Reviewed, UniProtKB/Swiss-Prot P10731 (AMD_BOVIN)

Names and origin

Protein names

Recommended name:
    Peptidyl-glycine alpha-amidating monooxygenase
      Short name=PAM
Including the following 2 domains:
    1- Recommended name:
            Peptidylglycine alpha-hydroxylating monooxygenase
                Short name=PHM
              EC=1.14.17.3
    2- Recommended name:
            Peptidyl-alpha-hydroxyglycine alpha-amidating lyase
              EC=4.3.2.5
        Alternative name(s):
            Peptidylamidoglycolate lyase
              Short name=PAL

Gene names

Name:

PAM

Organism

Bos taurus (Bovine)

Taxonomic identifier

9913 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

Protein attributes

Sequence length	972 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Bifunctional enzyme that catalyzes 2 sequencial 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 activity	Peptidylglycine + ascorbate + O(2) = peptidyl(2-hydroxyglycine) + dehydroascorbate + H(2)O. Peptidylamidoglycolate = peptidyl amide + glyoxylate.
Cofactor	Zinc; for the lyase reaction By similarity. Binds 2 copper ions per subunit; For the monoxygenase reaction By similarity.
Subunit structure	Monomer. Interacts with RASSF9 By similarity.
Subcellular location	Cytoplasmic vesicle › secretory vesicle membrane; Single-pass membrane protein. Note= Secretory granules.
Sequence similarities	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. Contains 5 NHL repeats.

Ontologies

Keywords
Cellular component	Cytoplasmic vesicle Membrane
Domain	Repeat Signal Transmembrane
Ligand	Copper Metal-binding Vitamin C Zinc
Molecular function	Lyase Monooxygenase Oxidoreductase
PTM	Cleavage on pair of basic residues Glycoprotein Phosphoprotein Sulfation
Technical term	Direct protein sequencing Multifunctional enzyme
Gene Ontology (GO)
Biological process	oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW peptide metabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasmic vesicle Inferred from electronic annotation. Source: UniProtKB-KW integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	L-ascorbic acid binding Inferred from electronic annotation. Source: UniProtKB-KW copper ion binding Inferred from electronic annotation. Source: InterPro peptidylamidoglycolate lyase activity Inferred from electronic annotation. Source: EC peptidylglycine monooxygenase activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 20	20	Potential
	Propeptide	21 – 30	10	Potential		PRO_0000006359
	Chain	31 – 972	942	Peptidyl-glycine alpha-amidating monooxygenase		PRO_0000006360
Regions
	Topological domain	31 – 873	843	Intragranular Potential
	Transmembrane	874 – 897	24	Potential
	Topological domain	898 – 972	75	Cytoplasmic Potential
	Repeat	498 – 541	44	NHL 1
	Repeat	567 – 608	42	NHL 2
	Repeat	617 – 662	46	NHL 3
	Repeat	670 – 714	45	NHL 4
	Repeat	766 – 809	44	NHL 5
	Region	1 – 494	494	Peptidylglycine alpha-hydroxylating monooxygenase By similarity
	Region	495 – 817	323	Peptidyl-alpha-hydroxyglycine alpha-amidating lyase By similarity
	Region	925 – 942	18	Interaction with RASSF9 By similarity
Sites
	Metal binding	102	1	Copper A By similarity
	Metal binding	103	1	Copper A By similarity
	Metal binding	167	1	Copper A By similarity
	Metal binding	237	1	Copper B By similarity
	Metal binding	239	1	Copper B By similarity
	Metal binding	309	1	Copper B By similarity
Amino acid modifications
	Modified residue	955	1	Phosphoserine By similarity
	Modified residue	957	1	Phosphoserine By similarity
	Modified residue	961	1	Sulfotyrosine By similarity
	Glycosylation	762	1	N-linked (GlcNAc...) Potential
	Disulfide bond	42 ↔ 181		By similarity
	Disulfide bond	76 ↔ 121		By similarity
	Disulfide bond	109 ↔ 126		By similarity
	Disulfide bond	222 ↔ 329		By similarity
	Disulfide bond	288 ↔ 310		By similarity
	Disulfide bond	631 ↔ 652		By similarity
	Disulfide bond	699 ↔ 710		By similarity

