SAHH2_HUMAN
ID SAHH2_HUMAN Reviewed; 530 AA.
AC O43865; B4E168; Q2TAJ6; Q502W8; Q5VSM0; Q6P171; Q96PK4; Q9UG84;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 04-APR-2006, sequence version 2.
DT 03-AUG-2022, entry version 202.
DE RecName: Full=S-adenosylhomocysteine hydrolase-like protein 1 {ECO:0000312|HGNC:HGNC:344};
DE AltName: Full=DC-expressed AHCY-like molecule;
DE AltName: Full=IP(3)Rs binding protein released with IP(3);
DE Short=IRBIT;
DE AltName: Full=Putative adenosylhomocysteinase 2;
DE AltName: Full=S-adenosyl-L-homocysteine hydrolase 2;
DE Short=AdoHcyase 2;
GN Name=AHCYL1 {ECO:0000312|HGNC:HGNC:344};
GN Synonyms=DCAL, IRBIT, XPVKONA {ECO:0000312|HGNC:HGNC:344};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=11904675; DOI=10.1007/s00251-001-0402-z;
RA Dekker J.W., Budhia S., Angel N.Z., Cooper B.J., Clark G.J., Hart D.N.,
RA Kato M.;
RT "Identification of an S-adenosylhomocysteine hydrolase-like transcript
RT induced during dendritic cell differentiation.";
RL Immunogenetics 53:993-1001(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Kidney, and Thalamus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 48-251 (ISOFORM 2).
RC TISSUE=Brain, Colon, Eye, Placenta, PNS, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 16-530 (ISOFORM 1).
RC TISSUE=Skin;
RA Volpe J.P.G., McDowell M., Jostes R.F., Afzal V., Sadinski W., Trask B.J.,
RA Legerski R., Cleaver J.E.;
RT "Complementation of chromosomal instability in the xeroderma pigmentosum
RT variant by a gene on human chromosome 1 with homology to S-adenosyl
RT homocysteine hydrolase.";
RL Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 48-164 (ISOFORM 2).
RC TISSUE=Chondrocyte;
RX PubMed=12878157; DOI=10.1016/s0014-4827(03)00130-7;
RA Imabayashi H., Mori T., Gojo S., Kiyono T., Sugiyama T., Irie R.,
RA Isogai T., Hata J., Toyama Y., Umezawa A.;
RT "Redifferentiation of dedifferentiated chondrocytes and chondrogenesis of
RT human bone marrow stromal cells via chondrosphere formation with expression
RT profiling by large-scale cDNA analysis.";
RL Exp. Cell Res. 288:35-50(2003).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 48-105 (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=7782076; DOI=10.1016/0888-7543(95)80096-5;
RA Pawlak A., Toussaint C., Levy I., Bulle F., Poyard M., Barouki R.,
RA Guellaen G.;
RT "Characterization of a large population of mRNAs from human testis.";
RL Genomics 26:151-158(1995).
RN [10]
RP IDENTIFICATION (ISOFORM 2).
RX PubMed=16754674; DOI=10.1074/jbc.m602520200;
RA Cooper B.J., Key B., Carter A., Angel N.Z., Hart D.N.J., Kato M.;
RT "Suppression and overexpression of adenosylhomocysteine hydrolase-like
RT protein 1 (AHCYL1) influences zebrafish embryo development: a possible role
RT for AHCYL1 in inositol phospholipid signaling.";
RL J. Biol. Chem. 281:22471-22484(2006).
RN [11]
RP FUNCTION, SUBUNIT, INTERACTION WITH ITPR1, PHOSPHORYLATION AT SER-68 AND
RP SER-71, AND MUTAGENESIS OF SER-64; SER-66; SER-68; SER-70; SER-71; THR-72;
RP SER-74; SER-76; SER-77; SER-80; THR-82; SER-84; SER-85; SER-90 AND THR-97.
RX PubMed=16793548; DOI=10.1016/j.molcel.2006.05.017;
RA Ando H., Mizutani A., Kiefer H., Tsuzurugi D., Michikawa T., Mikoshiba K.;
RT "IRBIT suppresses IP3 receptor activity by competing with IP3 for the
RT common binding site on the IP3 receptor.";
RL Mol. Cell 22:795-806(2006).
RN [12]
RP FUNCTION, INTERACTION WITH SLC4A4, AND MUTAGENESIS OF THR-52; THR-58;
RP SER-62; SER-64; SER-66; SER-68; SER-70; SER-71; THR-72; SER-74; SER-76;
RP SER-77; SER-80; THR-82; SER-84; SER-85; SER-90 AND THR-97.
RX PubMed=16769890; DOI=10.1073/pnas.0602250103;
RA Shirakabe K., Priori G., Yamada H., Ando H., Horita S., Fujita T.,
RA Fujimoto I., Mizutani A., Seki G., Mikoshiba K.;
RT "IRBIT, an inositol 1,4,5-trisphosphate receptor-binding protein,
RT specifically binds to and activates pancreas-type Na+/HCO3-cotransporter 1
RT (pNBC1).";
RL Proc. Natl. Acad. Sci. U.S.A. 103:9542-9547(2006).
RN [13]
RP FUNCTION, AND INTERACTION WITH SLC9A3.
