Q16555 (DPYL2_HUMAN) 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
N2A3
Unc-33-like phosphoprotein 2
Short name=ULIP-2

Gene names

Name:	DPYSL2
Synonyms:	CRMP2, ULIP2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

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

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. Ref.10
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. Ref.11 Ref.13 Ref.19
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.9 Ref.12 Ref.14 Ref.15 Ref.16 Ref.17
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
Coding sequence diversity	Polymorphism
Molecular function	Developmental protein
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	axon guidance Traceable author statement. Source: Reactome pyrimidine base catabolic process Inferred from electronic annotation. Source: InterPro signal transduction Traceable author statement. Source: ProtInc
Cellular component	cytosol Traceable author statement. Source: Reactome
Molecular function	dihydropyrimidinase activity Traceable author statement. Source: ProtInc protein binding Inferred from physical interaction Ref.11. Source: UniProtKB
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_0000165913

Amino acid modifications

Modified residue

32

1

Phosphotyrosine; by FYN Ref.16 Ref.17

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

509

1

Phosphothreonine Ref.9 Ref.12 Ref.14 Ref.15

Modified residue

512

1

Phosphothreonine Ref.15

Modified residue

514

1

Phosphothreonine Ref.15

Modified residue

517

1

Phosphoserine By similarity

Modified residue

518

1

Phosphoserine Ref.9 Ref.15

Modified residue

521

1

Phosphothreonine Ref.15

Modified residue

522

1

Phosphoserine Ref.9 Ref.15

Modified residue

542

1

Phosphoserine By similarity

Modified residue

555

1

Phosphothreonine; by ROCK2 By similarity

Natural variations

Natural variant

118

1

A → T.
Corresponds to variant rs2289593 [ dbSNP | Ensembl ].

VAR_022016

Natural variant

481

1

R → C in a colorectal cancer sample; somatic mutation. Ref.20

VAR_036316

Experimental info

Mutagenesis

71

1

D → N: Inhibits axon outgrowth formation in hippocampal neurons and decreases binding to CYFIP1. Ref.11

Mutagenesis

507

1

S → A: No effect. Ref.9

Mutagenesis

509

1

T → A: Greatly diminishes binding to 3F4 antibody. Ref.9

Mutagenesis

512

1

T → A: No effect. Ref.9

Mutagenesis

514

1

T → A: No effect. Ref.9

Mutagenesis

517

1

S → A: No effect. Ref.9

Mutagenesis

518

1

S → A: Greatly diminishes binding to 3F4 antibody. Ref.9

Mutagenesis

521

1

T → A: No effect. Ref.9

Mutagenesis

522

1

S → A: Greatly diminishes binding to 3F4 antibody. Ref.9

Secondary structure

1

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572

Helix Strand Turn

Details...

Beta strand

17 – 25

9

Beta strand

30 – 38

9

Beta strand

41 – 48

8

Beta strand

56 – 59

4

Beta strand

64 – 67

4

Beta strand

69 – 74

6

Helix

89 – 98

10

Beta strand

101 – 108

8

Helix

116 – 130

15

Beta strand

132 – 142

11

Helix

148 – 158

11

Beta strand

163 – 168

6

Turn

171 – 174

4

Helix

178 – 191

14

Beta strand

194 – 198

5

Helix

202 – 213

12

Turn

214 – 216

3

Helix

221 – 226

6

Helix

229 – 246

18

Beta strand

250 – 255

6

Helix

258 – 268

11

Turn

269 – 271

3

Beta strand

274 – 279

6

Helix

280 – 284

5

Helix

287 – 291

5

Helix

295 – 300

6

Helix

313 – 322

10

Helix

338 – 341

4

Helix

342 – 344

3

Helix

348 – 350

3

Turn

358 – 360

3

Helix

361 – 369

9

Turn

370 – 373

4

Helix

377 – 384

8

Helix

386 – 391

6

Turn

395 – 397

3

Beta strand

409 – 419

11

Turn

422 – 424

3

Beta strand

425 – 428

4

Turn

433 – 436

4

Beta strand

438 – 448

11

Beta strand

451 – 455

5

Helix

476 – 486

11

Sequences

	Sequence		Length	Mass (Da)
	Q16555 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 5CDB6CF7F5C308AD	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

