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Protein

Dihydropyrimidinase-related protein 2

Gene

DPYSL2

Organism
Homo sapiens (Human)
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.3 Publications

GO - Molecular functioni

  • dihydropyrimidinase activity Source: ProtInc

GO - Biological processi

  • axon guidance Source: InterPro
  • cytoskeleton organization Source: UniProtKB
  • endocytosis Source: UniProtKB
  • nervous system development Source: ProtInc
  • nucleobase-containing compound metabolic process Source: ProtInc
  • olfactory bulb development Source: Ensembl
  • positive regulation of glutamate secretion Source: Ensembl
  • regulation of axon extension Source: InterPro
  • response to amphetamine Source: Ensembl
  • response to cocaine Source: Ensembl
  • response to drug Source: Ensembl
  • signal transduction Source: ProtInc
  • spinal cord development Source: Ensembl
  • synaptic vesicle transport Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Differentiation, Neurogenesis

Enzyme and pathway databases

BioCyciZFISH:ENSG00000092964-MONOMER.
ReactomeiR-HSA-399956. CRMPs in Sema3A signaling.
R-HSA-437239. Recycling pathway of L1.
SIGNORiQ16555.

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
N2A3
Unc-33-like phosphoprotein 2
Short name:
ULIP-2
Gene namesi
Name:DPYSL2
Synonyms:CRMP2, ULIP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:3014. DPYSL2.

Subcellular locationi

GO - Cellular componenti

  • cytoskeleton Source: UniProtKB-SubCell
  • cytosol Source: UniProtKB
  • dendrite Source: Ensembl
  • extracellular exosome Source: UniProtKB
  • growth cone Source: Ensembl
  • membrane Source: UniProtKB-SubCell
  • mitochondrion Source: Ensembl
  • myelin sheath Source: Ensembl
  • neuronal cell body Source: Ensembl
  • protein complex Source: Ensembl
  • terminal bouton Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi71D → N: Inhibits axon outgrowth formation in hippocampal neurons and decreases binding to CYFIP1. 1 Publication1
Mutagenesisi507S → A: No effect. 1 Publication1
Mutagenesisi509T → A: Greatly diminishes binding to 3F4 antibody. 1 Publication1
Mutagenesisi512T → A: No effect. 1 Publication1
Mutagenesisi514T → A: No effect. 1 Publication1
Mutagenesisi517S → A: No effect. 1 Publication1
Mutagenesisi518S → A: Greatly diminishes binding to 3F4 antibody. 1 Publication1
Mutagenesisi521T → A: No effect. 1 Publication1
Mutagenesisi522S → A: Greatly diminishes binding to 3F4 antibody. 1 Publication1

Organism-specific databases

DisGeNETi1808.
OpenTargetsiENSG00000092964.
PharmGKBiPA27472.

Polymorphism and mutation databases

BioMutaiDPYSL2.
DMDMi3122051.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001659131 – 572Dihydropyrimidinase-related protein 2Add BLAST572

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei32Phosphotyrosine; by FYN1 Publication1
Modified residuei101PhosphothreonineBy similarity1
Modified residuei102PhosphothreonineBy similarity1
Modified residuei258N6-succinyllysineBy similarity1
Modified residuei259PhosphoserineBy similarity1
Modified residuei431PhosphotyrosineBy similarity1
Modified residuei465PhosphoserineBy similarity1
Modified residuei499PhosphotyrosineBy similarity1
Modified residuei504S-nitrosocysteineBy similarity1
Modified residuei507PhosphoserineBy similarity1
Modified residuei509PhosphothreonineCombined sources1 Publication1
Modified residuei512PhosphothreonineBy similarity1
Modified residuei514Phosphothreonine; by GSK3-betaCombined sources1
Modified residuei517PhosphoserineCombined sources1
Modified residuei518PhosphoserineCombined sources1 Publication1
Modified residuei521PhosphothreonineBy similarity1
Modified residuei522Phosphoserine; by DYRK2Combined sources2 Publications1
Modified residuei537PhosphoserineBy similarity1
Modified residuei540PhosphoserineBy similarity1
Modified residuei542PhosphoserineBy similarity1
Modified residuei555Phosphothreonine; by ROCK2By similarity1
Modified residuei565Asymmetric dimethylarginineBy similarity1

