CAPAM_HUMAN
ID CAPAM_HUMAN Reviewed; 704 AA.
AC Q9H4Z3; E1P5P1; Q54AB9; Q9NT85;
DT 06-DEC-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=mRNA (2'-O-methyladenosine-N(6)-)-methyltransferase;
DE EC=2.1.1.62 {ECO:0000269|PubMed:30467178, ECO:0000269|PubMed:30487554, ECO:0000269|PubMed:31279658, ECO:0000269|PubMed:31279659, ECO:0000269|PubMed:33428944};
DE AltName: Full=Cap-specific adenosine methyltransferase {ECO:0000303|PubMed:30467178};
DE Short=CAPAM {ECO:0000303|PubMed:30467178};
DE Short=hCAPAM {ECO:0000303|PubMed:30467178};
DE AltName: Full=Phosphorylated CTD-interacting factor 1 {ECO:0000303|PubMed:12565871};
DE Short=hPCIF1 {ECO:0000303|Ref.17};
DE AltName: Full=Protein phosphatase 1 regulatory subunit 121;
GN Name=PCIF1 {ECO:0000303|PubMed:12565871, ECO:0000312|HGNC:HGNC:16200};
GN Synonyms=C20orf67 {ECO:0000312|HGNC:HGNC:16200},
GN CAPAM {ECO:0000303|PubMed:30467178}, PPP1R121;
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], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP INTERACTION WITH POLR2A.
RC TISSUE=Hepatoma;
RX PubMed=12565871; DOI=10.1016/s0006-291x(02)03015-2;
RA Fan H., Sakuraba K., Komuro A., Kato S., Harada F., Hirose Y.;
RT "PCIF1, a novel human WW domain-containing protein, interacts with the
RT phosphorylated RNA polymerase II.";
RL Biochem. Biophys. Res. Commun. 301:378-385(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Muscle, and Pancreas;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 383-704.
RC TISSUE=Testis;
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 [6]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH POLR2A.
RX PubMed=18294453; DOI=10.1016/j.bbrc.2008.02.042;
RA Hirose Y., Iwamoto Y., Sakuraba K., Yunokuchi I., Harada F., Ohkuma Y.;
RT "Human phosphorylated CTD-interacting protein, PCIF1, negatively modulates
RT gene expression by RNA polymerase II.";
RL Biochem. Biophys. Res. Commun. 369:449-455(2008).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-30, 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 [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-116 AND THR-152, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-116, AND IDENTIFICATION BY
RP 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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-116, AND IDENTIFICATION BY
RP MASS 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 [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF ASN-553 AND PHE-556.
RX PubMed=30487554; DOI=10.1038/s41422-018-0117-4;
RA Sun H., Zhang M., Li K., Bai D., Yi C.;
RT "Cap-specific, terminal N6-methylation by a mammalian m6Am
RT methyltransferase.";
RL Cell Res. 29:80-82(2019).
RN [14]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF 553-SER--PHE-556.
RX PubMed=31279658; DOI=10.1016/j.molcel.2019.06.006;
RA Boulias K., Toczydlowska-Socha D., Hawley B.R., Liberman N., Takashima K.,
RA Zaccara S., Guez T., Vasseur J.J., Debart F., Aravind L., Jaffrey S.R.,
RA Greer E.L.;
RT "Identification of the m6Am methyltransferase PCIF1 reveals the location
RT and functions of m6Am in the transcriptome.";
RL Mol. Cell 0:0-0(2019).
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF 553-SER--PHE-556.
RX PubMed=31279659; DOI=10.1016/j.molcel.2019.05.030;
RA Sendinc E., Valle-Garcia D., Dhall A., Chen H., Henriques T.,
RA Navarrete-Perea J., Sheng W., Gygi S.P., Adelman K., Shi Y.;
RT "PCIF1 catalyzes m6Am mRNA methylation to regulate gene expression.";
RL Mol. Cell 0:0-0(2019).
RN [16]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY
RP REGULATION.
