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 27-MAR-2024, entry version 225. 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 -!- 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"; 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; 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; 112. DR ComplexPortal; CPX-2194; Ribonucleoside-diphosphate reductase RR1 complex, RRM2 variant. DR DIP; DIP-24232N; -. DR IntAct; P31350; 41. DR MINT; P31350; -. 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; 9606-ENSP00000353770; -. DR PeptideAtlas; P31350; -. DR ProteomicsDB; 54784; -. [P31350-1] DR Pumba; P31350; -. DR ABCD; P31350; 2 sequenced antibodies. DR Antibodypedia; 26663; 377 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 AGR; HGNC:10452; -. 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; 5487627at2759; -. DR PhylomeDB; P31350; -. DR TreeFam; TF300465; -. DR BioCyc; MetaCyc:HS10398-MONOMER; -. 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 BioGRID-ORCS; 6241; 846 hits in 1195 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 153 other cell types or tissues. DR ExpressionAtlas; P31350; baseline and differential. 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: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; Ribonucleotide Reductase, subunit A; 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; RIBONUCLEOSIDE-DIPHOSPHATE REDUCTASE SMALL CHAIN; 1. DR PANTHER; PTHR23409:SF20; RIBONUCLEOSIDE-DIPHOSPHATE REDUCTASE SUBUNIT M2; 1. DR Pfam; PF00268; Ribonuc_red_sm; 1. DR SUPFAM; SSF47240; Ferritin-like; 1. DR PROSITE; PS00368; RIBORED_SMALL; 1. DR Genevisible; P31350; HS. 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 //