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Protein

Adenosylhomocysteinase 2

Gene

Ahcyl1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Multifaceted cellular regulator which coordinates several essential cellular functions including regulation of epithelial HCO3- and fluid secretion, mRNA processing and DNA replication. Regulates ITPR1 sensitivity to inositol 1,4,5-trisphosphate competing for the common binding site and acting as endogenous 'pseudoligand' whose inhibitory activity can be modulated by its phosphorylation status. In the pancreatic and salivary ducts, at resting state, attenuates inositol 1,4,5-trisphosphate-induced calcium release by interacting with ITPR1 (By similarity). When extracellular stimuli induce ITPR1 phosphorylation or inositol 1,4,5-trisphosphate production, dissociates of ITPR1 to interact with CFTR and SLC26A6 mediating their synergistic activation by calcium and cAMP that stimulates the epithelial secretion of electrolytes and fluid (By similarity). Also activates basolateral SLC4A4 isoform 1 to coordinate fluid and HCO3- secretion (By similarity). Inhibits the effect of STK39 on SLC4A4 and CFTR by recruiting PP1 phosphatase which activates SLC4A4, SLC26A6 and CFTR through dephosphorylation (By similarity). Mediates the induction of SLC9A3 surface expression produced by Angiotensin-2 (PubMed:20584908). Depending on the cell type, activates SLC9A3 in response to calcium or reverses SLC9A3R2-dependent calcium inhibition. May modulate the polyadenylation state of specific mRNAs, both by controlling the subcellular location of FIP1L1 and by inhibiting PAPOLA activity, in response to a stimulus that alters its phosphorylation state. Acts as a (dATP)-dependent inhibitor of ribonucleotide reductase large subunit RRM1, controlling the endogenous dNTP pool and ensuring normal cell cycle progression (By similarity).By similarity1 Publication

Catalytic activityi

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

Cofactori

NAD+By similarityNote: Binds 1 NAD+ per subunit.By similarity

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 2 (Ahcyl1), Adenosylhomocysteinase (Ahcyl2), Adenosylhomocysteinase (Ahcy), Adenosylhomocysteinase (Ahcy)
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 sitei108SubstrateBy similarity1
Binding sitei182SubstrateBy similarity1
Binding sitei207SubstrateBy similarity1
Binding sitei237SubstrateBy similarity1
Binding sitei241SubstrateBy similarity1
Binding sitei294NADBy similarity1
Binding sitei329NADBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi271 – 275NADBy similarity5
Nucleotide bindingi350 – 352NADBy similarity3

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

One-carbon metabolism

Keywords - Ligandi

NAD, RNA-binding

Enzyme and pathway databases

ReactomeiR-RNO-5578775. Ion homeostasis.
UniPathwayiUPA00314; UER00076.

Names & Taxonomyi

Protein namesi
Recommended name:
Adenosylhomocysteinase 2 (EC:3.3.1.1)
Short name:
AdoHcyase 2
Alternative name(s):
IP3R-binding protein released with inositol 1,4,5-trisphosphate
S-adenosyl-L-homocysteine hydrolase 2
S-adenosylhomocysteine hydrolase-like protein 1
Gene namesi
Name:Ahcyl1Imported
Synonyms:Irbit1 Publication
OrganismiRattus norvegicus (Rat)Imported
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 2

Organism-specific databases

RGDi1309768. Ahcyl1.

Subcellular locationi

  • Endoplasmic reticulum By similarity
  • Apical cell membrane 1 Publication
  • Cytoplasmcytosol 1 Publication
  • Microsome By similarity

GO - Cellular componenti

  • apical plasma membrane Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • cytosol Source: UniProtKB-SubCell
  • endoplasmic reticulum Source: UniProtKB-SubCell
  • extracellular exosome Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Endoplasmic reticulum, Membrane, Microsome

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004333561 – 483Adenosylhomocysteinase 2Add BLAST483

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei21Phosphoserine; by PKDBy similarity1
Modified residuei37PhosphoserineBy similarity1
Modified residuei344PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated at Ser/Thr residues between Ser-21 and Thr-25 in the PEST region: required for interaction with dATP-bound RRM1 and ITPR1. Phosphorylation at Ser-21 by PRKD1 and CAMK4 is required for further phosphorylations by CSNK1A1. Phosphorylation is induced by oxidative stress. Probably phosphorylated by CAMK2A; phosphorylation at Ser-21 may be required for interaction with SLC9A3.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiB5DFN2.
PRIDEiB5DFN2.

