Dihydropyrimidinase-related protein 2

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Reviewed, UniProtKB/Swiss-Prot Q16555 (DPYL2_HUMAN)

Last modified November 3, 2009. Version 95. History...

Clusters with 100%, 90%, 50% identity |

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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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
    N2A3

Gene names

Name:	DPYSL2
Synonyms:	CRMP2

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	572 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance, neuronal growth cone collapse and cell migration By similarity.
Subunit structure	Homotetramer, and heterotetramer with CRMP1, DPYSL3, DPYSL4 or DPYSL5 By similarity. Interacts through its C-terminus with the C-terminus of CYFIP1/SRA1. Interacts with HTR4 By similarity.
Subcellular location	Cytoplasm By similarity.
Tissue specificity	Ubiquitous.
Post-translational modification	3F4, a monoclonal antibody which strongly stains neurofibrillary tangles in Alzheimer disease brains, specifically labels DPYSL2 when phosphorylated on Ser-518, Ser-522 and Thr-509. Ref.7 Ref.10 Ref.12
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.

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Ontologies

Keywords
Biological process	Differentiation Neurogenesis
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Molecular function	Developmental protein
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW nervous system development Ref.2 Traceable author statement. Source: ProtInc nucleobase, nucleoside, nucleotide and nucleic acid metabolic process Ref.2 Traceable author statement. Source: ProtInc signal transduction Ref.2 Traceable author statement. Source: ProtInc
Cellular component	cytoskeleton Inferred from direct assay. Source: HPA
Molecular function	dihydropyrimidinase activity Ref.2 Traceable author statement. Source: ProtInc protein binding Ref.9 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 572

572

Dihydropyrimidinase-related protein 2

PRO_0000165913

Amino acid modifications

Modified residue

Phosphotyrosine By similarity

Modified residue

431

Phosphotyrosine By similarity

Modified residue

462

Phosphothreonine By similarity

Modified residue

465

Phosphoserine By similarity

Modified residue

499

Phosphotyrosine By similarity

Modified residue

509

Phosphothreonine Ref.7 Ref.10 Ref.12

Modified residue

514

Phosphothreonine; in vitro

Modified residue

517

Phosphoserine By similarity

Modified residue

518

Phosphoserine Ref.7

Modified residue

522

Phosphoserine Ref.7

Modified residue

542

Phosphoserine By similarity

Natural variations

Natural variant

118

A → T: dbSNP rs2289593.

VAR_022016

Natural variant

481

R → C in a colorectal cancer sample; somatic mutation. Ref.15

VAR_036316

Experimental info

Mutagenesis

D → N: Inhibits axon outgrowth formation in hippocampal neurons and decreases binding to CYFIP1. Ref.9

Mutagenesis

507

S → A: No effect. Ref.7

Mutagenesis

509

T → A: Greatly diminishes binding to 3F4 antibody. Ref.7

Mutagenesis

512

T → A: No effect. Ref.7

Mutagenesis

514

T → A: No effect. Ref.7

Mutagenesis

517

S → A: No effect. Ref.7

Mutagenesis

518

S → A: Greatly diminishes binding to 3F4 antibody. Ref.7

Mutagenesis

521

T → A: No effect. Ref.7

Mutagenesis

522

S → A: Greatly diminishes binding to 3F4 antibody. Ref.7

Secondary structure

572

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

Q16555-1 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 5CDB6CF7F5C308AD
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FASTA

572

62,294

        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 ISEWHKGIQE EMEALVKDHG VNSFLVYMAF KDRFQLTDCQ 

       190        200        210        220        230        240 
IYEVLSVIRD IGAIAQVHAE NGDIIAEEQQ RILDLGITGP EGHVLSRPEE VEAEAVNRAI 

       250        260        270        280        290        300 
TIANQTNCPL YITKVMSKSS 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 IAVGSDADLV IWDPDSVKTI 

       430        440        450        460        470        480 
SAKTHNSSLE YNIFEGMECR GSPLVVISQG KIVLEDGTLH VTEGSGRYIP RKPFPDFVYK 

       490        500        510        520        530        540 
RIKARSRLAE LRGVPRGLYD GPVCEVSVTP KTVTPASSAK TSPAKQQAPP VRNLHQSGFS 