Sequences

	Sequence		Length	Mass (Da)
	P10731-1 [UniParc]. Last modified April 1, 1993. Version 2. Checksum: EBD41F83E341BAF1	FASTA	972	108,177
	10 20 30 40 50 60 MAGFRSLLVL LLVFPSGCVG FRSPLSVFKR FKETTRSFSN ECLGTTRPVI PIDSSDFALD 70 80 90 100 110 120 IRMPGVTPKQ SDTYFCMSVR LPMDEEAFVI DFKPRASMDT VHHMLLFGCN MPASTGNYWF 130 140 150 160 170 180 CDEGTCTDKA NILYAWARNA PPTRLPKGVG FRVGGETGSK YFVLQVHYGD ISAFRDNHKD 190 200 210 220 230 240 CSGVSLHLTR LPQPLIAGMY LMMSVDTVIP PGGKVVNSDI SCHYKKYPMH VFAYRVHTHH 250 260 270 280 290 300 LGKVVSGYRV RNGQWTLIGR QSPQLPQAFY PVEHPVDVSF GDILAARCVF TGEGRTEVTH 310 320 330 340 350 360 IGGTSSDEMC NLYIMYYMEA KHAVSFMTCT QNVAPDIFRT IPPEANIPIP VKSDMVMMHG 370 380 390 400 410 420 HHKETENKDK TSLLQQPKRE EEGVLEQGDF YSLLSKLLGE REDVVHVHKY NPTEKAESES 430 440 450 460 470 480 DLVAEIANVV QKKDLGRSDT RESAEQERGN AILVRDRIHK FHRLVSTLRP AESRVLSLQQ 490 500 510 520 530 540 PLPGEGTWEP EHTGDFHVEE ALDWPGVYLL PGQVSGVALD PQNNLVIFHR GDHVWDGNSF 550 560 570 580 590 600 DSKFVYQQRG LGPIEEDTIL VIDPNNAAVL QSSGKNLFYL PHGLSIDKDG NYWVTDVALH 610 620 630 640 650 660 QVFKLDPKSK EGPLLTLGRS MQPGSDQNHF CQPTDVAVDP DTGTIYVSDG YCNSRLVQFS 670 680 690 700 710 720 PSGKFITQWG EASLESSPKP GQFRVPHSLA LVPPLGQLCV ADRENGRIQC FKTDTKEFVR 730 740 750 760 770 780 EIKHPSFGRN VFAISYIPGL LFAVNGKPYF EDQEPVQGFV MNFSSGEIID VFKPVRKHFD 790 800 810 820 830 840 MPHDIAASED GTVYVGDAHT NTVWKFTSTE KMEHRSVKKA GIEVQEIKES EAVVETKMEN 850 860 870 880 890 900 KPASSELQKI QEKQKLVKEP GSGVPAVLIT TLLVIPVVVL LAIALFIRWK KSRAFGDSER 910 920 930 940 950 960 KLEASSGRVL GRLRGKGGGG LNLGNFFASR KGYSRKGFDR LSTEGSDQEK DEDASESEEE 970 YSAPPPAPAP SS

References

[1]	"Structure of the precursor to an enzyme mediating COOH-terminal amidation in peptide biosynthesis." Eipper B.A., Park L.P., Dickerson I.M., Keutmann H.T., Thiele E.A., Rodriguez H., Schofield P.R., Mains R.E. Mol. Endocrinol. 1:777-790(1987) [PubMed: 3153462] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE. Tissue: Pituitary.
[2]	"Functional and structural characterization of peptidylamidoglycolate lyase, the enzyme catalyzing the second step in peptide amidation." Katopodis A.G., Ping D.S., Smith C.E., May S.W. Biochemistry 30:6189-6194(1991) [PubMed: 2059626] [Abstract] Cited for: PROTEIN SEQUENCE OF 478-499; 544-575; 611-630 AND 665-695, FUNCTION, SUBCELLULAR LOCATION.

Cross-references

Sequence databases
EMBLGenBankDDBJ	M18683 mRNA. Translation: AAA30683.1.
PIR	URBOAP. A40063.
RefSeq	NP_776373.1.
UniGene	Bt.12303
3D structure databases
HSSP	HSSP built from PDB template 3PHM based on UniProtKB P14925.
SMR	P10731. Positions 40-351.
ModBase	Search...
Genome annotation databases
Ensembl	ENSBTAG00000012387. Bos taurus. [Contig view]
GeneID	280890.
KEGG	bta:280890.
Phylogenomic databases
HOVERGEN	P10731.
Family and domain databases
InterPro	IPR011042. 6-blade_b-propeller_TolB-like. IPR014783. Cu2_ascorb_mOase_C. IPR000323. Cu2_ascorb_mOase_N. IPR001258. NHL_repeat. IPR013017. NHL_repeat_subgr. IPR000720. Pep_amidat_mOase. [Graphical view]
Gene3D	G3DSA:2.120.10.30. 6-blade_b-propeller_TolB-like. 1 hit.
Pfam	PF03712. Cu2_monoox_C. 1 hit. PF01082. Cu2_monooxygen. 1 hit. PF01436. NHL. 4 hits. [Graphical view]
PRINTS	PR00790. PAMONOXGNASE.
PROSITE	PS00084. CU2_MONOOXYGENASE_1. 1 hit. PS00085. CU2_MONOOXYGENASE_2. 1 hit. PS51125. NHL. 5 hits. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

AMD_BOVIN

Accession

Primary (citable) accession number: P10731

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	April 1, 1993
Last modified:	November 25, 2008
This is version 83 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)