PAM

Summary

PAM (peptidylglycine alpha-amidating monooxygenase, HGNC:8596) is a protein-coding gene on chromosome 5q21.1, encoding Peptidyl-glycine alpha-amidating monooxygenase (P19021). Bifunctional enzyme that catalyzes amidation of the C-terminus of proteins.

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.

Source: NCBI Gene 5066 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 113 total
• GTEx eGene: eQTL in 28 tissues, sQTL in 33 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.86 (unconstrained)
• MANE Select transcript: NM_001177306
• Notable: 113 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8596
Approved symbol	PAM
Name	peptidylglycine alpha-amidating monooxygenase
Location	5q21.1
Locus type	gene with protein product
Status	Approved
Aliases	PAL, PHM, PAM-1
Ensembl gene	ENSG00000145730
Ensembl biotype	protein_coding
OMIM	170270
Entrez	5066

Gene structure

Transcript identifiers

Ensembl transcripts: 161 — 113 protein_coding, 41 nonsense_mediated_decay, 5 protein_coding_CDS_not_defined, 2 retained_intron

MANE Select: ENST00000438793

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 5, TSL 2: 4, TSL 3: 5, TSL 4: 9, TSL 5: 2

ENST00000438793, ENST00000304400, ENST00000345721, ENST00000346918, ENST00000348126, ENST00000379799, ENST00000455264, ENST00000504456, ENST00000504691, ENST00000505372, ENST00000505654, ENST00000506006, ENST00000506127, ENST00000506260, ENST00000508060, ENST00000509523, ENST00000509636, ENST00000509832, ENST00000510006, ENST00000510208, ENST00000511429, ENST00000511477, ENST00000511839, ENST00000512073, ENST00000513648, ENST00000682024, ENST00000682407, ENST00000682882, ENST00000682972, ENST00000684043, ENST00000684379, ENST00000684529, ENST00000890191, ENST00000890192, ENST00000890193, ENST00000890194, ENST00000890195, ENST00000890196, ENST00000890197, ENST00000890198, ENST00000890199, ENST00000890200, ENST00000890201, ENST00000890202, ENST00000890203, ENST00000890204, ENST00000890205, ENST00000890206, ENST00000890207, ENST00000890208, ENST00000890209, ENST00000890210, ENST00000890211, ENST00000890212, ENST00000890213, ENST00000890214, ENST00000890215, ENST00000890216, ENST00000890217, ENST00000890218, ENST00000890219, ENST00000890220, ENST00000890221, ENST00000890222, ENST00000939731, ENST00000939732, ENST00000939734, ENST00000939736, ENST00000939739, ENST00000939740, ENST00000939741, ENST00000939742, ENST00000957482, ENST00000957483, ENST00000957484, ENST00000957485, ENST00000957486, ENST00000957487, ENST00000957488, ENST00000957489, ENST00000957490, ENST00000957491, ENST00000957492, ENST00000957493, ENST00000957494, ENST00000957495, ENST00000957496, ENST00000957497, ENST00000957498, ENST00000957499, ENST00000957500, ENST00000957501, ENST00000957502, ENST00000957503, ENST00000957504, ENST00000957505, ENST00000957506, ENST00000957507, ENST00000957508, ENST00000957509, ENST00000957510, ENST00000957511, ENST00000957512, ENST00000957513, ENST00000957514, ENST00000957515, ENST00000957516, ENST00000957517, ENST00000957518, ENST00000957519, ENST00000990597, ENST00000990598, ENST00000990599, ENST00000990600, ENST00001057926, ENST00001057927, ENST00001057928, ENST00001057929, ENST00001057934, ENST00001057935, ENST00001057936, ENST00001057937, ENST00001057938, ENST00001057939, ENST00001057940, ENST00001057941, ENST00001057943, ENST00001057944, ENST00001057945, ENST00001057947, ENST00001057948, ENST00001057951, ENST00001057952, ENST00001057954, ENST00001057955, ENST00001057958, ENST00001057959, ENST00001057960, ENST00001057965, ENST00001057966, ENST00001057967, ENST00001057968, ENST00001057969, ENST00001057970, ENST00001057971, ENST00001057972, ENST00001057979, ENST00001107230, ENST00001107231, ENST00001113505, ENST00001113506, ENST00001113507, ENST00001113508, ENST00001119001, ENST00001124498, ENST00001124499, ENST00001124500, ENST00001124501, ENST00001124502, ENST00001124503, ENST00001135087

RefSeq mRNA: 20 — MANE Select: NM_001177306 NM_000919, NM_001177306, NM_001319943, NM_001364582, NM_001364583, NM_001364584, NM_001364585, NM_001364586, NM_001364587, NM_001364588, NM_001364589, NM_001364590, NM_001364591, NM_001364592, NM_001364593, NM_001364594, NM_001438446, NM_138766, NM_138821, NM_138822