Expressioni

Tissue specificityi

Expressed in kidney proximal tubules and outer medulla (at protein level) (PubMed:20584908).1 Publication

Gene expression databases

BgeeiENSRNOG00000018569.
ExpressionAtlasiB5DFN2. baseline and differential.

Interactioni

Subunit structurei

Forms multimers (By similarity). Forms heteromultimers with AHCYL2 (via the C-terminal region). Interacts (when phosphorylated) with ITPR1 (when not phosphorylated); the interaction suppresses inositol 1,4,5-trisphosphate binding to ITPR1 (By similarity). Interacts with CFTR and SLC26A6; the interactions take place once AHCYL1 is released from ITPR1 and increase CFTR and SLC26A6 activities (By similarity). Interacts with RRM1; in a phosphorylation- and (dATP)-dependent manner. Interacts (via PEST domain when phosphorylated) with SLC4A4 isoform 1 but not isoform 2; the interaction increases SLC4A4 isoform 1 activity. Interacts (when phosphorylated) with SLC9A3; the interaction is required for SLC9A3 apical location and activity (PubMed:20584908). Interacts (when phosphorylated) with FIP1L1; the interaction is direct and associates AHCYL1 with the CPSF complex and RNA. Interacts with PAPOLA (By similarity).By similarity1 Publication

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000059145.

Structurei

3D structure databases

ProteinModelPortaliB5DFN2.
SMRiB5DFN2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni18 – 45PESTBy similarityAdd BLAST28
Regioni234 – 401NAD bindingBy similarityAdd BLAST168
Regioni473 – 483PDZ-bindingBy similarityAdd BLAST11

Domaini

The PEST region is essential for the interaction with ITPR1, and, when phosphorylated, is also the RRM1-binding region. The PDZ-binding region is required for maximal interaction with ITPR1 and is also responsible for the IP3-insensitive interaction with ITPR1 (By similarity).By similarity

Sequence similaritiesi

Belongs to the adenosylhomocysteinase family.Curated

Phylogenomic databases

eggNOGiKOG1370. Eukaryota.
COG0499. LUCA.
GeneTreeiENSGT00390000003626.
HOGENOMiHOG000227986.
HOVERGENiHBG005041.
KOiK01251.
OMAiPVKKQIQ.

Family and domain databases

CDDicd00401. SAHH. 1 hit.
Gene3Di3.40.50.720. 1 hit.
InterProiIPR000043. Adenosylhomocysteinase.
IPR015878. Ado_hCys_hydrolase_NAD-bd.
IPR016040. NAD(P)-bd_dom.
IPR020082. S-Ado-L-homoCys_hydrolase_CS.
[Graphical view]
PANTHERiPTHR23420. PTHR23420. 1 hit.
PfamiPF05221. AdoHcyase. 1 hit.
PF00670. AdoHcyase_NAD. 1 hit.
[Graphical view]
PIRSFiPIRSF001109. Ad_hcy_hydrolase. 1 hit.
SMARTiSM00996. AdoHcyase. 1 hit.
SM00997. AdoHcyase_NAD. 1 hit.
[Graphical view]
SUPFAMiSSF51735. SSF51735. 1 hit.
TIGRFAMsiTIGR00936. ahcY. 1 hit.
PROSITEiPS00738. ADOHCYASE_1. 1 hit.
PS00739. ADOHCYASE_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

