Reviewed, UniProtKB/Swiss-Prot P17707 (DCAM_HUMAN)

Names and origin

Protein names

Recommended name:
    S-adenosylmethionine decarboxylase proenzyme
      Short name=AdoMetDC
      Short name=SAMDC
    EC=4.1.1.50
Cleaved into the following 2 chains:
    1- Recommended name:
            S-adenosylmethionine decarboxylase alpha chain
    2- Recommended name:
            S-adenosylmethionine decarboxylase beta chain

Gene names

Name:	AMD1
Synonyms:	AMD

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	334 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)

Catalytic activity	S-adenosyl-L-methionine = (5-deoxy-5-adenosyl)(3-aminopropyl)-methylsulfonium salt + CO2. Ref.6
Cofactor	Pyruvoyl group.
Enzyme regulation	Both proenzyme processing and catalytic activity are stimulated by putrescine. Catalytic activity is inhibited by iodoacetic acid.
Pathway	Amine and polyamine biosynthesis; S-adenosylmethioninamine biosynthesis; S-adenosylmethioninamine from S-adenosyl-L-methionine: step 1/1.
Subunit structure	Heterotetramer of two alpha and two beta chains.
Post-translational modification	Is synthesized initially as an inactive proenzyme. Formation of the active enzyme involves a self-maturation process in which the active site pyruvoyl group is generated from an internal serine residue via an autocatalytic post-translational modification. Two non-identical subunits are generated from the proenzyme in this reaction, and the pyruvate is formed at the N-terminus of the alpha chain, which is derived from the carboxyl end of the proenzyme. The post-translation cleavage follows an unusual pathway, termed non-hydrolytic serinolysis, in which the side chain hydroxyl group of the serine supplies its oxygen atom to form the C-terminus of the beta chain, while the remainder of the serine residue undergoes an oxidative deamination to produce ammonia and the pyruvoyl group blocking the N-terminus of the alpha chain.
Sequence similarities	Belongs to the eukaryotic AdoMetDC family.

Ontologies

Keywords
Biological process	Polyamine biosynthesis Spermidine biosynthesis
Ligand	Pyruvate S-adenosyl-L-methionine Schiff base
Molecular function	Decarboxylase Lyase
PTM	Autocatalytic cleavage Phosphoprotein Zymogen
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	spermidine biosynthetic process Non-traceable author statement. Source: UniProtKB spermine biosynthetic process Non-traceable author statement. Source: UniProtKB
Molecular function	adenosylmethionine decarboxylase activity Ref.1 Ref.4 Traceable author statement. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 67

67

S-adenosylmethionine decarboxylase beta chain

PRO_0000029959

Chain

68 – 334

267

S-adenosylmethionine decarboxylase alpha chain

PRO_0000029960

Sites

Active site

8

1

Active site

11

1

Active site

68

1

Schiff-base intermediate with substrate; via pyruvic acid

Active site

82

1

Proton donor; for catalytic activity

Active site

229

1

Proton acceptor; for processing activity

Active site

243

1

Proton acceptor; for processing activity

Binding site

7

1

Substrate

Binding site

67

1

Substrate

Binding site

223

1

Substrate

Binding site

247

1

Substrate

Site

67 – 68

2

Cleavage (non-hydrolytic); by autolysis

Amino acid modifications

Modified residue

68

1

Pyruvic acid (Ser); by autocatalysis

Modified residue

298

1

Phosphoserine Ref.7

Experimental info

Mutagenesis

7

1

F → A: No effect. Ref.9

Mutagenesis

8

1

E → Q: Loss of activity. Normal putrescine-stimulated processing.

Mutagenesis

11

1

E → Q: Loss of activity. Loss of putrescine-stimulated processing.

Mutagenesis

15

1

E → Q: Little effect.

Mutagenesis

49

1

C → A: Little effect.

Mutagenesis

61

1

E → Q: Little effect.

Mutagenesis

67

1

E → Q: Little effect.

Mutagenesis

80

1

K → A: Greatly reduced catalytic activity. No putrescine-stimulated processing.

Mutagenesis

82

1

C → A: Loss of activity. Greatly reduced putrescine-stimulated processing.

Mutagenesis

223

1

F → A: No effect. Ref.9

Mutagenesis

226

1

C → A: Little effect.

Mutagenesis

229

1

S → A: Loss of processing. Ref.5

Mutagenesis

229

1

S → C: Greatly reduced processing. Ref.5

Mutagenesis

229

1

S → T: Greatly reduced catalytic activity but little effect on processing. Ref.5

Mutagenesis

243

1

H → A: Greatly reduced catalytic activity and processing. Ref.5

Mutagenesis

243

1

H → E: Greatly reduced catalytic activity and processing. Ref.5

Mutagenesis

243

1

H → F: Loss of processing. Ref.5

Mutagenesis

243

1

H → Y: Loss of processing. Ref.5

Mutagenesis

247

1

E → Q: Little effect.