CCDS: CCDS4092, CCDS4093, CCDS4094, CCDS43348, CCDS54885, CCDS93753, CCDS93754, CCDS93755, CCDS93756, CCDS93757

Canonical transcript exons

ENST00000438793 — 26 exons

Exon	Start	End
ENSE00001957372	103028887	103029716
ENSE00003459027	102949902	102949978
ENSE00003461968	102990272	102990401
ENSE00003470536	102924957	102925042
ENSE00003474257	103003033	103003149
ENSE00003495205	103028185	103028238
ENSE00003505311	103017334	103017433
ENSE00003512809	103025131	103025334
ENSE00003549530	102949537	102949617
ENSE00003552953	103019790	103019843
ENSE00003554562	102959875	102960059
ENSE00003557513	103005154	103005226
ENSE00003563882	102913934	102914021
ENSE00003564668	102950717	102950820
ENSE00003573210	102946837	102946885
ENSE00003578298	102926585	102926668
ENSE00003582428	102974116	102974436
ENSE00003596818	102865823	102866284
ENSE00003609741	103006801	103007011
ENSE00003623893	102901356	102901413
ENSE00003624006	103009751	103009866
ENSE00003633981	103007457	103007657
ENSE00003634022	102867273	102867393
ENSE00003653909	102961158	102961229
ENSE00003678493	102948378	102948445
ENSE00003920269	102755305	102755348

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 99.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 71.7303 / max 2250.7789, expressed in 1767 samples.

Highest expression (Bgee): cardiac muscle of right atrium, heart right ventricle, cardiac atrium, atrium auricular region, corpus epididymis.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PAM is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 28 tissues and its splicing (sQTL) in 33 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 61 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	sqtl	2.0e-105	-1.09	5:102974462:G:A
Whole Blood	eqtl	5.0e-104	+0.68	5:102782303:C:T
Artery Tibial	sqtl	1.4e-47	-0.79	5:102974462:G:A
Thyroid	sqtl	1.7e-41	-0.63	5:102989988:T:C
Adipose Subcutaneous	sqtl	9.3e-39	-0.51	5:102989988:T:C
Nerve Tibial	sqtl	6.2e-34	-0.67	5:102989988:T:C
Lung	sqtl	8.8e-32	-0.58	5:102971151:T:TA
Adipose Visceral Omentum	sqtl	3.3e-31	-0.61	5:102989988:T:C
Artery Aorta	sqtl	1.1e-28	-0.75	5:102974462:G:A
Brain Cerebellar Hemisphere	eqtl	3.0e-25	-0.51	5:102628754:T:C
Cells EBV-transformed lymphocytes	sqtl	6.8e-25	-1.03	5:102989988:T:C
Whole Blood	sqtl	2.9e-20	-0.56	5:102990174:A:G
Breast Mammary Tissue	sqtl	9.1e-19	-0.57	5:103100407:T:A
Skin Sun Exposed Lower leg	sqtl	5.6e-18	-0.45	5:102990174:A:G
Esophagus Mucosa	sqtl	1.1e-17	-0.49	5:102989988:T:C
Brain Cerebellum	eqtl	1.4e-17	-0.49	5:102676962:C:T
Esophagus Muscularis	sqtl	2.5e-16	-0.40	5:102974462:G:A
Heart Atrial Appendage	sqtl	4.2e-16	+1.06	5:103025380:G:C
Thyroid	eqtl	1.4e-14	-0.20	5:102741554:T:C
Skin Not Sun Exposed Suprapubic	eqtl	1.4e-13	-0.16	5:102589070:T:G

FANTOM5 promoters

showing 10 of 26 alternative TSS:

Promoter ID	TPM avg	Samples expressed
57807	40.3293	1757
57830	10.7537	1318
57827	5.3529	982
57831	3.7186	967
57826	3.5171	879
57805	1.2074	800
57806	1.0653	711
57818	1.0508	182
57823	1.0014	592
57825	0.8933	439

