UniProtKB - P10731 (AMD_BOVIN)
Peptidyl-glycine alpha-amidating monooxygenase
PAM
Functioni
Bifunctional enzyme that catalyzes the post-translational modification of inactive peptidylglycine precursors to the corresponding bioactive alpha-amidated peptides, a terminal modification in biosynthesis of many neural and endocrine peptides (PubMed:2059626).
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 (PubMed:2059626).
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 (PubMed:2059626).
Similarly, catalyzes the two-step conversion of an N-fatty acylglycine to a primary fatty acid amide and glyoxylate (By similarity).
By similarity1 PublicationCatalytic activityi
- a [peptide]-C-terminal glycine + 2 L-ascorbate + O2 = a [peptide]-C-terminal (2S)-2-hydroxyglycine + H2O + 2 monodehydro-L-ascorbate radical1 PublicationEC:1.14.17.31 Publication
- a [peptide]-C-terminal (2S)-2-hydroxyglycine = a [peptide]-C-terminal amide + glyoxylate1 PublicationEC:4.3.2.51 Publication
- 2 L-ascorbate + N-dodecanoylglycine + O2 = H2O + 2 monodehydro-L-ascorbate radical + N-dodecanoyl-(2S)-hydroxyglycineBy similarity
- 2 L-ascorbate + N-(9Z-octadecenoyl)glycine + O2 = H2O + 2 monodehydro-L-ascorbate radical + N-(9Z-octadecenoyl)-(2S)-hydroxyglycineBy similarity
- 2 L-ascorbate + N-tetradecanoylglycine + O2 = H2O + 2 monodehydro-L-ascorbate radical + N-tetradecanoyl-(2S)-hydroxyglycineBy similarity
- 2 L-ascorbate + N-decanoylglycine + O2 = H2O + 2 monodehydro-L-ascorbate radical + N-decanoyl-(2S)-hydroxyglycineBy similarity
- 2 L-ascorbate + N-octanoylglycine + O2 = H2O + 2 monodehydro-L-ascorbate radical + N-octanoyl-(2S)-hydroxyglycineBy similarity
Cofactori
Protein has several cofactor binding sites:- Zn2+By similarityNote: Binds one Zn2+ ion per subunit.By similarity
- Cu2+1 PublicationNote: Binds 2 Cu2+ ions per subunit.By similarity
Activity regulationi
pH dependencei
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 102 | Copper 1; via pros nitrogen; catalyticBy similarity | 1 | |
Metal bindingi | 103 | Copper 1; via pros nitrogen; catalyticBy similarity | 1 | |
Metal bindingi | 167 | Copper 1; via pros nitrogen; catalyticBy similarity | 1 | |
Metal bindingi | 237 | Copper 2; via tele nitrogen; catalyticBy similarity | 1 | |
Metal bindingi | 239 | Copper 2; via tele nitrogen; catalyticBy similarity | 1 | |
Metal bindingi | 309 | Copper 2By similarity | 1 | |
Metal bindingi | 517 | Calcium; via carbonyl oxygen; structuralBy similarity | 1 | |
Binding sitei | 530 | SubstrateBy similarity | 1 | |
Metal bindingi | 582 | Zinc; via tele nitrogen; catalyticBy similarity | 1 | |
Metal bindingi | 584 | Calcium; via carbonyl oxygen; structuralBy similarity | 1 | |
Binding sitei | 651 | SubstrateBy similarity | 1 | |
Metal bindingi | 687 | Zinc; via tele nitrogen; catalyticBy similarity | 1 | |
Binding sitei | 703 | SubstrateBy similarity | 1 | |
Metal bindingi | 783 | Zinc; via tele nitrogen; catalyticBy similarity | 1 | |
Metal bindingi | 784 | Calcium; structuralBy similarity | 1 |
GO - Molecular functioni
- calcium ion binding Source: UniProtKB
- copper ion binding Source: UniProtKB
- 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
- fatty acid primary amide biosynthetic process Source: UniProtKB
- peptide amidation Source: UniProtKB
Keywordsi
Molecular function | Lyase, Monooxygenase, Multifunctional enzyme, Oxidoreductase |
Biological process | Lipid metabolism |