RX PubMed=33428944; DOI=10.1016/j.jbc.2021.100270;
RA Yu D., Kaur G., Blumenthal R.M., Zhang X., Cheng X.;
RT "Enzymatic characterization of three human RNA adenosine methyltransferases
RT reveals diverse substrate affinities and reaction optima.";
RL J. Biol. Chem. 296:100270-100270(2021).
RN [17] {ECO:0007744|PDB:2JX8}
RP STRUCTURE BY NMR OF 40-86.
RA Kouno T., Iwamoto Y., Hirose Y., Aizawa T., Demura M., Kawano K.,
RA Ohkuma Y., Mizuguchi M.;
RT "1H, 13C, and 15N resonance assignments of hPCIF1 WW domain.";
RL Submitted (NOV-2007) to the PDB data bank.
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 174-672 IN COMPLEX WITH
RP S-ADENOSYL-L-METHIONINE, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, INTERACTION WITH POLR2A, AND MUTAGENESIS OF ASN-553.
RX PubMed=30467178; DOI=10.1126/science.aav0080;
RA Akichika S., Hirano S., Shichino Y., Suzuki T., Nishimasu H., Ishitani R.,
RA Sugita A., Hirose Y., Iwasaki S., Nureki O., Suzuki T.;
RT "Cap-specific terminal N6-methylation of RNA by an RNA polymerase II-
RT associated methyltransferase.";
RL Science 0:0-0(2018).
CC -!- FUNCTION: Cap-specific adenosine methyltransferase that catalyzes
CC formation of N(6),2'-O-dimethyladenosine cap (m6A(m)) by methylating
CC the adenosine at the second transcribed position of capped mRNAs
CC (PubMed:30467178, PubMed:30487554, PubMed:31279658, PubMed:31279659,
CC PubMed:33428944). Recruited to the early elongation complex of RNA
CC polymerase II (RNAPII) via interaction with POLR2A and mediates
CC formation of m6A(m) co-transcriptionally (PubMed:30467178).
CC {ECO:0000269|PubMed:30467178, ECO:0000269|PubMed:30487554,
CC ECO:0000269|PubMed:31279658, ECO:0000269|PubMed:31279659,
CC ECO:0000269|PubMed:33428944}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-(2'-O-
CC methyladenosine) in mRNA + S-adenosyl-L-methionine = a 5'-end (N(7)-
CC methyl 5'-triphosphoguanosine)-(N(6),2'-O-dimethyladenosine) in mRNA
CC + H(+) + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:22744, Rhea:RHEA-
CC COMP:11518, Rhea:RHEA-COMP:11519, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:85958,
CC ChEBI:CHEBI:85959; EC=2.1.1.62;
CC Evidence={ECO:0000269|PubMed:30467178, ECO:0000269|PubMed:30487554,
CC ECO:0000269|PubMed:31279658, ECO:0000269|PubMed:31279659,
CC ECO:0000269|PubMed:33428944};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22745;
CC Evidence={ECO:0000269|PubMed:30467178, ECO:0000269|PubMed:30487554,
CC ECO:0000269|PubMed:31279658, ECO:0000269|PubMed:31279659,
CC ECO:0000269|PubMed:33428944};
CC -!- ACTIVITY REGULATION: Cap-specific adenosine methyltransferase activity
CC is inhibited by zinc. {ECO:0000269|PubMed:33428944}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3.5 uM for m7GpppAm {ECO:0000269|PubMed:30467178};
CC KM=82 nM for m7GpppAm oligonucleotide {ECO:0000269|PubMed:31279658};
CC KM=33.4 nM for m7GpppAm capped mRNA {ECO:0000269|PubMed:31279659};
CC KM=28 uM for m7GpppA {ECO:0000269|PubMed:30467178};
CC KM=630 uM for m7GpppA oligonucleotide {ECO:0000269|PubMed:31279658};
CC KM=208 nM for m7GpppAm dinucleotide {ECO:0000269|PubMed:31279659};