Top tissues by expression

showing 100 of 302 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cardiac muscle of right atrium	UBERON:0003379	99.89	gold quality
heart right ventricle	UBERON:0002080	99.86	gold quality
cardiac atrium	UBERON:0002081	99.86	gold quality
right atrium auricular region	UBERON:0006631	99.85	gold quality
corpus epididymis	UBERON:0004359	99.83	gold quality
myocardium	UBERON:0002349	99.80	gold quality
parotid gland	UBERON:0001831	99.75	gold quality
type B pancreatic cell	CL:0000169	99.70	gold quality
vena cava	UBERON:0004087	99.65	gold quality
islet of Langerhans	UBERON:0000006	99.64	gold quality
descending thoracic aorta	UBERON:0002345	99.60	gold quality
renal glomerulus	UBERON:0000074	99.59	gold quality
metanephric glomerulus	UBERON:0004736	99.58	gold quality
heart	UBERON:0000948	99.54	gold quality
thoracic aorta	UBERON:0001515	99.52	gold quality
blood vessel layer	UBERON:0004797	99.52	gold quality
tibia	UBERON:0000979	99.51	gold quality
ascending aorta	UBERON:0001496	99.51	gold quality
synovial joint	UBERON:0002217	99.50	gold quality
cardiac ventricle	UBERON:0002082	99.46	gold quality
visceral pleura	UBERON:0002401	99.46	gold quality
left ventricle myocardium	UBERON:0006566	99.46	gold quality
heart left ventricle	UBERON:0002084	99.45	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.45	gold quality
skin of hip	UBERON:0001554	99.44	gold quality
right coronary artery	UBERON:0001625	99.40	gold quality
seminal vesicle	UBERON:0000998	99.39	gold quality
palpebral conjunctiva	UBERON:0001812	99.36	gold quality
middle temporal gyrus	UBERON:0002771	99.32	gold quality
aorta	UBERON:0000947	99.31	gold quality
caput epididymis	UBERON:0004358	99.27	gold quality
endocervix	UBERON:0000458	99.25	gold quality
decidua	UBERON:0002450	99.25	gold quality
choroid plexus epithelium	UBERON:0003911	99.23	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.17	gold quality
urethra	UBERON:0000057	99.16	gold quality
calcaneal tendon	UBERON:0003701	99.16	gold quality
stromal cell of endometrium	CL:0002255	99.15	gold quality
popliteal artery	UBERON:0002250	99.15	gold quality
tibial artery	UBERON:0007610	99.14	gold quality
artery	UBERON:0001637	99.13	gold quality
coronary artery	UBERON:0001621	99.06	gold quality
left coronary artery	UBERON:0001626	99.05	gold quality
endometrium	UBERON:0001295	99.04	gold quality
cartilage tissue	UBERON:0002418	99.04	gold quality
pleura	UBERON:0000977	99.03	gold quality
apex of heart	UBERON:0002098	99.02	gold quality
kidney epithelium	UBERON:0004819	99.01	gold quality
saphenous vein	UBERON:0007318	98.99	gold quality
parietal pleura	UBERON:0002400	98.91	gold quality
layer of synovial tissue	UBERON:0007616	98.90	gold quality
smooth muscle tissue	UBERON:0001135	98.89	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	98.88	gold quality
upper leg skin	UBERON:0004262	98.87	gold quality
metanephros	UBERON:0000081	98.85	gold quality
right adrenal gland cortex	UBERON:0035827	98.85	gold quality
adrenal cortex	UBERON:0001235	98.84	gold quality
trachea	UBERON:0003126	98.84	gold quality
colonic epithelium	UBERON:0000397	98.82	gold quality
cauda epididymis	UBERON:0004360	98.82	gold quality
left adrenal gland cortex	UBERON:0035825	98.79	gold quality
endothelial cell	CL:0000115	98.78	gold quality
left adrenal gland	UBERON:0001234	98.78	gold quality
right adrenal gland	UBERON:0001233	98.77	gold quality
adrenal gland	UBERON:0002369	98.77	gold quality
adenohypophysis	UBERON:0002196	98.76	gold quality
nephron tubule	UBERON:0001231	98.75	gold quality
pons	UBERON:0000988	98.72	gold quality
pituitary gland	UBERON:0000007	98.70	gold quality
pylorus	UBERON:0001166	98.69	gold quality
substantia nigra pars compacta	UBERON:0001965	98.68	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.65	gold quality
adult organism	UBERON:0007023	98.65	gold quality
mucosa of stomach	UBERON:0001199	98.64	gold quality
superficial temporal artery	UBERON:0001614	98.53	gold quality
saliva-secreting gland	UBERON:0001044	98.52	gold quality
hypothalamus	UBERON:0001898	98.52	gold quality
ventricular zone	UBERON:0003053	98.50	gold quality
germinal epithelium of ovary	UBERON:0001304	98.48	gold quality
uterus	UBERON:0000995	98.42	gold quality
biceps brachii	UBERON:0001507	98.41	gold quality
adrenal tissue	UBERON:0018303	98.39	gold quality
gall bladder	UBERON:0002110	98.38	gold quality
epithelial cell of pancreas	CL:0000083	98.35	gold quality
myometrium	UBERON:0001296	98.29	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.29	gold quality
cardia of stomach	UBERON:0001162	98.28	gold quality
gluteal muscle	UBERON:0002000	98.28	gold quality
thoracic mammary gland	UBERON:0005200	98.28	gold quality
minor salivary gland	UBERON:0001830	98.27	gold quality
mammary gland	UBERON:0001911	98.25	gold quality
ectocervix	UBERON:0012249	98.23	gold quality
renal medulla	UBERON:0000362	98.22	gold quality
trigeminal ganglion	UBERON:0001675	98.22	gold quality
left ovary	UBERON:0002119	98.18	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.18	gold quality
vastus lateralis	UBERON:0001379	98.17	gold quality
nucleus accumbens	UBERON:0001882	98.17	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.16	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.15	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-9154	yes	2569.86
E-HCAD-35	yes	1447.03
E-HCAD-25	yes	1055.86
E-MTAB-10287	yes	47.29
E-MTAB-5061	yes	17.51
E-GEOD-125970	yes	9.44
E-GEOD-83139	yes	4.75
E-ENAD-17	no	623.84
E-CURD-114	no	17.96
E-GEOD-81608	no	7.90
E-ENAD-27	no	3.34
E-HCAD-31	no	2.15
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 155 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Heart muscle	tissue	1159.0	high
Epididymis	tissue	691.0	high
Cervix	tissue	574.4	medium
Locus coeruleus	tissue	276.2
Parathyroid gland	tissue	248.7	not detected
Seminal vesicle	tissue	204.2	not detected
Salivary gland	tissue	203.7	low
Adrenal gland	tissue	197.2	high
Ovary	tissue	157.8	not detected
Choroid plexus	tissue	156.8
Tongue	tissue	139.0
Smooth muscle	tissue	130.6	medium
Endometrium 1	tissue	125.7	medium
Putamen	tissue	122.9
Basal ganglia	tissue	119.5	low
Stomach 1	tissue	116.7	low
Pituitary gland	tissue	115.6
Cerebral cortex	tissue	114.0	medium
Motor cortex	tissue	114.0
Kidney	tissue	112.2	high
Hippocampal formation	tissue	109.7
Frontal cortex	tissue	109.5
Nucleus accumbens	tissue	107.3
Prefrontal cortex	tissue	105.3
Skeletal muscle	tissue	101.7	medium
Adipose tissue	tissue	99.9	not detected
Hypothalamus	tissue	99.6
Retrosplenial and cingulate cortex	tissue	97.7
Retrosplenial cortex	tissue	97.0
Vagina	tissue	96.5	not detected
Pancreas	tissue	93.9	medium
Breast	tissue	90.9	not detected
Septum	tissue	90.9
Urinary bladder	tissue	90.5	not detected
Temporal cortex	tissue	89.4
Thyroid gland	tissue	87.8	not detected
Caudate putamen	tissue	87.6
Ventral forebrain	tissue	83.7
Thalamus	tissue	83.1
Entorhinal cortex	tissue	82.9
Gallbladder	tissue	82.5	not detected
Insular cortex	tissue	82.3
Lung	tissue	82.1	not detected
Somatosensory cortex	tissue	81.5
Fallopian tube	tissue	81.2	high
Prostate	tissue	79.2	not detected
Substantia nigra	tissue	77.9
Pons	tissue	76.7
Midbrain	tissue	75.7
Periaqueductal gray	tissue	75.1
Hippocampus	tissue	74.1	low
Superior colliculi	tissue	73.4
Occipital cortex	tissue	72.0
Rectum	tissue	71.9	high
Postcentral gyrus	tissue	70.3
Amygdala	tissue	66.5
Medulla oblongata	tissue	66.0
Spinal cord	tissue	61.5
Colon	tissue	59.1	high
Esophagus	tissue	58.5	not detected