Ligand | Calcium, Copper, Metal-binding, Vitamin C, Zinc |
Names & Taxonomyi
Protein namesi | Recommended name: Peptidyl-glycine alpha-amidating monooxygenaseBy similarityShort name: PAM1 Publication Including the following 2 domains: |
Gene namesi | Name:PAM |
Organismi | Bos taurus (Bovine) |
Taxonomic identifieri | 9913 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Artiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos |
Proteomesi |
|
Subcellular locationi
Other locations
- secretory vesicle membrane 1 Publication; Single-pass membrane protein 1 Publication
Note: Secretory granules.1 Publication
Other locations
- integral component of membrane Source: UniProtKB-KW
- secretory granule membrane Source: UniProtKB
- transport vesicle membrane Source: UniProtKB-SubCell
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 31 – 873 | IntragranularSequence analysisAdd BLAST | 843 | |
Transmembranei | 874 – 897 | HelicalSequence analysisAdd BLAST | 24 | |
Topological domaini | 898 – 972 | CytoplasmicSequence analysisAdd BLAST | 75 |
Keywords - Cellular componenti
Cytoplasmic vesicle, MembranePTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 20 | Sequence analysisAdd BLAST | 20 | |
PropeptideiPRO_0000006359 | 21 – 30 | Sequence analysis | 10 | |
ChainiPRO_0000006360 | 31 – 972 | Peptidyl-glycine alpha-amidating monooxygenaseAdd BLAST | 942 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 42 ↔ 181 | By similarity | ||
Disulfide bondi | 76 ↔ 121 | By similarity | ||
Disulfide bondi | 109 ↔ 126 | By similarity | ||
Disulfide bondi | 222 ↔ 329 | By similarity | ||
Disulfide bondi | 288 ↔ 310 | By similarity | ||
Disulfide bondi | 631 ↔ 652 | By similarity | ||
Disulfide bondi | 699 ↔ 710 | By similarity | ||
Glycosylationi | 762 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Modified residuei | 929 | PhosphoserineBy similarity | 1 | |
Modified residuei | 942 | PhosphoserineBy similarity | 1 | |
Modified residuei | 943 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 946 | Phosphoserine; by UHMK1By similarity | 1 | |
Modified residuei | 957 | PhosphoserineBy similarity | 1 |
Keywords - PTMi
Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, PhosphoproteinProteomic databases
PaxDbi | P10731 |
PRIDEi | P10731 |
Interactioni
Subunit structurei
Monomer.
Interacts with RASSF9.
By similarityProtein-protein interaction databases
MINTi | P10731 |
STRINGi | 9913.ENSBTAP00000016466 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 498 – 541 | NHL 1Add BLAST | 44 | |
Repeati | 567 – 608 | NHL 2Add BLAST | 42 | |
Repeati | 617 – 662 | NHL 3Add BLAST | 46 | |
Repeati | 670 – 714 | NHL 4Add BLAST | 45 | |
Repeati | 766 – 809 | NHL 5Add BLAST | 44 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 494 | Peptidylglycine alpha-hydroxylating monooxygenaseBy similarityAdd BLAST | 494 | |
Regioni | 495 – 817 | Peptidyl-alpha-hydroxyglycine alpha-amidating lyaseBy similarityAdd BLAST | 323 | |
Regioni | 925 – 942 | Interaction with RASSF9By similarityAdd BLAST | 18 | |
Regioni | 937 – 972 | DisorderedSequence analysisAdd BLAST | 36 |
Sequence similaritiesi
Keywords - Domaini
Repeat, Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG3567, Eukaryota |
InParanoidi | P10731 |
OrthoDBi | 476471at2759 |
Family and domain databases
Gene3Di | 2.120.10.30, 1 hit 2.60.120.230, 1 hit 2.60.120.310, 1 hit |
InterProi | View 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 |
