ID DPYL2_MOUSE Reviewed; 572 AA. AC O08553; Q6P5D0; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 02-MAY-2006, sequence version 2. DT 27-MAR-2024, entry version 203. DE RecName: Full=Dihydropyrimidinase-related protein 2; DE Short=DRP-2; DE AltName: Full=Unc-33-like phosphoprotein 2; DE Short=ULIP-2; GN Name=Dpysl2; Synonyms=Crmp2, Ulip2; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=ICR; TISSUE=Brain; RX PubMed=9652388; DOI=10.1046/j.1432-1327.1998.2540014.x; RA Byk T., Ozon S., Sobel A.; RT "The Ulip family phosphoproteins -- common and specific properties."; RL Eur. J. Biochem. 254:14-24(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; TISSUE=Brain; 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 [3] RP PROTEIN SEQUENCE OF 44-56; 174-211; 239-254; 259-268; 391-397; 441-467 AND RP 533-552, AND IDENTIFICATION BY MASS SPECTROMETRY. RC STRAIN=C57BL/6J, and OF1; TISSUE=Brain, and Hippocampus; RA Lubec G., Klug S., Kang S.U., Sunyer B., Chen W.-Q.; RL Submitted (JAN-2009) to UniProtKB. RN [4] RP SUBUNIT. RX PubMed=9375656; DOI=10.1046/j.1471-4159.1997.69062261.x; RA Wang L.H., Strittmatter S.M.; RT "Brain CRMP forms heterotetramers similar to liver dihydropyrimidinase."; RL J. Neurochem. 69:2261-2269(1997). RN [5] RP SUBUNIT. RX PubMed=10956643; DOI=10.1074/jbc.m003277200; RA Fukada M., Watakabe I., Yuasa-Kawada J., Kawachi H., Kuroiwa A., RA Matsuda Y., Noda M.; RT "Molecular characterization of CRMP5, a novel member of the collapsin RT response mediator protein family."; RL J. Biol. Chem. 275:37957-37965(2000). RN [6] RP INTERACTION WITH HTR4. RX PubMed=15466885; DOI=10.1242/jcs.01379; RA Joubert L., Hanson B., Barthet G., Sebben M., Claeysen S., Hong W., RA Marin P., Dumuis A., Bockaert J.; RT "New sorting nexin (SNX27) and NHERF specifically interact with the 5-HT4a RT receptor splice variant: roles in receptor targeting."; RL J. Cell Sci. 117:5367-5379(2004). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic brain; RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200; RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.; RT "Phosphoproteomic analysis of the developing mouse brain."; RL Mol. Cell. Proteomics 3:1093-1101(2004). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-465, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=15648052; DOI=10.1002/pmic.200401066; RA Vosseller K., Hansen K.C., Chalkley R.J., Trinidad J.C., Wells L., RA Hart G.W., Burlingame A.L.; RT "Quantitative analysis of both protein expression and serine / threonine RT post-translational modifications through stable isotope labeling with RT dithiothreitol."; RL Proteomics 5:388-398(2005). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-431; TYR-499 AND THR-509, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain; RX PubMed=18034455; DOI=10.1021/pr0701254; RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.; RT "Large-scale identification and evolution indexing of tyrosine RT phosphorylation sites from murine brain."; RL J. Proteome Res. 7:311-318(2008). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-514; SER-517; SER-518 AND RP SER-522, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic fibroblast; RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200; RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.; RT "Large scale localization of protein phosphorylation by use of electron RT capture dissociation mass spectrometry."; RL Mol. Cell. Proteomics 8:904-912(2009). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-402; SER-507; THR-509; RP THR-512; THR-514; SER-517; SER-518; THR-521; SER-522; SER-537; SER-540 AND RP SER-542, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, RC Pancreas, Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [12] RP FUNCTION, PHOSPHORYLATION AT THR-514, AND MUTAGENESIS OF THR-514. RX PubMed=22057101; DOI=10.1038/ncb2373; RA Wakatsuki S., Saitoh F., Araki T.; RT "ZNRF1 promotes Wallerian degeneration by degrading AKT to induce GSK3B- RT dependent CRMP2 phosphorylation."; RL Nat. Cell Biol. 13:1415-1423(2011). RN [13] RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-258, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic fibroblast; RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001; RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.; RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic RT pathways."; RL Mol. Cell 50:919-930(2013). RN [14] RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-565, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain; RX PubMed=24129315; DOI=10.1074/mcp.o113.027870; RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M., RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V., RA Bedford M.T., Comb M.J.; RT "Immunoaffinity enrichment and mass spectrometry analysis of protein RT methylation."; RL Mol. Cell. Proteomics 13:372-387(2014). CC -!- FUNCTION: Plays a role in neuronal development and polarity, as well as CC in axon growth and guidance, neuronal growth cone collapse and cell CC migration. Necessary for signaling by class 3 semaphorins and CC subsequent remodeling of the cytoskeleton. May play a role in CC endocytosis. {ECO:0000269|PubMed:22057101}. CC -!- SUBUNIT: Homotetramer, and heterotetramer with CRMP1, DPYSL3, DPYSL4 or CC DPYSL5. Interacts through its C-terminus with the C-terminus of CC CYFIP1/SRA1. Interacts with HTR4. Interacts with CLN6. Interacts with CC MICALL1. {ECO:0000269|PubMed:10956643, ECO:0000269|PubMed:15466885, CC ECO:0000269|PubMed:9375656}. CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250}. Cytoplasm, CC cytoskeleton {ECO:0000250}. Membrane {ECO:0000250}. Note=Tightly but CC non-covalently associated with membranes. {ECO:0000250}. CC -!- PTM: Phosphorylation by DYRK2 at Ser-522 is required for subsequent CC phosphorylation by GSK3B (By similarity). Phosphorylation at Thr-514 by CC GSK3B abolishes tubulin-binding leading to destabilization of CC microtubule assembly in axons and neurodegeneration. {ECO:0000250, CC ECO:0000269|PubMed:22057101}. CC -!- SIMILARITY: Belongs to the metallo-dependent hydrolases superfamily. CC Hydantoinase/dihydropyrimidinase family. {ECO:0000305}. CC -!- CAUTION: Lacks most of the conserved residues that are essential for CC binding the metal cofactor and hence for dihydropyrimidinase activity. CC Its enzyme activity is therefore unsure. {ECO:0000305}. 