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Protein

Dihydropyrimidinase-related protein 2

Gene

Dpysl2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Plays a role in neuronal development and polarity, as well as in axon growth and guidance, neuronal growth cone collapse and cell migration. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. May play a role in endocytosis (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei486 – 4861Not phosphorylated

GO - Molecular functioni

  1. hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amides Source: InterPro

GO - Biological processi

  1. brain development Source: RGD
  2. cytoskeleton organization Source: UniProtKB
  3. endocytosis Source: UniProtKB
  4. olfactory bulb development Source: RGD
  5. positive regulation of glutamate secretion Source: RGD
  6. pyrimidine nucleobase catabolic process Source: InterPro
  7. regulation of axon extension Source: RGD
  8. regulation of neuron differentiation Source: RGD
  9. response to amphetamine Source: RGD
  10. response to cocaine Source: RGD
  11. response to drug Source: RGD
  12. spinal cord development Source: RGD
  13. synaptic vesicle transport Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Differentiation, Neurogenesis

Enzyme and pathway databases

ReactomeiREACT_254909. CRMPs in Sema3A signaling.
REACT_262886. Recycling pathway of L1.

Protein family/group databases

MEROPSiM38.975.

Names & Taxonomyi

Protein namesi
Recommended name:
Dihydropyrimidinase-related protein 2
Short name:
DRP-2
Alternative name(s):
Collapsin response mediator protein 2
Short name:
CRMP-2
Turned on after division 64 kDa protein
Short name:
TOAD-64
Gene namesi
Name:Dpysl2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 15

Organism-specific databases

RGDi2517. Dpysl2.

Subcellular locationi

Cytoplasmcytosol By similarity. Cytoplasmcytoskeleton By similarity. Membrane By similarity
Note: Tightly but noncovalently associated with membranes.1 Publication

GO - Cellular componenti

  1. axon Source: Ensembl
  2. cytosol Source: RGD
  3. dendrite Source: RGD
  4. extracellular vesicular exosome Source: Ensembl
  5. growth cone Source: RGD
  6. membrane Source: UniProtKB-SubCell
  7. microtubule Source: Ensembl
  8. mitochondrion Source: Ensembl
  9. neuronal cell body Source: RGD
  10. neuron projection Source: RGD
  11. protein complex Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 572572Dihydropyrimidinase-related protein 2PRO_0000165915Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei32 – 321Phosphotyrosine; by FYNBy similarity
Modified residuei101 – 1011PhosphothreonineBy similarity
Modified residuei102 – 1021PhosphothreonineBy similarity
Modified residuei258 – 2581N6-succinyllysineBy similarity
Modified residuei259 – 2591PhosphoserineBy similarity
Modified residuei431 – 4311PhosphotyrosineBy similarity
Modified residuei465 – 4651PhosphoserineBy similarity
Modified residuei499 – 4991PhosphotyrosineBy similarity
Modified residuei504 – 5041S-nitrosocysteine1 Publication
Modified residuei509 – 5091Phosphothreonine2 Publications
Modified residuei514 – 5141Phosphothreonine; by GSK3-betaBy similarity
Modified residuei517 – 5171PhosphoserineBy similarity
Modified residuei518 – 5181Phosphoserine1 Publication
Modified residuei522 – 5221Phosphoserine; alternate1 Publication
Modified residuei522 – 5221Phosphoserine; by DYRK2; alternateBy similarity
Modified residuei555 – 5551Phosphothreonine; by ROCK2By similarity

Post-translational modificationi

Phosphorylation by DYRK2 at Ser-522 is required for subsequent phosphorylation by GSK3B. Phosphorylation at Thr-514 by GSK3B abolishes tubulin-binding leading to destabilization of microtubule assembly in axons and neurodegeneration (By similarity).By similarity

Keywords - PTMi

Phosphoprotein, S-nitrosylation

Proteomic databases

PaxDbiP47942.
PRIDEiP47942.

2D gel databases

World-2DPAGE0004:P47942.

PTM databases

PhosphoSiteiP47942.

Expressioni

Developmental stagei

Expressed immediately after neuronal birth and is dramatically down-regulated in the adult.

