P47942 (DPYL2_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:

Dpysl2

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	572 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Plays a role in neuronal development and polarity, as well as in neuron projection morphogenesis, axon growth and guidance, neuronal growth cone collapse and cell migration. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton By similarity.
Subunit structure	Homotetramer, and heterotetramer with CRMP1, DPYSL3, DPYSL4 or DPYSL5. Interacts through its C-terminus with the C-terminus of CYFIP1/SRA1 By similarity. Interacts with HTR4 By similarity. Interacts with CLN6 By similarity. Ref.4
Subcellular location	Cytoplasm By similarity. Note: Tightly but noncovalently associated with membranes. Ref.1
Developmental stage	Expressed immediately after neuronal birth and is dramatically down-regulated in the adult.
Post-translational modification	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.
Sequence similarities	Belongs to the DHOase family. Hydantoinase/dihydropyrimidinase subfamily.
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.

Ontologies

Keywords
Biological process	Differentiation Neurogenesis
Cellular component	Cytoplasm
Molecular function	Developmental protein
PTM	Phosphoprotein S-nitrosylation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cytoskeleton organization Inferred from sequence or structural similarity. Source: UniProtKB olfactory bulb development Inferred from expression pattern PubMed 14751288. Source: RGD positive regulation of glutamate secretion Inferred from direct assay PubMed 19755421. Source: RGD pyrimidine nucleobase catabolic process Inferred from electronic annotation. Source: InterPro regulation of axon extension Non-traceable author statement Ref.1. Source: RGD response to amphetamine Inferred from expression pattern PubMed 20058175. Source: RGD response to cocaine Inferred from expression pattern PubMed 19457111. Source: RGD response to drug Inferred from expression pattern PubMed 12188101. Source: RGD spinal cord development Inferred from expression pattern PubMed 8946055. Source: RGD synaptic vesicle transport Inferred from direct assay PubMed 19755421. Source: RGD
Cellular_component	axon Inferred from electronic annotation. Source: Compara cytosol Inferred from direct assay PubMed 11741937. Source: RGD dendrite Inferred from direct assay PubMed 19755421. Source: RGD growth cone Inferred from direct assay Ref.1. Source: RGD mitochondrion Inferred from electronic annotation. Source: Compara neuronal cell body Inferred from direct assay PubMed 19457111. Source: RGD protein complex Inferred from direct assay PubMed 19755421. Source: RGD
Molecular_function	hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amides Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 572	572	Dihydropyrimidinase-related protein 2		PRO_0000165915
Sites
	Site	486	1	Not phosphorylated
Amino acid modifications
	Modified residue	32	1	Phosphotyrosine; by FYN By similarity
	Modified residue	431	1	Phosphotyrosine By similarity
	Modified residue	462	1	Phosphothreonine By similarity
	Modified residue	465	1	Phosphoserine By similarity
	Modified residue	499	1	Phosphotyrosine By similarity
	Modified residue	504	1	S-nitrosocysteine Ref.3
	Modified residue	509	1	Phosphothreonine Ref.5 Ref.6
	Modified residue	514	1	Phosphothreonine; by GSK3-beta By similarity
	Modified residue	517	1	Phosphoserine By similarity
	Modified residue	518	1	Phosphoserine Ref.5
	Modified residue	522	1	Phosphoserine; alternate Ref.5
	Modified residue	522	1	Phosphoserine; by DYRK2; alternate By similarity
	Modified residue	542	1	Phosphoserine By similarity
	Modified residue	555	1	Phosphothreonine; by ROCK2 By similarity

