CAPAM_DANRE
ID CAPAM_DANRE Reviewed; 721 AA.
AC A0A0R4IKJ1; A0A0R4IDC3; Q568T9;
DT 13-FEB-2019, integrated into UniProtKB/Swiss-Prot.
DT 20-JAN-2016, sequence version 1.
DT 03-AUG-2022, entry version 39.
DE RecName: Full=mRNA (2'-O-methyladenosine-N(6)-)-methyltransferase {ECO:0000250|UniProtKB:Q9H4Z3};
DE EC=2.1.1.62 {ECO:0000269|PubMed:30467178};
DE AltName: Full=Cap-specific adenosine methyltransferase {ECO:0000250|UniProtKB:Q9H4Z3};
DE Short=CAPAM {ECO:0000250|UniProtKB:Q9H4Z3};
DE Short=zCAPAM {ECO:0000303|PubMed:30467178};
DE AltName: Full=Phosphorylated CTD-interacting factor 1 {ECO:0000250|UniProtKB:Q9H4Z3};
GN Name=pcif1 {ECO:0000312|ZFIN:ZDB-GENE-120920-2};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-282.
RC TISSUE=Embryo;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 178-673 IN COMPLEX WITH
RP S-ADENOSYL-L-METHIONINE AND M7G-CAPPED RNA, FUNCTION, CATALYTIC ACTIVITY,
RP AND MUTAGENESIS OF ARG-239; ARG-269; ASN-558; PHE-561; GLU-563; TRP-593;
RP 596-PRO-PRO-597; HIS-612 AND PHE-619.
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). {ECO:0000269|PubMed:30467178}.
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};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22745;
CC Evidence={ECO:0000269|PubMed:30467178};
CC -!- ACTIVITY REGULATION: Cap-specific adenosine methyltransferase activity
CC is inhibited by zinc. {ECO:0000250|UniProtKB:Q9H4Z3}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9H4Z3}.
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. According to a
CC report, m6A(m) promotes the translation of capped mRNAs
CC (PubMed:30467178). However, another study did not observe a clear
CC effect on mRNA translation, but reported an increased stability of a
CC subset of m6A(m) transcripts (By similarity). According to a third
CC report, m6A(m) inhibits mRNA translation without affecting mRNA
CC stability (By similarity). {ECO:0000250|UniProtKB:Q9H4Z3,
CC ECO:0000269|PubMed:30467178}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH92722.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
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DR EMBL; CABZ01085327; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CU638700; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC092722; AAH92722.1; ALT_SEQ; mRNA.
DR RefSeq; XP_688220.3; XM_683128.8.
DR PDB; 6IRX; X-ray; 2.00 A; A=178-673.
DR PDB; 6IRY; X-ray; 1.80 A; A=178-673.
DR PDB; 6IRZ; X-ray; 2.00 A; A=178-673.
DR PDB; 6IS0; X-ray; 1.80 A; A=178-673.
DR PDBsum; 6IRX; -.
DR PDBsum; 6IRY; -.
DR PDBsum; 6IRZ; -.
DR PDBsum; 6IS0; -.
DR AlphaFoldDB; A0A0R4IKJ1; -.
DR SMR; A0A0R4IKJ1; -.
DR STRING; 7955.ENSDARP00000010989; -.
DR PaxDb; A0A0R4IKJ1; -.
DR Ensembl; ENSDART00000172081; ENSDARP00000135280; ENSDARG00000099084.
DR GeneID; 553360; -.
DR KEGG; dre:553360; -.
DR CTD; 63935; -.
DR ZFIN; ZDB-GENE-120920-2; pcif1.
DR eggNOG; ENOG502QVT7; Eukaryota.
DR GeneTree; ENSGT00390000016206; -.
DR OMA; VWCYPIQ; -.
DR OrthoDB; 1523233at2759; -.
DR PhylomeDB; A0A0R4IKJ1; -.
DR PRO; PR:A0A0R4IKJ1; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 6.
DR Bgee; ENSDARG00000099084; Expressed in gastrula and 20 other tissues.
DR GO; GO:0005634; C:nucleus; ISS: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; ISS:UniProtKB.
DR GO; GO:1904047; F:S-adenosyl-L-methionine binding; IDA:UniProtKB.
DR GO; GO:0080009; P:mRNA methylation; IDA:UniProtKB.
DR GO; GO:0045727; P:positive regulation of translation; ISS: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; Reference proteome; Transferase.