Gene expression databases

GenevestigatoriP47942.

Interactioni

Subunit structurei

Homotetramer, and heterotetramer with CRMP1, DPYSL3, DPYSL4 or DPYSL5. Interacts through its C-terminus with the C-terminus of CYFIP1/SRA1. Interacts with HTR4. Interacts with CLN6. Interacts with MICALL1.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
Ppp2caP633312EBI-917570,EBI-7050205

Protein-protein interaction databases

BioGridi247451. 6 interactions.
IntActiP47942. 4 interactions.
MINTiMINT-224453.
STRINGi10116.ENSRNOP00000012996.

Structurei

3D structure databases

ProteinModelPortaliP47942.
SMRiP47942. Positions 14-490.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG0044.
GeneTreeiENSGT00760000119241.
HOGENOMiHOG000219145.
HOVERGENiHBG000806.
InParanoidiP47942.
KOiK07528.
OMAiQGTKASL.
OrthoDBiEOG7SJD48.
PhylomeDBiP47942.
TreeFamiTF314706.

Family and domain databases

Gene3Di2.30.40.10. 2 hits.
InterProiIPR006680. Amidohydro_1.
IPR011778. Hydantoinase/dihydroPyrase.
IPR011059. Metal-dep_hydrolase_composite.
[Graphical view]
PfamiPF01979. Amidohydro_1. 1 hit.
[Graphical view]
SUPFAMiSSF51338. SSF51338. 2 hits.
TIGRFAMsiTIGR02033. D-hydantoinase. 1 hit.

Sequencei

Sequence statusi: Complete.

P47942-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSYQGKKNIP RITSDRLLIK GGKIVNDDQS FYADIYMEDG LIKQIGENLI
60 70 80 90 100
VPGGVKTIEA HSRMVIPGGI DVHTRFQMPD QGMTSADDFF QGTKAALAGG
110 120 130 140 150
TTMIIDHVVP EPGTSLLAAF DQWREWADSK SCCDYSLHVD ITEWHKGIQE
160 170 180 190 200
EMEALVKDHG VNSFLVYMAF KDRFQLTDSQ IYEVLSVIRD IGAIAQVHAE
210 220 230 240 250
NGDIIAEEQQ RILDLGITGP EGHVLSRPEE VEAEAVNRSI TIANQTNCPL
260 270 280 290 300
YVTKVMSKSA AEVIAQARKK GTVVYGEPIT ASLGTDGSHY WSKNWAKAAA
310 320 330 340 350
FVTSPPLSPD PTTPDFLNSL LSCGDLQVTG SAHCTFNTAQ KAVGKDNFTL
360 370 380 390 400
IPEGTNGTEE RMSVIWDKAV VTGKMDENQF VAVTSTNAAK VFNLYPRKGR
410 420 430 440 450
ISVGSDADLV IWDPDSVKTI SAKTHNSALE YNIFEGMECR GSPLVVISQG
460 470 480 490 500
KIVLEDGTLH VTEGSGRYIP RKPFPDFVYK RIKARSRLAE LRGVPRGLYD
510 520 530 540 550
GPVCEVSVTP KTVTPASSAK TSPAKQQAPP VRNLHQSGFS LSGAQIDDNI
560 570
PRRTTQRIVA PPGGRANITS LG
Length:572
Mass (Da):62,278
Last modified:February 1, 1996 - v1
Checksum:iC031F3BC038AA737
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z46882 mRNA. Translation: CAA86981.1.
PIRiA59280. S49985.
RefSeqiNP_001099187.1. NM_001105717.2.
UniGeneiRn.2889.

Genome annotation databases

EnsembliENSRNOT00000012996; ENSRNOP00000012996; ENSRNOG00000009625.
GeneIDi25416.
KEGGirno:25416.
UCSCiRGD:2517. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z46882 mRNA. Translation: CAA86981.1.
PIRiA59280. S49985.
RefSeqiNP_001099187.1. NM_001105717.2.
UniGeneiRn.2889.

3D structure databases

ProteinModelPortaliP47942.
SMRiP47942. Positions 14-490.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi247451. 6 interactions.
IntActiP47942. 4 interactions.
MINTiMINT-224453.
STRINGi10116.ENSRNOP00000012996.