Mutagenesis

249

1

E → Q: Little effect.

Sequence conflict

146

1

A → G in AAA51716. Ref.1

Secondary structure

1

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334

Helix Strand Turn

Details...

Beta strand

12 – 19

8

Helix

32 – 34

3

Helix

37 – 45

9

Turn

46 – 48

3

Beta strand

50 – 56

7

Beta strand

58 – 66

9

Beta strand

70 – 81

12

Helix

87 – 90

4

Helix

91 – 102

12

Beta strand

106 – 115

10

Helix

120 – 122

3

Helix

130 – 138

9

Beta strand

142 – 150

9

Beta strand

154 – 162

9

Beta strand

175 – 184

10

Helix

186 – 189

4

Helix

190 – 192

3

Helix

200 – 206

7

Helix

210 – 212

3

Beta strand

213 – 215

3

Beta strand

217 – 222

6

Beta strand

224 – 226

3

Beta strand

228 – 233

6

Beta strand

239 – 245

7

Beta strand

252 – 257

6

Helix

265 – 275

11

Beta strand

277 – 287

11

Beta strand

305 – 314

10

Beta strand

316 – 327

12

Sequences

	Sequence		Length	Mass (Da)
	P17707-1 [UniParc]. Last modified October 17, 2006. Version 2. Checksum: 1BB433AF412C9179	FASTA	334	38,340
	10 20 30 40 50 60 MEAAHFFEGT EKLLEVWFSR QQPDANQGSG DLRTIPRSEW DILLKDVQCS IISVTKTDKQ 70 80 90 100 110 120 EAYVLSESSM FVSKRRFILK TCGTTLLLKA LVPLLKLARD YSGFDSIQSF FYSRKNFMKP 130 140 150 160 170 180 SHQGYPHRNF QEEIEFLNAI FPNGAAYCMG RMNSDCWYLY TLDFPESRVI SQPDQTLEIL 190 200 210 220 230 240 MSELDPAVMD QFYMKDGVTA KDVTRESGIR DLIPGSVIDA TMFNPCGYSM NGMKSDGTYW 250 260 270 280 290 300 TIHITPEPEF SYVSFETNLS QTSYDDLIRK VVEVFKPGKF VTTLFVNQSS KCRTVLASPQ 310 320 330 KIEGFKRLDC QSAMFNDYNF VFTSFAKKQQ QQQS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure and regulation of mammalian S-adenosylmethionine decarboxylase." Pajunen A., Crozat A., Jaenne O.A., Ihalainen R., Laitinen P.H., Stanley B., Madhubala R., Pegg A.E. J. Biol. Chem. 263:17040-17049(1988) [PubMed: 2460457] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, PYRUVATE FORMATION AT SER-68.
[2]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta.
[4]	"Amino acid residues necessary for putrescine stimulation of human S-adenosylmethionine decarboxylase proenzyme processing and catalytic activity." Stanley B.A., Pegg A.E. J. Biol. Chem. 266:18502-18506(1991) [PubMed: 1917972] [Abstract] Cited for: MUTAGENESIS.
[5]	"Mechanistic studies of the processing of human S-adenosylmethionine decarboxylase proenzyme. Isolation of an ester intermediate." Xiong H., Pegg A.E. J. Biol. Chem. 274:35059-35066(1999) [PubMed: 10574985] [Abstract] Cited for: MUTAGENESIS OF SER-229 AND HIS-243.
[6]	"Role of cysteine-82 in the catalytic mechanism of human S-adenosylmethionine decarboxylase." Xiong H., Stanley B.A., Pegg A.E. Biochemistry 38:2462-2470(1999) [PubMed: 10029540] [Abstract] Cited for: IMPORTANCE OF CYS-82 IN CATALYTIC ACTIVITY, INHIBITION BY IODOACETIC ACID.
[7]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-298, MASS SPECTROMETRY.
[8]	"The crystal structure of human S-adenosylmethionine decarboxylase at 2.25-A resolution reveals a novel fold." Ekstrom J.L., Mathews I.I., Stanley B.A., Pegg A.E., Ealick S.E. Structure 7:583-595(1999) [PubMed: 10378277] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS).
[9]	"The structural basis for substrate specificity and inhibition of human S-adenosylmethionine decarboxylase." Tolbert W.D., Ekstrom J.L., Mathews I.I., Secrist J.A. III, Kapoor P., Pegg A.E., Ealick S.E. Biochemistry 40:9484-9494(2001) [PubMed: 11583147] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS), REACTION MECHANISM, MUTAGENESIS OF PHE-7 AND PHE-223.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

M21154 mRNA. Translation: AAA51716.1.
AL357515, AL365206 Genomic DNA. Translation: CAH73388.1.
AL365206, AL357515 Genomic DNA. Translation: CAI23233.1.
BC000171 mRNA. Translation: AAH00171.1.

