Summary: S-adenosyl-L-homocysteine hydrolase
Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.
This is the Wikipedia entry entitled "S-adenosyl-L-homocysteine hydrolase". More...
S-adenosyl-L-homocysteine hydrolase Edit Wikipedia article
S-adenosyl-L-homocysteine hydrolase | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
![]() Structure of S-adenosylhomocysteine hydrolase from rat liver.[1] | |||||||||||
Identifiers | |||||||||||
Symbol | Ad_hcy_hydrolase | ||||||||||
Pfam | PF05221 | ||||||||||
InterPro | IPR000043 | ||||||||||
PROSITE | PDOC00603 | ||||||||||
SCOPe | 1b3r / SUPFAM | ||||||||||
|
AdoHcyase NAD-binding domain | |||||||||
---|---|---|---|---|---|---|---|---|---|
![]() d244e mutant s-adenosylhomocysteine hydrolase refined with noncrystallographic restraints | |||||||||
Identifiers | |||||||||
Symbol | AdoHcyase_NAD | ||||||||
Pfam | PF00670 | ||||||||
Pfam clan | CL0063 | ||||||||
InterPro | IPR015878 | ||||||||
PROSITE | PDOC00603 | ||||||||
SCOPe | 1b3r / SUPFAM | ||||||||
|
S-adenosyl-L-homocysteine hydrolase (EC 3.3.1.1) (AdoHcyase) is an enzyme of the activated methyl cycle, responsible for the reversible hydration of S-adenosyl-L-homocysteine into adenosine and homocysteine.
AdoHcyase is a ubiquitous enzyme which binds and requires NAD+ as a cofactor. AdoHcyase is a highly conserved protein[2] of about 430 to 470 amino acids. The family contains a glycine-rich region in the central part of AdoHcyase; a region thought to be involved in NAD-binding.
AdoHcyase is significantly associated with adenosine deaminase deficiency, which classically manifests in severe combine immunodeficiency (SCID). Accumulated adenosine derivatives, dATPs, irreversibly bind to and inhibit AdoHcyase, promoting the buildup of S-adenosyl-L-homocystine (due to equilibrium constant favors S-adenosyl-L-homocystine), a potent inhibitor of methyl transfer reactions[3].
This protein may use the morpheein model of allosteric regulation.[4]
References
- ^ Hu Y, Komoto J, Huang Y, et al. (June 1999). "Crystal structure of S-adenosylhomocysteine hydrolase from rat liver". Biochemistry. 38 (26): 8323–33. doi:10.1021/bi990332k. PMID 10387078.
- ^ Sganga MW, Aksamit RR, Cantoni GL, Bauer CE (1992). "Mutational and nucleotide sequence analysis of S-adenosyl-L-homocysteine hydrolase from Rhodobacter capsulatus". Proc. Natl. Acad. Sci. U.S.A. 89 (14): 6328–6332. Bibcode:1992PNAS...89.6328S. doi:10.1073/pnas.89.14.6328. PMC 49494. PMID 1631127.
- ^ Hershfield, M S (1979). "In vivo inactivation of erythrocyte S-adenosylhomocysteine hydrolase by 2'-deoxyadenosine in adenosine deaminase-deficient patients". J Clin Invest. 63 (4): 807–811. doi:10.1172/JCI109367. PMC 372019. PMID 312296.
- ^ T. Selwood; E. K. Jaffe. (2011). "Dynamic dissociating homo-oligomers and the control of protein function". Arch. Biochem. Biophys. 519 (2): 131–43. doi:10.1016/j.abb.2011.11.020. PMC 3298769. PMID 22182754.
This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.
This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
S-adenosyl-L-homocysteine hydrolase Provide feedback
No Pfam abstract.
Internal database links
SCOOP: | 2-Hacid_dh_C AdoHcyase_NAD AlaDh_PNT_C IlvN NAD_binding_7 Shikimate_DH THF_DHG_CYH_C TrkA_N |
Similarity to PfamA using HHSearch: | AdoHcyase_NAD TrkA_N 2-Hacid_dh_C IlvN |
External database links
PROSITE: | PDOC00603 |
SCOP: | 1b3r |
This tab holds annotation information from the InterPro database.