RX PubMed=18829453; DOI=10.1074/jbc.m805534200;
RA He P., Zhang H., Yun C.C.;
RT "IRBIT, inositol 1,4,5-triphosphate (IP3) receptor-binding protein released
RT with IP3, binds Na+/H+ exchanger NHE3 and activates NHE3 activity in
RT response to calcium.";
RL J. Biol. Chem. 283:33544-33553(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-391, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [15]
RP FUNCTION, INTERACTION WITH FIP1L1 AND PAPOLA, RNA-BINDING, AND MUTAGENESIS
RP OF SER-62; SER-64; SER-66; SER-68; SER-70; SER-71; THR-72; SER-74; SER-76;
RP SER-77; SER-80; THR-82; SER-84; SER-85; SER-90 AND THR-97.
RX PubMed=19224921; DOI=10.1074/jbc.m807136200;
RA Kiefer H., Mizutani A., Iemura S., Natsume T., Ando H., Kuroda Y.,
RA Mikoshiba K.;
RT "Inositol 1,4,5-triphosphate receptor-binding protein released with
RT inositol 1,4,5-triphosphate (IRBIT) associates with components of the mRNA
RT 3' processing machinery in a phosphorylation-dependent manner and inhibits
RT polyadenylation.";
RL J. Biol. Chem. 284:10694-10705(2009).
RN [16]
RP INTERACTION WITH AHCYL2 AND ITPR1, AND PHOSPHORYLATION AT SER-68; SER-71;
RP SER-74 AND SER-77.
RX PubMed=19220705; DOI=10.1111/j.1471-4159.2009.05979.x;
RA Ando H., Mizutani A., Mikoshiba K.;
RT "An IRBIT homologue lacks binding activity to inositol 1,4,5-trisphosphate
RT receptor due to the unique N-terminal appendage.";
RL J. Neurochem. 109:539-550(2009).
RN [17]
RP FUNCTION, INTERACTION WITH SLC9A3, AND MUTAGENESIS OF SER-68; SER-71 AND
RP SER-74.
RX PubMed=20584908; DOI=10.1074/jbc.m110.133066;
RA He P., Klein J., Yun C.C.;
RT "Activation of Na+/H+ exchanger NHE3 by angiotensin II is mediated by
RT inositol 1,4,5-triphosphate (IP3) receptor-binding protein released with
RT IP3 (IRBIT) and Ca2+/calmodulin-dependent protein kinase II.";
RL J. Biol. Chem. 285:27869-27878(2010).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [19]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE
RP ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [20]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 (ISOFORM 2), AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [22]
RP FUNCTION, INTERACTION WITH BCL2L10 AND ITPR1, SUBCELLULAR LOCATION,
RP PHOSPHORYLATION AT SER-68; SER-71; SER-74 AND SER-77, DEPHOSPHORYLATION,
RP AND MUTAGENESIS OF SER-68.
RX PubMed=27995898; DOI=10.7554/elife.19896;
RA Bonneau B., Ando H., Kawaai K., Hirose M., Takahashi-Iwanaga H.,
RA Mikoshiba K.;
RT "IRBIT controls apoptosis by interacting with the Bcl-2 homolog, Bcl2l10,
RT and by promoting ER-mitochondria contact.";
RL Elife 5:e19896-e19896(2016).
RN [23]
RP INTERACTION WITH ZCCHC4.
RX PubMed=31799605; DOI=10.1093/nar/gkz1147;
RA Pinto R., Vaagboe C.B., Jakobsson M.E., Kim Y., Baltissen M.P.,
RA O'Donohue M.F., Guzman U.H., Malecki J.M., Wu J., Kirpekar F., Olsen J.V.,
RA Gleizes P.E., Vermeulen M., Leidel S.A., Slupphaug G., Falnes P.O.;
RT "The human methyltransferase ZCCHC4 catalyses N6-methyladenosine
RT modification of 28S ribosomal RNA.";
RL Nucleic Acids Res. 48:830-846(2020).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.64 ANGSTROMS) OF 89-530 OF MUTANT ALA-508 IN
RP COMPLEX WITH NAD, COFACTOR, FUNCTION, INTERACTION WITH RRM1, MISCELLANEOUS,
RP PEST REGION, AND PHOSPHORYLATION.
RX PubMed=25237103; DOI=10.1126/science.1251550;
RA Arnaoutov A., Dasso M.;
RT "Enzyme regulation. IRBIT is a novel regulator of ribonucleotide reductase
RT in higher eukaryotes.";
RL Science 345:1512-1515(2014).
CC -!- FUNCTION: Multifaceted cellular regulator which coordinates several
CC essential cellular functions including regulation of epithelial HCO3(-)
CC and fluid secretion, mRNA processing and DNA replication. Regulates
CC ITPR1 sensitivity to inositol 1,4,5-trisphosphate, competing for the
CC common binding site and acting as endogenous 'pseudoligand' whose
CC inhibitory activity can be modulated by its phosphorylation status.
