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Protein

S-adenosylmethionine decarboxylase proenzyme

Gene

AMD1

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

Functioni

Essential for biosynthesis of the polyamines spermidine and spermine. Promotes maintenance and self-renewal of embryonic stem cells, by maintaining spermine levels.By similarity

Catalytic activityi

S-adenosyl-L-methionine = S-adenosyl 3-(methylthio)propylamine + CO2.6 Publications

Cofactori

pyruvate1 PublicationNote: Binds 1 pyruvoyl group covalently per subunit.1 Publication

Enzyme regulationi

Both proenzyme processing and catalytic activity are stimulated by putrescine. Catalytic activity is inhibited by iodoacetic acid.

Pathwayi: S-adenosylmethioninamine biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes S-adenosylmethioninamine from S-adenosyl-L-methionine.6 Publications
Proteins known to be involved in this subpathway in this organism are:
  1. S-adenosylmethionine decarboxylase proenzyme (DKFZp686G18136), S-adenosylmethionine decarboxylase proenzyme (AMD1)
This subpathway is part of the pathway S-adenosylmethioninamine biosynthesis, which is itself part of Amine and polyamine biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes S-adenosylmethioninamine from S-adenosyl-L-methionine, the pathway S-adenosylmethioninamine biosynthesis and in Amine and polyamine biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei7Substrate1 Publication1
Active sitei81 Publication1
Active sitei111 Publication1
Binding sitei67Substrate1 Publication1
Active sitei68Schiff-base intermediate with substrate; via pyruvic acid1 Publication1
Active sitei82Proton donor; for catalytic activity2 Publications1
Binding sitei223Substrate1 Publication1
Active sitei229Proton acceptor; for processing activity1 Publication1
Active sitei243Proton acceptor; for processing activity1 Publication1
Binding sitei247Substrate1 Publication1

GO - Molecular functioni

  • adenosylmethionine decarboxylase activity Source: UniProtKB
  • putrescine binding Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionDecarboxylase, Lyase
Biological processPolyamine biosynthesis, Spermidine biosynthesis
LigandPyruvate, S-adenosyl-L-methionine, Schiff base

Enzyme and pathway databases

BRENDAi4.1.1.50 2681
ReactomeiR-HSA-351202 Metabolism of polyamines
SABIO-RKiP17707
UniPathwayiUPA00331; UER00451

Names & Taxonomyi

Protein namesi
Recommended name:
S-adenosylmethionine decarboxylase proenzyme (EC:4.1.1.506 Publications)
Short name:
AdoMetDC
Short name:
SAMDC
Cleaved into the following 2 chains:
Gene namesi
Name:AMD1
Synonyms:AMD
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000123505.14
HGNCiHGNC:457 AMD1
MIMi180980 gene
neXtProtiNX_P17707

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi7F → A: No effect. 1 Publication1
Mutagenesisi8E → Q: Loss of activity. Normal putrescine-stimulated processing. 2 Publications1
Mutagenesisi11E → Q: Loss of activity. Loss of putrescine-stimulated processing. 1 Publication1
Mutagenesisi15E → Q: Little effect. 1 Publication1
Mutagenesisi49C → A: Little effect. 1 Publication1
Mutagenesisi50S → A: 17 percent decrease in catalytic activity. No effect on processing. 1 Publication1
Mutagenesisi61E → Q: Little effect. 1 Publication1
Mutagenesisi66S → A: 38 percent decrease in catalytic activity. Slight reduction in processing. 1 Publication1
Mutagenesisi67E → Q: Little effect. 1 Publication1
Mutagenesisi68 – 69SS → II: Loss of catalytic activity and processing. 1 Publication2
Mutagenesisi68S → A: Loss of catalytic activity and processing. 1 Publication1
Mutagenesisi69S → A: 24 percent decrease in catalytic activity. Slight reduction in processing. 1 Publication1
Mutagenesisi80K → A: Greatly reduced catalytic activity. No putrescine-stimulated processing. 1 Publication1
Mutagenesisi82C → A: Loss of activity. Greatly reduced putrescine-stimulated processing. 1 Publication1
Mutagenesisi223F → A: No effect. 1 Publication1
Mutagenesisi226C → A: Little effect. 1 Publication1
Mutagenesisi229S → A: Loss of processing. 1 Publication1
Mutagenesisi229S → C: Greatly reduced processing. 1 Publication1
Mutagenesisi229S → T: Greatly reduced catalytic activity but little effect on processing. 1 Publication1
Mutagenesisi243H → A: Greatly reduced catalytic activity and processing. 1 Publication1
Mutagenesisi243H → E: Greatly reduced catalytic activity and processing. 1 Publication1
Mutagenesisi243H → F: Loss of processing. 1 Publication1
Mutagenesisi243H → Y: Loss of processing. 1 Publication1
Mutagenesisi247E → Q: Little effect. 1 Publication1
Mutagenesisi249E → Q: Little effect. 1 Publication1

