PAM
Peptidyl-glycine alpha-amidating monooxygenase
Also known as: AMD_HUMAN, PAL, PHM
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P19021
- Gene
- PAM
- Ensembl
- ENSG00000145730
- Chromosome
- 5
- Canonical length
- 973 aa
- Protein class
- Enzymes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins, Predicted secreted proteins
- Subcellular location
- Golgi apparatus,Cytosol
- Secretome location
- Secreted in other tissues
OverviewNCBI Gene
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]
Canonical amino-acid sequenceUniProt
973 residues, UniProt reviewed canonical sequence.
>P19021|PAM
1 MAGRVPSLLV LLVFPSSCLA FRSPLSVFKR FKETTRPFSN ECLGTTRPVV PIDSSDFALD
61 IRMPGVTPKQ SDTYFCMSMR IPVDEEAFVI DFKPRASMDT VHHMLLFGCN MPSSTGSYWF
121 CDEGTCTDKA NILYAWARNA PPTRLPKGVG FRVGGETGSK YFVLQVHYGD ISAFRDNNKD
181 CSGVSLHLTR LPQPLIAGMY LMMSVDTVIP AGEKVVNSDI SCHYKNYPMH VFAYRVHTHH
241 LGKVVSGYRV RNGQWTLIGR QSPQLPQAFY PVGHPVDVSF GDLLAARCVF TGEGRTEATH
301 IGGTSSDEMC NLYIMYYMEA KHAVSFMTCT QNVAPDMFRT IPPEANIPIP VKSDMVMMHE
361 HHKETEYKDK IPLLQQPKRE EEEVLDQGDF YSLLSKLLGE REDVVHVHKY NPTEKAESES
421 DLVAEIANVV QKKDLGRSDA REGAEHERGN AILVRDRIHK FHRLVSTLRP PESRVFSLQQ
481 PPPGEGTWEP EHTGDFHMEE ALDWPGVYLL PGQVSGVALD PKNNLVIFHR GDHVWDGNSF
541 DSKFVYQQIG LGPIEEDTIL VIDPNNAAVL QSSGKNLFYL PHGLSIDKDG NYWVTDVALH
601 QVFKLDPNNK EGPVLILGRS MQPGSDQNHF CQPTDVAVDP GTGAIYVSDG YCNSRIVQFS
661 PSGKFITQWG EESSGSSPLP GQFTVPHSLA LVPLLGQLCV ADRENGRIQC FKTDTKEFVR
721 EIKHSSFGRN VFAISYIPGL LFAVNGKPHF GDQEPVQGFV MNFSNGEIID IFKPVRKHFD
781 MPHDIVASED GTVYIGDAHT NTVWKFTLTE KLEHRSVKKA GIEVQEIKEA EAVVETKMEN
841 KPTSSELQKM QEKQKLIKEP GSGVPVVLIT TLLVIPVVVL LAIAIFIRWK KSRAFGDSEH
901 KLETSSGRVL GRFRGKGSGG LNLGNFFASR KGYSRKGFDR LSTEGSDQEK EDDGSESEEE
961 YSAPLPALAP SSSLocalizationUniProt · AlphaFold · HPA
Whether an antibody against PAM can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Secreted
- Secreted
- Yes
- Transmembrane segments
- 1
- Mean surface accessibility (rSASA)
- 0.39
- Highest tissue expression
- 1,159 nTPM
Expression across tissuesHPA
Tissue
- heart muscle: 1,159 nTPM
- epididymis: 691 nTPM
- cervix: 574 nTPM
- blood vessel: 428 nTPM
- parathyroid gland: 249 nTPM
- seminal vesicle: 204 nTPM
Single-cell type
- neuroendocrine cells: 1,549 nCPM
- pituicytes/fscs: 1,164 nCPM
- myonuclei: 1,099 nCPM
- cardiomyocytes: 905 nCPM
- gonadotrophs: 845 nCPM
- pancreatic islet cells: 839 nCPM
Immune cell
- NK-cell: 24 nTPM
- gdT-cell: 21 nTPM
- T-reg: 19 nTPM
- memory CD8 T-cell: 16 nTPM
- neutrophil: 16 nTPM
- MAIT T-cell: 14 nTPM
Brain region
- pons: 276 nTPM
- hypothalamus: 276 nTPM
- choroid plexus: 157 nTPM
- midbrain: 153 nTPM
- thalamus: 131 nTPM
- basal ganglia: 113 nTPM
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.52
- gnomAD pLI
- 0
- gnomAD missense Z
- 0.96
- DepMap mean gene effect
- 0.02
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- cellular response to oxidative stress
- peptide amidation
- response to zinc ion
- fatty acid primary amide biosynthetic process
Molecular functions
- calcium ion binding
- copper ion binding
- L-ascorbic acid binding
- zinc ion binding
- peptidylamidoglycolate lyase activity
- peptidylglycine monooxygenase activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Copper type II, ascorbate-dependent monooxygenase, N-terminal
- NHL repeat
- PHM/PNGase F domain superfamily
- Six-bladed beta-propeller, TolB-like
- Copper type II, ascorbate-dependent monooxygenase, histidine-cluster-2 conserved site
- Copper type II, ascorbate-dependent monooxygenase-like, C-terminal
- Copper type II, ascorbate-dependent monooxygenase, histidine-cluster-1 conserved site
- Copper type II ascorbate-dependent monooxygenase, C-terminal
- Copper type II, ascorbate-dependent monooxygenase, N-terminal domain superfamily
- Copper type II ascorbate-dependent monooxygenase, N-terminal domain
- NHL repeat
- Copper type II ascorbate-dependent monooxygenase, C-terminal domain
- Peptidylglycine alpha-hydroxylating monooxygenase/peptidyl-hydroxyglycine alpha-amidating lyase
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of PAM in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads PAM as an antibody target. Whether an autoantibody or antibody against PAM could matter depends on whether native PAM is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
PAM is annotated as secreted, so native PAM circulates and is directly accessible to antibodies. Secreted and cell-surface proteins are the autoantibody targets most likely to act like drugs, blocking or depleting the native protein.
Annotation status
The present source text does not explicitly label PAM as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
Loading the interactive Seroatlas protein explorer...