFO_0001360	7	4	1	1.1	94
balding measurement	EFO_0007825	1	2	2		81
appendicular lean mass	EFO_0004980	3	1	3		65.6
Drugs used in diabetes use measurement	EFO_0009924	1	1	1		64.4
sleep duration	EFO_0005271	2	2	1	1	63

• Explore on Target Illumination GWAS Analytics (TIGA)

Items per page:

5

1 – 5 of 18

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
type II diabetes mellitus	EFO_0001360	1	1.1	94
balding measurement	EFO_0007825	2		81
appendicular lean mass	EFO_0004980	3		65.6
Drugs used in diabetes use measurement	EFO_0009924	1		64.4
sleep duration	EFO_0005271	1	1	63

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UniProt Keyword Find Similar Targets

No Header	No Header
Alternative splicing
Cleavage on pair of basic residues
Complete proteome
Copper
Disulfide bond
Glycoprotein
Lyase
Membrane
Metal-binding
Monooxygenase

GWAS Trait Find Similar Targets

No Header	No Header
appendicular lean mass
balding measurement
BMI-adjusted waist-hip ratio
body mass index
cognitive function measurement
daytime rest measurement
Drugs used in diabetes use measurement
electrocardiography
glucose measurement
insomnia measurement

MGI Phenotype Find Similar Targets

No Header	No Header
adipose tissue phenotype
cardiovascular system phenotype
embryo phenotype
homeostasis/metabolism phenotype
mortality/aging
respiratory system phenotype

IDG Resources

No IDG generated resources found

Orthologs (14)

1 – 5 of 14

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	peptidylglycine alpha-amidating monooxygenase	VGNC:4116	461974
Macaque	peptidylglycine alpha-amidating monooxygenase		707733
Mouse	peptidylglycine alpha-amidating monooxygenase	MGI:97475	18484
Rat	peptidylglycine alpha-amidating monooxygenase	RGD:3252	25508
Dog	peptidylglycine alpha-amidating monooxygenase	VGNC:44250	479145

Species	Name	OMA	EggNOG	Inparanoid
Chimp	peptidylglycine alpha-amidating monooxygenase
Macaque	peptidylglycine alpha-amidating monooxygenase
Mouse	peptidylglycine alpha-amidating monooxygenase
Rat	peptidylglycine alpha-amidating monooxygenase
Dog	peptidylglycine alpha-amidating monooxygenase

Publication Statistics

PubMed Score 244.42

PubMed score by year

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PubTator Score 707.44

PubTator score by year

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Related Publications

Text Mined References (43)

GeneRif Annotations (12)

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10

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PMID	Year	Title