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; Y10339; CAA71370.1; -; mRNA. DR EMBL; BC062955; AAH62955.1; -; mRNA. DR CCDS; CCDS27224.1; -. DR RefSeq; NP_034085.2; NM_009955.3. DR PDB; 5UQC; X-ray; 1.78 A; A/B=15-496. DR PDBsum; 5UQC; -. DR AlphaFoldDB; O08553; -. DR SMR; O08553; -. DR BioGRID; 198891; 145. DR CORUM; O08553; -. DR IntAct; O08553; 30. DR MINT; O08553; -. DR STRING; 10090.ENSMUSP00000022629; -. DR ChEMBL; CHEMBL1075160; -. DR MEROPS; M38.975; -. DR GlyGen; O08553; 6 sites, 1 O-linked glycan (6 sites). DR iPTMnet; O08553; -. DR PhosphoSitePlus; O08553; -. DR SwissPalm; O08553; -. DR REPRODUCTION-2DPAGE; IPI00114375; -. DR REPRODUCTION-2DPAGE; O08553; -. DR CPTAC; non-CPTAC-3426; -. DR CPTAC; non-CPTAC-3911; -. DR EPD; O08553; -. DR jPOST; O08553; -. DR MaxQB; O08553; -. DR PaxDb; 10090-ENSMUSP00000022629; -. DR PeptideAtlas; O08553; -. DR ProteomicsDB; 279482; -. DR Pumba; O08553; -. DR Antibodypedia; 1039; 780 antibodies from 40 providers. DR DNASU; 12934; -. DR Ensembl; ENSMUST00000022629.9; ENSMUSP00000022629.9; ENSMUSG00000022048.9. DR GeneID; 12934; -. DR KEGG; mmu:12934; -. DR UCSC; uc007uko.1; mouse. DR AGR; MGI:1349763; -. DR CTD; 1808; -. DR MGI; MGI:1349763; Dpysl2. DR VEuPathDB; HostDB:ENSMUSG00000022048; -. DR eggNOG; KOG2584; Eukaryota. DR GeneTree; ENSGT01030000234527; -. DR HOGENOM; CLU_015572_2_2_1; -. DR InParanoid; O08553; -. DR OMA; HCETAEI; -. DR OrthoDB; 1772494at2759; -. DR PhylomeDB; O08553; -. DR TreeFam; TF314706; -. DR Reactome; R-MMU-399956; CRMPs in Sema3A signaling. DR Reactome; R-MMU-437239; Recycling pathway of L1. DR BioGRID-ORCS; 12934; 1 hit in 78 CRISPR screens. DR ChiTaRS; Dpysl2; mouse. DR PRO; PR:O08553; -. DR Proteomes; UP000000589; Chromosome 14. DR RNAct; O08553; Protein. DR Bgee; ENSMUSG00000022048; Expressed in medial preoptic region and 223 other cell types or tissues. DR GO; GO:0030424; C:axon; IDA:MGI. DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell. DR GO; GO:0005829; C:cytosol; ISS:UniProtKB. DR GO; GO:0030425; C:dendrite; IDA:MGI. DR GO; GO:0030426; C:growth cone; ISO:MGI. DR GO; GO:0005739; C:mitochondrion; HDA:MGI. DR GO; GO:0043209; C:myelin sheath; HDA:UniProtKB. DR GO; GO:0043025; C:neuronal cell body; IDA:MGI. DR GO; GO:0005886; C:plasma membrane; ISO:MGI. DR GO; GO:0098793; C:presynapse; ISO:MGI. DR GO; GO:0032991; C:protein-containing complex; ISO:MGI. DR GO; GO:0045202; C:synapse; ISO:MGI. DR GO; GO:0016812; F:hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amides; IBA:GO_Central. DR GO; GO:0042802; F:identical protein binding; ISO:MGI. DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB. DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW. DR GO; GO:0007010; P:cytoskeleton organization; IDA:UniProtKB. DR GO; GO:0006897; P:endocytosis; ISS:UniProtKB. DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW. DR GO; GO:0014049; P:positive regulation of glutamate secretion; ISO:MGI. DR GO; GO:0045664; P:regulation of neuron differentiation; ISO:MGI. DR GO; GO:0010975; P:regulation of neuron projection