Brain sub-regions (HPA Brain Atlas): detected in 380; highest nTPM — Blood vessel (428.3), Arcuate nucleus (275.5), Lateral hypothalamic area (195.3), Ventromedial nucleus (162.6), Periaquaductal grey, anterior (152.9).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting PAM by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 144 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798

Functional genomics

gnomAD constraint: pLI 0.000642, LOEUF 0.863, missense Z 1.26 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000438793 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
5:102,866,196–103,003,111	670 / 690.3	0.97	no
5:103,003,112–103,007,535	103 / 157.9	0.65	no
5:103,007,536–103,029,062	333 / 335.6	0.99	no

Literature-anchored findings (GeneRIF, showing 19)

• nuclear retention of PAM mRNA is lost upon expressing the La proteins that lack a conserved nuclear retention element, suggesting a direct association between PAM mRNA and La protein in vivo (PMID:16107699)
• Data indicate that catalytic inactivation of PHM caused by pH changes is accompanied by structural change between two states of the protein involving strong Cu-S interaction that does not involve M314. (PMID:22080626)
• Detail the production of the catalytic core of human peptidylglycine alpha-hydroxylating monooxygenase (hPHMcc) in Escherichia coli possessing a N-terminal fusion to thioredoxin (Trx). (PMID:22554821)
• Two missense variants in PAM, encoding p.Asp563Gly (frequency of 4.98%) and p.Ser539Trp (frequency of 0.65%), confer moderately higher risk of type 2 diabetes (OR = 1.23, P = 3.9 x 10(-10) and OR = 1.47, P = 1.7 x 10(-5), respectively) (PMID:24464100)
• Oxygen Sensitivity of the Peptidylglycine alpha-Amidating Monooxygenase (PAM) in Neuroendocrine Cells (PMID:26296884)
• PAM expression is increased in the secretory pathway of differentiated neurons. (PMID:26879543)
• Data suggest that His108 and a substrate molecule are involved in the reductive pathway while His172 and Tyr79 are important in the catalytic pathway in the copper-centered electron transfer catalyzed by peptidylglycine monooxygenase. (PMID:26982589)
• The ancient ability of PAM to localize to ciliary membranes, which release bioactive ectosomes, may be related to its ability to accumulate in intralumenal vesicles and exosomes (PMID:28377049)
• PAM single nucleotide polymorphism rs13175330 is associated with hypertension and insulin resistance in a Korean population. (PMID:29162152)
• PAM polyubiquitinates NMNAT2 and regulates NMNAT2 protein stability and degradation by the proteasome. (PMID:29997255)
• A role for PAM in beta-cell function. (PMID:30054598)
• The T2D risk-associated rs35658696 (p.Asp563Gly) allele of PAM confers decreased PAM expression in human islets. (PMID:30054598)
• The T2D risk-associated rs35658696 (p.Asp563Gly) allele of PAM confers reduced amidating activity. (PMID:30054598)
• siRNA-mediated knockdown of PAM in EndoC-BetaH1 cells caused reductions in insulin secretion and content. These effects were also observed in primary islets from human donors heterozygous for the T2D risk-associated rs35658696 variant. (PMID:30054598)
• PAM haploinsufficiency does not accelerate the development of diet- and human IAPP-induced diabetes in mice. (PMID:31984442)
• Mitochondrial Oxidative Stress Induces Rapid Intermembrane Space/Matrix Translocation of Apurinic/Apyrimidinic Endonuclease 1 Protein through TIM23 Complex. (PMID:33197464)
• PAM variants were associated with type 2 diabetes mellitus risk in the Chinese population. (PMID:35394266)
• Peptidylglycine alpha-amidating monooxygenase and adrenomedullin measurement in patients with hepatic cirrhosis. (PMID:37812053)
• PAM variants in patients with thyrotrophinomas, cyclical Cushing’s disease and prolactinomas. (PMID:38075079)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	pam	ENSDARG00000100170
mus_musculus	Pam	ENSMUSG00000026335
rattus_norvegicus	Pam	ENSRNOG00000033280
drosophila_melanogaster	Pal2	FBGN0262728
drosophila_melanogaster	Pal1	FBGN0283510
caenorhabditis_elegans	pgal-1	WBGENE00017671