CC KM=0.32 uM for capped mRNA analog (at pH 9.4)
CC {ECO:0000269|PubMed:33428944};
CC KM=0.70 uM for S-adenosyl-L-methionine (at pH 9.4)
CC {ECO:0000269|PubMed:33428944};
CC KM=0.30 uM for capped mRNA analog (at pH 8.0)
CC {ECO:0000269|PubMed:33428944};
CC KM=0.65 uM for S-adenosyl-L-methionine (at pH 8.0)
CC {ECO:0000269|PubMed:33428944};
CC KM=1.2 uM for capped mRNA analog (at pH 5.4)
CC {ECO:0000269|PubMed:33428944};
CC KM=0.94 uM for S-adenosyl-L-methionine (at pH 5.4)
CC {ECO:0000269|PubMed:33428944};
CC Note=kcat is 0.036 min(-1) for m7GpppAm capped mRNA
CC (PubMed:31279659). kcat is 0.34 min(-1) for m7GpppAm dinucleotide
CC (PubMed:31279659). kcat is 1.76 min(-1) for capped mRNA analog (at pH
CC 5.4) (PubMed:33428944). kcat is 1.44 min(-1) for S-adenosyl-L-
CC methionine (at pH 5.4) (PubMed:33428944). kcat is 0.67 min(-1) for
CC capped mRNA analog (at pH 8.0) (PubMed:33428944). kcat is 0.63 min(-
CC 1) for S-adenosyl-L-methionine (at pH 8.0) (PubMed:33428944). kcat is
CC 1.18 min(-1) for capped mRNA analog (at pH 9.4) (PubMed:33428944).
CC kcat is 1.68 min(-1) for S-adenosyl-L-methionine (at pH 9.4)
CC (PubMed:33428944). {ECO:0000269|PubMed:31279659,
CC ECO:0000269|PubMed:33428944};
CC -!- SUBUNIT: Interacts with POLR2A; interacts with the phosphorylated C-
CC terminal domain (CTD) of POLR2A. {ECO:0000269|PubMed:12565871,
CC ECO:0000269|PubMed:18294453, ECO:0000269|PubMed:30467178}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12565871,
CC ECO:0000269|PubMed:18294453, ECO:0000269|PubMed:31279659}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:12565871}.
CC -!- DOMAIN: The WW domain is sufficient for direct and specific interaction
CC with the phosphorylated CTD of RNAPII largest subunit.
CC {ECO:0000269|PubMed:12565871}.
CC -!- SIMILARITY: Belongs to the CAPAM family. {ECO:0000305}.
CC -!- CAUTION: The role of N(6),2'-O-dimethyladenosine cap (m6A(m)) on
CC transcripts is unclear and subject to discussion (PubMed:31279658,
CC PubMed:31279659, PubMed:30467178). According to a report, m6A(m)
CC promotes translation of capped mRNAs (PubMed:30467178). In contrast,
CC another study did not observe a clear effect on mRNA translation, but
CC reported an increased stability of a subset of m6A(m) transcripts
CC (PubMed:31279658). According to a third report, m6A(m) inhibits mRNA
CC translation without affecting mRNA stability (PubMed:31279659).
CC {ECO:0000269|PubMed:30467178, ECO:0000269|PubMed:31279658,
CC ECO:0000269|PubMed:31279659}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB050014; BAC45238.1; -; mRNA.
DR EMBL; AL162458; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471077; EAW75778.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW75780.1; -; Genomic_DNA.
DR EMBL; BC013365; AAH13365.1; -; mRNA.
DR EMBL; BC010005; AAH10005.1; -; mRNA.
DR EMBL; AL137473; CAB70757.2; -; mRNA.
DR CCDS; CCDS13388.1; -.
DR RefSeq; NP_071387.1; NM_022104.3.
DR RefSeq; XP_011527282.1; XM_011528980.2.
DR RefSeq; XP_011527283.1; XM_011528981.2.
DR RefSeq; XP_016883502.1; XM_017028013.1.
DR PDB; 2JX8; NMR; -; A=40-86.
DR PDB; 6IRV; X-ray; 2.70 A; A/B=174-672.
DR PDB; 6IRW; X-ray; 2.90 A; A/B=174-672.
