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Protein

S-adenosylhomocysteine hydrolase-like protein 1

Gene

Ahcyl1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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). In vitro does not exhibit any S-adenosyl-L-homocysteine hydrolase activity (By similarity).By similarity1 Publication

Caution

In spite of its similarity with AHCY, which catalyzes the reversible hydrolysis of S-adenosyl-L-homocysteine to adenosine and homocysteine, recombinant AHCYL1 expressed in bacteria shows no hydrolysase activity, nor does it affect the enzyme activity of AHCY.By similarity

Cofactori

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

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

Keywordsi

Molecular functionRNA-binding
Biological processOne-carbon metabolism
LigandNAD

Enzyme and pathway databases

ReactomeiR-RNO-5578775 Ion homeostasis

Names & Taxonomyi

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

Organism-specific databases

RGDi1309768 Ahcyl1

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

Cell membrane, Cytoplasm, Endoplasmic reticulum, Membrane, Microsome

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004333561 – 483S-adenosylhomocysteine hydrolase-like protein 1Add BLAST483

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei21Phosphoserine; by PKDBy similarity1
Modified residuei24PhosphoserineBy similarity1
Modified residuei27PhosphoserineBy similarity1
Modified residuei30PhosphoserineBy 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

GO - Molecular functioni

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
OMAiHKPVKKQ

Family and domain databases

CDDicd00401 SAHH, 1 hit
InterProiView protein in InterPro
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

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

Similar proteinsi

Entry informationi

Entry nameiSAHH2_RAT
AccessioniPrimary (citable) accession number: B5DFN2
Secondary accession number(s): D4A5X8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 24, 2015
Last sequence update: June 24, 2015
Last modified: May 23, 2018
This is version 61 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

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