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Protein

Adenosylhomocysteinase

Gene

AHCY

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

Functioni

Adenosylhomocysteine is a competitive inhibitor of S-adenosyl-L-methionine-dependent methyl transferase reactions; therefore adenosylhomocysteinase may play a key role in the control of methylations via regulation of the intracellular concentration of adenosylhomocysteine.1 Publication

Catalytic activityi

S-adenosyl-L-homocysteine + H2O = L-homocysteine + adenosine.

Cofactori

NAD+2 PublicationsNote: Binds 1 NAD+ per subunit.2 Publications

Pathwayi: L-homocysteine biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes L-homocysteine from S-adenosyl-L-homocysteine.
Proteins known to be involved in this subpathway in this organism are:
  1. Adenosylhomocysteinase (AHCYL1), Adenosylhomocysteinase (AHCYL2), Adenosylhomocysteinase (AHCYL1), Adenosylhomocysteinase (AHCY), Adenosylhomocysteinase, Adenosylhomocysteinase (AHCY), Adenosylhomocysteinase (FGFR2-AHCYL1), Adenosylhomocysteinase 3 (AHCYL2)
This subpathway is part of the pathway L-homocysteine biosynthesis, which is itself part of Amino-acid biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes L-homocysteine from S-adenosyl-L-homocysteine, the pathway L-homocysteine biosynthesis and in Amino-acid biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei57SubstrateBy similarity1
Binding sitei131SubstrateBy similarity1
Binding sitei156SubstrateBy similarity1
Binding sitei186SubstrateBy similarity1
Binding sitei190SubstrateBy similarity1
Binding sitei243NAD2 Publications1
Binding sitei248NAD2 Publications1
Binding sitei346NAD2 Publications1
Binding sitei353NAD2 Publications1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi157 – 159NAD2 Publications3
Nucleotide bindingi222 – 227NAD2 Publications6
Nucleotide bindingi299 – 301NAD2 Publications3

GO - Molecular functioni

  • adenosylhomocysteinase activity Source: UniProtKB
  • adenyl nucleotide binding Source: Ensembl
  • identical protein binding Source: Ensembl
  • NAD binding Source: Ensembl

GO - Biological processi

Keywordsi

Molecular functionHydrolase
Biological processOne-carbon metabolism
LigandNAD

Enzyme and pathway databases

BRENDAi3.3.1.1 2681
ReactomeiR-HSA-156581 Methylation
R-HSA-1614635 Sulfur amino acid metabolism
R-HSA-2408508 Metabolism of ingested SeMet, Sec, MeSec into H2Se
R-HSA-5578997 Defective AHCY causes Hypermethioninemia with S-adenosylhomocysteine hydrolase deficiency (HMAHCHD)
SABIO-RKiP23526
UniPathwayiUPA00314; UER00076

Names & Taxonomyi

Protein namesi
Recommended name:
Adenosylhomocysteinase (EC:3.3.1.1)
Short name:
AdoHcyase
Alternative name(s):
S-adenosyl-L-homocysteine hydrolase
Gene namesi
Name:AHCY
Synonyms:SAHH
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

EuPathDBiHostDB:ENSG00000101444.12
HGNCiHGNC:343 AHCY
MIMi180960 gene
neXtProtiNX_P23526

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

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Hypermethioninemia with S-adenosylhomocysteine hydrolase deficiency (HMAHCHD)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA metabolic disorder characterized by hypermethioninemia associated with failure to thrive, mental and motor retardation, facial dysmorphism with abnormal hair and teeth, and myocardiopathy.
See also OMIM:613752
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05858849R → C in HMAHCHD. 2 PublicationsCorresponds to variant dbSNP:rs369428934Ensembl.1
Natural variantiVAR_05858986D → G in HMAHCHD. 2 PublicationsCorresponds to variant dbSNP:rs773162208Ensembl.1
Natural variantiVAR_05859089A → V in HMAHCHD. 1 PublicationCorresponds to variant dbSNP:rs755222515Ensembl.1
Natural variantiVAR_058591143Y → C in HMAHCHD. 2 PublicationsCorresponds to variant dbSNP:rs121918608Ensembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi191
MalaCardsiAHCY
MIMi613752 phenotype
OpenTargetsiENSG00000101444
Orphaneti88618 Psychomotor retardation due to S-adenosylhomocysteine hydrolase deficiency
PharmGKBiPA24636

Chemistry databases

ChEMBLiCHEMBL2664
DrugBankiDB03273 3'-Oxo-Adenosine
DB03769 D-Eritadenine
DB02325 Isopropyl Alcohol
GuidetoPHARMACOLOGYi1233