Protein family/group databases

MEROPSiM38.975.

PTM databases

PhosphoSiteiP47942.

2D gel databases

World-2DPAGE0004:P47942.

Proteomic databases

PaxDbiP47942.
PRIDEiP47942.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000012996; ENSRNOP00000012996; ENSRNOG00000009625.
GeneIDi25416.
KEGGirno:25416.
UCSCiRGD:2517. rat.

Organism-specific databases

CTDi1808.
RGDi2517. Dpysl2.

Phylogenomic databases

eggNOGiCOG0044.
GeneTreeiENSGT00760000119241.
HOGENOMiHOG000219145.
HOVERGENiHBG000806.
InParanoidiP47942.
KOiK07528.
OMAiQGTKASL.
OrthoDBiEOG7SJD48.
PhylomeDBiP47942.
TreeFamiTF314706.

Enzyme and pathway databases

ReactomeiREACT_254909. CRMPs in Sema3A signaling.
REACT_262886. Recycling pathway of L1.

Miscellaneous databases

NextBioi606559.
PROiP47942.

Gene expression databases

GenevestigatoriP47942.

Family and domain databases

Gene3Di2.30.40.10. 2 hits.
InterProiIPR006680. Amidohydro_1.
IPR011778. Hydantoinase/dihydroPyrase.
IPR011059. Metal-dep_hydrolase_composite.
[Graphical view]
PfamiPF01979. Amidohydro_1. 1 hit.
[Graphical view]
SUPFAMiSSF51338. SSF51338. 2 hits.
TIGRFAMsiTIGR02033. D-hydantoinase. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "TOAD-64, a gene expressed early in neuronal differentiation in the rat, is related to unc-33, a C. elegans gene involved in axon outgrowth."
    Minturn J.E., Fryer H.J.L., Geschwind D.H., Hockfield S.
    J. Neurosci. 15:6757-6766(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 136-142; 402-418; 441-450 AND 499-511, SUBCELLULAR LOCATION.
    Strain: Sprague-Dawley.
    Tissue: Brain.
  2. Lubec G., Afjehi-Sadat L., Chen W.-Q., Kang S.U.
    Submitted (JUL-2007) to UniProtKB
    Cited for: PROTEIN SEQUENCE OF 44-56; 76-94; 147-157; 174-238; 259-268; 375-397; 424-467; 472-480; 533-552 AND 558-565, IDENTIFICATION BY MASS SPECTROMETRY.
    Strain: Sprague-Dawley.
    Tissue: Brain, Hippocampus and Spinal cord.
  3. "Brain CRMP forms heterotetramers similar to liver dihydropyrimidinase."
    Wang L.H., Strittmatter S.M.
    J. Neurochem. 69:2261-2269(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CRMP1; DPYSL3 AND DPYSL4, SUBUNIT.
  4. "Neurofibrillary tangle-associated collapsin response mediator protein-2 (CRMP-2) is highly phosphorylated on Thr-509, Ser-518, and Ser-522."
    Gu Y., Hamajima N., Ihara Y.
    Biochemistry 39:4267-4275(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT THR-509; SER-518 AND SER-522, IDENTIFICATION BY MASS SPECTROMETRY.
  5. "SNOSID, a proteomic method for identification of cysteine S-nitrosylation sites in complex protein mixtures."
    Hao G., Derakhshan B., Shi L., Campagne F., Gross S.S.
    Proc. Natl. Acad. Sci. U.S.A. 103:1012-1017(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: S-NITROSYLATION [LARGE SCALE ANALYSIS] AT CYS-504, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  6. Lubec G., Chen W.-Q.
    Submitted (FEB-2007) to UniProtKB
    Cited for: PHOSPHORYLATION AT THR-509, IDENTIFICATION BY MASS SPECTROMETRY.

Entry informationi

Entry nameiDPYL2_RAT
AccessioniPrimary (citable) accession number: P47942
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: March 4, 2015
This is version 127 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

Lacks most of the conserved residues that are essential for binding the metal cofactor and hence for dihydropyrimidinase activity. Its enzyme activity is therefore unsure.Curated

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.