Post-translational modificationi

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-509.2 Publications
Phosphorylation at Thr-514 by GSK3B abolishes tubulin-binding leading to destabilization of microtubule assembly in axons and neurodegeneration (By similarity). Phosphorylation by DYRK2 at Ser-522 is required for subsequent phosphorylation by GSK3B.By similarity2 Publications

Keywords - PTMi

Methylation, Phosphoprotein, S-nitrosylation

Proteomic databases

EPDiQ16555.
MaxQBiQ16555.
PaxDbiQ16555.
PeptideAtlasiQ16555.
PRIDEiQ16555.
TopDownProteomicsiQ16555-1. [Q16555-1]

2D gel databases

REPRODUCTION-2DPAGEIPI00257508.
Q16555.
UCD-2DPAGEQ16555.

PTM databases

iPTMnetiQ16555.
PhosphoSitePlusiQ16555.
SwissPalmiQ16555.

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiENSG00000092964.
CleanExiHS_DPYSL2.
ExpressionAtlasiQ16555. baseline and differential.
GenevisibleiQ16555. HS.

Organism-specific databases

HPAiCAB018719.
HPA002381.

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 MICALL1.5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself4EBI-1104711,EBI-1104711
CRMP1Q141943EBI-1104711,EBI-473101
DPYSL3Q14195-25EBI-1104711,EBI-10232496
DPYSL3Q8IXW63EBI-1104711,EBI-10262612
DPYSL5Q9BPU67EBI-1104711,EBI-724653
GORASP2Q9H8Y85EBI-1104711,EBI-739467

Protein-protein interaction databases

BioGridi108142. 54 interactors.
IntActiQ16555. 18 interactors.
MINTiMINT-3032752.
STRINGi9606.ENSP00000309539.

Structurei

Secondary structure

1572
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi17 – 25Combined sources9
Beta strandi30 – 38Combined sources9
Beta strandi41 – 48Combined sources8
Beta strandi53 – 55Combined sources3
Beta strandi57 – 59Combined sources3
Beta strandi64 – 67Combined sources4
Beta strandi69 – 74Combined sources6
Helixi89 – 98Combined sources10
Beta strandi101 – 108Combined sources8
Helixi116 – 130Combined sources15
Beta strandi132 – 140Combined sources9
Helixi146 – 158Combined sources13
Beta strandi163 – 170Combined sources8
Turni171 – 173Combined sources3
Helixi178 – 191Combined sources14
Beta strandi194 – 198Combined sources5
Helixi202 – 213Combined sources12
Turni214 – 216Combined sources3
Helixi221 – 226Combined sources6
Helixi229 – 246Combined sources18
Beta strandi250 – 255Combined sources6
Helixi258 – 269Combined sources12
Beta strandi274 – 279Combined sources6
Helixi280 – 284Combined sources5
Helixi287 – 291Combined sources5
Helixi295 – 300Combined sources6
Helixi313 – 322Combined sources10
Helixi338 – 341Combined sources4
Helixi342 – 344Combined sources3
Helixi348 – 350Combined sources3
Turni358 – 360Combined sources3
Helixi361 – 369Combined sources9
Turni370 – 373Combined sources4
Helixi377 – 384Combined sources8
Helixi386 – 392Combined sources7
Turni395 – 397Combined sources3
Beta strandi409 – 419Combined sources11
Turni422 – 424Combined sources3
Beta strandi425 – 428Combined sources4
Turni433 – 436Combined sources4
Beta strandi438 – 448Combined sources11
Beta strandi451 – 455Combined sources5
Helixi476 – 487Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2GSEX-ray2.40A/B/C/D13-490[»]
2VM8X-ray1.90A/B/C/D13-490[»]
ProteinModelPortaliQ16555.
SMRiQ16555.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ16555.

