RIR2_HUMAN
ID RIR2_HUMAN Reviewed; 389 AA.
AC P31350; B2R9B5; J3KP43; Q5WRU7;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1993, sequence version 1.
DT 03-AUG-2022, entry version 216.
DE RecName: Full=Ribonucleoside-diphosphate reductase subunit M2;
DE EC=1.17.4.1;
DE AltName: Full=Ribonucleotide reductase small chain;
DE AltName: Full=Ribonucleotide reductase small subunit;
GN Name=RRM2; Synonyms=RR2;
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).
RC TISSUE=Mammary carcinoma;
RX PubMed=1627826; DOI=10.3109/10425179209020807;
RA Pavloff N., Rivard D., Masson S., Shen S.-H., Mes-Masson A.-M.;
RT "Sequence analysis of the large and small subunits of human ribonucleotide
RT reductase.";
RL DNA Seq. 2:227-234(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11978970; DOI=10.1159/000057017;
RA Zhou B., Yen Y.;
RT "Characterization of the human ribonucleotide reductase M2 subunit gene;
RT genomic structure and promoter analyses.";
RL Cytogenet. Cell Genet. 95:52-59(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 1-94 (ISOFORM 2).
RC TISSUE=Neonatal skin;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Muscle, and Skin;
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [7]
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 [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [9]
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 [10]
RP IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH CCNF, SUBCELLULAR
RP LOCATION, INDUCTION BY DNA DAMAGE, PHOSPHORYLATION AT THR-33,
RP UBIQUITINATION, AND MUTAGENESIS OF THR-33 AND 49-ARG--ILE-51.
RX PubMed=22632967; DOI=10.1016/j.cell.2012.03.043;
RA D'Angiolella V., Donato V., Forrester F.M., Jeong Y.T., Pellacani C.,
RA Kudo Y., Saraf A., Florens L., Washburn M.P., Pagano M.;
RT "Cyclin F-mediated degradation of ribonucleotide reductase M2 controls
RT genome integrity and DNA repair.";
RL Cell 149:1023-1034(2012).
CC -!- FUNCTION: Provides the precursors necessary for DNA synthesis.
CC Catalyzes the biosynthesis of deoxyribonucleotides from the
CC corresponding ribonucleotides. Inhibits Wnt signaling.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[thioredoxin]-disulfide + a 2'-deoxyribonucleoside 5'-
CC diphosphate + H2O = [thioredoxin]-dithiol + a ribonucleoside 5'-
CC diphosphate; Xref=Rhea:RHEA:23252, Rhea:RHEA-COMP:10698, Rhea:RHEA-
CC COMP:10700, ChEBI:CHEBI:15377, ChEBI:CHEBI:29950, ChEBI:CHEBI:50058,
CC ChEBI:CHEBI:57930, ChEBI:CHEBI:73316; EC=1.17.4.1;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10014};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875; Evidence={ECO:0000250};
CC Note=Binds 2 iron ions per subunit. {ECO:0000250};
CC -!- PATHWAY: Genetic information processing; DNA replication.
CC -!- SUBUNIT: Heterodimer of a large and a small subunit. Interacts (via Cy
CC motif and when phosphorylated at Thr-33) with CCNF; the interaction
CC occurs exclusively in G2 and early M (PubMed:22632967).
CC {ECO:0000269|PubMed:22632967}.
CC -!- INTERACTION:
CC P31350; P41002: CCNF; NbExp=12; IntAct=EBI-2339245, EBI-1207574;
CC P31350; Q9UM11: FZR1; NbExp=2; IntAct=EBI-2339245, EBI-724997;
CC P31350; P23921: RRM1; NbExp=6; IntAct=EBI-2339245, EBI-717006;
CC P31350; O00560: SDCBP; NbExp=3; IntAct=EBI-2339245, EBI-727004;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22632967}. Nucleus
CC {ECO:0000269|PubMed:22632967}. Note=Localized to the cytoplasm in S
CC phase cells. May localize to the nucleus in G2 phase cells.
CC {ECO:0000269|PubMed:22632967}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P31350-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P31350-2; Sequence=VSP_044917;
CC -!- INDUCTION: Up-regulated in response to DNA damage induced by
CC doxorubicin, camptothecin, UV-C, methyl methanesulfonate, nocodazole,
CC or gamma-irradiation. {ECO:0000269|PubMed:22632967}.
