Reviewed, UniProtKB/Swiss-Prot P10760 (SAHH_RAT)

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

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

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 By similarity.
Sequence similarities	Belongs to the adenosylhomocysteinase family.

Ontologies

Keywords
Biological process	One-carbon metabolism
Cellular component	Cytoplasm
Ligand	NAD
Molecular function	Hydrolase
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	S-adenosylhomocysteine catabolic process Ref.7 Inferred from direct assay. Source: RGD chronic inflammatory response to antigenic stimulus Inferred from mutant phenotype. Source: RGD circadian sleep/wake cycle Inferred from direct assay. Source: RGD one-carbon compound metabolic process Inferred from electronic annotation. Source: UniProtKB-KW response to hypoxia Inferred from expression pattern. Source: RGD response to nutrient Inferred from direct assay. Source: RGD
Cellular component	cytosol Inferred from direct assay. Source: RGD melanosome Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from direct assay. Source: RGD synaptosome Inferred from direct assay. Source: RGD
Molecular function	NAD or NADH binding Inferred from direct assay. Source: RGD adenosylhomocysteinase activity Ref.7 Inferred from direct assay. Source: RGD adenyl nucleotide binding Inferred from direct assay. Source: RGD identical protein binding Inferred from direct assay. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 432

431

Adenosylhomocysteinase

PRO_0000116905

Regions

Region

183 – 350

168

NAD binding

Sites

Binding site

57

1

Substrate

Binding site

131

1

Substrate

Binding site

156

1

Substrate

Binding site

186

1

Substrate

Binding site

190

1

Substrate

Experimental info

Mutagenesis

131

1

D → N: Strongly reduces activity. Ref.8

Mutagenesis

186

1

K → N: Strongly reduces activity. Ref.8

Mutagenesis

190

1

D → N: Strongly reduces activity. Ref.8

Mutagenesis

191

1

N → S: Strongly reduces activity. Ref.8

Mutagenesis

245

1

D → E: Changes active site geometry and alters affinity for NAD.

Secondary structure

1

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432

Helix Strand Turn

Details...

Beta strand

8 – 10

3

Turn

12 – 14

3

Helix

15 – 25

11

Helix

26 – 28

3

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

Turn

81 – 83

3

Helix

86 – 94

9

Beta strand

99 – 101

3

Helix

107 – 116

10

Beta strand

127 – 133

7

Helix

134 – 142

9

Helix

144 – 147

4

Beta strand

152 – 155

4

Helix

158 – 169

12

Beta strand

177 – 179

3

Helix

184 – 190

7

Helix

192 – 207

16

Beta strand

215 – 219

5

Helix

223 – 234

12

Beta strand

238 – 242

5

Helix

246 – 253

8

Turn

254 – 256

3

Beta strand

258 – 260

3

Helix

262 – 265

4

Turn

266 – 268

3

Beta strand

270 – 274

5

Beta strand

277 – 279

3

Helix

284 – 287

4

Beta strand

294 – 298

5

Turn

302 – 304

3

Helix

308 – 314

7

Beta strand

315 – 322

8

Beta strand

325 – 330

6

Beta strand

335 – 339

5

Helix

340 – 342

3

Helix

345 – 349

5

Helix

355 – 374

20

Turn

376 – 378

3

Beta strand

381 – 385

5

Helix

388 – 398

11

Turn

399 – 402

4

Helix

411 – 417

7

Beta strand

421 – 423

3

Sequences

	Sequence		Length	Mass (Da)
	P10760-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 93CA5BED07B4FCDE	FASTA	432	47,538
	10 20 30 40 50 60 MADKLPYKVA DIGLAAWGRK ALDIAENEMP GLMRMREMYS ASKPLKGARI AGCLHMTVET 70 80 90 100 110 120 AVLIETLVAL GAEVRWSSCN IFSTQDHAAA AIAKAGIPVF AWKGETDEEY LWCIEQTLHF 130 140 150 160 170 180 KDGPLNMILD DGGDLTNLIH TKHPQLLSGI RGISEETTTG VHNLYKMMAN GILKVPAINV 190 200 210 220 230 240 NDSVTKSKFD NLYGCRESLI DGIKRATDVM IAGKVAVVAG YGDVGKGCAQ ALRGFGARVI 250 260 270 280 290 300 ITEIDPINAL QAAMEGYEVT TMDEACKEGN IFVTTTGCVD IILGRHFEQM KDDAIVCNIG 310 320 330 340 350 360 HFDVEIDVKW LNENAVEKVN IKPQVDRYLL KNGHRIILLA EGRLVNLGCA MGHPSFVMSN 370 380 390 400 410 420 SFTNQVMAQI ELWTHPDKYP VGVHFLPKKL DEAVAEAHLG KLNVKLTKLT EKQAQYLGMP 430 INGPFKPDHY RY