IPI

IPI00016708.

PIR

DCHUDM. A31786.

RefSeq

NP_001625.2.

UniGene

Hs.159118

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1I72	X-ray	2.00	B	1-67	[»]
			A	69-334	[»]
1I79	X-ray	2.01	B	1-67	[»]
			A	69-334	[»]
1I7B	X-ray	1.90	B	1-67	[»]
			A	69-334	[»]
1I7C	X-ray	2.40	B	1-67	[»]
			A	69-334	[»]
1I7M	X-ray	2.24	B/D	1-67	[»]
			A/C	69-334	[»]
1JEN	X-ray	2.25	B/D	1-67	[»]
			A/C	69-334	[»]
1JL0	X-ray	1.50	A/B	1-334	[»]
1MSV	X-ray	1.75	A/B	1-334	[»]
3DZ2	X-ray	1.86	B	1-67	[»]
			A	69-334	[»]
3DZ3	X-ray	2.62	B	1-67	[»]
			A	69-334	[»]
3DZ4	X-ray	1.84	B	1-67	[»]
			A	69-334	[»]
3DZ5	X-ray	2.43	B	1-67	[»]
			A	69-334	[»]
3DZ6	X-ray	1.83	B	1-67	[»]
			A	69-334	[»]
3DZ7	X-ray	1.91	B	1-67	[»]
			A	69-334	[»]
3EP3	X-ray	1.84	B	1-67	[»]
			A	69-328	[»]
3EP4	X-ray	1.89	B	1-67	[»]
			A	69-328	[»]
3EP5	X-ray	1.99	B	1-67	[»]
			A	69-328	[»]
3EP6	X-ray	1.70	B	1-67	[»]
			A	69-328	[»]
3EP7	X-ray	2.00	B	1-67	[»]
			A	69-328	[»]
3EP8	X-ray	1.97	B	1-67	[»]
			A	69-328	[»]
3EP9	X-ray	2.35	B	1-67	[»]
			A	69-328	[»]
3EPA	X-ray	2.10	B	1-67	[»]
			A	69-328	[»]
3EPB	X-ray	1.75	B	1-67	[»]
			A	69-328	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:363N.

PTM databases

PhosphoSite

P17707.

Proteomic databases

PRIDE

P17707.

Genome annotation databases

Ensembl

ENSG00000123505. Homo sapiens. [Contig view]

GeneID

262.

Organism-specific databases

GeneCards

GC06P111304.

HGNC

HGNC:457. AMD1.

MIM

180980. gene.

PharmGKB

PA24763.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P17707.

HOVERGEN

P17707.

OMA

P17707. ILILTCG.

Enzyme and pathway databases

BRENDA

4.1.1.50. 247.

Reactome

REACT_13. Metabolism of amino acids.

Gene expression databases

ArrayExpress

P17707.

Bgee

P17707.

CleanEx

HS_AMD1.

GermOnline

ENSG00000123505. Homo sapiens.

Family and domain databases

InterPro

IPR001985. S-AdoMet_decarboxylase.
IPR018167. S-AdoMet_decarboxylase_sg.
IPR016067. S-AdoMet_deCO2ase_core.
IPR018166. S-AdoMet_deCO2ase_CS.
[Graphical view]

Gene3D

G3DSA:3.60.90.10. SAM_decarbox. 1 hit.

PANTHER

PTHR11570. SAM_decarbox. 1 hit.

Pfam

PF01536. SAM_decarbox. 1 hit.
[Graphical view]

PIRSF

PIRSF001355. S-AdenosylMet_decarboxylase. 1 hit.

ProDom

PD002379. SAM_decarbox. 1 hit.
[Graphical view] [Entries sharing at least one domain]

TIGRFAMs

TIGR00535. SAM_DCase. 1 hit.

PROSITE

PS01336. ADOMETDC. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00118. S-Adenosylmethionine.

NextBio

1029.

PMAP-CutDB

P17707.

SOURCE

Search...

Entry information

Entry name

DCAM_HUMAN

Accession

Primary (citable) accession number: P17707
Secondary accession number(s): Q5VXN6, Q9BWK4

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	October 17, 2006
Last modified:	June 16, 2009
This is version 114 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)