CC Promotes the formation of contact points between the endoplasmic
CC reticulum (ER) and mitochondria, facilitating transfer of Ca(2+) from
CC the ER to mitochondria (PubMed:27995898). Under normal cellular
CC conditions, functions cooperatively with BCL2L10 to limit ITPR1-
CC mediated Ca(2+) release but, under apoptotic stress conditions,
CC dephosphorylated which promotes dissociation of both AHCYL1 and BCL2L10
CC from mitochondria-associated endoplasmic reticulum membranes, inhibits
CC BCL2L10 interaction with ITPR1 and leads to increased Ca(2+) transfer
CC to mitochondria which promotes apoptosis (PubMed:27995898). In the
CC pancreatic and salivary ducts, at resting state, attenuates inositol
CC 1,4,5-trisphosphate-induced calcium release by interacting with ITPR1
CC (PubMed:16793548). When extracellular stimuli induce ITPR1
CC phosphorylation or inositol 1,4,5-trisphosphate production, dissociates
CC from ITPR1 to interact with CFTR and SLC26A6, mediating their
CC synergistic activation by calcium and cAMP that stimulates the
CC epithelial secretion of electrolytes and fluid (By similarity). Also
CC activates basolateral SLC4A4 isoform 1 to coordinate fluid and HCO3(-)
CC secretion (PubMed:16769890). Inhibits the effect of STK39 on SLC4A4 and
CC CFTR by recruiting PP1 phosphatase which activates SLC4A4, SLC26A6 and
CC CFTR through dephosphorylation (By similarity). Mediates the induction
CC of SLC9A3 surface expression produced by Angiotensin-2
CC (PubMed:20584908). Depending on the cell type, activates SLC9A3 in
CC response to calcium or reverses SLC9A3R2-dependent calcium inhibition
CC (PubMed:18829453). May modulate the polyadenylation state of specific
CC mRNAs, both by controlling the subcellular location of FIP1L1 and by
CC inhibiting PAPOLA activity, in response to a stimulus that alters its
CC phosphorylation state (PubMed:19224921). Acts as a (dATP)-dependent
CC inhibitor of ribonucleotide reductase large subunit RRM1, controlling
CC the endogenous dNTP pool and ensuring normal cell cycle progression
CC (PubMed:25237103). In vitro does not exhibit any S-adenosyl-L-
CC homocysteine hydrolase activity (By similarity).
CC {ECO:0000250|UniProtKB:B5DFN2, ECO:0000250|UniProtKB:Q80SW1,
CC ECO:0000269|PubMed:16769890, ECO:0000269|PubMed:16793548,
CC ECO:0000269|PubMed:18829453, ECO:0000269|PubMed:19224921,
CC ECO:0000269|PubMed:20584908, ECO:0000269|PubMed:25237103,
CC ECO:0000269|PubMed:27995898}.
CC -!- COFACTOR:
CC Name=NAD(+); Xref=ChEBI:CHEBI:57540;
CC Evidence={ECO:0000269|PubMed:25237103};
CC Note=Binds 1 NAD(+) per subunit. {ECO:0000269|PubMed:25237103};
CC -!- SUBUNIT: Forms multimers (PubMed:16793548). Forms heteromultimers with
CC AHCYL2 (via the C-terminal region) (PubMed:19220705). Interacts (when
CC phosphorylated) with ITPR1 (when not phosphorylated); the interaction
CC suppresses inositol 1,4,5-trisphosphate binding to ITPR1
CC (PubMed:16793548, PubMed:27995898). Interacts with BCL2L10; this
CC strengthens the interaction of AHCYL1 with ITPR1 (PubMed:27995898).
CC Interacts with CFTR and SLC26A6; the interactions take place once
CC AHCYL1 is released from ITPR1 and increase CFTR and SLC26A6 activities
CC (By similarity). Interacts with RRM1; in a phosphorylation- and (dATP)-
CC dependent manner. Interacts (via PEST domain when phosphorylated) with
CC SLC4A4 isoform 1 but not isoform 2; the interaction increases SLC4A4
CC isoform 1 activity (PubMed:16769890). Interacts (when phosphorylated)
CC with SLC9A3; the interaction is required for SLC9A3 apical location and
CC activity (PubMed:18829453, PubMed:20584908). Interacts (when
CC phosphorylated) with FIP1L1; the interaction is direct and associates
CC AHCYL1 with the CPSF complex and RNA (PubMed:19224921). Interacts with
CC PAPOLA (PubMed:19224921). Interacts with ZCCHC4 (PubMed:31799605).
CC {ECO:0000250|UniProtKB:B5DFN2, ECO:0000250|UniProtKB:Q80SW1,
CC ECO:0000269|PubMed:16769890, ECO:0000269|PubMed:16793548,
CC ECO:0000269|PubMed:18829453, ECO:0000269|PubMed:19220705,
CC ECO:0000269|PubMed:19224921, ECO:0000269|PubMed:20584908,
CC ECO:0000269|PubMed:25237103, ECO:0000269|PubMed:27995898,
CC ECO:0000269|PubMed:31799605}.
