Peptidylglycine alpha-hydroxylating monooxygenase
     (PHM)
     (EC 1.14.17.3)
Peptidyl-alpha-hydroxyglycine alpha-amidating lyase
     (EC 4.3.2.5)
     (Peptidylamidoglycolate lyase)
     (PAL)

Gene name

Name:

PAM

From

Homo sapiens (Human)

[TaxID: 9606]

Taxonomy

Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Protein existence

1: Evidence at protein level;

References

[1]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). TISSUE=Thyroid carcinoma; DOI=10.1016/0006-291X(90)90366-U; PubMed=2357221 [NCBI, ExPASy, EBI, Israel, Japan] Glauder J., Ragg H., Rauch J., Engels J.W.; "Human peptidylglycine alpha-amidating monooxygenase: cDNA, cloning and functional expression of a truncated form in COS cells."; Biochem. Biophys. Res. Commun. 169:551-558(1990).
[2]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3). DOI=10.1006/bbrc.1994.2662; PubMed=7999037 [NCBI, ExPASy, EBI, Israel, Japan] Tateishi K., Arakawa F., Misumi Y., Treston A.M., Vos M., Matsuoka Y.; "Isolation and functional expression of human pancreatic peptidylglycine alpha-amidating monooxygenase."; Biochem. Biophys. Res. Commun. 205:282-290(1994).
[3]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.; "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
[4]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). TISSUE=Lung; DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[5]	NUCLEOTIDE SEQUENCE [MRNA] OF 29-973 (ISOFORM 4). TISSUE=Kidney; Chung B.H., Oh G.H., Choi E.S.; "The alpha-amidating monooxygenase gene of human kidney."; Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases.
[6]	PROTEIN SEQUENCE OF 21-49. PubMed=8486658 [NCBI, ExPASy, EBI, Israel, Japan] Husten E.J., Tausk F.A., Keutmann H.T., Eipper B.A.; "Use of endoproteases to identify catalytic domains, linker regions, and functional interactions in soluble peptidylglycine alpha-amidating monooxygenase."; J. Biol. Chem. 268:9709-9717(1993).
[7]	SULFATION AT TYR-961. PubMed=8144680 [NCBI, ExPASy, EBI, Israel, Japan] Yun H.Y., Keutmann H.T., Eipper B.A.; "Alternative splicing governs sulfation of tyrosine or oligosaccharide on peptidylglycine alpha-amidating monooxygenase."; J. Biol. Chem. 269:10946-10955(1994).
[8]	PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-955 AND SER-957, AND MASS SPECTROMETRY. TISSUE=Epithelium; DOI=10.1016/j.cell.2006.09.026; PubMed=17081983 [NCBI, ExPASy, EBI, Israel, Japan] Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."; Cell 127:635-648(2006).

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 + O₂ = peptidyl(2-hydroxyglycine) + dehydroascorbate + H₂O.
CATALYTIC ACTIVITY: Peptidylamidoglycolate = peptidyl amide + glyoxylate.
COFACTOR: Zinc; for the lyase reaction.
COFACTOR: Binds 2 copper ions per subunit; For the monoxygenase reaction.
SUBUNIT: Monomer. Interacts with RASSF9 (By similarity).
SUBCELLULAR LOCATION: Isoform 1: Membrane; Single-pass type I membrane protein.
SUBCELLULAR LOCATION: Isoform 2: Membrane; Single-pass type I membrane protein.
SUBCELLULAR LOCATION: Isoform 3: Secreted. Note=Secreted from secretory granules.
SUBCELLULAR LOCATION: Isoform 4: Secreted. Note=Secreted from secretory granules.

ALTERNATIVE PRODUCTS: 4 named isoforms [FASTA] produced by alternative splicing. Additional isoforms seem to exist.

Name	1
Isoform ID	P19021-1
This is the isoform sequence displayed in this entry.

Name	2
Isoform ID	P19021-2
Features which should be applied to build the isoform sequence: VSP_001227.

Name	3
Isoform ID	P19021-3
Features which should be applied to build the isoform sequence: VSP_001228.

Name	4
Isoform ID	P19021-4
Features which should be applied to build the isoform sequence: VSP_001229.

