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Protein

Peptidyl-glycine alpha-amidating monooxygenase

Gene

PAM

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.

Catalytic activityi

Peptidylglycine + ascorbate + O2 = peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O.
Peptidylamidoglycolate = peptidyl amide + glyoxylate.

Cofactori

Protein has several cofactor binding sites:

Enzyme regulationi

Inhibited by EDTA, phenylglyoxal and diethyl pyrocarbonate.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi102Copper ABy similarity1
Metal bindingi103Copper ABy similarity1
Metal bindingi167Copper ABy similarity1
Metal bindingi237Copper BBy similarity1
Metal bindingi239Copper BBy similarity1
Metal bindingi309Copper BBy similarity1

GO - Molecular functioni

  • calcium ion binding Source: Ensembl
  • copper ion binding Source: Ensembl
  • L-ascorbic acid binding Source: UniProtKB-KW
  • peptidylamidoglycolate lyase activity Source: UniProtKB
  • peptidylglycine monooxygenase activity Source: UniProtKB
  • zinc ion binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionLyase, Monooxygenase, Multifunctional enzyme, Oxidoreductase
LigandCopper, Metal-binding, Vitamin C, Zinc

Enzyme and pathway databases

BRENDAi1.14.17.3 2681
4.3.2.5 2681
SignaLinkiP19021
SIGNORiP19021

Names & Taxonomyi

Protein namesi
Recommended name:
Peptidyl-glycine alpha-amidating monooxygenase
Short name:
PAM
Including the following 2 domains:
Peptidylglycine alpha-hydroxylating monooxygenase (EC:1.14.17.3)
Short name:
PHM
Peptidyl-alpha-hydroxyglycine alpha-amidating lyase (EC:4.3.2.5)
Alternative name(s):
Peptidylamidoglycolate lyase
Short name:
PAL
Gene namesi
Name:PAM
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000145730.20
HGNCiHGNC:8596 PAM
MIMi170270 gene
neXtProtiNX_P19021

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini31 – 863IntragranularSequence analysisAdd BLAST833
Transmembranei864 – 887HelicalSequence analysisAdd BLAST24
Topological domaini888 – 973CytoplasmicSequence analysisAdd BLAST86

Keywords - Cellular componenti

Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi5066
OpenTargetsiENSG00000145730
PharmGKBiPA32926

Chemistry databases

ChEMBLiCHEMBL2544
DrugBankiDB04150 Threonine Derivative
DB00126 Vitamin C

Polymorphism and mutation databases

BioMutaiPAM
DMDMi23503036

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20CuratedAdd BLAST20
PropeptideiPRO_000000636121 – 30Curated10
ChainiPRO_000000636231 – 973Peptidyl-glycine alpha-amidating monooxygenaseAdd BLAST943

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi42 ↔ 181By similarity
Disulfide bondi76 ↔ 121By similarity
Disulfide bondi109 ↔ 126By similarity
Disulfide bondi222 ↔ 329By similarity
Disulfide bondi288 ↔ 310By similarity
Disulfide bondi631 ↔ 652By similarity
Disulfide bondi699 ↔ 710By similarity
Glycosylationi762N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei918PhosphoserineCombined sources1
Modified residuei929PhosphoserineCombined sources1
Modified residuei942PhosphoserineCombined sources1
Modified residuei943Phosphothreonine1 Publication1
Modified residuei946Phosphoserine; by UHMK1; in vitroCombined sources1 Publication1
Modified residuei957PhosphoserineBy similarity1
Isoform 4 (identifier: P19021-4)
Modified residuei875Sulfotyrosine1 Publication1
Isoform 3 (identifier: P19021-3)
Modified residuei893Sulfotyrosine1 Publication1

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Phosphoprotein, Sulfation

Proteomic databases

EPDiP19021
MaxQBiP19021
PaxDbiP19021
PeptideAtlasiP19021
PRIDEiP19021

PTM databases

iPTMnetiP19021
PhosphoSitePlusiP19021

Expressioni

Gene expression databases

BgeeiENSG00000145730
CleanExiHS_PAM
ExpressionAtlasiP19021 baseline and differential
GenevisibleiP19021 HS

Organism-specific databases

HPAiCAB026119
HPA042260

Interactioni

Subunit structurei

Monomer. Interacts with RASSF9 (By similarity).By similarity

Protein-protein interaction databases

BioGridi111101, 25 interactors
CORUMiP19021
IntActiP19021, 2 interactors
STRINGi9606.ENSP00000306100

Chemistry databases

BindingDBiP19021

Structurei

3D structure databases

ProteinModelPortaliP19021
SMRiP19021
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati498 – 541NHL 1Add BLAST44
Repeati567 – 608NHL 2Add BLAST42
Repeati617 – 662NHL 3Add BLAST46
Repeati670 – 714NHL 4Add BLAST45
Repeati766 – 809NHL 5Add BLAST44

