ID DPYL2_RAT Reviewed; 572 AA. AC P47942; DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1996, sequence version 1. DT 24-JAN-2024, entry version 187. DE RecName: Full=Dihydropyrimidinase-related protein 2; DE Short=DRP-2; DE AltName: Full=Collapsin response mediator protein 2; DE Short=CRMP-2; DE AltName: Full=Turned on after division 64 kDa protein; DE Short=TOAD-64; GN Name=Dpysl2; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 136-142; 402-418; 441-450 RP AND 499-511, AND SUBCELLULAR LOCATION. RC STRAIN=Sprague-Dawley; TISSUE=Brain; RX PubMed=7472434; DOI=10.1523/jneurosci.15-10-06757.1995; RA Minturn J.E., Fryer H.J.L., Geschwind D.H., Hockfield S.; RT "TOAD-64, a gene expressed early in neuronal differentiation in the rat, is RT related to unc-33, a C. elegans gene involved in axon outgrowth."; RL J. Neurosci. 15:6757-6766(1995). RN [2] RP PROTEIN SEQUENCE OF 44-56; 76-94; 147-157; 174-238; 259-268; 375-397; RP 424-467; 472-480; 533-552 AND 558-565, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC STRAIN=Sprague-Dawley; TISSUE=Brain, Hippocampus, and Spinal cord; RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Kang S.U.; RL Submitted (JUL-2007) to UniProtKB. RN [3] RP INTERACTION WITH CRMP1; DPYSL3 AND DPYSL4, AND 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 [4] RP PHOSPHORYLATION AT THR-509; SER-518 AND SER-522, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RX PubMed=10757975; DOI=10.1021/bi992323h; RA Gu Y., Hamajima N., Ihara Y.; RT "Neurofibrillary tangle-associated collapsin response mediator protein-2 RT (CRMP-2) is highly phosphorylated on Thr-509, Ser-518, and Ser-522."; RL Biochemistry 39:4267-4275(2000). RN [5] RP S-NITROSYLATION [LARGE SCALE ANALYSIS] AT CYS-504, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=16418269; DOI=10.1073/pnas.0508412103; RA Hao G., Derakhshan B., Shi L., Campagne F., Gross S.S.; RT "SNOSID, a proteomic method for identification of cysteine S-nitrosylation RT sites in complex protein mixtures."; RL Proc. Natl. Acad. Sci. U.S.A. 103:1012-1017(2006). RN [6] RP PHOSPHORYLATION AT THR-509, AND IDENTIFICATION BY MASS SPECTROMETRY. RA Lubec G., Chen W.-Q.; RL Submitted (FEB-2007) to UniProtKB. RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-259; THR-509; THR-514 AND RP SER-540, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., RA Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 different rat RT organs and tissues."; RL Nat. Commun. 3:876-876(2012). 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 (By similarity). {ECO:0000250}. 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:9375656}. CC -!- INTERACTION: CC P47942; P63331: Ppp2ca; NbExp=2; IntAct=EBI-917570, EBI-7050205; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250}. Cytoplasm, CC cytoskeleton {ECO:0000250}. Membrane {ECO:0000250}. Note=Tightly but CC noncovalently associated with membranes. {ECO:0000269|PubMed:7472434}. CC -!- DEVELOPMENTAL STAGE: Expressed immediately after neuronal birth and is CC dramatically down-regulated in the adult. CC -!- PTM: Phosphorylation by DYRK2 at Ser-522 is required for subsequent CC phosphorylation by GSK3B. Phosphorylation at Thr-514 by GSK3B abolishes CC tubulin-binding leading to destabilization of microtubule assembly in CC axons and neurodegeneration (By similarity). {ECO:0000250}. 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; Z46882; CAA86981.1; -; mRNA. DR PIR; A59280; S49985. DR RefSeq; NP_001099187.1; NM_001105717.2. DR AlphaFoldDB; P47942; -. DR SMR; P47942; -. DR BioGRID; 247451; 15. DR CORUM; P47942; -. DR IntAct; P47942; 9. DR MINT; P47942; -. DR STRING; 10116.ENSRNOP00000012996; -. DR MEROPS; M38.975; -. DR GlyGen; P47942; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P47942; -. DR PhosphoSitePlus; P47942; -. DR SwissPalm; P47942; -. DR jPOST; P47942; -. DR PaxDb; 10116-ENSRNOP00000012996; -. DR Ensembl; ENSRNOT00000012996.7; ENSRNOP00000012996.4; ENSRNOG00000009625.7. DR Ensembl; ENSRNOT00055011125; ENSRNOP00055008706; ENSRNOG00055006785. DR Ensembl; ENSRNOT00060019934; ENSRNOP00060015658; ENSRNOG00060011761. DR