Pfami | View protein in Pfam PF03712, Cu2_monoox_C, 1 hit PF01082, Cu2_monooxygen, 1 hit PF01436, NHL, 3 hits |
PRINTSi | PR00790, PAMONOXGNASE |
SUPFAMi | SSF49742, SSF49742, 2 hits |
PROSITEi | View protein in PROSITE PS00084, CU2_MONOOXYGENASE_1, 1 hit PS00085, CU2_MONOOXYGENASE_2, 1 hit PS51125, NHL, 5 hits |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MAGFRSLLVL LLVFPSGCVG FRSPLSVFKR FKETTRSFSN ECLGTTRPVI
60 70 80 90 100
PIDSSDFALD IRMPGVTPKQ SDTYFCMSVR LPMDEEAFVI DFKPRASMDT
110 120 130 140 150
VHHMLLFGCN MPASTGNYWF CDEGTCTDKA NILYAWARNA PPTRLPKGVG
160 170 180 190 200
FRVGGETGSK YFVLQVHYGD ISAFRDNHKD CSGVSLHLTR LPQPLIAGMY
210 220 230 240 250
LMMSVDTVIP PGGKVVNSDI SCHYKKYPMH VFAYRVHTHH LGKVVSGYRV
260 270 280 290 300
RNGQWTLIGR QSPQLPQAFY PVEHPVDVSF GDILAARCVF TGEGRTEVTH
310 320 330 340 350
IGGTSSDEMC NLYIMYYMEA KHAVSFMTCT QNVAPDIFRT IPPEANIPIP
360 370 380 390 400
VKSDMVMMHG HHKETENKDK TSLLQQPKRE EEGVLEQGDF YSLLSKLLGE
410 420 430 440 450
REDVVHVHKY NPTEKAESES DLVAEIANVV QKKDLGRSDT RESAEQERGN
460 470 480 490 500
AILVRDRIHK FHRLVSTLRP AESRVLSLQQ PLPGEGTWEP EHTGDFHVEE
510 520 530 540 550
ALDWPGVYLL PGQVSGVALD PQNNLVIFHR GDHVWDGNSF DSKFVYQQRG
560 570 580 590 600
LGPIEEDTIL VIDPNNAAVL QSSGKNLFYL PHGLSIDKDG NYWVTDVALH
610 620 630 640 650
QVFKLDPKSK EGPLLTLGRS MQPGSDQNHF CQPTDVAVDP DTGTIYVSDG
660 670 680 690 700
YCNSRLVQFS PSGKFITQWG EASLESSPKP GQFRVPHSLA LVPPLGQLCV
710 720 730 740 750
ADRENGRIQC FKTDTKEFVR EIKHPSFGRN VFAISYIPGL LFAVNGKPYF
760 770 780 790 800
EDQEPVQGFV MNFSSGEIID VFKPVRKHFD MPHDIAASED GTVYVGDAHT
810 820 830 840 850
NTVWKFTSTE KMEHRSVKKA GIEVQEIKES EAVVETKMEN KPASSELQKI
860 870 880 890 900
QEKQKLVKEP GSGVPAVLIT TLLVIPVVVL LAIALFIRWK KSRAFGDSER
910 920 930 940 950
KLEASSGRVL GRLRGKGGGG LNLGNFFASR KGYSRKGFDR LSTEGSDQEK
960 970
DEDASESEEE YSAPPPAPAP SS
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M18683 mRNA Translation: AAA30683.1 |
PIRi | A40063, URBOAP |
RefSeqi | NP_776373.1, NM_173948.2 |
Genome annotation databases
GeneIDi | 280890 |
KEGGi | bta:280890 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M18683 mRNA Translation: AAA30683.1 |
PIRi | A40063, URBOAP |
RefSeqi | NP_776373.1, NM_173948.2 |
3D structure databases
SMRi | P10731 |
ModBasei | Search... |
Protein-protein interaction databases
MINTi | P10731 |
STRINGi | 9913.ENSBTAP00000016466 |
Proteomic databases
PaxDbi | P10731 |
PRIDEi | P10731 |
Genome annotation databases
GeneIDi | 280890 |
KEGGi | bta:280890 |
Organism-specific databases
CTDi | 5066 |
Phylogenomic databases
eggNOGi | KOG3567, Eukaryota |
InParanoidi | P10731 |
OrthoDBi | 476471at2759 |
Family and domain databases
Gene3Di | 2.120.10.30, 1 hit 2.60.120.230, 1 hit 2.60.120.310, 1 hit |
InterProi | View 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 |
Pfami | View protein in Pfam PF03712, Cu2_monoox_C, 1 hit PF01082, Cu2_monooxygen, 1 hit PF01436, NHL, 3 hits |
PRINTSi | PR00790, PAMONOXGNASE |
SUPFAMi | SSF49742, SSF49742, 2 hits |
PROSITEi | View protein in PROSITE PS00084, CU2_MONOOXYGENASE_1, 1 hit PS00085, CU2_MONOOXYGENASE_2, 1 hit PS51125, NHL, 5 hits |
MobiDBi | Search... |
Entry informationi
Entry namei | AMD_BOVIN | |
Accessioni | P10731Primary (citable) accession number: P10731 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 1, 1989 |
Last sequence update: | April 1, 1993 | |
Last modified: | February 23, 2022 | |
This is version 169 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families