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG2584. Eukaryota.
COG0044. LUCA.
GeneTreeiENSGT00760000119241.
HOGENOMiHOG000219145.
HOVERGENiHBG000806.
InParanoidiQ16555.
KOiK07528.
OMAiQQRDVAH.
OrthoDBiEOG091G05F3.
PhylomeDBiQ16555.
TreeFamiTF314706.

Family and domain databases

CDDicd01314. D-HYD. 1 hit.
Gene3Di2.30.40.10. 2 hits.
InterProiIPR006680. Amidohydro-rel.
IPR030615. DRP2.
IPR011778. Hydantoinase/dihydroPyrase.
IPR011059. Metal-dep_hydrolase_composite.
IPR032466. Metal_Hydrolase.
[Graphical view]
PANTHERiPTHR11647:SF56. PTHR11647:SF56. 1 hit.
PfamiPF01979. Amidohydro_1. 1 hit.
[Graphical view]
SUPFAMiSSF51338. SSF51338. 2 hits.
SSF51556. SSF51556. 1 hit.
TIGRFAMsiTIGR02033. D-hydantoinase. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q16555-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« 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 ISEWHKGIQE
160 170 180 190 200
EMEALVKDHG VNSFLVYMAF KDRFQLTDCQ IYEVLSVIRD IGAIAQVHAE
210 220 230 240 250
NGDIIAEEQQ RILDLGITGP EGHVLSRPEE VEAEAVNRAI TIANQTNCPL
260 270 280 290 300
YITKVMSKSS 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
IAVGSDADLV IWDPDSVKTI SAKTHNSSLE 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):62,294
Last modified:November 1, 1996 - v1
Checksum:i5CDB6CF7F5C308AD
GO
Isoform 2 (identifier: Q16555-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: Missing.

Note: No experimental confirmation available.
Show »
Length:536
Mass (Da):58,163
Checksum:i31806BFCB5FAE16D
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_022016118A → T.Corresponds to variant rs2289593dbSNPEnsembl.1
Natural variantiVAR_036316481R → C in a colorectal cancer sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0449411 – 36Missing in isoform 2. 1 PublicationAdd BLAST36

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
AK299077 mRNA. Translation: BAG61143.1.
AC015564 Genomic DNA. No translation available.
AC015743 Genomic DNA. No translation available.
CH471080 Genomic DNA. Translation: EAW63573.1.
CH471080 Genomic DNA. Translation: EAW63574.1.
BC056408 mRNA. Translation: AAH56408.1.
BC067109 mRNA. Translation: AAH67109.1.
CCDSiCCDS59096.1. [Q16555-2]
CCDS6051.1. [Q16555-1]
PIRiJC5317.
RefSeqiNP_001184222.1. NM_001197293.2.
NP_001231533.1. NM_001244604.1. [Q16555-2]
NP_001377.1. NM_001386.5. [Q16555-1]
UniGeneiHs.593187.

Genome annotation databases

EnsembliENST00000311151; ENSP00000309539; ENSG00000092964. [Q16555-1]
ENST00000523027; ENSP00000431117; ENSG00000092964. [Q16555-2]
GeneIDi1808.
KEGGihsa:1808.
UCSCiuc003xfb.3. human. [Q16555-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
AK299077 mRNA. Translation: BAG61143.1.
AC015564 Genomic DNA. No translation available.
AC015743 Genomic DNA. No translation available.
CH471080 Genomic DNA. Translation: EAW63573.1.
CH471080 Genomic DNA. Translation: EAW63574.1.
BC056408 mRNA. Translation: AAH56408.1.
BC067109 mRNA. Translation: AAH67109.1.
CCDSiCCDS59096.1. [Q16555-2]
CCDS6051.1. [Q16555-1]
PIRiJC5317.
RefSeqiNP_001184222.1. NM_001197293.2.
NP_001231533.1. NM_001244604.1. [Q16555-2]
NP_001377.1. NM_001386.5. [Q16555-1]
UniGeneiHs.593187.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2GSEX-ray2.40A/B/C/D13-490[»]
2VM8X-ray1.90A/B/C/D13-490[»]
ProteinModelPortaliQ16555.
SMRiQ16555.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108142. 54 interactors.
IntActiQ16555. 18 interactors.
MINTiMINT-3032752.
STRINGi9606.ENSP00000309539.