InterPro entry IPR000043
Adenosylhomocysteinase (S-adenosyl-L-homocysteine hydrolase, EC) (AdoHcyase) is an enzyme of the activated methyl cycle, responsible for the reversible hydration of S-adenosyl-L-homocysteine into adenosine and homocysteine. This enzyme is ubiquitous, highly conserved, and may play a key role in the regulation of the intracellular concentration of adenosylhomocysteine. AdoHcyase requires NAD+ as a cofactor and contains a central glycine-rich region which is thought to be involved in NAD-binding. Since AdoHyc is a potent inhibitor of S-adenosyl-L-methionine dependent methyltransferases, AdoHycase plays a critical role in the modulation of the activity of various methyltransferases. The enzyme forms homotetramers, with each monomer binding one molecule of NAD+ [PUBMED:9586999,PUBMED:16061414,PUBMED:11325033,PUBMED:15165742].
This family also includes S-adenosylhomocysteine hydrolase-like 1 (Ahcyl1), also known as IRBIT, and S-adenosylhomocysteine hydrolase-like protein 2 (Ahcyl2). Ahcyl1/IRBIT was shown to interact with inositol 1,4,5-trisphosphate receptors (IP3Rs), which function as intracellular Ca(2+) channels, and suppresses IP3 binding of IP3R [PUBMED:16793548, PUBMED:16527252]. By competing with IP3, it modulates the threshold IP3 concentration required for the activation of the receptor [PUBMED:16793548]. Further studies indicate that Ahcyl1/IRBIT is in fact a multifunctional protein that regulates several ion channels and ion transporters [PUBMED:24518248, PUBMED:21152975]. Despite its homology to S-adenosylhomocysteine hydrolases, Ahcyl1 has neither enzyme activity nor any effects on the enzyme activity of S-adenosylhomocysteine hydrolase [PUBMED:12525476]. Ahcyl2 lacks binding activity to IP3R [PUBMED:19220705]. Ahcyl2 upregulates NBCe1-B, which plays an important role in intracellular pH regulation [PUBMED:27382360].
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
Loading domain graphics...
Pfam Clan
This family is a member of clan Form_Glyc_dh (CL0325), which has the following description:
This superfamily includes the catalytic domain of a variety of dehydrogenase enzymes. The domain has a flavodoxin-like fold and contains an inserted Rossman fold NAD-binding domain.
The clan contains the following 4 members:
2-Hacid_dh AdoHcyase AlaDh_PNT_N DpaA_NAlignments
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...
View options
We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
Seed (150) |
Full (11650) |
Representative proteomes | UniProt (43012) |
NCBI (49093) |
Meta (5741) |
||||
---|---|---|---|---|---|---|---|---|---|
RP15 (1712) |
RP35 (5132) |
RP55 (10404) |
RP75 (16982) |
||||||
Jalview | |||||||||
HTML | |||||||||
PP/heatmap | 1 |
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key:
available,
not generated,
— not available.
Format an alignment
Download options
We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.
Seed (150) |
Full (11650) |
Representative proteomes | UniProt (43012) |
NCBI (49093) |
Meta (5741) |
||||
---|---|---|---|---|---|---|---|---|---|
RP15 (1712) |
RP35 (5132) |
RP55 (10404) |
RP75 (16982) |
||||||
Raw Stockholm | |||||||||
Gzipped |
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
HMM logo
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
Trees
This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
Note: You can also download the data file for the tree.
Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
Curation
Seed source: | Pfam-B_157 (release 2.1) |
Previous IDs: | none |
Type: | Domain |
Sequence Ontology: | SO:0000417 |
Author: |
Finn RD |
Number in seed: | 150 |
Number in full: | 11650 |
Average length of the domain: | 277.80 aa |
Average identity of full alignment: | 36 % |
Average coverage of the sequence by the domain: | 94.65 % |
HMM information
HMM build commands: |
build method: hmmbuild -o /dev/null --hand HMM SEED
search method: hmmsearch -Z 47079205 -E 1000 --cpu 4 HMM pfamseq
|
||||||||||||
Model details: |
|
||||||||||||
Model length: | 299 | ||||||||||||
Family (HMM) version: | 18 | ||||||||||||
Download: | download the raw HMM for this family |
Species distribution
Sunburst controls
HideWeight segments by...
Change the size of the sunburst
Colour assignments
![]() |
![]() |
![]() |
![]() |
![]() |
![]() |
![]() |
![]() |
Selections
Align selected sequences to HMM
Generate a FASTA-format file
Clear selection
This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...
Tree controls
HideThe tree shows the occurrence of this domain across different species. More...
Loading...
Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.
Interactions
Structures
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the AdoHcyase domain has been found. There are 328 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
Loading structure mapping...