Organism-specific databases

DisGeNETi262
OpenTargetsiENSG00000123505
PharmGKBiPA24763

Chemistry databases

ChEMBLiCHEMBL4181
DrugBankiDB08163 5'-{[4-(aminooxy)butyl](methyl)amino}-5'-deoxy-8-ethenyladenosine
DB01917 Putrescine
DB00118 S-Adenosylmethionine
DB03754 Tris

Polymorphism and mutation databases

DMDMi116241324

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000299591 – 67S-adenosylmethionine decarboxylase beta chainAdd BLAST67
ChainiPRO_000002996068 – 334S-adenosylmethionine decarboxylase alpha chainAdd BLAST267

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei68Pyruvic acid (Ser); by autocatalysis2 Publications1
Modified residuei298PhosphoserineCombined sources1

Post-translational modificationi

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.4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei67 – 68Cleavage (non-hydrolytic); by autolysis2 Publications2

Keywords - PTMi

Autocatalytic cleavage, Phosphoprotein, Zymogen

Proteomic databases

EPDiP17707
MaxQBiP17707
PaxDbiP17707
PeptideAtlasiP17707
PRIDEiP17707

PTM databases

iPTMnetiP17707
PhosphoSitePlusiP17707

Miscellaneous databases

PMAP-CutDBiP17707

Expressioni

Gene expression databases

BgeeiENSG00000123505
CleanExiHS_AMD1
ExpressionAtlasiP17707 baseline and differential
GenevisibleiP17707 HS

Organism-specific databases

HPAiHPA029281
HPA029282

Interactioni

Subunit structurei

Heterotetramer of two alpha and two beta chains.1 Publication

Protein-protein interaction databases

BioGridi106759, 35 interactors
DIPiDIP-363N
IntActiP17707, 2 interactors
STRINGi9606.ENSP00000357880

Chemistry databases

BindingDBiP17707

Structurei

Secondary structure

1334
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi12 – 19Combined sources8
Helixi32 – 34Combined sources3
Helixi37 – 45Combined sources9
Turni46 – 48Combined sources3
Beta strandi51 – 56Combined sources6
Beta strandi58 – 65Combined sources8
Beta strandi68 – 81Combined sources14
Helixi87 – 90Combined sources4
Helixi91 – 102Combined sources12
Beta strandi106 – 115Combined sources10
Helixi120 – 122Combined sources3
Helixi130 – 138Combined sources9
Beta strandi142 – 150Combined sources9
Beta strandi157 – 162Combined sources6
Beta strandi175 – 183Combined sources9
Helixi186 – 189Combined sources4
Helixi190 – 192Combined sources3
Helixi200 – 206Combined sources7
Helixi209 – 211Combined sources3
Beta strandi212 – 215Combined sources4
Beta strandi217 – 222Combined sources6
Beta strandi224 – 226Combined sources3
Beta strandi228 – 233Combined sources6
Beta strandi239 – 245Combined sources7
Helixi248 – 250Combined sources3
Beta strandi252 – 257Combined sources6
Helixi265 – 275Combined sources11
Beta strandi278 – 287Combined sources10
Helixi291 – 296Combined sources6
Beta strandi305 – 314Combined sources10
Beta strandi316 – 327Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1I72X-ray2.00A68-334[»]
B1-67[»]
1I79X-ray2.01A68-334[»]
B1-67[»]
1I7BX-ray1.90A68-334[»]
B1-67[»]
1I7CX-ray2.40A68-334[»]
B1-67[»]
1I7MX-ray2.24A/C68-334[»]
B/D1-67[»]
1JENX-ray2.25A/C69-334[»]
B/D1-67[»]
1JL0X-ray1.50A/B1-334[»]
1MSVX-ray1.75A/B1-334[»]
3DZ2X-ray1.86A69-334[»]
B1-67[»]
3DZ3X-ray2.62A69-334[»]
B1-67[»]
3DZ4X-ray1.84A69-334[»]
B1-67[»]
3DZ5X-ray2.43A69-334[»]
B1-67[»]
3DZ6X-ray1.83A69-334[»]
B1-67[»]
3DZ7X-ray1.91A69-334[»]
B1-67[»]
3EP3X-ray1.84A69-328[»]
B1-67[»]
3EP4X-ray1.89A69-328[»]
B1-67[»]
3EP5X-ray1.99A69-328[»]
B1-67[»]
3EP6X-ray1.70A69-328[»]
B1-67[»]
3EP7X-ray2.00A69-328[»]
B1-67[»]
3EP8X-ray1.97A69-328[»]
B1-67[»]
3EP9X-ray2.35A69-328[»]
B1-67[»]
3EPAX-ray2.10A69-328[»]
B1-67[»]
3EPBX-ray1.75A69-328[»]
B1-67[»]
3H0VX-ray2.24A69-334[»]
B1-67[»]
3H0WX-ray1.81A69-334[»]
B1-67[»]
ProteinModelPortaliP17707
SMRiP17707
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP17707