References

[1]	"Amino acid sequence of S-adenosyl-L-homocysteine hydrolase from rat liver as derived from the cDNA sequence." Ogawa H., Gomi T., Mueckler M.M., Fujioka M., Backlund P.S. Jr., Aksamit R.R., Unson C.G., Cantoni G.L. Proc. Natl. Acad. Sci. U.S.A. 84:719-723(1987) [PubMed: 3027698] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
[2]	"The gene and pseudogenes of rat S-adenosyl-L-homocysteine hydrolase." Merta A., Aksamit R.R., Kasir J., Cantoni G.L. Eur. J. Biochem. 229:575-582(1995) [PubMed: 7744082] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: Fischer 344.
[3]	"S-adenosylhomocysteinase from rat liver. Amino acid sequences of the peptides containing active site cysteine residues modified by treatment with 5'-p-fluorosulfonylbenzoyladenosine." Gomi T., Ogawa H., Fujioka M. J. Biol. Chem. 261:13422-13425(1986) [PubMed: 3759971] [Abstract] Cited for: PROTEIN SEQUENCE OF 76-94.
[4]	Lubec G., Afjehi-Sadat L., Diao W. Submitted (APR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 143-151 AND 268-285, MASS SPECTROMETRY. Strain: Sprague-Dawley. Tissue: Hippocampus and Spinal cord.
[5]	"Crystal structure of S-adenosylhomocysteine hydrolase from rat liver." Hu Y., Komoto J., Huang Y., Gomi T., Ogawa H., Takata Y., Fujioka M., Takusagawa F. Biochemistry 38:8323-8333(1999) [PubMed: 10387078] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS). Tissue: Liver.
[6]	"Effects of site-directed mutagenesis on structure and function of recombinant rat liver S-adenosylhomocysteine hydrolase. Crystal structure of D244E mutant enzyme." Komoto J., Huang Y., Gomi T., Ogawa H., Takata Y., Fujioka M., Takusagawa F. J. Biol. Chem. 275:32147-32156(2000) [PubMed: 10913437] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF MUTANT GLU-245.
[7]	"Inhibition of S-adenosylhomocysteine hydrolase by acyclic sugar adenosine analogue D-eritadenine. Crystal structure of S-adenosylhomocysteine hydrolase complexed with D-eritadenine." Huang Y., Komoto J., Takata Y., Powell D.R., Gomi T., Ogawa H., Fujioka M., Takusagawa F. J. Biol. Chem. 277:7477-7482(2002) [PubMed: 11741948] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) IN COMPLEX WITH INHIBITOR.
[8]	"Catalytic mechanism of S-adenosylhomocysteine hydrolase. Site-directed mutagenesis of Asp-130, Lys-185, Asp-189, and Asn-190." Takata Y., Yamada T., Huang Y., Komoto J., Gomi T., Ogawa H., Fujioka M., Takusagawa F. J. Biol. Chem. 277:22670-22676(2002) [PubMed: 11927587] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS), MUTAGENESIS OF ASP-131; LYS-186; ASP-190 AND ASN-191.

Cross-references

Sequence databases

EMBLGenBankDDBJ

M15185 mRNA. Translation: AAA40705.1.
U14937 Genomic DNA. Translation: AAA92043.1.

IPI

IPI00476295.

PIR

A26583.

RefSeq

NP_058897.1.

UniGene

Rn.5878

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1B3R	X-ray	2.80	A/B/C/D	2-432	[»]
1D4F	X-ray	2.80	A/B/C/D	2-432	[»]
1K0U	X-ray	3.00	A/B/C/D/E/F/G/H	2-432	[»]
1KY4	X-ray	2.80	A/B/C/D	2-432	[»]
1KY5	X-ray	2.80	A/B/C/D	2-432	[»]
1XWF	X-ray	2.80	A/B/C/D	2-431	[»]
2H5L	X-ray	2.80	A/B/C/D/E/F/G/H	2-431	[»]

ModBase

Search...

Proteomic databases

PRIDE

P10760.

Genome annotation databases

Ensembl

ENSRNOG00000017777. Rattus norvegicus. [Contig view]

GeneID

29443.

KEGG

rno:29443.

NMPDR

fig|10116.3.peg.20074.

Organism-specific databases

RGD

69260. Ahcy.

Phylogenomic databases

HOVERGEN

P10760.

OMA

P10760. HMRAMKD.

Enzyme and pathway databases

BioCyc

MetaCyc:MON-8582.

BRENDA

3.3.1.1. 248.

Gene expression databases

ArrayExpress

P10760.

GermOnline

ENSRNOG00000017777. Rattus norvegicus.

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

609197.

Entry information

Entry name

SAHH_RAT

Accession

Primary (citable) accession number: P10760

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 97 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)