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:97475) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 8 distinct phenotype terms.

Mouse phenotype (MP)	Records
edema	1
abnormal artery morphology	1
abnormal vitelline vasculature morphology	1
impaired glucose tolerance	1
increased total body fat amount	1
abnormal bronchus epithelium morphology	1
lethality throughout fetal growth and development, complete penetrance	1
umbilical vein stenosis	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	P10731	92.4%	Diamond
Xenopus laevis	P08478	86.7%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SLCO6A1-DT	ncRNA	124901035
LINC00491	ncRNA	285708
LINC00492	ncRNA	100861468
PPIP5K2	protein-coding	23262
GIN1	protein-coding	54826

Protein

Protein identifiers

Peptidyl-glycine alpha-amidating monooxygenase — P19021 (reviewed: P19021)

All UniProt accessions (19): A0A804HI59, A0A804HIQ0, A0A804HJJ2, A0A804HK31, A0A804HKM7, A0A804HKV8, A0A804HLE0, A0A804HLJ2, A0A8C8KD64, D6R961, D6RAQ2, D6RCD5, D6RDU2, D6RF09, D6RG20, P19021, F8W8D9, H0Y9I4, H7BYD9

UniProt curated annotations — full annotation on UniProt →

Function. Bifunctional enzyme that catalyzes amidation of the C-terminus of proteins. Alpha-amidation is present at the C-terminus of many endocrine hormones and neuropeptides and is required for their activity. C-terminal amidation also takes place in response to protein fragmentation triggered by oxidative stress, promoting degradation of amidated protein fragments by the proteasome. Alpha-amidation involves two sequential reactions, both of which are catalyzed by separate catalytic domains of the enzyme. The first step, catalyzed by peptidyl alpha-hydroxylating monooxygenase (PHM) domain, is the copper-, ascorbate-, and O2- dependent stereospecific hydroxylation (with S stereochemistry) at the alpha-carbon (C-alpha) of the C-terminal glycine of the peptidylglycine substrate. The second step, catalyzed by the peptidylglycine amidoglycolate lyase (PAL) domain, is the zinc-dependent cleavage of the N-C-alpha bond, producing the alpha-amidated peptide and glyoxylate. Similarly, catalyzes the two-step conversion of an N-fatty acylglycine to a primary fatty acid amide and glyoxylate.

Subunit / interactions. Monomer. Interacts with RASSF9.

Subcellular location. Cytoplasmic vesicle. Secretory vesicle membrane Membrane Membrane Secreted Secreted.

Activity regulation. PAM activity is inhibited by EDTA, phenylglyoxal and diethyl pyrocarbonate. PAL activity is stimulated by cadmium and inhibited by mercury.

Cofactor. Binds one Zn(2+) ion per subunit. Binds 2 Cu(2+) ions per subunit.

Miscellaneous. Soluble. Soluble.

Similarity. In the C-terminal section; belongs to the peptidyl-alpha-hydroxyglycine alpha-amidating lyase family. In the N-terminal section; belongs to the copper type II ascorbate-dependent monooxygenase family.

Isoforms (6)

UniProt ID	Names	Canonical?
P19021-1	1	yes
P19021-2	2
P19021-3	3
P19021-4	4
P19021-5	5
P19021-6	6

RefSeq proteins (20): NP_000910, NP_001170777, NP_001306872, NP_001351511, NP_001351512, NP_001351513, NP_001351514, NP_001351515, NP_001351516, NP_001351517, NP_001351518, NP_001351519, NP_001351520, NP_001351521, NP_001351522, NP_001351523, NP_001425375, NP_620121, NP_620176, NP_620177 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000323	Cu2_ascorb_mOase_N	Domain
IPR000720	PHM/PAL	Family
IPR001258	NHL_repeat	Repeat
IPR008977	PHM/PNGase_F_dom_sf	Homologous_superfamily
IPR011042	6-blade_b-propeller_TolB-like	Homologous_superfamily
IPR014783	Cu2_ascorb_mOase_CS-2	Conserved_site
IPR014784	Cu2_ascorb_mOase-like_C	Homologous_superfamily
IPR020611	Cu2_ascorb_mOase_CS-1	Conserved_site
IPR024548	Cu2_monoox_C	Domain
IPR036939	Cu2_ascorb_mOase_N_sf	Homologous_superfamily

Pfam: PF01082, PF01436, PF03712

Enzyme classification (BRENDA)