CC -!- INTERACTION:
CC O43865; O43865: AHCYL1; NbExp=5; IntAct=EBI-2371423, EBI-2371423;
CC O43865; Q9HD36: BCL2L10; NbExp=4; IntAct=EBI-2371423, EBI-2126349;
CC O43865; P55957: BID; NbExp=3; IntAct=EBI-2371423, EBI-519672;
CC O43865; P55957-2: BID; NbExp=3; IntAct=EBI-2371423, EBI-10215147;
CC O43865; P42773: CDKN2C; NbExp=10; IntAct=EBI-2371423, EBI-711290;
CC O43865; Q9UI36-2: DACH1; NbExp=10; IntAct=EBI-2371423, EBI-10186082;
CC O43865; P55040: GEM; NbExp=8; IntAct=EBI-2371423, EBI-744104;
CC O43865; P09105: HBQ1; NbExp=6; IntAct=EBI-2371423, EBI-10193656;
CC O43865; Q96MH2: HEXIM2; NbExp=4; IntAct=EBI-2371423, EBI-5460660;
CC O43865; P17066: HSPA6; NbExp=3; IntAct=EBI-2371423, EBI-355106;
CC O43865; Q14643: ITPR1; NbExp=3; IntAct=EBI-2371423, EBI-465548;
CC O43865; Q8TAC2: JOSD2; NbExp=4; IntAct=EBI-2371423, EBI-12205593;
CC O43865; Q5S007: LRRK2; NbExp=3; IntAct=EBI-2371423, EBI-5323863;
CC O43865; P43356: MAGEA2B; NbExp=3; IntAct=EBI-2371423, EBI-5650739;
CC O43865; P50222: MEOX2; NbExp=3; IntAct=EBI-2371423, EBI-748397;
CC O43865; Q8NCR3: MFI; NbExp=3; IntAct=EBI-2371423, EBI-744790;
CC O43865; Q8N323: NXPE1; NbExp=3; IntAct=EBI-2371423, EBI-25834085;
CC O43865; Q8N2W9: PIAS4; NbExp=3; IntAct=EBI-2371423, EBI-473160;
CC O43865; O94827-4: PLEKHG5; NbExp=3; IntAct=EBI-2371423, EBI-11980215;
CC O43865; O14829: PPEF1; NbExp=3; IntAct=EBI-2371423, EBI-2931238;
CC O43865; O60437: PPL; NbExp=3; IntAct=EBI-2371423, EBI-368321;
CC O43865; Q9NQX0: PRDM6; NbExp=3; IntAct=EBI-2371423, EBI-11320284;
CC O43865; O00233: PSMD9; NbExp=3; IntAct=EBI-2371423, EBI-750973;
CC O43865; A0A0S2Z4G9: RNF6; NbExp=3; IntAct=EBI-2371423, EBI-16428950;
CC O43865; Q9UHI7: SLC23A1; NbExp=3; IntAct=EBI-2371423, EBI-1759386;
CC O43865; Q9UHI7-3: SLC23A1; NbExp=3; IntAct=EBI-2371423, EBI-11998660;
CC O43865; Q02978: SLC25A11; NbExp=3; IntAct=EBI-2371423, EBI-359174;
CC O43865; O94993: SOX30; NbExp=3; IntAct=EBI-2371423, EBI-742973;
CC O43865; P48775: TDO2; NbExp=3; IntAct=EBI-2371423, EBI-743494;
CC O43865; Q9BZF9: UACA; NbExp=3; IntAct=EBI-2371423, EBI-350510;
CC O43865; P49910: ZNF165; NbExp=3; IntAct=EBI-2371423, EBI-741694;
CC O43865; Q53Z40: ZNF165; NbExp=5; IntAct=EBI-2371423, EBI-10186058;
CC O43865; P04608: tat; Xeno; NbExp=5; IntAct=EBI-2371423, EBI-6164389;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000269|PubMed:27995898}. Cytoplasm, cytosol
CC {ECO:0000269|PubMed:27995898}. Apical cell membrane
CC {ECO:0000250|UniProtKB:B5DFN2}; Peripheral membrane protein
CC {ECO:0000305}. Microsome {ECO:0000250|UniProtKB:Q80SW1}.
CC Note=Associates with membranes when phosphorylated, probably through
CC interaction with ITPR1 (By similarity). Localizes to mitochondria-
CC associated endoplasmic reticulum membranes (MAMs) (PubMed:27995898).
CC Localization to MAMs is greatly reduced under apoptotic stress
CC conditions (PubMed:27995898). {ECO:0000250|UniProtKB:Q80SW1,
CC ECO:0000269|PubMed:27995898}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O43865-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O43865-2; Sequence=VSP_021751;
CC -!- TISSUE SPECIFICITY: Expressed in dendritic cells.
CC {ECO:0000269|PubMed:11904675}.
CC -!- DEVELOPMENTAL STAGE: Expression increases markedly during activation of
CC blood and skin DC (Langerhans cells), but is diminished in terminally
CC differentiated tonsil DC. {ECO:0000269|PubMed:11904675}.
CC -!- DOMAIN: The PEST region is essential for the interaction with ITPR1,
CC and, when phosphorylated, is also the RRM1-binding region. The PDZ-
CC binding region is required for maximal interaction with ITPR1 and is
CC also responsible for the IP3-insensitive interaction with ITPR1 (By
CC similarity). {ECO:0000250|UniProtKB:Q80SW1,
CC ECO:0000269|PubMed:25237103}.
CC -!- PTM: Phosphorylated at Ser/Thr residues between Ser-68 and Thr-72 in
CC the PEST region: required for interaction with dATP-bound RRM1 and
CC ITPR1. Phosphorylation at Ser-68 by PRKD1 and CAMK4 is required for
CC further phosphorylations by CSNK1A1 (PubMed:16793548). Phosphorylation
CC is induced by oxidative stress (PubMed:19224921). Probably
CC phosphorylated by CAMK2A; phosphorylation at Ser-68 may be required for
CC interaction with SLC9A3 (PubMed:20584908). Dephosphorylated in response
CC to apoptotic stress conditions which causes translocation of both
CC AHCYL1 and BCL2L10 from mitochondria-associated endoplasmic reticulum
CC membranes and promotes apoptosis (PubMed:27995898).
CC {ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:19224921,
CC ECO:0000269|PubMed:25237103, ECO:0000269|PubMed:27995898,
CC ECO:0000305|PubMed:20584908}.
