Reviewed, UniProtKB/Swiss-Prot P23526 (SAHH_HUMAN)

Names and origin

Protein names

Recommended name:
    Adenosylhomocysteinase
      Short name=AdoHcyase
    EC=3.3.1.1
Alternative name(s):
    S-adenosyl-L-homocysteine hydrolase

Gene names

Name:	AHCY
Synonyms:	SAHH

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	432 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)

Function	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.
Catalytic activity	S-adenosyl-L-homocysteine + H2O = L-homocysteine + adenosine.
Cofactor	Binds 1 NAD per subunit.
Pathway	Amino-acid biosynthesis; homocysteine biosynthesis; L-homocysteine from S-adenosyl-L-homocysteine: step 1/1.
Subunit structure	Homotetramer.
Subcellular location	Cytoplasm. Melanosome. Note: Identified by mass spectrometry in melanosome fractions from stage I to stage IV. Ref.9
Involvement in disease	Defects in AHCY are a cause of hypermethioninemia [MIM:180960]. It is a disease characterized by elevated levels of methionine in the sera.
Sequence similarities	Belongs to the adenosylhomocysteinase family.

Ontologies

Keywords
Biological process	One-carbon metabolism
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	NAD
Molecular function	Hydrolase
PTM	Acetylation
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	one-carbon compound metabolic process Non-traceable author statement. Source: UniProtKB
Cellular component	melanosome Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	adenosylhomocysteinase activity Ref.1 Traceable author statement. Source: UniProtKB protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
HLA-B	P30480	1	EBI-1053240,EBI-1054175
PINX1	Q96BK5	1	EBI-1053240,EBI-721782

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.5 Ref.6

Chain

2 – 432

431

Adenosylhomocysteinase

PRO_0000116902

Regions

Region

183 – 350

168

NAD binding By similarity

Sites

Binding site

57

1

Substrate By similarity

Binding site

131

1

Substrate By similarity

Binding site

156

1

Substrate By similarity

Binding site

186

1

Substrate By similarity

Binding site

190

1

Substrate By similarity

Amino acid modifications

Modified residue

2

1

N-acetylserine Ref.6

Natural variations

Natural variant

38

1

R → W: dbSNP rs13043752.

VAR_052286

Natural variant

86

1

D → N Ref.1

VAR_006934

Secondary structure

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432

Helix Strand Turn

Details...