Protein family/group databases

MEROPSiM38.975.

PTM databases

iPTMnetiQ16555.
PhosphoSitePlusiQ16555.
SwissPalmiQ16555.

Polymorphism and mutation databases

BioMutaiDPYSL2.
DMDMi3122051.

2D gel databases

REPRODUCTION-2DPAGEIPI00257508.
Q16555.
UCD-2DPAGEQ16555.

Proteomic databases

EPDiQ16555.
MaxQBiQ16555.
PaxDbiQ16555.
PeptideAtlasiQ16555.
PRIDEiQ16555.
TopDownProteomicsiQ16555-1. [Q16555-1]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000311151; ENSP00000309539; ENSG00000092964. [Q16555-1]
ENST00000523027; ENSP00000431117; ENSG00000092964. [Q16555-2]
GeneIDi1808.
KEGGihsa:1808.
UCSCiuc003xfb.3. human. [Q16555-1]

Organism-specific databases

CTDi1808.
DisGeNETi1808.
GeneCardsiDPYSL2.
HGNCiHGNC:3014. DPYSL2.
HPAiCAB018719.
HPA002381.
MIMi602463. gene.
neXtProtiNX_Q16555.
OpenTargetsiENSG00000092964.
PharmGKBiPA27472.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2584. Eukaryota.
COG0044. LUCA.
GeneTreeiENSGT00760000119241.
HOGENOMiHOG000219145.
HOVERGENiHBG000806.
InParanoidiQ16555.
KOiK07528.
OMAiQQRDVAH.
OrthoDBiEOG091G05F3.
PhylomeDBiQ16555.
TreeFamiTF314706.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000092964-MONOMER.
ReactomeiR-HSA-399956. CRMPs in Sema3A signaling.
R-HSA-437239. Recycling pathway of L1.
SIGNORiQ16555.

Miscellaneous databases

ChiTaRSiDPYSL2. human.
EvolutionaryTraceiQ16555.
GeneWikiiDPYSL2.
GenomeRNAii1808.
PROiQ16555.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000092964.
CleanExiHS_DPYSL2.
ExpressionAtlasiQ16555. baseline and differential.
GenevisibleiQ16555. HS.

Family and domain databases

CDDicd01314. D-HYD. 1 hit.
Gene3Di2.30.40.10. 2 hits.
InterProiIPR006680. Amidohydro-rel.
IPR030615. DRP2.
IPR011778. Hydantoinase/dihydroPyrase.
IPR011059. Metal-dep_hydrolase_composite.
IPR032466. Metal_Hydrolase.
[Graphical view]
PANTHERiPTHR11647:SF56. PTHR11647:SF56. 1 hit.
PfamiPF01979. Amidohydro_1. 1 hit.
[Graphical view]
SUPFAMiSSF51338. SSF51338. 2 hits.
SSF51556. SSF51556. 1 hit.
TIGRFAMsiTIGR02033. D-hydantoinase. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiDPYL2_HUMAN
AccessioniPrimary (citable) accession number: Q16555
Secondary accession number(s): A8K5H2
, B4DR31, D3DSS7, O00424
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: November 1, 1996
Last modified: November 30, 2016
This is version 171 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

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

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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 one 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.