DR PDBsum; 2JX8; -.
DR PDBsum; 6IRV; -.
DR PDBsum; 6IRW; -.
DR AlphaFoldDB; Q9H4Z3; -.
DR BMRB; Q9H4Z3; -.
DR SMR; Q9H4Z3; -.
DR BioGRID; 122003; 17.
DR IntAct; Q9H4Z3; 15.
DR MINT; Q9H4Z3; -.
DR STRING; 9606.ENSP00000361486; -.
DR iPTMnet; Q9H4Z3; -.
DR PhosphoSitePlus; Q9H4Z3; -.
DR BioMuta; PCIF1; -.
DR DMDM; 26392546; -.
DR EPD; Q9H4Z3; -.
DR jPOST; Q9H4Z3; -.
DR MassIVE; Q9H4Z3; -.
DR MaxQB; Q9H4Z3; -.
DR PaxDb; Q9H4Z3; -.
DR PeptideAtlas; Q9H4Z3; -.
DR PRIDE; Q9H4Z3; -.
DR ProteomicsDB; 80885; -.
DR Antibodypedia; 27891; 89 antibodies from 18 providers.
DR DNASU; 63935; -.
DR Ensembl; ENST00000372409.8; ENSP00000361486.3; ENSG00000100982.12.
DR GeneID; 63935; -.
DR KEGG; hsa:63935; -.
DR MANE-Select; ENST00000372409.8; ENSP00000361486.3; NM_022104.4; NP_071387.1.
DR UCSC; uc002xqs.4; human.
DR CTD; 63935; -.
DR DisGeNET; 63935; -.
DR GeneCards; PCIF1; -.
DR HGNC; HGNC:16200; PCIF1.
DR HPA; ENSG00000100982; Low tissue specificity.
DR MIM; 618626; gene.
DR neXtProt; NX_Q9H4Z3; -.
DR OpenTargets; ENSG00000100982; -.
DR PharmGKB; PA162398977; -.
DR VEuPathDB; HostDB:ENSG00000100982; -.
DR eggNOG; ENOG502QVT7; Eukaryota.
DR GeneTree; ENSGT00390000016206; -.
DR HOGENOM; CLU_014369_0_0_1; -.
DR InParanoid; Q9H4Z3; -.
DR OMA; VWCYPIQ; -.
DR OrthoDB; 1523233at2759; -.
DR PhylomeDB; Q9H4Z3; -.
DR TreeFam; TF350163; -.
DR PathwayCommons; Q9H4Z3; -.
DR SignaLink; Q9H4Z3; -.
DR BioGRID-ORCS; 63935; 25 hits in 1093 CRISPR screens.
DR ChiTaRS; PCIF1; human.
DR EvolutionaryTrace; Q9H4Z3; -.
DR GenomeRNAi; 63935; -.
DR Pharos; Q9H4Z3; Tbio.
DR PRO; PR:Q9H4Z3; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9H4Z3; protein.
DR Bgee; ENSG00000100982; Expressed in mucosa of stomach and 161 other tissues.
DR ExpressionAtlas; Q9H4Z3; baseline and differential.
DR Genevisible; Q9H4Z3; HS.
DR GO; GO:0045171; C:intercellular bridge; IDA:HPA.
DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0016422; F:mRNA (2'-O-methyladenosine-N6-)-methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0099122; F:RNA polymerase II C-terminal domain binding; IDA:UniProtKB.
DR GO; GO:1990269; F:RNA polymerase II C-terminal domain phosphoserine binding; IDA:FlyBase.
DR GO; GO:1904047; F:S-adenosyl-L-methionine binding; IDA:UniProtKB.
DR GO; GO:0080009; P:mRNA methylation; IDA:UniProtKB.
DR GO; GO:0017148; P:negative regulation of translation; IDA:UniProtKB.
DR GO; GO:0045727; P:positive regulation of translation; IMP:UniProtKB.
DR CDD; cd00201; WW; 1.
DR Gene3D; 1.20.1270.10; -; 1.
DR InterPro; IPR029048; HSP70_C_sf.