Beta strand

8 – 10

3

Helix

12 – 14

3

Helix

15 – 26

12

Helix

30 – 39

10

Turn

40 – 42

3

Turn

44 – 47

4

Beta strand

49 – 54

6

Helix

58 – 69

12

Beta strand

73 – 77

5

Helix

86 – 94

9

Beta strand

99 – 101

3

Helix

107 – 115

9

Beta strand

118 – 120

3

Beta strand

126 – 133

8

Helix

134 – 142

9

Helix

144 – 149

6

Beta strand

152 – 155

4

Helix

158 – 169

12

Beta strand

175 – 179

5

Helix

184 – 187

4

Helix

190 – 207

18

Beta strand

215 – 219

5

Helix

223 – 234

12

Beta strand

238 – 242

5

Helix

246 – 254

9

Helix

262 – 265

4

Turn

266 – 268

3

Beta strand

270 – 274

5

Helix

284 – 287

4

Beta strand

294 – 298

5

Beta strand

300 – 302

3

Helix

308 – 314

7

Beta strand

316 – 322

7

Beta strand

325 – 329

5

Beta strand

335 – 339

5

Helix

340 – 342

3

Helix

345 – 348

4

Helix

355 – 374

20

Helix

376 – 378

3

Beta strand

381 – 384

4

Helix

388 – 399

12

Turn

400 – 403

4

Helix

411 – 417

7

Sequences

	Sequence		Length	Mass (Da)
	P23526-1 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: 2833C025F969553E	FASTA	432	47,716
	10 20 30 40 50 60 MSDKLPYKVA DIGLAAWGRK ALDIAENEMP GLMRMRERYS ASKPLKGARI AGCLHMTVET 70 80 90 100 110 120 AVLIETLVTL GAEVQWSSCN IFSTQDHAAA AIAKAGIPVY AWKGETDEEY LWCIEQTLYF 130 140 150 160 170 180 KDGPLNMILD DGGDLTNLIH TKYPQLLPGI RGISEETTTG VHNLYKMMAN GILKVPAINV 190 200 210 220 230 240 NDSVTKSKFD NLYGCRESLI DGIKRATDVM IAGKVAVVAG YGDVGKGCAQ ALRGFGARVI 250 260 270 280 290 300 ITEIDPINAL QAAMEGYEVT TMDEACQEGN IFVTTTGCID IILGRHFEQM KDDAIVCNIG 310 320 330 340 350 360 HFDVEIDVKW LNENAVEKVN IKPQVDRYRL KNGRRIILLA EGRLVNLGCA MGHPSFVMSN 370 380 390 400 410 420 SFTNQVMAQI ELWTHPDKYP VGVHFLPKKL DEAVAEAHLG KLNVKLTKLT EKQAQYLGMS 430 CDGPFKPDHY RY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence of full length cDNA for human S-adenosylhomocysteine hydrolase." Coulter-Karis D.E., Hershfield M.S. Ann. Hum. Genet. 53:169-175(1989) [PubMed: 2596825] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ASN-86. Tissue: Placenta.
[2]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." 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. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed: 11780052] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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 and Skin.
[5]	"Limited proteolysis of S-adenosylhomocysteine hydrolase: implications for the three-dimensional structure." Gupta R.A., Yuan C.-S., Ault-Riche D.B., Borchardt R.T. Arch. Biochem. Biophys. 319:365-371(1995) [PubMed: 7786017] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-6; 104-108 AND 198-202.
[6]	Bienvenut W.V., Heiserich L., Gottlieb E. Submitted (MAR-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-34; 95-103; 143-186; 215-226; 336-343 AND 389-405, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, MASS SPECTROMETRY. Tissue: Colon carcinoma.
[7]	"Isozyme and DNA analysis of human S-adenosyl-L-homocysteine hydrolase (AHCY)." Arredondo-Vega F.X., Charlton J.A., Edwards Y.H., Hopkinson D.A., Whitehouse D.B. Ann. Hum. Genet. 53:157-167(1989) [PubMed: 2574561] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 122-432. Tissue: Placenta.
[8]	"Photoaffinity labeling of human placental S-adenosylhomocysteine hydrolase with [2-3H]8-azido-adenosine." Yuan C.S., Borchardt R.T. J. Biol. Chem. 270:16140-16146(1995) [PubMed: 7608178] [Abstract] Cited for: PROTEIN SEQUENCE OF 175-186 AND 319-327.
[9]	"Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes." Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F. J. Proteome Res. 5:3135-3144(2006) [PubMed: 17081065] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[10]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[11]	"Structure determination of selenomethionyl S-adenosylhomocysteine hydrolase using data at a single wavelength." Turner M.A., Yuan C.S., Borchardt R.T., Hershfield M.S., Smith G.D., Howell P.L. Nat. Struct. Biol. 5:369-376(1998) [PubMed: 9586999] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS). Tissue: Placenta.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

M61831 mRNA. Translation: AAA51681.1.
M61832 mRNA. Translation: AAA51682.1.
BT006697 mRNA. Translation: AAP35343.1.
AL356299 Genomic DNA. Translation: CAC09528.1.
BC010018 mRNA. Translation: AAH10018.1.
BC011606 mRNA. Translation: AAH11606.1.

IPI

IPI00012007.

PIR

A43629.

RefSeq

NP_000678.1.

UniGene

Hs.388004

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1A7A	X-ray	2.80	A/B	1-432	[»]
1LI4	X-ray	2.01	A	1-432	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P23526. 8 interactions.

PTM databases

PhosphoSite

P23526.

2-D gel databases

REPRODUCTION-2DPAGE

IPI00012007.

Proteomic databases

PeptideAtlas

P23526.

PRIDE

P23526.

Genome annotation databases

Ensembl

ENSG00000101444. Homo sapiens. [Contig view]

GeneID

191.

KEGG

hsa:191.

Organism-specific databases

GeneCards

GC20M032331.

H-InvDB

HIX0015744.

HGNC

HGNC:343. AHCY.

MIM

180960. gene+phenotype.

Orphanet

88618. Psychomotor retardation due to S-adenosylhomocysteine hydrolase deficiency.

PharmGKB

PA24636.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P23526.

HOVERGEN

P23526.

OMA

P23526. HMRAMKD.

Enzyme and pathway databases

BRENDA

3.3.1.1. 247.

Reactome

REACT_13433. Biological oxidations.

Gene expression databases

ArrayExpress

P23526.

Bgee

P23526.

CleanEx

HS_AHCY.

GermOnline

ENSG00000101444. Homo sapiens.

Family and domain databases

InterPro

IPR000043. Ad_hcy_hydrolase.
IPR015878. Ado_hCys_hydrolase_NAD-bd.
[Graphical view]

Gene3D

G3DSA:3.40.50.1480. Ad_hcy_hydrolase. 1 hit.

PANTHER

PTHR23420. Ad_hcy_hydrolase. 1 hit.

Pfam

PF05221. AdoHcyase. 1 hit.
PF00670. AdoHcyase_NAD. 1 hit.
[Graphical view]

PIRSF

PIRSF001109. Ad_hcy_hydrolase. 1 hit.

TIGRFAMs

TIGR00936. ahcY. 1 hit.

PROSITE

PS00738. ADOHCYASE_1. 1 hit.
PS00739. ADOHCYASE_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

780.

SOURCE

Search...

Entry information

Entry name

SAHH_HUMAN

Accession

Primary (citable) accession number: P23526
Secondary accession number(s): Q96A36

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1991
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 103 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)