       550        560        570 
LSGAQIDDNI PRRTTQRIVA PPGGRANITS LG

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Collapsin-induced growth cone collapse mediated by an intracellular protein related to UNC-33." Goshima Y., Nakamura F., Strittmatter P., Strittmatter S.M. Nature 376:509-514(1995) [PubMed: 7637782] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"A novel gene family defined by human dihydropyrimidinase and three related proteins with differential tissue distribution." Hamajima N., Matsuda K., Sakata S., Tamaki N., Sasaki M., Nonaka M. Gene 180:157-163(1996) [PubMed: 8973361] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[3]	"A cDNA clone highly expressed in human brain and deleted in liver cancer." Zhou J., Chen Y., Gu J.R. Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fetal liver.
[4]	"Characterization of the human dihydropyrimidinase-related protein 2 (DRP-2) gene." Kitamura K., Takayama M., Hamajima N., Nakanishi M., Sasaki M., Endo Y., Takemoto T., Kimura H., Iwaki M., Nonaka M. DNA Res. 6:291-297(1999) [PubMed: 10574455] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Eye and Testis.
[6]	Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 44-56; 64-75; 147-157; 174-211; 239-254; 375-390; 401-418; 424-467; 497-511 AND 533-552, MASS SPECTROMETRY. Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
[7]	"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: 10757975] [Abstract] Cited for: PHOSPHORYLATION AT SER-518; SER-522 AND THR-509, MUTAGENESIS OF SER-507; THR-509; THR-512; THR-514; SER-517; SER-518; THR-521 AND SER-522.
[8]	"CRMP-2 induces axons in cultured hippocampal neurons." Inagaki N., Chihara K., Arimura N., Menager C., Kawano Y., Matsuo N., Nishimura T., Amano M., Kaibuchi K. Nat. Neurosci. 4:781-782(2001) [PubMed: 11477421] [Abstract] Cited for: FUNCTION.
[9]	"CRMP-2 is involved in kinesin-1-dependent transport of the Sra-1/WAVE1 complex and axon formation." Kawano Y., Yoshimura T., Tsuboi D., Kawabata S., Kaneko-Kawano T., Shirataki H., Takenawa T., Kaibuchi K. Mol. Cell. Biol. 25:9920-9935(2005) [PubMed: 16260607] [Abstract] Cited for: INTERACTION WITH CYFIP1, MUTAGENESIS OF ASP-71.
[10]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-509, MASS SPECTROMETRY. Tissue: Epithelium.
[11]	"Structural bases for CRMP function in plexin-dependent semaphorin3A signaling." Deo R.C., Schmidt E.F., Elhabazi A., Togashi H., Burley S.K., Strittmatter S.M. EMBO J. 23:9-22(2004) [PubMed: 14685275] [Abstract] Cited for: INTERACTION WITH PLEXNA1, SUBUNIT.
[12]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-509, MASS SPECTROMETRY.
[13]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[14]	"The structure of human collapsin response mediator protein 2, a regulator of axonal growth." Stenmark P., Ogg D., Flodin S., Flores A., Kotenyova T., Nyman T., Nordlund P., Kursula P. J. Neurochem. 101:906-917(2007) [PubMed: 17250651] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 12-490, SUBUNIT.
[15]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] CYS-481.
+	Additional computationally mapped references.

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Cross-references

Sequence databases

U17279 mRNA. Translation: AAA93202.1.
D78013 mRNA. Translation: BAA11191.1.
U97105 mRNA. Translation: AAC05793.1.
AB020777 Genomic DNA. Translation: BAA86991.1.
BC056408 mRNA. Translation: AAH56408.1.
BC067109 mRNA. Translation: AAH67109.1.

IPI

IPI00257508.

PIR

JC5317.

RefSeq

NP_001377.1.

UniGene

Hs.173381

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2GSE	X-ray	2.40	A/B/C/D	13-490	[»]
2VM8	X-ray	1.90	A/B/C/D	13-490	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q16555. 1 interaction.

STRING

Q16555.

Protein family/group databases

MEROPS

M38.975.

PTM databases

PhosphoSite

Q16555.

2-D gel databases

REPRODUCTION-2DPAGE

IPI00257508.
Q16555.

Proteomic databases

PeptideAtlas

Q16555.

PRIDE

Q16555.

Genome annotation databases

Ensembl

ENST00000311151; ENSP00000309539; ENSG00000092964; Homo sapiens. [Genome view]
ENST00000436721; ENSP00000413876; ENSG00000092964; Homo sapiens. [Genome view]

GeneID

1808.

KEGG

hsa:1808.

NMPDR

fig|9606.3.peg.30095.

UCSC

uc003xfb.1. human.

Organism-specific databases

CTD

1808.

GeneCards

GC08P026491.

H-InvDB

HIX0007403.

HGNC

HGNC:3014. DPYSL2.

HPA

CAB018719.
HPA002381.

MIM

602463. gene.

PharmGKB

PA27472.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

Q16555.

OMA

AQARKKX.

Enzyme and pathway databases

Reactome

REACT_18266. Axon guidance.

Gene expression databases

ArrayExpress

Q16555.

Bgee

Q16555.

CleanEx

HS_DPYSL2.

Genevestigator

Q16555.

GermOnline

ENSG00000092964. Homo sapiens.

Family and domain databases

InterPro

IPR006680. Amidohydro_1.
IPR011778. D-hydantoinase.
[Graphical view]

Pfam

PF01979. Amidohydro_1. 1 hit.
[Graphical view]

ProDom

PD000518. DHOase. 1 hit.
[Graphical view] [Entries sharing at least one domain]

TIGRFAMs

TIGR02033. D-hydantoinase. 1 hit.

ProtoNet

Search...

Other Resources

NextBio

7369.

SOURCE

Search...

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Entry information

Entry name

DPYL2_HUMAN

Accession

Primary (citable) accession number: Q16555
Secondary accession number(s): O00424

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	November 1, 1996
Last modified:	November 3, 2009
This is version 95 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

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