SIMILARITY: In the C-terminal section; belongs to the peptidyl-alpha-hydroxyglycine alpha-amidating lyase family.
SIMILARITY: In the N-terminal section; belongs to the copper type II ascorbate-dependent monooxygenase family.
SIMILARITY: Contains 5 NHL repeats.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

M37721; AAA36414.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
S75037; AAB32775.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
S75038; AAB32776.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BT007419; AAP36087.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC018127; AAH18127.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF010472; AAD01439.1; ALT_INIT; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

PIR

A35477; URHUAP.

RefSeq

NP_000910.2; -.
NP_620121.1; -.
NP_620176.1; -.
NP_620177.1; -.

UniGene

Hs.369430

3D structure databases

HSSP

P14925; 1PHM. [HSSP ENTRY / PDB]

P19021; 40-351.

PTM databases

P19021; -.

Organism-specific databases

HIX0021107; -.

HGNC:8596; PAM.

PAM.

170270; gene. [NCBI / EBI]

PharmGKB

PA134983031; -.

GeneCards

P19021.

Gene expression databases

ArrayExpress

P19021; -.

CleanEx

HS_PAM; -.

GermOnline

ENSG00000145730; Homo sapiens.

Ontologies

GO:0030141;	Cellular component: secretory granule (non-traceable author statement from UniProtKB).
GO:0004504;	Molecular function: peptidylglycine monooxygenase activity (non-traceable author statement from UniProtKB).
GO:0005515;	Molecular function: protein binding (inferred from physical interaction from UniProtKB).
GO:0006518;	Biological process: peptide metabolic process (non-traceable author statement from UniProtKB).
GO:0006464;	Biological process: protein modification process (traceable author statement from ProtInc).
QuickGo view.

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 of domain structure.

Gene3D

G3DSA:2.120.10.30; 6-blade_b-propeller_TolB-like; 1.

Pfam

PF03712; Cu2_monoox_C; 1.
PF01082; Cu2_monooxygen; 1.
PF01436; NHL; 4.
Pfam graphical view of domain structure.

PRINTS

PR00790; PAMONOXGNASE.

PROSITE

PS00084; CU2_MONOOXYGENASE_1; 1.
PS00085; CU2_MONOOXYGENASE_2; 1.
PS51125; NHL; 5.
PROSITE graphical view of domain structure (profiles).

BLOCKS

P19021.

Genome annotation databases

Ensembl

ENSG00000145730; Homo sapiens. [Contig view]

GeneID

5066; -.

KEGG

hsa:5066; -.

Phylogenomic databases

HOVERGEN

P19021; -.

Other

DB00126; Vitamin C.

P19021; -.

PAM; Homo sapiens.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Alternative splicing; Cleavage on pair of basic residues; Copper; Direct protein sequencing; Glycoprotein; Lyase; Membrane; Metal-binding; Monooxygenase; Multifunctional enzyme; Oxidoreductase; Phosphoprotein; Repeat; Secreted; Signal; Sulfation; Transmembrane; Vitamin C; Zinc.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`SIGNAL`	`1 20`	`20`	`Probable.`
`PROPEP`	`21 30`	`10`	`Probable.`	`PRO_0000006361`
`CHAIN`	`31 973`	`943`	`Peptidyl-glycine alpha-amidating monooxygenase.`	`PRO_0000006362`
`TOPO_DOM`	`31 863`	`833`	`Intragranular (Potential).`
`TRANSMEM`	`864 887`	`24`	`Potential.`
`TOPO_DOM`	`888 973`	`86`	`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).`
`METAL`	`102 102`		`Copper A (By similarity).`
`METAL`	`103 103`		`Copper A (By similarity).`
`METAL`	`167 167`		`Copper A (By similarity).`
`METAL`	`237 237`		`Copper B (By similarity).`
`METAL`	`239 239`		`Copper B (By similarity).`
`METAL`	`309 309`		`Copper B (By similarity).`
`MOD_RES`	`918 918`		`Phosphoserine (By similarity).`
`MOD_RES`	`955 955`		`Phosphoserine.`
`MOD_RES`	`957 957`		`Phosphoserine.`
`MOD_RES`	`961 961`		`Sulfotyrosine.`
`CARBOHYD`	`762 762`		`N-linked (GlcNAc...) (Potential).`
`DISULFID`	`42 181`		`By similarity.`
`DISULFID`	`76 121`		`By similarity.`
`DISULFID`	`109 126`		`By similarity.`
`DISULFID`	`222 329`		`By similarity.`
`DISULFID`	`288 310`		`By similarity.`
`DISULFID`	`631 652`		`By similarity.`
`DISULFID`	`699 710`		`By similarity.`
`VAR_SEQ`	`388 494`		`Missing (in isoform 2).`	`VSP_001227`
`VAR_SEQ`	`829 914`		`Missing (in isoform 4).`	`VSP_001229`
`VAR_SEQ`	`829 896`		`Missing (in isoform 3).`	`VSP_001228`
`CONFLICT`	`37 37`		`P -> S (in Ref. 6; AA sequence).`
`CONFLICT`	`46 47`		`TR -> IG (in Ref. 6; AA sequence).`
`CONFLICT`	`574 574`		`G -> E (in Ref. 1; AAA36414).`
`CONFLICT`	`830 831`		`Missing (in Ref. 2).`
`CONFLICT`	`896 896`		`G -> GA (in Ref. 1; AAA36414).`