CC -!- MISCELLANEOUS: Ablation of expression in HeLa cells causes imbalanced
CC dNTP pools and altered cell cycle progression.
CC {ECO:0000269|PubMed:25237103}.
CC -!- SIMILARITY: Belongs to the adenosylhomocysteinase family.
CC {ECO:0000305}.
CC -!- CAUTION: In spite of its similarity with AHCY, which catalyzes the
CC reversible hydrolysis of S-adenosyl-L-homocysteine to adenosine and
CC homocysteine, recombinant AHCYL1 expressed in bacteria shows no
CC hydrolase activity, nor does it affect the enzyme activity of AHCY.
CC {ECO:0000250|UniProtKB:Q80SW1}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC01960.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BI460083; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAB43223.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF315687; AAL26869.1; -; mRNA.
DR EMBL; AL036027; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK303690; BAG64680.1; -; mRNA.
DR EMBL; AK316110; BAH14481.1; -; mRNA.
DR EMBL; AL049954; CAB43223.2; ALT_INIT; mRNA.
DR EMBL; AL772411; CAH70965.1; -; Genomic_DNA.
DR EMBL; AL772411; CAH70966.1; -; Genomic_DNA.
DR EMBL; CH471122; EAW56426.1; -; Genomic_DNA.
DR EMBL; BC007576; AAH07576.3; -; mRNA.
DR EMBL; BC010681; AAH10681.3; -; mRNA.
DR EMBL; BC016942; AAH16942.3; -; mRNA.
DR EMBL; BC065254; AAH65254.2; -; mRNA.
DR EMBL; BC095476; AAH95476.2; -; mRNA.
DR EMBL; BC110896; AAI10897.2; -; mRNA.
DR EMBL; BI460083; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; U82761; AAC01960.1; ALT_INIT; mRNA.
DR EMBL; AU279527; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; T19009; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BK005418; DAA05763.1; -; mRNA.
DR EMBL; BK005417; DAA05762.1; -; mRNA.
DR CCDS; CCDS55620.1; -. [O43865-2]
DR CCDS; CCDS818.1; -. [O43865-1]
DR PIR; T08681; T08681.
DR RefSeq; NP_001229602.1; NM_001242673.1. [O43865-2]
DR RefSeq; NP_001229603.1; NM_001242674.1. [O43865-2]
DR RefSeq; NP_001229604.1; NM_001242675.1. [O43865-2]
DR RefSeq; NP_001229605.1; NM_001242676.1. [O43865-2]
DR RefSeq; NP_006612.2; NM_006621.5. [O43865-1]
DR PDB; 3MTG; X-ray; 2.64 A; A/B=89-530.
DR PDBsum; 3MTG; -.
DR AlphaFoldDB; O43865; -.
DR SMR; O43865; -.
DR BioGRID; 115987; 301.
DR IntAct; O43865; 90.
DR MINT; O43865; -.
DR STRING; 9606.ENSP00000358814; -.
DR BindingDB; O43865; -.
DR ChEMBL; CHEMBL3751646; -.
DR iPTMnet; O43865; -.
DR MetOSite; O43865; -.
DR PhosphoSitePlus; O43865; -.
DR BioMuta; AHCYL1; -.
DR EPD; O43865; -.
DR jPOST; O43865; -.
DR MassIVE; O43865; -.
DR MaxQB; O43865; -.
DR PaxDb; O43865; -.
DR PeptideAtlas; O43865; -.
DR PRIDE; O43865; -.
DR ProteomicsDB; 49211; -. [O43865-1]
DR ProteomicsDB; 49212; -. [O43865-2]
DR Antibodypedia; 33777; 183 antibodies from 28 providers.
DR DNASU; 10768; -.
DR Ensembl; ENST00000359172.3; ENSP00000352092.3; ENSG00000168710.18. [O43865-2]
DR Ensembl; ENST00000369799.10; ENSP00000358814.5; ENSG00000168710.18. [O43865-1]
DR Ensembl; ENST00000393614.8; ENSP00000377238.4; ENSG00000168710.18. [O43865-2]
DR GeneID; 10768; -.
DR KEGG; hsa:10768; -.
DR MANE-Select; ENST00000369799.10; ENSP00000358814.5; NM_006621.7; NP_006612.2.
DR UCSC; uc001dyx.4; human. [O43865-1]
DR CTD; 10768; -.
DR DisGeNET; 10768; -.
DR GeneCards; AHCYL1; -.
DR HGNC; HGNC:344; AHCYL1.
DR HPA; ENSG00000168710; Tissue enhanced (brain).
DR MIM; 607826; gene.
DR neXtProt; NX_O43865; -.
DR OpenTargets; ENSG00000168710; -.
DR PharmGKB; PA24637; -.
DR VEuPathDB; HostDB:ENSG00000168710; -.
DR eggNOG; KOG1370; Eukaryota.
DR GeneTree; ENSGT00950000182981; -.
DR HOGENOM; CLU_025194_2_1_1; -.
DR InParanoid; O43865; -.
DR OMA; PVGRYKQ; -.
DR PhylomeDB; O43865; -.
DR TreeFam; TF300415; -.
DR PathwayCommons; O43865; -.
DR Reactome; R-HSA-112043; PLC beta mediated events.
DR Reactome; R-HSA-1489509; DAG and IP3 signaling.
DR Reactome; R-HSA-2029485; Role of phospholipids in phagocytosis.