CC -!- PTM: Phosphorylation on Ser-20 relieves the inhibitory effect on Wnt
CC signaling. Phosphorylated on Thr-33 by CDK1 and CDK2; predominantly in
CC G2 and M phase (PubMed:22632967). {ECO:0000269|PubMed:22632967}.
CC -!- PTM: Ubiquitinated by the SCF(CCNF) E3 ubiquitin-protein ligase
CC complex; leading to its degradation by the proteasome.
CC {ECO:0000269|PubMed:22632967}.
CC -!- MISCELLANEOUS: Two distinct regulatory sites have been defined: the
CC specificity site, which controls substrate specificity, and the
CC activity site which regulates overall catalytic activity. A substrate-
CC binding catalytic site, located on M1, is formed only in the presence
CC of the second subunit M2.
CC -!- SIMILARITY: Belongs to the ribonucleoside diphosphate reductase small
CC chain family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=DA477511; Type=Frameshift; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Ribonucleotide reductase entry;
CC URL="https://en.wikipedia.org/wiki/Ribonucleotide_reductase";
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DR EMBL; X59618; CAA42181.1; -; mRNA.
DR EMBL; S40301; AAA09577.1; -; mRNA.
DR EMBL; AY032750; AAK51163.1; -; Genomic_DNA.
DR EMBL; AK313719; BAG36462.1; -; mRNA.
DR EMBL; DA477511; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC104794; AAX93099.1; -; Genomic_DNA.
DR EMBL; AC118058; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001886; AAH01886.1; -; mRNA.
DR EMBL; BC030154; AAH30154.1; -; mRNA.
DR CCDS; CCDS1669.1; -. [P31350-1]
DR CCDS; CCDS54334.1; -. [P31350-2]
DR PIR; S25854; S25854.
DR RefSeq; NP_001025.1; NM_001034.3. [P31350-1]
DR RefSeq; NP_001159403.1; NM_001165931.1. [P31350-2]
DR PDB; 2UW2; X-ray; 2.80 A; A=60-389.
DR PDB; 3OLJ; X-ray; 2.10 A; A/B/C/D=66-350.
DR PDB; 3VPM; X-ray; 2.70 A; A/B=66-350.
DR PDB; 3VPN; X-ray; 2.25 A; A/B=66-350.
DR PDB; 3VPO; X-ray; 2.30 A; A/B=66-350.
DR PDBsum; 2UW2; -.
DR PDBsum; 3OLJ; -.
DR PDBsum; 3VPM; -.
DR PDBsum; 3VPN; -.
DR PDBsum; 3VPO; -.
DR AlphaFoldDB; P31350; -.
DR SMR; P31350; -.
DR BioGRID; 112155; 89.
DR ComplexPortal; CPX-2194; Ribonucleoside-diphosphate reductase RR1 complex, RRM2 variant.
DR DIP; DIP-24232N; -.
DR IntAct; P31350; 34.
DR STRING; 9606.ENSP00000353770; -.
DR BindingDB; P31350; -.
DR ChEMBL; CHEMBL1954; -.
DR DrugBank; DB00242; Cladribine.
DR DrugBank; DB05260; Gallium nitrate.
DR DrugBank; DB05801; GTI 2040.
DR DrugBank; DB05003; Imexon.
DR DrugBank; DB05428; Motexafin gadolinium.
DR DrugCentral; P31350; -.
DR GuidetoPHARMACOLOGY; 2631; -.
DR GlyGen; P31350; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P31350; -.
DR MetOSite; P31350; -.
DR PhosphoSitePlus; P31350; -.
DR BioMuta; RRM2; -.
DR DMDM; 400979; -.
DR CPTAC; CPTAC-3255; -.
DR CPTAC; CPTAC-725; -.
DR EPD; P31350; -.
DR jPOST; P31350; -.
DR MassIVE; P31350; -.
DR MaxQB; P31350; -.
DR PaxDb; P31350; -.
DR PeptideAtlas; P31350; -.
DR PRIDE; P31350; -.
DR ProteomicsDB; 54784; -. [P31350-1]
DR ABCD; P31350; 2 sequenced antibodies.
DR Antibodypedia; 26663; 318 antibodies from 36 providers.
DR CPTC; P31350; 2 antibodies.
DR DNASU; 6241; -.
DR Ensembl; ENST00000304567.10; ENSP00000302955.4; ENSG00000171848.16. [P31350-1]
DR Ensembl; ENST00000360566.6; ENSP00000353770.2; ENSG00000171848.16. [P31350-2]
DR Ensembl; ENST00000641198.1; ENSP00000493399.1; ENSG00000171848.16. [P31350-1]
DR GeneID; 6241; -.