• EC 1.14.17.3 — peptidylglycine monooxygenase (BRENDA: 16 organisms, 234 substrates, 143 inhibitors, 170 Km, 30 kcat entries)
• EC 4.3.2.5 — peptidylamidoglycolate lyase (BRENDA: 28 organisms, 21 substrates, 22 inhibitors, 30 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

131 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
NALPHA-ACETYL-TYR-VAL-ALPHA-HYDROXYGLYCINE	0.0102–0.33	10
O2	0.1–658.1	9
DANSYL-D-TYR-VAL-GLY	0.0009–0.8	6
N-ACETYL-TYR-VAL-GLY	0.0012–0.0098	6
N-ACETYLGLYCINE	9.3–18	5
TRINITROPHENYL-D-TYR-L-VAL-ALPHA-HYDROXY-GLY	0.014–0.033	5
D-TYR-PRO-GLY-GLY	0.033–0.289	4
D-TYR-VAL-GLY	0.007–0.22	4
DANSYL-L-TYR-L-VAL-GLY	0.0033–0.0194	4
PEPTIDYLGLYCINE	0.009–0.018	4
N-DANSYL-L-TYR-L-PHE-GLY	3.5–4.5	3
N-DECANOYLGLYCINE	0.1–0.2	3
ALPHA-N-ACETYL-TYR-VAL-ALPHA-HYDROXYGLYCINE	0.013–0.238	3
ACETYL-L-TYR-L-PHE-GLY	0.0003–1.39	2
DABSYL-GLY-PHE-GLY	0.022–0.143	2

Catalyzed reactions (Rhea)

• a [peptide]-C-terminal (2S)-2-hydroxyglycine = a [peptide]-C-terminal amide + glyoxylate (RHEA:20924)
• a [peptide]-C-terminal glycine + 2 L-ascorbate + O2 = a [peptide]-C-terminal (2S)-2-hydroxyglycine + 2 monodehydro-L-ascorbate radical + H2O (RHEA:21452)
• N-dodecanoylglycine + 2 L-ascorbate + O2 = N-dodecanoyl-(2S)-hydroxyglycine + 2 monodehydro-L-ascorbate radical + H2O (RHEA:58540)
• N-tetradecanoylglycine + 2 L-ascorbate + O2 = N-tetradecanoyl-(2S)-hydroxyglycine + 2 monodehydro-L-ascorbate radical + H2O (RHEA:58544)
• N-(9Z,12Z,15Z)-octadecatrienoylglycine + 2 L-ascorbate + O2 = N-(9Z,12Z,15Z)-octadecatrienoyl-(2S)-hydroxyglycine + 2 monodehydro-L-ascorbate radical + H2O (RHEA:58548)
• N-(9Z-octadecenoyl)glycine + 2 L-ascorbate + O2 = N-(9Z-octadecenoyl)-(2S)-hydroxyglycine + 2 monodehydro-L-ascorbate radical + H2O (RHEA:58600)
• N-decanoylglycine + 2 L-ascorbate + O2 = N-decanoyl-(2S)-hydroxyglycine + 2 monodehydro-L-ascorbate radical + H2O (RHEA:58608)
• N-octanoylglycine + 2 L-ascorbate + O2 = N-octanoyl-(2S)-hydroxyglycine + 2 monodehydro-L-ascorbate radical + H2O (RHEA:58612)
• N-octanoyl-(2S)-hydroxyglycine = octanamide + glyoxylate (RHEA:58616)
• N-decanoyl-(2S)-hydroxyglycine = decanamide + glyoxylate (RHEA:58620)
• N-dodecanoyl-(2S)-hydroxyglycine = dodecanamide + glyoxylate (RHEA:58624)
• N-tetradecanoyl-(2S)-hydroxyglycine = tetradecamide + glyoxylate (RHEA:58632)

UniProt features (58 total): binding site 15, modified residue 8, disulfide bond 7, repeat 5, splice variant 5, region of interest 4, sequence conflict 4, compositionally biased region 2, topological domain 2, signal peptide 1, propeptide 1, chain 1, glycosylation site 1, transmembrane region 1, sequence variant 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P19021-F1	71.54	0.44

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Metabolic proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; cytosol; vesicles

Antibody reliability (HPA): IF supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (15)

Position	Role
102	Cu(2+)
103	Cu(2+)
167	Cu(2+)
237	Cu(2+)
239	Cu(2+)
309	Cu(2+)
517	Ca(2+)
530	a protein
582	Zn(2+)
584	Ca(2+)
651	a protein
687	Zn(2+)
703	a protein
783	Zn(2+)
784	Ca(2+)

Post-translational modifications (8)

Type	Positions
Phosphoserine	918, 929, 942, 946, 957
Phosphothreonine	943
Sulfotyrosine	893, 875

Disulfide bonds (7)

Type	Positions
Disulfide bond	42–181, 76–121, 109–126, 222–329, 288–310, 631–652, 699–710

Glycosylation sites (1)

Type	Positions
N-linked (glcnac…) asparagine	762

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 322 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, VERHAAK_AML_WITH_NPM1_MUTATED_DN, MODULE_93, ZHAN_LATE_DIFFERENTIATION_GENES_UP, GOBP_RESPONSE_TO_ZINC_ION, GGTGTGT_MIR329, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GOCC_SECRETORY_GRANULE, GCANCTGNY_MYOD_Q6, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, SHAFFER_IRF4_TARGETS_IN_ACTIVATED_B_LYMPHOCYTE, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, CAGCTG_AP4_Q5, GOBP_RESPONSE_TO_METAL_ION, SHAFFER_IRF4_TARGETS_IN_PLASMA_CELL_VS_MATURE_B_LYMPHOCYTE