Sequences

	Sequence		Length	Mass (Da)
	P47942 [UniParc]. Last modified February 1, 1996. Version 1. Checksum: C031F3BC038AA737	FASTA	572	62,278
	10 20 30 40 50 60 MSYQGKKNIP RITSDRLLIK GGKIVNDDQS FYADIYMEDG LIKQIGENLI VPGGVKTIEA 70 80 90 100 110 120 HSRMVIPGGI DVHTRFQMPD QGMTSADDFF QGTKAALAGG TTMIIDHVVP EPGTSLLAAF 130 140 150 160 170 180 DQWREWADSK SCCDYSLHVD ITEWHKGIQE EMEALVKDHG VNSFLVYMAF KDRFQLTDSQ 190 200 210 220 230 240 IYEVLSVIRD IGAIAQVHAE NGDIIAEEQQ RILDLGITGP EGHVLSRPEE VEAEAVNRSI 250 260 270 280 290 300 TIANQTNCPL YVTKVMSKSA AEVIAQARKK GTVVYGEPIT ASLGTDGSHY WSKNWAKAAA 310 320 330 340 350 360 FVTSPPLSPD PTTPDFLNSL LSCGDLQVTG SAHCTFNTAQ KAVGKDNFTL IPEGTNGTEE 370 380 390 400 410 420 RMSVIWDKAV VTGKMDENQF VAVTSTNAAK VFNLYPRKGR ISVGSDADLV IWDPDSVKTI 430 440 450 460 470 480 SAKTHNSALE YNIFEGMECR GSPLVVISQG KIVLEDGTLH VTEGSGRYIP RKPFPDFVYK 490 500 510 520 530 540 RIKARSRLAE LRGVPRGLYD GPVCEVSVTP KTVTPASSAK TSPAKQQAPP VRNLHQSGFS 550 560 570 LSGAQIDDNI PRRTTQRIVA PPGGRANITS LG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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, MASS SPECTROMETRY. Strain: Sprague-Dawley. Tissue: Brain, Hippocampus and Spinal cord.
[3]	"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: PROTEIN SEQUENCE OF 497-511, S-NITROSYLATION [LARGE SCALE ANALYSIS] AT CYS-504, MASS SPECTROMETRY. Tissue: Cerebellum.
[4]	"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.
[5]	"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, MASS SPECTROMETRY.
[6]	Lubec G., Chen W.-Q. Submitted (FEB-2007) to UniProtKB Cited for: PHOSPHORYLATION AT THR-509, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	Z46882 mRNA. Translation: CAA86981.1.
IPI	IPI00870112.
PIR	S49985. A59280.
RefSeq	NP_001099187.1. NM_001105717.2.
UniGene	Rn.2889.
3D structure databases
ProteinModelPortal	P47942.
SMR	P47942. Positions 14-490.
ModBase	Search...
Protein-protein interaction databases
IntAct	P47942. 1 interaction.
MINT	MINT-224453.
STRING	10116.ENSRNOP00000012996.
Protein family/group databases
MEROPS	M38.975.
PTM databases
PhosphoSite	P47942.
2D gel databases
World-2DPAGE	0004:P47942.
Proteomic databases
PaxDb	P47942.
PRIDE	P47942.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000012996; ENSRNOP00000012996; ENSRNOG00000009625.
GeneID	25416.
KEGG	rno:25416.
UCSC	RGD:2517. rat.
Organism-specific databases
CTD	1808.
RGD	2517. Dpysl2.
Phylogenomic databases
eggNOG	COG0044.
GeneTree	ENSGT00550000074371.
HOGENOM	HOG000219145.
HOVERGEN	HBG000806.
InParanoid	P47942.
KO	K07528.
OMA	TEWHKGV.
OrthoDB	EOG48PMJT.
Gene expression databases
Genevestigator	P47942.
GermOnline	ENSRNOG00000009625. Rattus norvegicus.
Family and domain databases
InterPro	IPR006680. Amidohydro_1. IPR011778. Hydantoinase/dihydroPyrase. IPR011059. Metal-dep_hydrolase_composite. [Graphical view]
Pfam	PF01979. Amidohydro_1. 1 hit. [Graphical view]
SUPFAM	SSF51338. Metalo_hydrolase. 2 hits.
TIGRFAMs	TIGR02033. D-hydantoinase. 1 hit.
ProtoNet	Search...
Other
NextBio	606559.

Entry information

Entry name

DPYL2_RAT

Accession

Primary (citable) accession number: P47942

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	February 1, 1996
Last modified:	April 3, 2013
This is version 112 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program