Polymorphism and mutation databases

BioMutaiAHCY
DMDMi20141702

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved2 Publications
ChainiPRO_00001169022 – 432AdenosylhomocysteinaseAdd BLAST431

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserine1 Publication1
Modified residuei183PhosphoserineCombined sources1
Modified residuei193PhosphotyrosineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP23526
MaxQBiP23526
PaxDbiP23526
PeptideAtlasiP23526
PRIDEiP23526

2D gel databases

REPRODUCTION-2DPAGEiIPI00012007

PTM databases

iPTMnetiP23526
PhosphoSitePlusiP23526
SwissPalmiP23526

Expressioni

Gene expression databases

BgeeiENSG00000101444
CleanExiHS_AHCY
GenevisibleiP23526 HS

Organism-specific databases

HPAiHPA041225
HPA044675

Interactioni

Subunit structurei

Homotetramer.2 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi106696, 76 interactors
DIPiDIP-50557N
IntActiP23526, 34 interactors
MINTiP23526
STRINGi9606.ENSP00000217426

Chemistry databases

BindingDBiP23526

Structurei

Secondary structure

1432
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi8 – 10Combined sources3
Helixi12 – 14Combined sources3
Helixi15 – 26Combined sources12
Helixi30 – 39Combined sources10
Turni40 – 42Combined sources3
Turni44 – 47Combined sources4
Beta strandi49 – 54Combined sources6
Helixi58 – 69Combined sources12
Beta strandi73 – 77Combined sources5
Beta strandi79 – 82Combined sources4
Helixi86 – 94Combined sources9
Beta strandi99 – 101Combined sources3
Helixi107 – 115Combined sources9
Beta strandi118 – 120Combined sources3
Beta strandi121 – 124Combined sources4
Beta strandi126 – 133Combined sources8
Helixi134 – 142Combined sources9
Helixi144 – 149Combined sources6
Beta strandi152 – 155Combined sources4
Helixi158 – 169Combined sources12
Beta strandi175 – 179Combined sources5
Helixi184 – 187Combined sources4
Helixi190 – 207Combined sources18
Beta strandi215 – 219Combined sources5
Helixi223 – 234Combined sources12
Beta strandi238 – 242Combined sources5
Helixi246 – 254Combined sources9
Helixi262 – 265Combined sources4
Turni266 – 268Combined sources3
Beta strandi270 – 274Combined sources5
Beta strandi277 – 279Combined sources3
Helixi284 – 287Combined sources4
Beta strandi294 – 298Combined sources5
Beta strandi300 – 302Combined sources3
Helixi308 – 314Combined sources7
Beta strandi316 – 322Combined sources7
Beta strandi325 – 329Combined sources5
Beta strandi335 – 339Combined sources5
Helixi340 – 342Combined sources3
Helixi345 – 348Combined sources4
Helixi355 – 374Combined sources20
Helixi376 – 378Combined sources3
Beta strandi381 – 384Combined sources4
Helixi388 – 399Combined sources12
Turni400 – 403Combined sources4
Helixi411 – 417Combined sources7
Beta strandi421 – 423Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1A7AX-ray2.80A/B1-432[»]
1LI4X-ray2.01A1-432[»]
3NJ4X-ray2.50A/B/C/D1-432[»]
4PFJX-ray2.30A/B1-432[»]
4PGFX-ray2.59A/B1-432[»]
4YVFX-ray2.70A/B1-432[»]
5W49X-ray2.40A/B4-432[»]
5W4BX-ray2.65A/B/C/D/E/F4-432[»]
ProteinModelPortaliP23526
SMRiP23526
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP23526

Family & Domainsi

Sequence similaritiesi

Belongs to the adenosylhomocysteinase family.Curated

Phylogenomic databases

eggNOGiKOG1370 Eukaryota
COG0499 LUCA
GeneTreeiENSGT00390000003626
HOGENOMiHOG000227987
HOVERGENiHBG005041
InParanoidiP23526
KOiK01251
OMAiTGNRDII
OrthoDBiEOG091G06EB
PhylomeDBiP23526
TreeFamiTF300415