B5DFN2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQEFTKFPTK TGRRSLSRSI SQSSTDSYSS AASYTDSSDD EVSPREKQQT
60 70 80 90 100
NSKGSSNFCV KNIKQAEFGR REIEIAEQDM SALISLRKRA QGEKPLAGAK
110 120 130 140 150
IVGCTHITAQ TAVLIETLCA LGAQCRWSAC NIYSTQNEVA AALAEAGVAV
160 170 180 190 200
FAWKGESEDD FWWCIDRCVN MDGWQANMIL DDGGDLTHWV YKKYPNVFKK
210 220 230 240 250
IRGIVEESVT GVHRLYQLSK AGKLCVPAMN VNDSVTKQKF DNLYCCRESI
260 270 280 290 300
LDGLKRTTDV MFGGKQVVVC GYGEVGKGCC AALKALGAIV YITEIDPICA
310 320 330 340 350
LQACMDGFRV VKLNEVIRQV DVVITCTGNK NVVTREHLDR MKNSCIVCNM
360 370 380 390 400
GHSNTEIDVT SLRTPELTWE RVRSQVDHVI WPDGKRVVLL AEGRLLNLSC
410 420 430 440 450
STVPTFVLSI TATTQALALI ELYNAPEGRY KQDVYLLPKK MDEYVASLHL
460 470 480
PSFDAHLTEL TDDQAKYLGL NKNGPFKPNY YRY
Length:483
Mass (Da):53,753
Last modified:June 24, 2015 - v2
Checksum:i18DFC7E74697E1D4
GO

Sequence cautioni

The sequence EDL81885 differs from that shown. Reason: Erroneous gene model prediction.Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR06019878 Genomic DNA. No translation available.
CH473952 Genomic DNA. Translation: EDL81885.1. Sequence problems.
BC169126 mRNA. Translation: AAI69126.1.
RefSeqiNP_001102031.1. NM_001108561.1.
XP_006233227.1. XM_006233165.1.
XP_006233228.1. XM_006233166.3.
XP_008759627.1. XM_008761405.2.
UniGeneiRn.17493.

Genome annotation databases

EnsembliENSRNOT00000079993; ENSRNOP00000072856; ENSRNOG00000018569.
GeneIDi362013.
KEGGirno:362013.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR06019878 Genomic DNA. No translation available.
CH473952 Genomic DNA. Translation: EDL81885.1. Sequence problems.
BC169126 mRNA. Translation: AAI69126.1.
RefSeqiNP_001102031.1. NM_001108561.1.
XP_006233227.1. XM_006233165.1.
XP_006233228.1. XM_006233166.3.
XP_008759627.1. XM_008761405.2.
UniGeneiRn.17493.

3D structure databases

ProteinModelPortaliB5DFN2.
SMRiB5DFN2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000059145.

Proteomic databases

PaxDbiB5DFN2.
PRIDEiB5DFN2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000079993; ENSRNOP00000072856; ENSRNOG00000018569.
GeneIDi362013.
KEGGirno:362013.

Organism-specific databases

CTDi10768.
RGDi1309768. Ahcyl1.

Phylogenomic databases

eggNOGiKOG1370. Eukaryota.
COG0499. LUCA.
GeneTreeiENSGT00390000003626.
HOGENOMiHOG000227986.
HOVERGENiHBG005041.
KOiK01251.
OMAiPVKKQIQ.

Enzyme and pathway databases

UniPathwayiUPA00314; UER00076.
ReactomeiR-RNO-5578775. Ion homeostasis.

Miscellaneous databases

PROiB5DFN2.

Gene expression databases

BgeeiENSRNOG00000018569.
ExpressionAtlasiB5DFN2. baseline and differential.

Family and domain databases

CDDicd00401. SAHH. 1 hit.
Gene3Di3.40.50.720. 1 hit.
InterProiIPR000043. Adenosylhomocysteinase.
IPR015878. Ado_hCys_hydrolase_NAD-bd.
IPR016040. NAD(P)-bd_dom.
IPR020082. S-Ado-L-homoCys_hydrolase_CS.
[Graphical view]
PANTHERiPTHR23420. PTHR23420. 1 hit.
PfamiPF05221. AdoHcyase. 1 hit.
PF00670. AdoHcyase_NAD. 1 hit.
[Graphical view]
PIRSFiPIRSF001109. Ad_hcy_hydrolase. 1 hit.
SMARTiSM00996. AdoHcyase. 1 hit.
SM00997. AdoHcyase_NAD. 1 hit.
[Graphical view]
SUPFAMiSSF51735. SSF51735. 1 hit.
TIGRFAMsiTIGR00936. ahcY. 1 hit.
PROSITEiPS00738. ADOHCYASE_1. 1 hit.
PS00739. ADOHCYASE_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSAHH2_RAT
AccessioniPrimary (citable) accession number: B5DFN2
Secondary accession number(s): D4A5X8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 24, 2015
Last sequence update: June 24, 2015
Last modified: November 30, 2016
This is version 52 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. 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.