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 494Peptidylglycine alpha-hydroxylating monooxygenaseBy similarityAdd BLAST494
Regioni495 – 817Peptidyl-alpha-hydroxyglycine alpha-amidating lyaseBy similarityAdd BLAST323
Regioni925 – 942Interaction with RASSF9By similarityAdd BLAST18

Sequence similaritiesi

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

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3567 Eukaryota
ENOG410XS0X LUCA
GeneTreeiENSGT00530000063085
HOVERGENiHBG004218
InParanoidiP19021
KOiK00504
K18200
OMAiFVLQVHY
OrthoDBiEOG091G067T
PhylomeDBiP19021
TreeFamiTF320698

Family and domain databases

Gene3Di2.120.10.30, 1 hit
2.60.120.230, 1 hit
2.60.120.310, 1 hit
InterProiView protein in InterPro
IPR011042 6-blade_b-propeller_TolB-like
IPR014784 Cu2_ascorb_mOase-like_C
IPR020611 Cu2_ascorb_mOase_CS-1
IPR014783 Cu2_ascorb_mOase_CS-2
IPR000323 Cu2_ascorb_mOase_N
IPR036939 Cu2_ascorb_mOase_N_sf
IPR024548 Cu2_monoox_C
IPR001258 NHL_repeat
IPR013017 NHL_repeat_subgr
IPR000720 PHM/PAL
IPR008977 PHM/PNGase_F_dom_sf
PfamiView protein in Pfam
PF03712 Cu2_monoox_C, 1 hit
PF01082 Cu2_monooxygen, 1 hit
PF01436 NHL, 3 hits
PRINTSiPR00790 PAMONOXGNASE
SUPFAMiSSF49742 SSF49742, 2 hits
PROSITEiView protein in PROSITE
PS00084 CU2_MONOOXYGENASE_1, 1 hit
PS00085 CU2_MONOOXYGENASE_2, 1 hit
PS51125 NHL, 5 hits

Sequences (6)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: P19021-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAGRVPSLLV LLVFPSSCLA FRSPLSVFKR FKETTRPFSN ECLGTTRPVV
60 70 80 90 100
PIDSSDFALD IRMPGVTPKQ SDTYFCMSMR IPVDEEAFVI DFKPRASMDT
110 120 130 140 150
VHHMLLFGCN MPSSTGSYWF CDEGTCTDKA NILYAWARNA PPTRLPKGVG
160 170 180 190 200
FRVGGETGSK YFVLQVHYGD ISAFRDNNKD CSGVSLHLTR LPQPLIAGMY
210 220 230 240 250
LMMSVDTVIP AGEKVVNSDI SCHYKNYPMH VFAYRVHTHH LGKVVSGYRV
260 270 280 290 300
RNGQWTLIGR QSPQLPQAFY PVGHPVDVSF GDLLAARCVF TGEGRTEATH
310 320 330 340 350
IGGTSSDEMC NLYIMYYMEA KHAVSFMTCT QNVAPDMFRT IPPEANIPIP
360 370 380 390 400
VKSDMVMMHE HHKETEYKDK IPLLQQPKRE EEEVLDQGDF YSLLSKLLGE
410 420 430 440 450
REDVVHVHKY NPTEKAESES DLVAEIANVV QKKDLGRSDA REGAEHERGN
460 470 480 490 500
AILVRDRIHK FHRLVSTLRP PESRVFSLQQ PPPGEGTWEP EHTGDFHMEE
510 520 530 540 550
ALDWPGVYLL PGQVSGVALD PKNNLVIFHR GDHVWDGNSF DSKFVYQQIG
560 570 580 590 600
LGPIEEDTIL VIDPNNAAVL QSSGKNLFYL PHGLSIDKDG NYWVTDVALH
610 620 630 640 650
QVFKLDPNNK EGPVLILGRS MQPGSDQNHF CQPTDVAVDP GTGAIYVSDG
660 670 680 690 700
YCNSRIVQFS PSGKFITQWG EESSGSSPLP GQFTVPHSLA LVPLLGQLCV
710 720 730 740 750
ADRENGRIQC FKTDTKEFVR EIKHSSFGRN VFAISYIPGL LFAVNGKPHF
760 770 780 790 800
GDQEPVQGFV MNFSNGEIID IFKPVRKHFD MPHDIVASED GTVYIGDAHT
810 820 830 840 850
NTVWKFTLTE KLEHRSVKKA GIEVQEIKEA EAVVETKMEN KPTSSELQKM
860 870 880 890 900
QEKQKLIKEP GSGVPVVLIT TLLVIPVVVL LAIAIFIRWK KSRAFGDSEH
910 920 930 940 950
KLETSSGRVL GRFRGKGSGG LNLGNFFASR KGYSRKGFDR LSTEGSDQEK
960 970
EDDGSESEEE YSAPLPALAP SSS
Length:973
Mass (Da):108,332
Last modified:September 19, 2002 - v2
Checksum:i8A089B657F56EE39
GO
Isoform 2 (identifier: P19021-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     388-494: Missing.