Ensembl; ENSRNOT00065030193; ENSRNOP00065023986; ENSRNOG00065017984. DR GeneID; 25416; -. DR KEGG; rno:25416; -. DR UCSC; RGD:2517; rat. DR AGR; RGD:2517; -. DR CTD; 1808; -. DR RGD; 2517; Dpysl2. DR eggNOG; KOG2584; Eukaryota. DR GeneTree; ENSGT01030000234527; -. DR HOGENOM; CLU_015572_2_2_1; -. DR InParanoid; P47942; -. DR OrthoDB; 1772494at2759; -. DR PhylomeDB; P47942; -. DR TreeFam; TF314706; -. DR Reactome; R-RNO-399956; CRMPs in Sema3A signaling. DR Reactome; R-RNO-437239; Recycling pathway of L1. DR PRO; PR:P47942; -. DR Proteomes; UP000002494; Chromosome 15. DR Bgee; ENSRNOG00000009625; Expressed in frontal cortex and 18 other cell types or tissues. DR GO; GO:0030424; C:axon; ISO:RGD. DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell. DR GO; GO:0005829; C:cytosol; ISO:RGD. DR GO; GO:0030425; C:dendrite; IDA:RGD. DR GO; GO:0030426; C:growth cone; IDA:RGD. DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell. DR GO; GO:0043209; C:myelin sheath; IDA:UniProtKB. DR GO; GO:0043025; C:neuronal cell body; IDA:RGD. DR GO; GO:0098793; C:presynapse; IDA:SynGO. DR GO; GO:0032991; C:protein-containing complex; IDA:RGD. DR GO; GO:0045202; C:synapse; IDA:SynGO. 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:RGD. DR GO; GO:0019901; F:protein kinase binding; ISO:RGD. DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW. DR GO; GO:0007010; P:cytoskeleton organization; ISS:UniProtKB. DR GO; GO:0006897; P:endocytosis; ISS:UniProtKB. DR GO; GO:0021772; P:olfactory bulb development; IEP:RGD. DR GO; GO:0014049; P:positive regulation of glutamate secretion; IDA:RGD. DR GO; GO:0030516; P:regulation of axon extension; NAS:RGD. DR GO; GO:0045664; P:regulation of neuron differentiation; IMP:RGD. DR GO; GO:0010975; P:regulation of neuron projection development; ISO:RGD. DR GO; GO:0001975; P:response to amphetamine; IEP:RGD. DR GO; GO:0042220; P:response to cocaine; IEP:RGD. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD. DR GO; GO:0021510; P:spinal cord development; IEP:RGD. DR GO; GO:0048489; P:synaptic vesicle transport; IDA:RGD. 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 World-2DPAGE; 0004:P47942; -. PE 1: Evidence at protein level; KW Cytoplasm; Cytoskeleton; Developmental protein; Differentiation; KW Direct protein sequencing; Membrane; Methylation; Neurogenesis; KW Phosphoprotein; Reference proteome; S-nitrosylation. FT CHAIN 1..572 FT /note="Dihydropyrimidinase-related protein 2" FT /id="PRO_0000165915" 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 SITE 486 FT /note="Not phosphorylated" 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:0000250|UniProtKB:O08553" FT MOD_RES 259 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 402 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O08553" FT MOD_RES 431 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:O08553" FT MOD_RES 465 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O08553" FT MOD_RES 499 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:O08553" FT MOD_RES 504 FT /note="S-nitrosocysteine" FT /evidence="ECO:0007744|PubMed:16418269" FT MOD_RES 507 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O08553" FT MOD_RES 509 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:10757975, ECO:0000269|Ref.6, FT ECO:0007744|PubMed:22673903" FT MOD_RES 512 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:O08553" FT MOD_RES 514 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 517 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q16555" FT MOD_RES 518 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:10757975" FT MOD_RES 521 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:O08553" FT MOD_RES 522 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:10757975" FT MOD_RES 522 FT /note="Phosphoserine; by DYRK2" FT /evidence="ECO:0000250" FT MOD_RES 537 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O08553" FT MOD_RES 540 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 542 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O08553" 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:0000250|UniProtKB:O08553" 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 //