DR KEGG; hsa:6241; -.
DR MANE-Select; ENST00000304567.10; ENSP00000302955.4; NM_001034.4; NP_001025.1.
DR UCSC; uc021vdr.3; human. [P31350-1]
DR CTD; 6241; -.
DR DisGeNET; 6241; -.
DR GeneCards; RRM2; -.
DR HGNC; HGNC:10452; RRM2.
DR HPA; ENSG00000171848; Group enriched (bone marrow, esophagus, intestine, lymphoid tissue).
DR MIM; 180390; gene.
DR neXtProt; NX_P31350; -.
DR OpenTargets; ENSG00000171848; -.
DR PharmGKB; PA299; -.
DR VEuPathDB; HostDB:ENSG00000171848; -.
DR eggNOG; KOG1567; Eukaryota.
DR GeneTree; ENSGT00390000013305; -.
DR HOGENOM; CLU_035339_0_1_1; -.
DR InParanoid; P31350; -.
DR OMA; KVGEYQR; -.
DR OrthoDB; 680824at2759; -.
DR PhylomeDB; P31350; -.
DR TreeFam; TF300465; -.
DR BioCyc; MetaCyc:HS10398-MON; -.
DR BRENDA; 1.17.4.1; 2681.
DR PathwayCommons; P31350; -.
DR Reactome; R-HSA-499943; Interconversion of nucleotide di- and triphosphates.
DR Reactome; R-HSA-69205; G1/S-Specific Transcription.
DR Reactome; R-HSA-8953750; Transcriptional Regulation by E2F6.
DR SignaLink; P31350; -.
DR SIGNOR; P31350; -.
DR UniPathway; UPA00326; -.
DR BioGRID-ORCS; 6241; 805 hits in 1106 CRISPR screens.
DR ChiTaRS; RRM2; human.
DR EvolutionaryTrace; P31350; -.
DR GeneWiki; RRM2; -.
DR GenomeRNAi; 6241; -.
DR Pharos; P31350; Tclin.
DR PRO; PR:P31350; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P31350; protein.
DR Bgee; ENSG00000171848; Expressed in secondary oocyte and 151 other tissues.
DR ExpressionAtlas; P31350; baseline and differential.
DR Genevisible; P31350; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005971; C:ribonucleoside-diphosphate reductase complex; IPI:ComplexPortal.
DR GO; GO:0008199; F:ferric iron binding; IEA:Ensembl.
DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR GO; GO:0004748; F:ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor; ISS:UniProtKB.
DR GO; GO:0009265; P:2'-deoxyribonucleotide biosynthetic process; IDA:ComplexPortal.
DR GO; GO:0001824; P:blastocyst development; IEA:Ensembl.
DR GO; GO:0009263; P:deoxyribonucleotide biosynthetic process; ISS:UniProtKB.
DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-UniPathway.
DR GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; IDA:ComplexPortal.
DR GO; GO:0051290; P:protein heterotetramerization; IEA:Ensembl.
DR GO; GO:0009185; P:ribonucleoside diphosphate metabolic process; IDA:ComplexPortal.
DR CDD; cd01049; RNRR2; 1.
DR Gene3D; 1.10.620.20; -; 1.
DR InterPro; IPR009078; Ferritin-like_SF.
DR InterPro; IPR012348; RNR-like.
DR InterPro; IPR033909; RNR_small.
DR InterPro; IPR030475; RNR_small_AS.
DR InterPro; IPR000358; RNR_small_fam.
DR PANTHER; PTHR23409; PTHR23409; 1.
DR Pfam; PF00268; Ribonuc_red_sm; 1.
DR SUPFAM; SSF47240; SSF47240; 1.
DR PROSITE; PS00368; RIBORED_SMALL; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm;
KW Deoxyribonucleotide synthesis; Iron; Metal-binding; Nucleus;
KW Oxidoreductase; Phosphoprotein; Reference proteome; Ubl conjugation.
FT CHAIN 1..389
FT /note="Ribonucleoside-diphosphate reductase subunit M2"
FT /id="PRO_0000190447"
FT MOTIF 49..51
FT /note="Cy"
FT /evidence="ECO:0000269|PubMed:22632967"
FT ACT_SITE 176
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10014"
FT BINDING 138
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10014"
FT BINDING 169
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10014"
FT BINDING 169
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 172
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10014"
FT BINDING 232
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 266
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 269
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT MOD_RES 20
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11157"
FT MOD_RES 33
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:22632967"
FT VAR_SEQ 1
FT /note="M -> MGRVGGMAQPMGRAGAPKPMGRAGSARRGRFKGCWSEGSPVHPVPAV
FT LSWLLALLRCASTM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044917"
FT MUTAGEN 20
FT /note="S->A: Enhances inhibitory effect on Wnt signaling."