development; IGI:MGI. DR GO; GO:0048489; P:synaptic vesicle transport; ISO:MGI. DR CDD; cd01314; D-HYD; 1. DR Gene3D; 3.20.20.140; Metal-dependent hydrolases; 1. DR Gene3D; 2.30.40.10; Urease, subunit C, domain 1; 1. DR InterPro; IPR006680; Amidohydro-rel. DR InterPro; IPR011778; Hydantoinase/dihydroPyrase. DR InterPro; IPR011059; Metal-dep_hydrolase_composite. DR InterPro; IPR032466; Metal_Hydrolase. DR NCBIfam; TIGR02033; D-hydantoinase; 1. DR PANTHER; PTHR11647:SF56; DIHYDROPYRIMIDINASE-RELATED PROTEIN 2; 1. DR PANTHER; PTHR11647; HYDRANTOINASE/DIHYDROPYRIMIDINASE FAMILY MEMBER; 1. DR Pfam; PF01979; Amidohydro_1; 1. DR SUPFAM; SSF51338; Composite domain of metallo-dependent hydrolases; 2. DR SUPFAM; SSF51556; Metallo-dependent hydrolases; 1. DR UCD-2DPAGE; O08553; -. DR Genevisible; O08553; MM. PE 1: Evidence at protein level; KW 3D-structure; Cytoplasm; Cytoskeleton; Developmental protein; KW Differentiation; Direct protein sequencing; Membrane; Methylation; KW Neurogenesis; Phosphoprotein; Reference proteome; S-nitrosylation. FT CHAIN 1..572 FT /note="Dihydropyrimidinase-related protein 2" FT /id="PRO_0000165914" FT REGION 512..572 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 512..552 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 32 FT /note="Phosphotyrosine; by FYN" FT /evidence="ECO:0000250|UniProtKB:Q16555" FT MOD_RES 258 FT /note="N6-succinyllysine" FT /evidence="ECO:0007744|PubMed:23806337" FT MOD_RES 259 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P47942" FT MOD_RES 402 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 431 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:18034455" FT MOD_RES 465 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:15648052" FT MOD_RES 499 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:18034455" FT MOD_RES 504 FT /note="S-nitrosocysteine" FT /evidence="ECO:0000250|UniProtKB:P47942" FT MOD_RES 507 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 509 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18034455, FT ECO:0007744|PubMed:21183079" FT MOD_RES 512 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 514 FT /note="Phosphothreonine; by GSK3-beta" FT /evidence="ECO:0000269|PubMed:22057101, FT ECO:0007744|PubMed:19131326, ECO:0007744|PubMed:21183079" FT MOD_RES 517 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19131326, FT ECO:0007744|PubMed:21183079" FT MOD_RES 518 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19131326, FT ECO:0007744|PubMed:21183079" FT MOD_RES 521 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 522 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19131326, FT ECO:0007744|PubMed:21183079" FT MOD_RES 537 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 540 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 542 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 555 FT /note="Phosphothreonine; by ROCK2" FT /evidence="ECO:0000250|UniProtKB:O02675" FT MOD_RES 565 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0007744|PubMed:24129315" FT MUTAGEN 514 FT /note="T->A: Delayed neurite degeneration." FT /evidence="ECO:0000269|PubMed:22057101" FT