DR Reactome; R-HSA-2871809; FCERI mediated Ca+2 mobilization.
DR Reactome; R-HSA-422356; Regulation of insulin secretion.
DR Reactome; R-HSA-5218921; VEGFR2 mediated cell proliferation.
DR Reactome; R-HSA-5578775; Ion homeostasis.
DR Reactome; R-HSA-5607763; CLEC7A (Dectin-1) induces NFAT activation.
DR Reactome; R-HSA-9664323; FCGR3A-mediated IL10 synthesis.
DR Reactome; R-HSA-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
DR SignaLink; O43865; -.
DR SIGNOR; O43865; -.
DR BioGRID-ORCS; 10768; 264 hits in 1078 CRISPR screens.
DR ChiTaRS; AHCYL1; human.
DR EvolutionaryTrace; O43865; -.
DR GeneWiki; AHCYL1; -.
DR GenomeRNAi; 10768; -.
DR Pharos; O43865; Tchem.
DR PRO; PR:O43865; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O43865; protein.
DR Bgee; ENSG00000168710; Expressed in lateral globus pallidus and 218 other tissues.
DR ExpressionAtlas; O43865; baseline and differential.
DR Genevisible; O43865; HS.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0044233; C:mitochondria-associated endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0038166; P:angiotensin-activated signaling pathway; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IMP:UniProtKB.
DR GO; GO:0042045; P:epithelial fluid transport; IEA:Ensembl.
DR GO; GO:1990456; P:mitochondrion-endoplasmic reticulum membrane tethering; IMP:UniProtKB.
DR GO; GO:0006378; P:mRNA polyadenylation; IDA:UniProtKB.
DR GO; GO:0006730; P:one-carbon metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0010765; P:positive regulation of sodium ion transport; IMP:UniProtKB.
DR GO; GO:0006611; P:protein export from nucleus; IEA:Ensembl.
DR GO; GO:0044070; P:regulation of anion transport; IEA:Ensembl.
DR GO; GO:0032412; P:regulation of ion transmembrane transporter activity; IMP:UniProtKB.
DR GO; GO:0031440; P:regulation of mRNA 3'-end processing; IDA:UniProtKB.
DR GO; GO:0051592; P:response to calcium ion; IDA:UniProtKB.
DR GO; GO:0033353; P:S-adenosylmethionine cycle; IBA:GO_Central.
DR CDD; cd00401; SAHH; 1.
DR Gene3D; 3.40.50.1480; -; 3.
DR InterPro; IPR042172; Adenosylhomocyst_ase-like_sf.
DR InterPro; IPR000043; Adenosylhomocysteinase-like.
DR InterPro; IPR015878; Ado_hCys_hydrolase_NAD-bd.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020082; S-Ado-L-homoCys_hydrolase_CS.
DR PANTHER; PTHR23420; PTHR23420; 1.
DR Pfam; PF05221; AdoHcyase; 1.
DR Pfam; PF00670; AdoHcyase_NAD; 1.
DR PIRSF; PIRSF001109; Ad_hcy_hydrolase; 1.
DR SMART; SM00996; AdoHcyase; 1.
DR SMART; SM00997; AdoHcyase_NAD; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR00936; ahcY; 1.
DR PROSITE; PS00738; ADOHCYASE_1; 1.
DR PROSITE; PS00739; ADOHCYASE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell membrane; Cytoplasm;
KW Endoplasmic reticulum; Membrane; Microsome; NAD; One-carbon metabolism;
KW Phosphoprotein; Reference proteome; RNA-binding.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:21406692"
FT CHAIN 2..530
FT /note="S-adenosylhomocysteine hydrolase-like protein 1"
FT /id="PRO_0000116908"
FT REGION 53..103
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 65..92
FT /note="PEST"
FT /evidence="ECO:0000269|PubMed:25237103"
FT REGION 138..201
FT /note="Interaction with BCL2L10"
FT /evidence="ECO:0000269|PubMed:27995898"
FT REGION 281..448
FT /note="NAD binding"
FT /evidence="ECO:0000250"
FT REGION 520..530
FT /note="PDZ-binding"
FT /evidence="ECO:0000250"
FT COMPBIAS 55..85
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 155
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 229
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 254
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 284
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 288
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 318..322
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:25237103"
FT BINDING 341
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:25237103"
FT BINDING 376
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:25237103"
FT BINDING 397..399
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:25237103"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 40
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q80SW1"
FT MOD_RES 68
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:27995898,
FT ECO:0000305|PubMed:16793548, ECO:0000305|PubMed:19220705"
FT MOD_RES 71
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:27995898,
FT ECO:0000305|PubMed:16793548, ECO:0000305|PubMed:19220705"
FT MOD_RES 74
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:27995898,
FT ECO:0000305|PubMed:19220705"
FT MOD_RES 77
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:27995898,
FT ECO:0000305|PubMed:19220705"
FT MOD_RES 84
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80SW1"
FT MOD_RES 391
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT VAR_SEQ 1..47
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12878157,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:17974005, ECO:0000303|PubMed:7782076"
FT /id="VSP_021751"
FT MUTAGEN 52
FT /note="T->A: No effect on interaction with SLC4A4."
FT /evidence="ECO:0000269|PubMed:16769890"
FT MUTAGEN 58
FT /note="T->A: No effect on interaction with SLC4A4."