GO Biological Process (6): peptide amidation (GO:0001519), response to zinc ion (GO:0010043), cellular response to oxidative stress (GO:0034599), fatty acid primary amide biosynthetic process (GO:0062112), peptide metabolic process (GO:0006518), lipid metabolic process (GO:0006629)

GO Molecular Function (13): peptidylglycine monooxygenase activity (GO:0004504), peptidylamidoglycolate lyase activity (GO:0004598), copper ion binding (GO:0005507), calcium ion binding (GO:0005509), zinc ion binding (GO:0008270), L-ascorbic acid binding (GO:0031418), catalytic activity (GO:0003824), monooxygenase activity (GO:0004497), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced ascorbate as one donor, and incorporation of one atom of oxygen (GO:0016715), lyase activity (GO:0016829), metal ion binding (GO:0046872)

GO Cellular Component (6): extracellular region (GO:0005576), membrane (GO:0016020), transport vesicle membrane (GO:0030658), secretory granule membrane (GO:0030667), extracellular exosome (GO:0070062), cytoplasmic vesicle (GO:0031410)

GO top-level categories

32 GO namespaces:

Category	Terms
transition metal ion binding	2
catalytic activity	2
cellular anatomical structure	2
cytoplasmic vesicle membrane	2
bounding membrane of organelle	2
peptide modification	1
response to metal ion	1
response to oxidative stress	1
cellular response to chemical stress	1
fatty acid primary amide metabolic process	1
fatty acid derivative biosynthetic process	1
metabolic process	1
primary metabolic process	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced ascorbate as one donor, and incorporation of one atom of oxygen	1
amidine-lyase activity	1
catalytic activity, acting on a protein	1
metal ion binding	1
vitamin binding	1
carboxylic acid binding	1
monosaccharide binding	1
heterocyclic compound binding	1
molecular_function	1
oxidoreductase activity	1
binding	1
monooxygenase activity	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	1
cation binding	1
transport vesicle	1
secretory granule	1
extracellular vesicle	1
cytoplasm	1
intracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 7 of 25 annotations. The rest are phylogenetic / computational / electronic (IEA).

7 experimentally-supported GO terms:

GO term	NS	Evidence
peptide amidation	BP	direct assay
response to zinc ion	BP	direct assay
extracellular exosome	CC	high-throughput assay
membrane	CC	high-throughput assay
peptidylamidoglycolate lyase activity	MF	direct assay
peptidylglycine monooxygenase activity	MF	direct assay
zinc ion binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 492 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PAM	CYB561	P49447	846
PAM	TOR2A	Q5JU69	830
PAM	KALRN	O60229	806
PAM	RASSF9	O75901	719
PAM	CPE	P16870	697
PAM	PCSK1	P29120	625
PAM	DAPK1	P53355	552
PAM	IAPP	P10997	526
PAM	ATP7A	Q04656	512
PAM	MCF2	P10911	504
PAM	PCSK2	P16519	500
PAM	SHD	Q96IW2	497
PAM	TOR1A	O14656	494
PAM	CHGA	P10645	487
PAM	F11R	Q9Y624	481

IntAct

Human interaction partners of PAM in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

4 partners by confidence:

Partner	Interaction type	MIscore	Records
UBR2	association	0.530	1
DEDD	physical association	0.000	1
DISC1	physical association	0.000	1
PRKAR1A	physical association	0.000	1

BioGRID (78 interactions; top human partners by supporting records): ART3 (Affinity Capture-MS; 3 records), B3GNT2 (Affinity Capture-MS; 3 records), PTCH1 (Affinity Capture-MS; 3 records), SERPINA6 (Affinity Capture-MS; 3 records), TAZ (Affinity Capture-MS; 3 records), TMEM25 (Affinity Capture-MS; 3 records), TSC2 (Two-hybrid; 3 records), UBR2 (Affinity Capture-MS; 3 records), DKKL1 (Affinity Capture-MS; 2 records), GAA (Affinity Capture-MS; 2 records), IDS (Affinity Capture-MS; 2 records), KALRN (Two-hybrid; 2 records), RALB (Affinity Capture-MS; 2 records), RASSF9 (Two-hybrid; 2 records), ADAMTS12 (Affinity Capture-MS)

SIGNOR signaling

2 signaling interactions:

A	Effect	B	Mechanism
UHMK1	unknown	PAM	phosphorylation
PAM	“up-regulates activity”	Oxytocin	cleavage

Disease & clinical

Genetic variants

Variant evidence for PAM: 113 ClinVar records (0 pathogenic / likely pathogenic).

