dbPAF Protein Information


Tag Content
dbPAF ID dbPAF-0001666
Uniprot Accession O43865; SAHH2_HUMAN; B4E168; Q2TAJ6; Q502W8; Q5VSM0; Q6P171; Q96PK4; Q9UG84;
Genbank Protein ID NP_001229602.1; NP_001229603.1; NP_001229604.1; NP_001229605.1; NP_006612.2;
Genbank Nucleotide ID NM_001242673.1; NM_001242674.1; NM_001242675.1; NM_001242676.1; NM_006621.5;
Protein Name Adenosylhomocysteinase 2
Protein Synonyms/Alias
Gene Name AHCYL1
Gene Synonyms/Alias DCAL;IRBIT;XPVKONA;
Organism Homo sapiens(Human)
NCBI Taxa ID 9606
Functional Description
(View all)
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 (PubMed:16793548). 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 (PubMed:16769890). 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 (PubMed:18829453). 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 (PubMed:19224921). Acts as a (dATP)-dependent inhibitor of ribonucleotide reductase large subunit RRM1, controlling the endogenous dNTP pool and ensuring normal cell cycle progression (PubMed:25237103).
Phosphorylation Sites
dbPAF PTMs: 26 (View all)
PositionPeptidesSourceReferences ( PMIDs )
2------MSMPDAMPLdbPTM 3.0;HPRD 9;PhosphoSitePlus;UniProt;curated20068231; 21406692; 16381945; 23193290; 18988627; 22135298;
28EIEDAEKYSFMATVTdbPTM 3.0;Phospho.ELM 9.0;HPRD 9;PhosphoSitePlus;SysPTM 2.0;curated15951569; 16381945; 23193290; 17016520; 18180459; 18707149;
29IEDAEKYSFMATVTKdbPTM 3.0;PhosphoSitePlus;SysPTM 2.018707149; 16381945; 23193290; 22135298; 19366988
35YSFMATVTKAPKKQIPhosphoSitePlus22135298
64KTGRRSLSRSISQSSPhosphoSitePlus22135298
66GRRSLSRSISQSSTDPhosphoSitePlus22135298
68RSLSRSISQSSTDSYdbPTM 3.0;PhosphoSitePlus;UniProt;curated19220705; 16381945; 23193290; 22135298; 16793548; 23090842;
70LSRSISQSSTDSYSSPhosphoSitePlus;curated22135298; 23090842
71SRSISQSSTDSYSSAdbPTM 3.0;PhosphoSitePlus;UniProt;curated19220705; 16381945; 23193290; 22135298; 16793548; 22817900
72RSISQSSTDSYSSAAPhosphoSitePlus22135298
74ISQSSTDSYSSAASYdbPTM 3.0;PhosphoSitePlus;UniProt;curated19220705; 16381945; 23193290; 22135298; 22817900
77SSTDSYSSAASYTDSdbPTM 3.0;PhosphoSitePlus;UniProt;curated19220705; 16381945; 23193290; 22135298; 22817900
82YSSAASYTDSSDDEVPhosphoSitePlus22135298
84SAASYTDSSDDEVSPPhosphoSitePlus22135298
257GIVEESVTGVHRLYQPhosphoSitePlus22135298
263VTGVHRLYQLSKAGKPhosphoSitePlus22135298
283MNVNDSVTKQKFDNLHPRD 9;curated20068231; 18988627
372RQVDVVITCTGNKNVPhosphoSitePlus22135298
374VDVVITCTGNKNVVTPhosphoSitePlus22135298
391HLDRMKNSCIVCNMGdbPTM 3.0;Phospho.ELM 9.0;HPRD 9;PhosphoPep 2.0;PhosphoSitePlus;SysPTM 2.0;UniProt18669648; 16381945; 23193290; 18988627; 19060867; 22135298;
Sequence
(Fasta)
MSMPDAMPLP GVGEELKQAK EIEDAEKYSF MATVTKAPKK QIQFADDMQE FTKFPTKTGR 60
RSLSRSISQS STDSYSSAAS YTDSSDDEVS PREKQQTNSK GSSNFCVKNI KQAEFGRREI 120
EIAEQDMSAL ISLRKRAQGE KPLAGAKIVG CTHITAQTAV LIETLCALGA QCRWSACNIY 180
STQNEVAAAL AEAGVAVFAW KGESEDDFWW CIDRCVNMDG WQANMILDDG GDLTHWVYKK 240
YPNVFKKIRG IVEESVTGVH RLYQLSKAGK LCVPAMNVND SVTKQKFDNL YCCRESILDG 300
LKRTTDVMFG GKQVVVCGYG EVGKGCCAAL KALGAIVYIT EIDPICALQA CMDGFRVVKL 360
NEVIRQVDVV ITCTGNKNVV TREHLDRMKN SCIVCNMGHS NTEIDVTSLR TPELTWERVR 420
SQVDHVIWPD GKRVVLLAEG RLLNLSCSTV PTFVLSITAT TQALALIELY NAPEGRYKQD 480
VYLLPKKMDE YVASLHLPSF DAHLTELTDD QAKYLGLNKN GPFKPNYYRY 531
Keyword

KW-0002--3D-structure
KW-0007--Acetylation
KW-0025--Alternative splicing
KW-1003--Cell membrane
KW-0181--Complete proteome
KW-0963--Cytoplasm
KW-0256--Endoplasmic reticulum
KW-0378--Hydrolase
KW-0472--Membrane
KW-0492--Microsome
KW-0520--NAD
KW-0554--One-carbon metabolism
KW-0597--Phosphoprotein
KW-1185--Reference proteome
KW-0694--RNA-binding

Interpro

IPR000043--Adenosylhomocysteinase
IPR015878--Ado_hCys_hydrolase_NAD-bd
IPR016040--NAD(P)-bd_dom
IPR020082--S-Ado-L-homoCys_hydrolase_CS

PROSITE

PS00738--ADOHCYASE_1
PS00739--ADOHCYASE_2

Pfam

PF05221--AdoHcyase
PF00670--AdoHcyase_NAD

Gene Ontology

GO:0016324--C:apical plasma membrane
GO:0005737--C:cytoplasm
GO:0005829--C:cytosol
GO:0005783--C:endoplasmic reticulum
GO:0070062--C:extracellular exosome
GO:0016787--F:hydrolase activity
GO:0003723--F:RNA binding
GO:0038166--P:angiotensin-activated signaling pathway
GO:0042045--P:epithelial fluid transport
GO:0006378--P:mRNA polyadenylation
GO:0006730--P:one-carbon metabolic process
GO:0010765--P:positive regulation of sodium ion transport
GO:0006611--P:protein export from nucleus
GO:0044070--P:regulation of anion transport
GO:0032412--P:regulation of ion transmembrane transporter activity
GO:0031440--P:regulation of mRNA 3'-end processing
GO:0051592--P:response to calcium ion
GO:0033353--P:S-adenosylmethionine cycle