FT /evidence="ECO:0000269|PubMed:16769890"
FT MUTAGEN 62
FT /note="S->A: No effect on interaction with SLC4A4. No
FT effect on interaction with FIP1L1."
FT /evidence="ECO:0000269|PubMed:16769890,
FT ECO:0000269|PubMed:19224921"
FT MUTAGEN 64
FT /note="S->A: No effect on interaction with ITPR1. No effect
FT on phosphorylation. No effect on interaction with SLC4A4.
FT No effect on interaction with FIP1L1."
FT /evidence="ECO:0000269|PubMed:16769890,
FT ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:19224921"
FT MUTAGEN 66
FT /note="S->A: Slightly decreases interaction with ITPR1.
FT Slightly decreases phosphorylation. No effect on
FT interaction with SLC4A4. Abolishes interaction with
FT FIP1L1."
FT /evidence="ECO:0000269|PubMed:16769890,
FT ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:19224921"
FT MUTAGEN 68
FT /note="S->A: Highly decreases phosphorylation. Abolishes
FT interaction with ITPR1. No effect on interaction with
FT BCL2L10. Marked decrease in interaction of BCL2L10 with
FT ITPR1. Decreased ability of BCL2L10 to reduce ITPR1-
FT mediated calcium release and to prevent apoptosis. No
FT effect on formation of multimers. Abolishes interaction
FT with SLC4A4. Abolishes interaction with FIP1L1. Highly
FT decreases interaction with SLC9A3. Highly decreases
FT interaction with SLC9A3; when associated with A-71 and A-
FT 74."
FT /evidence="ECO:0000269|PubMed:16769890,
FT ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:19224921,
FT ECO:0000269|PubMed:20584908, ECO:0000269|PubMed:27995898"
FT MUTAGEN 70
FT /note="S->A: Highly decreases interaction with ITPR1. No
FT effect on phosphorylation. No effect on interaction with
FT SLC4A4. Abolishes interaction with FIP1L1."
FT /evidence="ECO:0000269|PubMed:16769890,
FT ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:19224921"
FT MUTAGEN 71
FT /note="S->A: Abolishes interaction with ITPR1. Highly
FT decreases phosphorylation. Abolishes interaction with
FT SLC4A4. Abolishes interaction with FIP1L1. Highly decreases
FT interaction with SLC9A3; when associated with A-68 and A-
FT 74."
FT /evidence="ECO:0000269|PubMed:16769890,
FT ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:19224921,
FT ECO:0000269|PubMed:20584908"
FT MUTAGEN 72
FT /note="T->A: Highly decreases interaction with ITPR1.
FT Slightly increases phosphorylation. No effect on
FT interaction with SLC4A4. Highly decreases interaction with
FT FIP1L1."
FT /evidence="ECO:0000269|PubMed:16769890,
FT ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:19224921"
FT MUTAGEN 74
FT /note="S->G: Abolishes interaction with ITPR1. Slightly
FT decreases phosphorylation. Strongly decreases interaction
FT with SLC4A4. Abolishes interaction with FIP1L1. Highly
FT decreases interaction with SLC9A3; when associated with A-
FT 68 and A-71."
FT /evidence="ECO:0000269|PubMed:16769890,
FT ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:19224921,
FT ECO:0000269|PubMed:20584908"
FT MUTAGEN 76
FT /note="S->G: No effect on interaction with ITPR1. No effect
FT on phosphorylation. No effect on interaction with SLC4A4.
FT No effect on interaction with FIP1L1."
FT /evidence="ECO:0000269|PubMed:16769890,
FT ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:19224921"
FT MUTAGEN 77
FT /note="S->A: Highly decreases interaction with ITPR1.
FT Slightly decreases phosphorylation. Strongly decreases
FT interaction with SLC4A4. Abolishes interaction with
FT FIP1L1."
FT /evidence="ECO:0000269|PubMed:16769890,
FT ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:19224921"
FT MUTAGEN 80
FT /note="S->A: No effect on interaction with SLC4A4. Highly
FT decreases interaction with FIP1L1."
FT /evidence="ECO:0000269|PubMed:16769890,
FT ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:19224921"
FT MUTAGEN 82
FT /note="T->A: No effect on interaction with ITPR1. No effect
FT on phosphorylation. No effect on interaction with SLC4A4.
FT Decreases interaction with FIP1L1."
FT /evidence="ECO:0000269|PubMed:16769890,
FT ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:19224921"
FT MUTAGEN 84
FT /note="S->A: Slightly decreases interaction with ITPR1. No
FT effect on phosphorylation. No effect on interaction with
FT SLC4A4. Decreases interaction with FIP1L1."
FT /evidence="ECO:0000269|PubMed:16769890,
FT ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:19224921"
FT MUTAGEN 85
FT /note="S->A: Slightly decreases interaction with ITPR1. No
FT effect on phosphorylation. No effect on interaction with
FT SLC4A4. Decreases interaction with FIP1L1."
FT /evidence="ECO:0000269|PubMed:16769890,
FT ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:19224921"
FT MUTAGEN 90
FT /note="S->A: No effect on interaction with ITPR1. No effect
FT on phosphorylation. No effect on interaction with SLC4A4.
FT No effect on interaction with FIP1L1."
FT /evidence="ECO:0000269|PubMed:16769890,
FT ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:19224921"
FT MUTAGEN 97
FT /note="T->A: No effect on interaction with ITPR1. No effect
FT on interaction with SLC4A4. No effect on interaction with
FT FIP1L1."