DR InterPro; IPR039881; PCIF1-like.
DR InterPro; IPR022035; PCIF1_WW.
DR InterPro; IPR001202; WW_dom.
DR InterPro; IPR036020; WW_dom_sf.
DR PANTHER; PTHR21727; PTHR21727; 1.
DR Pfam; PF12237; PCIF1_WW; 1.
DR Pfam; PF00397; WW; 1.
DR SMART; SM00456; WW; 1.
DR SUPFAM; SSF51045; SSF51045; 1.
DR PROSITE; PS50020; WW_DOMAIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Methyltransferase; Nucleus; Phosphoprotein;
KW Reference proteome; Transferase.
FT CHAIN 1..704
FT /note="mRNA (2'-O-methyladenosine-N(6)-)-methyltransferase"
FT /id="PRO_0000076087"
FT DOMAIN 43..77
FT /note="WW"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT REGION 1..33
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 88..151
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 663..704
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 109..113
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOTIF 669..684
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 1..32
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 136..151
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 666..685
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 686..704
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 235
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A0A0R4IKJ1"
FT BINDING 265
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A0A0R4IKJ1"
FT BINDING 553..556
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:30467178,
FT ECO:0007744|PDB:6IRW"
FT BINDING 558
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A0A0R4IKJ1"
FT BINDING 588..592
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A0A0R4IKJ1"
FT BINDING 614..616
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:30467178,
FT ECO:0007744|PDB:6IRW"
FT MOD_RES 30
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 116
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 152
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MUTAGEN 553..556
FT /note="NPPF->APPA,SPPG: Abolishes formation of N(6),2'-O-
FT dimethyladenosine cap (m6A(m))."
FT /evidence="ECO:0000269|PubMed:31279658,
FT ECO:0000269|PubMed:31279659"
FT MUTAGEN 553
FT /note="N->A: Strongly reduced formation of N(6),2'-O-
FT dimethyladenosine cap (m6A(m))."
FT /evidence="ECO:0000269|PubMed:30467178,
FT ECO:0000269|PubMed:30487554"
FT MUTAGEN 556
FT /note="F->G: Strongly reduced formation of N(6),2'-O-
FT dimethyladenosine cap (m6A(m))."
FT /evidence="ECO:0000269|PubMed:30487554"
FT HELIX 42..47
FT /evidence="ECO:0007829|PDB:2JX8"
FT STRAND 51..54
FT /evidence="ECO:0007829|PDB:2JX8"
FT TURN 55..58
FT /evidence="ECO:0007829|PDB:2JX8"
FT STRAND 59..64
FT /evidence="ECO:0007829|PDB:2JX8"
FT TURN 65..68
FT /evidence="ECO:0007829|PDB:2JX8"
FT STRAND 69..73
FT /evidence="ECO:0007829|PDB:2JX8"
FT STRAND 185..187
FT /evidence="ECO:0007829|PDB:6IRV"
FT STRAND 192..194
