DPYL2_RAT
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 03-AUG-2022, entry version 179.
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}.
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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; 8.
DR MINT; P47942; -.
DR STRING; 10116.ENSRNOP00000012996; -.
DR MEROPS; M38.975; -.
DR iPTMnet; P47942; -.
DR PhosphoSitePlus; P47942; -.
DR World-2DPAGE; 0004:P47942; -.
DR jPOST; P47942; -.
DR PaxDb; P47942; -.
DR PRIDE; P47942; -.
DR Ensembl; ENSRNOT00000012996; ENSRNOP00000012996; ENSRNOG00000009625.
DR GeneID; 25416; -.
DR KEGG; rno:25416; -.
DR UCSC; RGD:2517; rat.
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 OMA; FTHRENF; -.
DR OrthoDB; 719800at2759; -.
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 tissues.
DR GO; GO:0030424; C:axon; ISO:RGD.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IDA: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:0043005; C:neuron projection; IDA:RGD.
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:0016810; F:hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds; IEA:InterPro.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0008017; F:microtubule binding; IEA:InterPro.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0007411; P:axon guidance; IEA:InterPro.
DR GO; GO:0007420; P:brain development; IEP:RGD.
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; 2.30.40.10; -; 1.
DR InterPro; IPR006680; Amidohydro-rel.
DR InterPro; IPR030615; DRP2.
DR InterPro; IPR011778; Hydantoinase/dihydroPyrase.
DR InterPro; IPR011059; Metal-dep_hydrolase_composite.
DR InterPro; IPR032466; Metal_Hydrolase.
DR PANTHER; PTHR11647:SF56; PTHR11647:SF56; 1.
DR Pfam; PF01979; Amidohydro_1; 1.
DR SUPFAM; SSF51338; SSF51338; 2.
DR SUPFAM; SSF51556; SSF51556; 1.
DR TIGRFAMs; TIGR02033; D-hydantoinase; 1.
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