Sequence information

Length: 973 AA [This is the length of the unprocessed precursor]

Molecular weight: 108332 Da [This is the MW of the unprocessed precursor]

CRC64: 8A089B657F56EE39 [This is a checksum on the sequence]

        10         20         30         40         50         60 
MAGRVPSLLV LLVFPSSCLA FRSPLSVFKR FKETTRPFSN ECLGTTRPVV PIDSSDFALD 

        70         80         90        100        110        120 
IRMPGVTPKQ SDTYFCMSMR IPVDEEAFVI DFKPRASMDT VHHMLLFGCN MPSSTGSYWF 

       130        140        150        160        170        180 
CDEGTCTDKA NILYAWARNA PPTRLPKGVG FRVGGETGSK YFVLQVHYGD ISAFRDNNKD 

       190        200        210        220        230        240 
CSGVSLHLTR LPQPLIAGMY LMMSVDTVIP AGEKVVNSDI SCHYKNYPMH VFAYRVHTHH 

       250        260        270        280        290        300 
LGKVVSGYRV RNGQWTLIGR QSPQLPQAFY PVGHPVDVSF GDLLAARCVF TGEGRTEATH 

       310        320        330        340        350        360 
IGGTSSDEMC NLYIMYYMEA KHAVSFMTCT QNVAPDMFRT IPPEANIPIP VKSDMVMMHE 

       370        380        390        400        410        420 
HHKETEYKDK IPLLQQPKRE EEEVLDQGDF YSLLSKLLGE REDVVHVHKY NPTEKAESES 

       430        440        450        460        470        480 
DLVAEIANVV QKKDLGRSDA REGAEHERGN AILVRDRIHK FHRLVSTLRP PESRVFSLQQ 

       490        500        510        520        530        540 
PPPGEGTWEP EHTGDFHMEE ALDWPGVYLL PGQVSGVALD PKNNLVIFHR GDHVWDGNSF 

       550        560        570        580        590        600 
DSKFVYQQIG LGPIEEDTIL VIDPNNAAVL QSSGKNLFYL PHGLSIDKDG NYWVTDVALH 

       610        620        630        640        650        660 
QVFKLDPNNK EGPVLILGRS MQPGSDQNHF CQPTDVAVDP GTGAIYVSDG YCNSRIVQFS 

       670        680        690        700        710        720 
PSGKFITQWG EESSGSSPLP GQFTVPHSLA LVPLLGQLCV ADRENGRIQC FKTDTKEFVR 

       730        740        750        760        770        780 
EIKHSSFGRN VFAISYIPGL LFAVNGKPHF GDQEPVQGFV MNFSNGEIID IFKPVRKHFD 

       790        800        810        820        830        840 
MPHDIVASED GTVYIGDAHT NTVWKFTLTE KLEHRSVKKA GIEVQEIKEA EAVVETKMEN 

       850        860        870        880        890        900 
KPTSSELQKM QEKQKLIKEP GSGVPVVLIT TLLVIPVVVL LAIAIFIRWK KSRAFGDSEH 

       910        920        930        940        950        960 
KLETSSGRVL GRFRGKGSGG LNLGNFFASR KGYSRKGFDR LSTEGSDQEK EDDGSESEEE 

       970 
YSAPLPALAP SSS

P19021 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools