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Protein

S-adenosylhomocysteine hydrolase-like protein 1

Gene

Ahcyl1

Organism
Mus musculus (Mouse)
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 (PubMed:12525476, PubMed:23542070). Also activates basolateral SLC4A4 isoform 1 to coordinate fluid and HCO3- secretion (PubMed:19224921). Inhibits the effect of STK39 on SLC4A4 and CFTR by recruiting PP1 phosphatase which activates SLC4A4, SLC26A6 and CFTR through dephosphorylation (PubMed:19033647, PubMed:21317537). Mediates the induction of SLC9A3 surface expression produced by Angiotensin-2. 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 (PubMed:12525476).By similarity6 Publications

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.1 Publication

Cofactori

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei155SubstrateBy similarity1
Binding sitei229SubstrateBy similarity1
Binding sitei254SubstrateBy similarity1
Binding sitei284SubstrateBy similarity1
Binding sitei288SubstrateBy similarity1
Binding sitei341NADBy similarity1
Binding sitei376NADBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi318 – 322NADBy similarity5
Nucleotide bindingi397 – 399NADBy similarity3

GO - Molecular functioni

GO - Biological processi

  • angiotensin-activated signaling pathway Source: UniProtKB
  • epithelial fluid transport Source: UniProtKB
  • mRNA polyadenylation Source: MGI
  • one-carbon metabolic process Source: UniProtKB-KW
  • positive regulation of sodium ion transport Source: MGI
  • protein export from nucleus Source: MGI
  • regulation of anion transport Source: MGI
  • regulation of ion transmembrane transporter activity Source: MGI
  • regulation of mRNA 3'-end processing Source: MGI
  • response to calcium ion Source: MGI
  • S-adenosylmethionine cycle Source: GO_Central

Keywordsi

Molecular functionRNA-binding
Biological processOne-carbon metabolism
LigandNAD

Enzyme and pathway databases

ReactomeiR-MMU-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:Ahcyl1
Synonyms:Irbit
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:2385184 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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi42 – 44IQF → AQA: Inhibits SLC4A4 dephosphorylation by PP1 phosphatase and activity. 1 Publication3
Mutagenesisi70 – 73Missing : Inhibits interaction with ITPR1. 1 Publication4
Mutagenesisi73D → R: Inhibits interaction with ITPR1. 1 Publication1
Mutagenesisi82 – 88Missing : Inhibits interaction with ITPR1. 1 Publication7
Mutagenesisi86 – 88DDE → KKK: Does not inhibits interaction with ITPR1. 1 Publication3

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00002303002 – 530S-adenosylhomocysteine hydrolase-like protein 1Add BLAST529

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineBy similarity1
Modified residuei2PhosphoserineBy similarity1
Modified residuei40N6-acetyllysineCombined sources1
Modified residuei68Phosphoserine; by PKDBy similarity1
Modified residuei71PhosphoserineBy similarity1
Modified residuei74PhosphoserineBy similarity1
Modified residuei77PhosphoserineBy similarity1
Modified residuei84PhosphoserineCombined sources1
Modified residuei391PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated at Ser/Thr residues between Ser-68 and Thr-72 in the PEST region: required for interaction with dATP-bound RRM1 and ITPR1. Phosphorylation at Ser-68 by PRKD1 and CAMK4 is required for further phosphorylations by CSNK1A1. Phosphorylation is induced by oxidative stress. Probably phosphorylated by CAMK2A; phosphorylation at Ser-68 may be required for interaction with SLC9A3.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ80SW1
MaxQBiQ80SW1
PaxDbiQ80SW1
PeptideAtlasiQ80SW1
PRIDEiQ80SW1

PTM databases

iPTMnetiQ80SW1
PhosphoSitePlusiQ80SW1
SwissPalmiQ80SW1

Expressioni

Tissue specificityi

Widely expressed (at protein level). Expressed in the lateral and luminal poles of the pancreatic duct (at protein level).3 Publications

Gene expression databases

BgeeiENSMUSG00000027893
CleanExiMM_AHCYL1
ExpressionAtlasiQ80SW1 baseline and differential
GenevisibleiQ80SW1 MM

Interactioni

Subunit structurei

Forms multimers (By similarity). Forms heteromultimers with AHCYL2 (via the C-terminal region) (PubMed:19220705). Interacts (when phosphorylated) with ITPR1 (when not phosphorylated); the interaction suppresses inositol 1,4,5-trisphosphate binding to ITPR1 (PubMed:23542070). Interacts with CFTR and SLC26A6; the interactions take place once AHCYL1 is released from ITPR1 and increase CFTR and SLC26A6 activities (PubMed:19033647, PubMed:21317537, PubMed:23542070). 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 (PubMed:16769890, PubMed:19033647, PubMed:21317537). Interacts (when phosphorylated) with SLC9A3; the interaction is required for SLC9A3 apical location and activity (PubMed:19224921). Interacts (when phosphorylated) with FIP1L1; the interaction is direct and associates AHCYL1 with the CPSF complex and RNA Interacts with PAPOLA (By similarity).By similarity8 Publications

GO - Molecular functioni

Protein-protein interaction databases

CORUMiQ80SW1
IntActiQ80SW1, 1 interactor
MINTiQ80SW1
STRINGi10090.ENSMUSP00000029490

Structurei

3D structure databases

ProteinModelPortaliQ80SW1
SMRiQ80SW1
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni65 – 92PEST1 PublicationAdd BLAST28
Regioni281 – 448NAD bindingBy similarityAdd BLAST168
Regioni520 – 530PDZ-bindingAdd 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 similarity1 Publication

Sequence similaritiesi

Belongs to the adenosylhomocysteinase family.Curated

Phylogenomic databases

eggNOGiKOG1370 Eukaryota
COG0499 LUCA
GeneTreeiENSGT00390000003626
HOGENOMiHOG000227986
HOVERGENiHBG005041
InParanoidiQ80SW1
KOiK01251
OMAiHKPVKKQ
OrthoDBiEOG091G06EB
PhylomeDBiQ80SW1
TreeFamiTF300415

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.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q80SW1-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSMPDAMPLP GVGEELKQAK EIEDAEKYSF MATVTKAPKK QIQFADDMQE
60 70 80 90 100
FTKFPTKTGR RSLSRSISQS STDSYSSAAS YTDSSDDEVS PREKQQTNSK
110 120 130 140 150
GSSNFCVKNI KQAEFGRREI EIAEQDMSAL ISLRKRAQGE KPLAGAKIVG
160 170 180 190 200
CTHITAQTAV LIETLCALGA QCRWSACNIY STQNEVAAAL AEAGVAVFAW
210 220 230 240 250
KGESEDDFWW CIDRCVNMDG WQANMILDDG GDLTHWVYKK YPNVFKKIRG
260 270 280 290 300
IVEESVTGVH RLYQLSKAGK LCVPAMNVND SVTKQKFDNL YCCRESILDG
310 320 330 340 350
LKRTTDVMFG GKQVVVCGYG EVGKGCCAAL KALGAIVYIT EIDPICALQA
360 370 380 390 400
CMDGFRVVKL NEVIRQVDVV ITCTGNKNVV TREHLDRMKN SCIVCNMGHS
410 420 430 440 450
NTEIDVTSLR TPELTWERVR SQVDHVIWPD GKRVVLLAEG RLLNLSCSTV
460 470 480 490 500
PTFVLSITAT TQALALIELY NAPEGRYKQD VYLLPKKMDE YVASLHLPSF
510 520 530
DAHLTELTDD QAKYLGLNKN GPFKPNYYRY
Length:530
Mass (Da):58,951
Last modified:June 1, 2003 - v1
Checksum:i974D23361A245D04
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB092504 mRNA Translation: BAC65166.1
BC018218 mRNA Translation: AAH18218.2
BK000547 mRNA Translation: DAA00059.1
CCDSiCCDS38593.1
RefSeqiNP_663517.2, NM_145542.3
UniGeneiMm.220328

Genome annotation databases

EnsembliENSMUST00000029490; ENSMUSP00000029490; ENSMUSG00000027893
GeneIDi229709
KEGGimmu:229709
UCSCiuc008qxi.1 mouse

Similar proteinsi

Entry informationi

Entry nameiSAHH2_MOUSE
AccessioniPrimary (citable) accession number: Q80SW1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 4, 2006
Last sequence update: June 1, 2003
Last modified: March 28, 2018
This is version 135 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

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