FT /evidence="ECO:0000269|PubMed:16769890,
FT ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:19224921"
FT CONFLICT 94
FT /note="K -> M (in Ref. 9; T19009)"
FT /evidence="ECO:0000305"
FT CONFLICT 99
FT /note="S -> F (in Ref. 9; T19009)"
FT /evidence="ECO:0000305"
FT HELIX 113..124
FT /evidence="ECO:0007829|PDB:3MTG"
FT HELIX 128..137
FT /evidence="ECO:0007829|PDB:3MTG"
FT TURN 142..145
FT /evidence="ECO:0007829|PDB:3MTG"
FT STRAND 147..152
FT /evidence="ECO:0007829|PDB:3MTG"
FT HELIX 156..167
FT /evidence="ECO:0007829|PDB:3MTG"
FT STRAND 171..175
FT /evidence="ECO:0007829|PDB:3MTG"
FT STRAND 177..180
FT /evidence="ECO:0007829|PDB:3MTG"
FT HELIX 184..193
FT /evidence="ECO:0007829|PDB:3MTG"
FT STRAND 196..198
FT /evidence="ECO:0007829|PDB:3MTG"
FT HELIX 205..216
FT /evidence="ECO:0007829|PDB:3MTG"
FT STRAND 224..231
FT /evidence="ECO:0007829|PDB:3MTG"
FT HELIX 232..240
FT /evidence="ECO:0007829|PDB:3MTG"
FT HELIX 242..245
FT /evidence="ECO:0007829|PDB:3MTG"
FT STRAND 249..253
FT /evidence="ECO:0007829|PDB:3MTG"
FT HELIX 256..265
FT /evidence="ECO:0007829|PDB:3MTG"
FT TURN 266..269
FT /evidence="ECO:0007829|PDB:3MTG"
FT STRAND 275..277
FT /evidence="ECO:0007829|PDB:3MTG"
FT HELIX 282..293
FT /evidence="ECO:0007829|PDB:3MTG"
FT HELIX 299..305
FT /evidence="ECO:0007829|PDB:3MTG"
FT STRAND 313..317
FT /evidence="ECO:0007829|PDB:3MTG"
FT HELIX 321..333
FT /evidence="ECO:0007829|PDB:3MTG"
FT STRAND 336..340
FT /evidence="ECO:0007829|PDB:3MTG"
FT HELIX 344..352
FT /evidence="ECO:0007829|PDB:3MTG"
FT HELIX 360..362
FT /evidence="ECO:0007829|PDB:3MTG"
FT TURN 363..366
FT /evidence="ECO:0007829|PDB:3MTG"
FT STRAND 368..372
FT /evidence="ECO:0007829|PDB:3MTG"
FT HELIX 382..387
FT /evidence="ECO:0007829|PDB:3MTG"
FT STRAND 392..396
FT /evidence="ECO:0007829|PDB:3MTG"
FT TURN 400..403
FT /evidence="ECO:0007829|PDB:3MTG"
FT HELIX 406..409
FT /evidence="ECO:0007829|PDB:3MTG"
FT STRAND 415..420
FT /evidence="ECO:0007829|PDB:3MTG"
FT STRAND 423..427
FT /evidence="ECO:0007829|PDB:3MTG"
FT STRAND 433..437
FT /evidence="ECO:0007829|PDB:3MTG"
FT HELIX 438..440
FT /evidence="ECO:0007829|PDB:3MTG"
FT HELIX 444..446
FT /evidence="ECO:0007829|PDB:3MTG"
FT HELIX 452..471
FT /evidence="ECO:0007829|PDB:3MTG"
FT STRAND 479..482
FT /evidence="ECO:0007829|PDB:3MTG"
FT HELIX 486..496
FT /evidence="ECO:0007829|PDB:3MTG"
FT HELIX 497..500
FT /evidence="ECO:0007829|PDB:3MTG"
FT HELIX 509..514
FT /evidence="ECO:0007829|PDB:3MTG"
FT STRAND 519..521
FT /evidence="ECO:0007829|PDB:3MTG"
FT MOD_RES O43865-2:1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
SQ SEQUENCE 530 AA; 58951 MW; 974D23361A245D04 CRC64;
MSMPDAMPLP GVGEELKQAK EIEDAEKYSF MATVTKAPKK QIQFADDMQE FTKFPTKTGR
RSLSRSISQS STDSYSSAAS YTDSSDDEVS PREKQQTNSK GSSNFCVKNI KQAEFGRREI
EIAEQDMSAL ISLRKRAQGE KPLAGAKIVG CTHITAQTAV LIETLCALGA QCRWSACNIY
STQNEVAAAL AEAGVAVFAW KGESEDDFWW CIDRCVNMDG WQANMILDDG GDLTHWVYKK
YPNVFKKIRG IVEESVTGVH RLYQLSKAGK LCVPAMNVND SVTKQKFDNL YCCRESILDG
LKRTTDVMFG GKQVVVCGYG EVGKGCCAAL KALGAIVYIT EIDPICALQA CMDGFRVVKL
NEVIRQVDVV ITCTGNKNVV TREHLDRMKN SCIVCNMGHS NTEIDVTSLR TPELTWERVR
SQVDHVIWPD GKRVVLLAEG RLLNLSCSTV PTFVLSITAT TQALALIELY NAPEGRYKQD
VYLLPKKMDE YVASLHLPSF DAHLTELTDD QAKYLGLNKN GPFKPNYYRY