Show »
Length:866
Mass (Da):96,258
Checksum:i41F0822F95AC3B0E
GO
Isoform 3 (identifier: P19021-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     829-896: Missing.

Note: Soluble.1 Publication
Show »
Length:905
Mass (Da):100,818
Checksum:i5A5EAAC529E267AE
GO
Isoform 4 (identifier: P19021-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     829-914: Missing.

Note: Soluble.1 Publication
Show »
Length:887
Mass (Da):98,762
Checksum:i5F3E355C256FF35C
GO
Isoform 5 (identifier: P19021-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     896-896: G → GA

Show »
Length:974
Mass (Da):108,403
Checksum:iF6D51C73F6E264A3
GO
Isoform 6 (identifier: P19021-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     897-914: Missing.

Show »
Length:955
Mass (Da):106,276
Checksum:iEE05609B9A7F1772
GO

Sequence cautioni

The sequence AAD01439 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti26S → P in BAF82847 (PubMed:14702039).Curated1
Sequence conflicti574G → E in AAA36414 (PubMed:2357221).Curated1
Sequence conflicti774P → L in BAF82847 (PubMed:14702039).Curated1
Sequence conflicti830 – 831Missing in AAB32775 (PubMed:7999037).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05569449V → L. Corresponds to variant dbSNP:rs2230458Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_001227388 – 494Missing in isoform 2. 2 PublicationsAdd BLAST107
Alternative sequenceiVSP_001229829 – 914Missing in isoform 4. 1 PublicationAdd BLAST86
Alternative sequenceiVSP_001228829 – 896Missing in isoform 3. 1 PublicationAdd BLAST68
Alternative sequenceiVSP_038691896G → GA in isoform 5. 1 Publication1
Alternative sequenceiVSP_042209897 – 914Missing in isoform 6. 1 PublicationAdd BLAST18

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M37721 mRNA Translation: AAA36414.1
S75037 mRNA Translation: AAB32775.1
S75038 mRNA Translation: AAB32776.1
AB095007 mRNA Translation: BAC22594.1
AK290158 mRNA Translation: BAF82847.1
BT007419 mRNA Translation: AAP36087.1
AC008779 Genomic DNA No translation available.
AC010250 Genomic DNA No translation available.
AC113373 Genomic DNA No translation available.
CH471086 Genomic DNA Translation: EAW49085.1
BC018127 mRNA Translation: AAH18127.1
AF010472 mRNA Translation: AAD01439.1 Different initiation.
AF035320 mRNA Translation: AAB88190.1
CCDSiCCDS4092.1 [P19021-3]
CCDS4093.1 [P19021-2]
CCDS4094.1 [P19021-4]
CCDS43348.1 [P19021-5]
CCDS54885.1 [P19021-1]
PIRiA35477 URHUAP
RefSeqiNP_000910.2, NM_000919.3 [P19021-5]
NP_001170777.1, NM_001177306.1 [P19021-1]
NP_001306872.1, NM_001319943.1
NP_620121.1, NM_138766.2 [P19021-3]
NP_620176.1, NM_138821.2 [P19021-2]
NP_620177.1, NM_138822.2 [P19021-4]
XP_016864986.1, XM_017009497.1 [P19021-5]
XP_016864990.1, XM_017009501.1 [P19021-6]
XP_016864994.1, XM_017009505.1 [P19021-3]
UniGeneiHs.369430

Genome annotation databases

EnsembliENST00000304400; ENSP00000306100; ENSG00000145730 [P19021-5]
ENST00000346918; ENSP00000282992; ENSG00000145730 [P19021-4]
ENST00000348126; ENSP00000314638; ENSG00000145730 [P19021-2]
ENST00000438793; ENSP00000396493; ENSG00000145730 [P19021-1]
ENST00000455264; ENSP00000403461; ENSG00000145730 [P19021-3]
GeneIDi5066
KEGGihsa:5066
UCSCiuc003kns.4 human [P19021-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiAMD_HUMAN
AccessioniPrimary (citable) accession number: P19021
Secondary accession number(s): A6NMR0
, A8K293, O43211, O95080, Q16252, Q16253, Q54A45, Q86U53, Q8WVC7, Q9UCG0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: September 19, 2002
Last modified: May 23, 2018
This is version 203 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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