Family and domain databases

CDDicd00401 SAHH, 1 hit
HAMAPiMF_00563 AdoHcyase, 1 hit
InterProiView protein in InterPro
IPR034373 Adenosylhomocysteinase
IPR000043 Adenosylhomocysteinase-like
IPR015878 Ado_hCys_hydrolase_NAD-bd
IPR036291 NAD(P)-bd_dom_sf
IPR020082 S-Ado-L-homoCys_hydrolase_CS
PANTHERiPTHR23420 PTHR23420, 1 hit
PfamiView protein in Pfam
PF05221 AdoHcyase, 1 hit
PF00670 AdoHcyase_NAD, 1 hit
PIRSFiPIRSF001109 Ad_hcy_hydrolase, 1 hit
SMARTiView protein in SMART
SM00996 AdoHcyase, 1 hit
SM00997 AdoHcyase_NAD, 1 hit
SUPFAMiSSF51735 SSF51735, 1 hit
TIGRFAMsiTIGR00936 ahcY, 1 hit
PROSITEiView protein in PROSITE
PS00738 ADOHCYASE_1, 1 hit
PS00739 ADOHCYASE_2, 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: P23526-1) [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
MSDKLPYKVA DIGLAAWGRK ALDIAENEMP GLMRMRERYS ASKPLKGARI
60 70 80 90 100
AGCLHMTVET AVLIETLVTL GAEVQWSSCN IFSTQDHAAA AIAKAGIPVY
110 120 130 140 150
AWKGETDEEY LWCIEQTLYF KDGPLNMILD DGGDLTNLIH TKYPQLLPGI
160 170 180 190 200
RGISEETTTG VHNLYKMMAN GILKVPAINV NDSVTKSKFD NLYGCRESLI
210 220 230 240 250
DGIKRATDVM IAGKVAVVAG YGDVGKGCAQ ALRGFGARVI ITEIDPINAL
260 270 280 290 300
QAAMEGYEVT TMDEACQEGN IFVTTTGCID IILGRHFEQM KDDAIVCNIG
310 320 330 340 350
HFDVEIDVKW LNENAVEKVN IKPQVDRYRL KNGRRIILLA EGRLVNLGCA
360 370 380 390 400
MGHPSFVMSN SFTNQVMAQI ELWTHPDKYP VGVHFLPKKL DEAVAEAHLG
410 420 430
KLNVKLTKLT EKQAQYLGMS CDGPFKPDHY RY
Length:432
Mass (Da):47,716
Last modified:January 23, 2007 - v4
Checksum:i2833C025F969553E
GO
Isoform 2 (identifier: P23526-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-28: Missing.

Note: No experimental confirmation available.
Show »
Length:404
Mass (Da):44,659
Checksum:i4AF904249AD2F35F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti249A → V in BAG53495 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05228638R → W1 PublicationCorresponds to variant dbSNP:rs13043752Ensembl.1
Natural variantiVAR_05858849R → C in HMAHCHD. 2 PublicationsCorresponds to variant dbSNP:rs369428934Ensembl.1
Natural variantiVAR_05858986D → G in HMAHCHD. 2 PublicationsCorresponds to variant dbSNP:rs773162208Ensembl.1
Natural variantiVAR_00693486D → N1 Publication1
Natural variantiVAR_05859089A → V in HMAHCHD. 1 PublicationCorresponds to variant dbSNP:rs755222515Ensembl.1
Natural variantiVAR_058591143Y → C in HMAHCHD. 2 PublicationsCorresponds to variant dbSNP:rs121918608Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0454041 – 28Missing in isoform 2. 1 PublicationAdd BLAST28

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M61831 mRNA Translation: AAA51681.1
M61832 mRNA Translation: AAA51682.1
BT006697 mRNA Translation: AAP35343.1
AK097610 mRNA Translation: BAG53495.1
AK290422 mRNA Translation: BAF83111.1
AL356299 Genomic DNA No translation available.
CH471077 Genomic DNA Translation: EAW76279.1
CH471077 Genomic DNA Translation: EAW76280.1
BC010018 mRNA Translation: AAH10018.1
BC011606 mRNA Translation: AAH11606.1
CCDSiCCDS13233.1 [P23526-1]
CCDS54457.1 [P23526-2]
PIRiA43629
RefSeqiNP_000678.1, NM_000687.3 [P23526-1]
NP_001155238.1, NM_001161766.1 [P23526-2]
NP_001309013.1, NM_001322084.1 [P23526-2]
NP_001309014.1, NM_001322085.1 [P23526-2]
XP_005260374.1, XM_005260317.2 [P23526-2]
XP_011526961.1, XM_011528659.1 [P23526-2]
XP_016883197.1, XM_017027708.1 [P23526-1]
XP_016883198.1, XM_017027709.1 [P23526-1]
UniGeneiHs.388004

Genome annotation databases

EnsembliENST00000217426; ENSP00000217426; ENSG00000101444 [P23526-1]
ENST00000538132; ENSP00000442820; ENSG00000101444 [P23526-2]
GeneIDi191
KEGGihsa:191
UCSCiuc002xai.4 human [P23526-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSAHH_HUMAN
AccessioniPrimary (citable) accession number: P23526
Secondary accession number(s): A8K307
, B3KUN3, E1P5P2, F5H737, Q96A36
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: January 23, 2007
Last modified: April 25, 2018
This is version 197 of the entry and version 4 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