FT /evidence="ECO:0007829|PDB:6IRW"
FT HELIX 199..224
FT /evidence="ECO:0007829|PDB:6IRV"
FT HELIX 232..243
FT /evidence="ECO:0007829|PDB:6IRV"
FT STRAND 249..251
FT /evidence="ECO:0007829|PDB:6IRV"
FT STRAND 256..259
FT /evidence="ECO:0007829|PDB:6IRV"
FT HELIX 261..269
FT /evidence="ECO:0007829|PDB:6IRV"
FT HELIX 281..301
FT /evidence="ECO:0007829|PDB:6IRV"
FT HELIX 308..325
FT /evidence="ECO:0007829|PDB:6IRV"
FT HELIX 331..352
FT /evidence="ECO:0007829|PDB:6IRV"
FT HELIX 354..385
FT /evidence="ECO:0007829|PDB:6IRV"
FT STRAND 401..403
FT /evidence="ECO:0007829|PDB:6IRV"
FT STRAND 409..411
FT /evidence="ECO:0007829|PDB:6IRV"
FT STRAND 420..432
FT /evidence="ECO:0007829|PDB:6IRV"
FT STRAND 435..440
FT /evidence="ECO:0007829|PDB:6IRV"
FT HELIX 441..454
FT /evidence="ECO:0007829|PDB:6IRV"
FT HELIX 459..461
FT /evidence="ECO:0007829|PDB:6IRV"
FT HELIX 464..478
FT /evidence="ECO:0007829|PDB:6IRV"
FT HELIX 495..505
FT /evidence="ECO:0007829|PDB:6IRV"
FT STRAND 509..512
FT /evidence="ECO:0007829|PDB:6IRV"
FT TURN 515..517
FT /evidence="ECO:0007829|PDB:6IRV"
FT STRAND 519..521
FT /evidence="ECO:0007829|PDB:6IRV"
FT HELIX 528..531
FT /evidence="ECO:0007829|PDB:6IRV"
FT HELIX 532..534
FT /evidence="ECO:0007829|PDB:6IRV"
FT HELIX 540..542
FT /evidence="ECO:0007829|PDB:6IRW"
FT STRAND 546..552
FT /evidence="ECO:0007829|PDB:6IRV"
FT HELIX 558..573
FT /evidence="ECO:0007829|PDB:6IRV"
FT STRAND 579..586
FT /evidence="ECO:0007829|PDB:6IRV"
FT STRAND 589..591
FT /evidence="ECO:0007829|PDB:6IRW"
FT HELIX 594..601
FT /evidence="ECO:0007829|PDB:6IRV"
FT STRAND 605..611
FT /evidence="ECO:0007829|PDB:6IRV"
FT STRAND 617..619
FT /evidence="ECO:0007829|PDB:6IRV"
FT TURN 621..625
FT /evidence="ECO:0007829|PDB:6IRV"
FT HELIX 628..630
FT /evidence="ECO:0007829|PDB:6IRV"
FT STRAND 631..634
FT /evidence="ECO:0007829|PDB:6IRV"
FT STRAND 639..645
FT /evidence="ECO:0007829|PDB:6IRV"
FT HELIX 647..652
FT /evidence="ECO:0007829|PDB:6IRV"
FT HELIX 657..665
FT /evidence="ECO:0007829|PDB:6IRV"
SQ SEQUENCE 704 AA; 80670 MW; 83647BC8408BA9E9 CRC64;
MANENHGSPR EEASLLSHSP GTSNQSQPCS PKPIRLVQDL PEELVHAGWE KCWSRRENRP
YYFNRFTNQS LWEMPVLGQH DVISDPLGLN ATPLPQDSSL VETPPAENKP RKRQLSEEQP
SGNGVKKPKI EIPVTPTGQS VPSSPSIPGT PTLKMWGTSP EDKQQAALLR PTEVYWDLDI
QTNAVIKHRG PSEVLPPHPE VELLRSQLIL KLRQHYRELC QQREGIEPPR ESFNRWMLER
KVVDKGSDPL LPSNCEPVVS PSMFREIMND IPIRLSRIKF REEAKRLLFK YAEAARRLIE
SRSASPDSRK VVKWNVEDTF SWLRKDHSAS KEDYMDRLEH LRRQCGPHVS AAAKDSVEGI
CSKIYHISLE YVKRIREKHL AILKENNISE EVEAPEVEPR LVYCYPVRLA VSAPPMPSVE
MHMENNVVCI RYKGEMVKVS RNYFSKLWLL YRYSCIDDSA FERFLPRVWC LLRRYQMMFG
VGLYEGTGLQ GSLPVHVFEA LHRLFGVSFE CFASPLNCYF RQYCSAFPDT DGYFGSRGPC
LDFAPLSGSF EANPPFCEEL MDAMVSHFER LLESSPEPLS FIVFIPEWRE PPTPALTRME
QSRFKRHQLI LPAFEHEYRS GSQHICKKEE MHYKAVHNTA VLFLQNDPGF AKWAPTPERL
QELSAAYRQS GRSHSSGSSS SSSSEAKDRD SGREQGPSRE PHPT