FT CHAIN 1..721
FT /note="mRNA (2'-O-methyladenosine-N(6)-)-methyltransferase"
FT /id="PRO_0000446373"
FT DOMAIN 43..77
FT /note="WW"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT REGION 1..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 93..170
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 675..721
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 149..165
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 700..721
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 239
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:30467178,
FT ECO:0007744|PDB:6IRZ, ECO:0007744|PDB:6IS0"
FT BINDING 269
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:30467178,
FT ECO:0007744|PDB:6IRZ, ECO:0007744|PDB:6IS0"
FT BINDING 558..561
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:30467178,
FT ECO:0007744|PDB:6IRY, ECO:0007744|PDB:6IRZ,
FT ECO:0007744|PDB:6IS0"
FT BINDING 563
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:30467178,
FT ECO:0007744|PDB:6IRZ, ECO:0007744|PDB:6IS0"
FT BINDING 593..597
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:30467178,
FT ECO:0007744|PDB:6IRZ, ECO:0007744|PDB:6IS0"
FT BINDING 619..621
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:30467178,
FT ECO:0007744|PDB:6IRY, ECO:0007744|PDB:6IRZ,
FT ECO:0007744|PDB:6IS0"
FT MUTAGEN 239
FT /note="R->A: Strongly reduced methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:30467178"
FT MUTAGEN 269
FT /note="R->A: Strongly reduced methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:30467178"
FT MUTAGEN 558
FT /note="N->A: Strongly reduced methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:30467178"
FT MUTAGEN 561
FT /note="F->A: Strongly reduced methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:30467178"
FT MUTAGEN 563
FT /note="E->A: Strongly reduced methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:30467178"
FT MUTAGEN 593
FT /note="W->A: Abolished methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:30467178"
FT MUTAGEN 596..597
FT /note="PP->AA: Abolished methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:30467178"
FT MUTAGEN 612
FT /note="H->A: Strongly reduced methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:30467178"
FT MUTAGEN 619
FT /note="F->A: Reduced methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:30467178"
FT STRAND 189..191
FT /evidence="ECO:0007829|PDB:6IRY"
FT HELIX 203..228
FT /evidence="ECO:0007829|PDB:6IRY"
FT HELIX 236..247
FT /evidence="ECO:0007829|PDB:6IRY"
FT STRAND 253..255
FT /evidence="ECO:0007829|PDB:6IRY"
FT STRAND 260..263
FT /evidence="ECO:0007829|PDB:6IRY"
FT HELIX 265..273
FT /evidence="ECO:0007829|PDB:6IRY"
FT HELIX 285..305
FT /evidence="ECO:0007829|PDB:6IRY"
FT HELIX 310..327
FT /evidence="ECO:0007829|PDB:6IRY"
FT STRAND 329..331
FT /evidence="ECO:0007829|PDB:6IRY"
FT HELIX 335..389
FT /evidence="ECO:0007829|PDB:6IRY"
FT STRAND 406..408
FT /evidence="ECO:0007829|PDB:6IRY"
FT STRAND 414..416
FT /evidence="ECO:0007829|PDB:6IRY"
FT STRAND 424..429
FT /evidence="ECO:0007829|PDB:6IRY"
FT STRAND 432..437
FT /evidence="ECO:0007829|PDB:6IRY"
FT STRAND 440..445
FT /evidence="ECO:0007829|PDB:6IRY"
FT HELIX 446..459
FT /evidence="ECO:0007829|PDB:6IRY"
FT HELIX 469..484
FT /evidence="ECO:0007829|PDB:6IRY"
FT HELIX 500..510
FT /evidence="ECO:0007829|PDB:6IRY"
FT STRAND 514..517
FT /evidence="ECO:0007829|PDB:6IRY"
FT TURN 520..522
FT /evidence="ECO:0007829|PDB:6IRY"
FT STRAND 524..526
FT /evidence="ECO:0007829|PDB:6IRY"
FT HELIX 533..536
FT /evidence="ECO:0007829|PDB:6IRY"
FT HELIX 537..539
FT /evidence="ECO:0007829|PDB:6IRY"
FT HELIX 545..547
FT /evidence="ECO:0007829|PDB:6IRY"
FT STRAND 550..557
FT /evidence="ECO:0007829|PDB:6IRY"
FT HELIX 563..579
FT /evidence="ECO:0007829|PDB:6IRY"
FT STRAND 584..591
FT /evidence="ECO:0007829|PDB:6IRY"
FT TURN 594..597
FT /evidence="ECO:0007829|PDB:6IS0"
FT HELIX 599..605
FT /evidence="ECO:0007829|PDB:6IRY"
FT STRAND 610..616
FT /evidence="ECO:0007829|PDB:6IRY"
FT HELIX 638..640
FT /evidence="ECO:0007829|PDB:6IRX"
FT STRAND 644..650
FT /evidence="ECO:0007829|PDB:6IRY"
FT HELIX 652..657
FT /evidence="ECO:0007829|PDB:6IRY"
FT HELIX 662..670
FT /evidence="ECO:0007829|PDB:6IRY"
SQ SEQUENCE 721 AA; 81297 MW; 2EACAAACD0F74FCC CRC64;
MTSENHTTIK ADSALVMSPT GSTSQAAPFS PSTSKPIQEL PDELIQAGWS KCWSKRENRP
YYFNRFTNQS LWEMPVLGQH DVISDPLGLN AAPASGEANA DAGLGNGQRK RHPSEDASQA
GPNSFKRPKV EIPATPTTPT VPISPSTPGV KPWVNTTTDE KQGQASTPAP APYRPSVVYW
DLDIQTNAVI RERAPADHLP PHPEIELQRA QLTTKLRQHY HELCSQREGI EPPRESFNRW
LLERKVVDKG LDPLLPSECD PVISPSMFRE IMNDIPIRLS RIKYKEEARK LLFKYAEAAK
KMIDSRNATP ESRKVVKWNV EDTMNWLRRD HSASKEDYMD RLEHLRKQCG PHVASVAKDS
VEGICSKIYH ISAEYVRRIR QAHLTLLKEC NISVDGTESA EVQDRLVYCY PVRLSIPAPP
QTRVELHFEN DIACLRFKGE MVKVSRGHFN KLELLYRYSC IDDPRFEKFL SRVWCLIKRY
QVMFGSGVNE GSGLQGSLPV PVFEALNKQF GVTFECFASP LNCYFKQFCS AFPDIDGFFG
SRGPFLSFSP ASGSFEANPP FCEELMDAMV THFEDLLGRS SEPLSFIIFV PEWRDPPTPA
LTRMEASRFR RHQMTVPAFE HEYRSGSQHI CKREEIYYKA IHGTAVIFLQ NNAGFAKWEP
TTERIQELLA AYKVSGRSLP SPGPSSTNTG EKDSKPAPER TAPSQDNSSP VDKTAQDTTN
T
