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Protein

S-adenosylmethionine decarboxylase proenzyme

Gene

AMD1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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).By similarity

Catalytic activityi

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

Cofactori

pyruvateNote: Binds 1 pyruvoyl group covalently per subunit.

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.
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
Active sitei111
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

Complete GO annotation...

Keywords - Molecular functioni

Decarboxylase, Lyase

Keywords - Biological processi

Polyamine biosynthesis, Spermidine biosynthesis

Keywords - Ligandi

Pyruvate, S-adenosyl-L-methionine, Schiff base

Enzyme and pathway databases

BRENDAi4.1.1.50. 2681.
ReactomeiR-HSA-351202. Metabolism of polyamines.
SABIO-RKP17707.
UniPathwayiUPA00331; UER00451.

Names & Taxonomyi

Protein namesi
Recommended name:
S-adenosylmethionine decarboxylase proenzyme (EC:4.1.1.50)
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

HGNCiHGNC:457. AMD1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi7F → A: No effect. 1 Publication1
Mutagenesisi8E → Q: Loss of activity. Normal putrescine-stimulated processing. 1 Publication1
Mutagenesisi11E → Q: Loss of activity. Loss of putrescine-stimulated processing. 1 Publication1
Mutagenesisi15E → Q: Little effect. 1 Publication1
Mutagenesisi49C → A: Little effect. 1 Publication1
Mutagenesisi61E → Q: Little effect. 1 Publication1
Mutagenesisi67E → Q: Little effect. 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.
DrugBankiDB00118. 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 autocatalysis1
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.

Sites

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

Keywords - PTMi

Autocatalytic cleavage, Phosphoprotein, Zymogen

Proteomic databases

EPDiP17707.
MaxQBiP17707.
PaxDbiP17707.
PeptideAtlasiP17707.
PRIDEiP17707.

PTM databases

iPTMnetiP17707.
PhosphoSitePlusiP17707.

Miscellaneous databases

PMAP-CutDBP17707.

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.

Protein-protein interaction databases

BioGridi106759. 30 interactors.
DIPiDIP-363N.
IntActiP17707. 1 interactor.
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.
OMAiENFFYSR.
OrthoDBiEOG091G1467.
PhylomeDBiP17707.
TreeFamiTF313561.

Family and domain databases

Gene3Di3.60.90.10. 1 hit.
InterProiIPR001985. S-AdoMet_decarboxylase.
IPR018167. S-AdoMet_decarboxylase_subgr.
IPR016067. S-AdoMet_deCO2ase_core.
IPR018166. S-AdoMet_deCO2ase_CS.
[Graphical view]
PANTHERiPTHR11570. PTHR11570. 1 hit.
PfamiPF01536. SAM_decarbox. 1 hit.
[Graphical view]
PIRSFiPIRSF001355. S-AdenosylMet_decarboxylase. 1 hit.
SUPFAMiSSF56276. SSF56276. 1 hit.
TIGRFAMsiTIGR00535. SAM_DCase. 1 hit.
PROSITEiPS01336. ADOMETDC. 1 hit.
[Graphical view]

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

Cross-referencesi

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.

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...

Protein-protein interaction databases

BioGridi106759. 30 interactors.
DIPiDIP-363N.
IntActiP17707. 1 interactor.
STRINGi9606.ENSP00000357880.

Chemistry databases

BindingDBiP17707.
ChEMBLiCHEMBL4181.
DrugBankiDB00118. S-Adenosylmethionine.
DB03754. Tris.

PTM databases

iPTMnetiP17707.
PhosphoSitePlusiP17707.

Polymorphism and mutation databases

DMDMi116241324.

Proteomic databases

EPDiP17707.
MaxQBiP17707.
PaxDbiP17707.
PeptideAtlasiP17707.
PRIDEiP17707.

Protocols and materials databases

DNASUi262.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi262.
DisGeNETi262.
GeneCardsiAMD1.
HGNCiHGNC:457. AMD1.
HPAiHPA029281.
HPA029282.
MIMi180980. gene.
neXtProtiNX_P17707.
OpenTargetsiENSG00000123505.
PharmGKBiPA24763.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

UniPathwayiUPA00331; UER00451.
BRENDAi4.1.1.50. 2681.
ReactomeiR-HSA-351202. Metabolism of polyamines.
SABIO-RKP17707.

Miscellaneous databases

ChiTaRSiAMD1. human.
EvolutionaryTraceiP17707.
GenomeRNAii262.
PMAP-CutDBP17707.
PROiP17707.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000123505.
CleanExiHS_AMD1.
ExpressionAtlasiP17707. baseline and differential.
GenevisibleiP17707. HS.

Family and domain databases

Gene3Di3.60.90.10. 1 hit.
InterProiIPR001985. S-AdoMet_decarboxylase.
IPR018167. S-AdoMet_decarboxylase_subgr.
IPR016067. S-AdoMet_deCO2ase_core.
IPR018166. S-AdoMet_deCO2ase_CS.
[Graphical view]
PANTHERiPTHR11570. PTHR11570. 1 hit.
PfamiPF01536. SAM_decarbox. 1 hit.
[Graphical view]
PIRSFiPIRSF001355. S-AdenosylMet_decarboxylase. 1 hit.
SUPFAMiSSF56276. SSF56276. 1 hit.
TIGRFAMsiTIGR00535. SAM_DCase. 1 hit.
PROSITEiPS01336. ADOMETDC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiDCAM_HUMAN
AccessioniPrimary (citable) accession number: P17707
Secondary accession number(s): E1P5F7
, Q5VXN4, Q5VXN6, Q9BWK4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: October 17, 2006
Last modified: November 2, 2016
This is version 181 of the entry and version 2 of the sequence. [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

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.