CONFLICT 11 FT /note="R -> P (in Ref. 1; CAA71370)" FT /evidence="ECO:0000305" FT CONFLICT 208 FT /note="E -> A (in Ref. 1; CAA71370)" FT /evidence="ECO:0000305" FT CONFLICT 257 FT /note="S -> P (in Ref. 1; CAA71370)" FT /evidence="ECO:0000305" FT STRAND 17..25 FT /evidence="ECO:0007829|PDB:5UQC" FT STRAND 30..38 FT /evidence="ECO:0007829|PDB:5UQC" FT STRAND 41..48 FT /evidence="ECO:0007829|PDB:5UQC" FT STRAND 56..59 FT /evidence="ECO:0007829|PDB:5UQC" FT STRAND 64..67 FT /evidence="ECO:0007829|PDB:5UQC" FT STRAND 69..72 FT /evidence="ECO:0007829|PDB:5UQC" FT HELIX 89..98 FT /evidence="ECO:0007829|PDB:5UQC" FT STRAND 101..108 FT /evidence="ECO:0007829|PDB:5UQC" FT HELIX 116..130 FT /evidence="ECO:0007829|PDB:5UQC" FT STRAND 132..140 FT /evidence="ECO:0007829|PDB:5UQC" FT HELIX 148..158 FT /evidence="ECO:0007829|PDB:5UQC" FT STRAND 163..170 FT /evidence="ECO:0007829|PDB:5UQC" FT TURN 171..174 FT /evidence="ECO:0007829|PDB:5UQC" FT HELIX 178..191 FT /evidence="ECO:0007829|PDB:5UQC" FT STRAND 194..198 FT /evidence="ECO:0007829|PDB:5UQC" FT HELIX 202..214 FT /evidence="ECO:0007829|PDB:5UQC" FT HELIX 221..225 FT /evidence="ECO:0007829|PDB:5UQC" FT HELIX 229..246 FT /evidence="ECO:0007829|PDB:5UQC" FT STRAND 250..255 FT /evidence="ECO:0007829|PDB:5UQC" FT HELIX 258..270 FT /evidence="ECO:0007829|PDB:5UQC" FT STRAND 274..279 FT /evidence="ECO:0007829|PDB:5UQC" FT HELIX 280..284 FT /evidence="ECO:0007829|PDB:5UQC" FT HELIX 287..291 FT /evidence="ECO:0007829|PDB:5UQC" FT HELIX 295..300 FT /evidence="ECO:0007829|PDB:5UQC" FT HELIX 313..322 FT /evidence="ECO:0007829|PDB:5UQC" FT HELIX 338..341 FT /evidence="ECO:0007829|PDB:5UQC" FT HELIX 342..344 FT /evidence="ECO:0007829|PDB:5UQC" FT HELIX 348..350 FT /evidence="ECO:0007829|PDB:5UQC" FT TURN 358..360 FT /evidence="ECO:0007829|PDB:5UQC" FT HELIX 361..369 FT /evidence="ECO:0007829|PDB:5UQC" FT TURN 370..373 FT /evidence="ECO:0007829|PDB:5UQC" FT HELIX 377..384 FT /evidence="ECO:0007829|PDB:5UQC" FT HELIX 386..391 FT /evidence="ECO:0007829|PDB:5UQC" FT TURN 395..397 FT /evidence="ECO:0007829|PDB:5UQC" FT STRAND 409..419 FT /evidence="ECO:0007829|PDB:5UQC" FT TURN 422..424 FT /evidence="ECO:0007829|PDB:5UQC" FT STRAND 426..428 FT /evidence="ECO:0007829|PDB:5UQC" FT TURN 433..436 FT /evidence="ECO:0007829|PDB:5UQC" FT STRAND 438..448 FT /evidence="ECO:0007829|PDB:5UQC" FT STRAND 451..455 FT /evidence="ECO:0007829|PDB:5UQC" FT HELIX 476..488 FT /evidence="ECO:0007829|PDB:5UQC" SQ SEQUENCE 572 AA; 62278 MW; C031F3BC038AA737 CRC64; MSYQGKKNIP RITSDRLLIK GGKIVNDDQS FYADIYMEDG LIKQIGENLI VPGGVKTIEA HSRMVIPGGI DVHTRFQMPD QGMTSADDFF QGTKAALAGG TTMIIDHVVP EPGTSLLAAF DQWREWADSK SCCDYSLHVD ITEWHKGIQE EMEALVKDHG VNSFLVYMAF KDRFQLTDSQ IYEVLSVIRD IGAIAQVHAE NGDIIAEEQQ RILDLGITGP EGHVLSRPEE VEAEAVNRSI TIANQTNCPL YVTKVMSKSA AEVIAQARKK GTVVYGEPIT ASLGTDGSHY WSKNWAKAAA FVTSPPLSPD PTTPDFLNSL LSCGDLQVTG SAHCTFNTAQ KAVGKDNFTL IPEGTNGTEE RMSVIWDKAV VTGKMDENQF VAVTSTNAAK VFNLYPRKGR ISVGSDADLV IWDPDSVKTI SAKTHNSALE YNIFEGMECR GSPLVVISQG KIVLEDGTLH VTEGSGRYIP RKPFPDFVYK RIKARSRLAE LRGVPRGLYD GPVCEVSVTP KTVTPASSAK TSPAKQQAPP VRNLHQSGFS LSGAQIDDNI PRRTTQRIVA PPGGRANITS LG //