Family & Domainsi

Sequence similaritiesi

Belongs to the eukaryotic AdoMetDC family.Curated

Phylogenomic databases

eggNOGiKOG0788 Eukaryota
ENOG410XRN0 LUCA
GeneTreeiENSGT00390000011776
HOGENOMiHOG000159915
HOVERGENiHBG000761
InParanoidiP17707
KOiK01611
OMAiGDHWYLY
OrthoDBiEOG091G1467
PhylomeDBiP17707
TreeFamiTF313561

Family and domain databases

InterProiView protein in InterPro
IPR001985 S-AdoMet_decarboxylase
IPR016067 S-AdoMet_deCO2ase_core
IPR018166 S-AdoMet_deCO2ase_CS
PANTHERiPTHR11570 PTHR11570, 1 hit
PfamiView protein in Pfam
PF01536 SAM_decarbox, 1 hit
PIRSFiPIRSF001355 S-AdenosylMet_decarboxylase, 1 hit
SUPFAMiSSF56276 SSF56276, 1 hit
TIGRFAMsiTIGR00535 SAM_DCase, 1 hit
PROSITEiView protein in PROSITE
PS01336 ADOMETDC, 1 hit

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P17707-1) [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
MEAAHFFEGT EKLLEVWFSR QQPDANQGSG DLRTIPRSEW DILLKDVQCS
60 70 80 90 100
IISVTKTDKQ EAYVLSESSM FVSKRRFILK TCGTTLLLKA LVPLLKLARD
110 120 130 140 150
YSGFDSIQSF FYSRKNFMKP SHQGYPHRNF QEEIEFLNAI FPNGAAYCMG
160 170 180 190 200
RMNSDCWYLY TLDFPESRVI SQPDQTLEIL MSELDPAVMD QFYMKDGVTA
210 220 230 240 250
KDVTRESGIR DLIPGSVIDA TMFNPCGYSM NGMKSDGTYW TIHITPEPEF
260 270 280 290 300
SYVSFETNLS QTSYDDLIRK VVEVFKPGKF VTTLFVNQSS KCRTVLASPQ
310 320 330
KIEGFKRLDC QSAMFNDYNF VFTSFAKKQQ QQQS
Length:334
Mass (Da):38,340
Last modified:October 17, 2006 - v2
Checksum:i1BB433AF412C9179
GO
Isoform 2 (identifier: P17707-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-148: Missing.

Show »
Length:186
Mass (Da):21,301
Checksum:iAB97D68DA1BDB447
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti146A → G in AAA51716 (PubMed:2460457).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0432091 – 148Missing in isoform 2. 1 PublicationAdd BLAST148

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M21154 mRNA Translation: AAA51716.1
AL832698 mRNA Translation: CAI46113.1
AL357515, AL365206 Genomic DNA Translation: CAH73388.1
AL365206, AL357515 Genomic DNA Translation: CAI23233.1
AL357515, AL365206 Genomic DNA Translation: CAH73390.1
AL365206 Genomic DNA Translation: CAI23235.1
CH471051 Genomic DNA Translation: EAW48307.1
CH471051 Genomic DNA Translation: EAW48308.1
CH471051 Genomic DNA Translation: EAW48309.1
BC000171 mRNA Translation: AAH00171.1
CCDSiCCDS5086.1 [P17707-1]
PIRiA31786 DCHUDM
RefSeqiNP_001625.2, NM_001634.5 [P17707-1]
UniGeneiHs.159118

Genome annotation databases

EnsembliENST00000368885; ENSP00000357880; ENSG00000123505 [P17707-1]
GeneIDi262
KEGGihsa:262
UCSCiuc003puk.3 human [P17707-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiDCAM_HUMAN
AccessioniPrimary (citable) accession number: P17707
Secondary accession number(s): E1P5F7
, Q5VXN4, Q5VXN6, Q9BWK4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: October 17, 2006
Last modified: April 25, 2018
This is version 191 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

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome
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Main funding by: National Institutes of Health