ClinVar

113 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	77
Likely benign	4
Benign	7

AlphaMissense

2,006 missense substitutions predicted likely pathogenic (of 6,412 scored), across 492 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M309	9	0.976	0.995
M315	9	0.867	0.984
H103	8	0.994	0.997
H167	8	0.990	0.998
H237	8	0.987	0.997
D180	8	0.984	0.996
F269	8	0.978	0.998
D649	8	0.978	0.995
H239	8	0.976	0.993
D596	8	0.976	0.995
F232	8	0.972	0.997
F151	8	0.966	0.998
F540	8	0.965	0.997
H582	8	0.964	0.990
H102	8	0.963	0.987
F290	8	0.963	0.997
H600	8	0.963	0.991
F174	8	0.962	0.995
D282	8	0.960	0.987
F92	8	0.953	0.997

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	3.37e-06

Disease associations

OMIM: gene MIM:170270 | disease phenotypes:

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2544 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

16 measured of 16 human assays (17 total across all organisms); most potent 16 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
((E)-Styrylsulfanyl)-acetic acid	KI	0.1 nM
Phenylethynylsulfanyl-acetic acid	KI	0.19 nM
CHEMBL2207130	IC50	2000 nM
CHEMBL2207128	IC50	3000 nM
CHEMBL2207127	IC50	11000 nM
CHEMBL2207143	IC50	12000 nM
CHEMBL2207129	IC50	38000 nM
CHEMBL2207141	IC50	120000 nM
CHEMBL2207133	IC50	160000 nM
CHEMBL2207142	IC50	180000 nM
CHEMBL2207145	IC50	290000 nM
CHEMBL2207132	IC50	350000 nM
CHEMBL2207144	IC50	500000 nM
CHEMBL2207131	IC50	1.1e+06 nM
CHEMBL2207146	IC50	1.1e+06 nM
CHEMBL2207140	IC50	1.8e+06 nM

ChEMBL bioactivities

14 potent at pChembl≥5 of 25 total, top 14 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	Ki	0.1	nM	CHEMBL127222
9.72	Ki	0.19	nM	CHEMBL335660
7.40	IC50	40	nM	CHEMBL3221589
7.30	IC50	50	nM	CHEMBL3221589
7.22	IC50	60	nM	CHEMBL3221585
7.02	Ki	96	nM	CHEMBL2269608
6.92	IC50	120	nM	CHEMBL3221589
5.70	IC50	2000	nM	CHEMBL2207130
5.70	IC50	2000	nM	CHEMBL3217795
5.52	IC50	3000	nM	CHEMBL2207128
5.30	IC50	5000	nM	CHEMBL2207127
5.22	IC50	6000	nM	CHEMBL2207129
5.22	IC50	6000	nM	CHEMBL2207127
5.05	IC50	9000	nM	CHEMBL2207128

PubChem BioAssay actives

5 with measured affinity, of 68 total; 4 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(2S)-2-[[(2S)-2-[[(2S)-1-[(4R,7S,10S,13S,16S,19R)-19-amino-7-(2-amino-2-oxoethyl)-10-(3-amino-3-oxopropyl)-13-[(2S)-butan-2-yl]-16-[(4-hydroxyphenyl)methyl]-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]pyrrolidine-2-carbonyl]amino]-4-methylpentanoyl]amino]-3-phenylpropanoyl]oxyacetic acid	717278: Competitive inhibition of PAM in human DMS53 cells using as(R)-Tyr-(S)-Val-Gly as substrate after 2 hrs by HPLC analysis	ic50	2.0000	uM
2-[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-3-phenylpropanoyl]oxyacetic acid	717278: Competitive inhibition of PAM in human DMS53 cells using as(R)-Tyr-(S)-Val-Gly as substrate after 2 hrs by HPLC analysis	ic50	3.0000	uM
2-[(2S)-2-acetamido-3-phenylpropanoyl]oxyacetic acid	717278: Competitive inhibition of PAM in human DMS53 cells using as(R)-Tyr-(S)-Val-Gly as substrate after 2 hrs by HPLC analysis	ic50	5.0000	uM
2-[(2S)-2-[[(2S)-2-[[(2S)-1-acetylpyrrolidine-2-carbonyl]amino]-4-methylpentanoyl]amino]-3-phenylpropanoyl]oxyacetic acid	717278: Competitive inhibition of PAM in human DMS53 cells using as(R)-Tyr-(S)-Val-Gly as substrate after 2 hrs by HPLC analysis	ic50	6.0000	uM

CTD chemical–gene interactions

50 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	3
Cadmium Chloride	decreases expression, increases abundance, increases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
Air Pollutants	increases abundance, increases oxidation, decreases expression, affects cotreatment	2
Estradiol	increases expression, affects cotreatment, decreases expression	2
Oxygen	increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	decreases methylation	1
terbufos	increases methylation	1
beta-lapachone	decreases expression	1
arsenite	affects expression	1
nickel sulfate	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
chloropicrin	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
NSC 689534	increases expression	1
Irinotecan	decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Ethanol	affects cotreatment, increases expression	1
Allergens	decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, increases expression	1
Cisplatin	affects cotreatment, decreases expression	1

ChEMBL screening assays

14 unique, capped per target: 14 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2211742	Binding	Binding affinity to secreted PAM in human DMS53 cell culture medium after 2 hrs by HPLC analysis	Prohormone-substrate peptide sequence recognition by peptidylglycine α-amidating monooxygenase and its reflection in increased glycolate inhibitor potency. — *Bioorg Med Chem Lett*

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_YB09	EndoC-betaH1 PAM-KO	Transformed cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PAM across ~30M SureChEMBL compounds — explore on Sugi Predict.