FT MUTAGEN 20
FT /note="S->E: Prevents inhibitory effect on Wnt signaling."
FT MUTAGEN 33
FT /note="T->A: Strongly reduces the interaction with CCNF.
FT Lack of proteasomal degradation. Increase in the cellular
FT concentration of dATP and dGTP, but not dCTP and dTTP,
FT leading to an imbalance in dNTP pools and genome
FT instability."
FT /evidence="ECO:0000269|PubMed:22632967"
FT MUTAGEN 49..51
FT /note="RRI->ARA: Abolishes the interaction with CCNF. Lack
FT of proteasomal degradation. Increase in the cellular
FT concentration of dATP and dGTP, but not dCTP and dTTP,
FT leading to an imbalance in dNTP pools and genome
FT instability."
FT /evidence="ECO:0000269|PubMed:22632967"
FT TURN 71..73
FT /evidence="ECO:0007829|PDB:3OLJ"
FT TURN 77..80
FT /evidence="ECO:0007829|PDB:3OLJ"
FT HELIX 88..99
FT /evidence="ECO:0007829|PDB:3OLJ"
FT HELIX 104..106
FT /evidence="ECO:0007829|PDB:3OLJ"
FT HELIX 110..112
FT /evidence="ECO:0007829|PDB:2UW2"
FT HELIX 113..118
FT /evidence="ECO:0007829|PDB:3OLJ"
FT HELIX 121..147
FT /evidence="ECO:0007829|PDB:3OLJ"
FT HELIX 149..152
FT /evidence="ECO:0007829|PDB:3OLJ"
FT HELIX 156..183
FT /evidence="ECO:0007829|PDB:3OLJ"
FT HELIX 187..194
FT /evidence="ECO:0007829|PDB:3OLJ"
FT HELIX 196..199
FT /evidence="ECO:0007829|PDB:3OLJ"
FT HELIX 201..203
FT /evidence="ECO:0007829|PDB:3OLJ"
FT HELIX 204..215
FT /evidence="ECO:0007829|PDB:3OLJ"
FT STRAND 217..219
FT /evidence="ECO:0007829|PDB:3OLJ"
FT HELIX 221..233
FT /evidence="ECO:0007829|PDB:3OLJ"
FT TURN 234..236
FT /evidence="ECO:0007829|PDB:3OLJ"
FT HELIX 237..248
FT /evidence="ECO:0007829|PDB:3OLJ"
FT HELIX 253..278
FT /evidence="ECO:0007829|PDB:3OLJ"
FT HELIX 286..305
FT /evidence="ECO:0007829|PDB:3OLJ"
FT HELIX 310..313
FT /evidence="ECO:0007829|PDB:3OLJ"
FT HELIX 317..335
FT /evidence="ECO:0007829|PDB:3OLJ"
FT CONFLICT P31350-2:28
FT /note="R -> H (in Ref. 3; DA477511)"
FT /evidence="ECO:0000305"
FT CONFLICT P31350-2:59
FT /note="S -> A (in Ref. 3; DA477511)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 389 AA; 44878 MW; 10E6F5F84D34DA94 CRC64;
MLSLRVPLAP ITDPQQLQLS PLKGLSLVDK ENTPPALSGT RVLASKTARR IFQEPTEPKT
KAAAPGVEDE PLLRENPRRF VIFPIEYHDI WQMYKKAEAS FWTAEEVDLS KDIQHWESLK
PEERYFISHV LAFFAASDGI VNENLVERFS QEVQITEARC FYGFQIAMEN IHSEMYSLLI
DTYIKDPKER EFLFNAIETM PCVKKKADWA LRWIGDKEAT YGERVVAFAA VEGIFFSGSF
ASIFWLKKRG LMPGLTFSNE LISRDEGLHC DFACLMFKHL VHKPSEERVR EIIINAVRIE
QEFLTEALPV KLIGMNCTLM KQYIEFVADR LMLELGFSKV FRVENPFDFM ENISLEGKTN
FFEKRVGEYQ RMGVMSSPTE NSFTLDADF