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]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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.
[8]	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.
[9]	"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.
[10]	"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.
[11]	"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.
[12]	"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: Cervix carcinoma.
[13]	"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.
[14]	"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. Tissue: Cervix carcinoma.
[15]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-509; THR-512; THR-514; SER-518; THR-521 AND SER-522, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[16]	"Semaphorin3A signaling mediated by Fyn-dependent tyrosine phosphorylation of collapsin response mediator protein 2 at tyrosine 32." Uchida Y., Ohshima T., Yamashita N., Ogawara M., Sasaki Y., Nakamura F., Goshima Y. J. Biol. Chem. 284:27393-27401(2009) [PubMed: 19652227] [Abstract] Cited for: PHOSPHORYLATION AT TYR-32 BY FYN.
[17]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-32, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[18]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[19]	"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.
[20]	"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. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] CYS-481.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U17279 mRNA. Translation: AAA93202.1.
D78013 mRNA. Translation: BAA11191.1.
U97105 mRNA. Translation: AAC05793.1.
AB020777 Genomic DNA. Translation: BAA86991.1.
AK291287 mRNA. Translation: BAF83976.1.
CH471080 Genomic DNA. Translation: EAW63573.1.
CH471080 Genomic DNA. Translation: EAW63574.1.
BC056408 mRNA. Translation: AAH56408.1.
BC067109 mRNA. Translation: AAH67109.1.

IPI

IPI00257508.

PIR

JC5317.

RefSeq

NP_001184222.1. NM_001197293.2.
NP_001231533.1. NM_001244604.1.
NP_001377.1. NM_001386.5.

UniGene

Hs.173381.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]

ProteinModelPortal

Q16555.

SMR

Q16555. Positions 14-490.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q16555. 4 interactions.

MINT

MINT-3032752.

STRING

Q16555.

Protein family/group databases

MEROPS

M38.975.

PTM databases

PhosphoSite

Q16555.

Polymorphism databases

DMDM

3122051.

2D gel databases

REPRODUCTION-2DPAGE

IPI00257508.
Q16555.

UCD-2DPAGE

Q16555.

Proteomic databases

PeptideAtlas

Q16555.

PRIDE

Q16555.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000311151; ENSP00000309539; ENSG00000092964.

GeneID

1808.

KEGG

hsa:1808.

NMPDR

fig|9606.3.peg.30095.

UCSC

uc003xfb.1. human.

Organism-specific databases

CTD

1808.

GeneCards

GC08P026371.

H-InvDB

HIX0007403.

HGNC

HGNC:3014. DPYSL2.

HPA

CAB018719.
HPA002381.

MIM

602463. gene.

neXtProt

NX_Q16555.

PharmGKB

PA27472.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG09339.

HOVERGEN

HBG000806.

InParanoid

Q16555.

OMA

TEWHKGV.

OrthoDB

EOG48PMJT.

PhylomeDB

Q16555.

Enzyme and pathway databases

Reactome

REACT_111045. Developmental Biology.

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. Hydantoinase/dihydroPyrase.
IPR011059. Metal-dep_hydrolase_composite.
[Graphical view]

KO

K07528.

Pfam

PF01979. Amidohydro_1. 1 hit.
[Graphical view]

SUPFAM

SSF51338. Metalo_hydrolase. 2 hits.

TIGRFAMs

TIGR02033. D-hydantoinase. 1 hit.

ProtoNet

Search...

Other

NextBio

7369.

SOURCE

Search...

Entry information

Entry name

DPYL2_HUMAN

Accession

Primary (citable) accession number: Q16555
Secondary accession number(s): A8K5H2, D3DSS7, O00424

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	November 1, 1996
Last modified:	January 25, 2012
This is version 120 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.