DPYL5_HUMAN
ID DPYL5_HUMAN Reviewed; 564 AA.
AC Q9BPU6; Q8TCL6; Q9NQC4; Q9NRY9;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Dihydropyrimidinase-related protein 5;
DE Short=DRP-5;
DE AltName: Full=CRMP3-associated molecule;
DE Short=CRAM;
DE AltName: Full=Collapsin response mediator protein 5;
DE Short=CRMP-5;
DE AltName: Full=UNC33-like phosphoprotein 6;
DE Short=ULIP-6;
GN Name=DPYSL5; Synonyms=CRMP5, ULIP6;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Spinal cord;
RA Aguera M., Antoine J.-C., Belin M.-F., Charrier E., Honnorat J.,
RA Rogemond V.;
RT "Ulip6, a new human Unc-33-like phosphoprotein.";
RL Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Spinal cord;
RX PubMed=11034345; DOI=10.1016/s0014-5793(00)01952-9;
RA Horiuchi M., El Far O., Betz H.;
RT "Ulip6, a novel unc-33 and dihydropyrimidinase related protein highly
RT expressed in developing rat brain.";
RL FEBS Lett. 480:283-286(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11220734;
RX DOI=10.1002/1531-8249(20010201)49:2<146::aid-ana34>3.0.co;2-e;
RA Yu Z., Kryzer T.J., Griesmann G.E., Kim K., Benarroch E.E., Lennon V.A.;
RT "CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related
RT autoimmunity.";
RL Ann. Neurol. 49:146-154(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PROTEIN SEQUENCE OF 17-40; 204-231; 239-261; 373-383; 394-431; 490-504 AND
RP 527-546, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 101-564.
RC TISSUE=Amygdala;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP VARIANTS RTSC4 LYS-41 AND ARG-47, INVOLVEMENT IN RTSC4, FUNCTION,
RP INTERACTION WITH MAP2 AND TUBB3, AND CHARACTERIZATION OF VARIANTS RTSC4
RP LYS-41 AND ARG-47.
RX PubMed=33894126; DOI=10.1016/j.ajhg.2021.04.004;
RA Jeanne M., Demory H., Moutal A., Vuillaume M.L., Blesson S., Thepault R.A.,
RA Marouillat S., Halewa J., Maas S.M., Motazacker M.M., Mancini G.M.S.,
RA van Slegtenhorst M.A., Andreou A., Cox H., Vogt J., Laufman J.,
RA Kostandyan N., Babikyan D., Hancarova M., Bendova S., Sedlacek Z.,
RA Aldinger K.A., Sherr E.H., Argilli E., England E.M., Audebert-Bellanger S.,
RA Bonneau D., Colin E., Denomme-Pichon A.S., Gilbert-Dussardier B.,
RA Isidor B., Kuery S., Odent S., Redon R., Khanna R., Dobyns W.B.,
RA Bezieau S., Honnorat J., Lohkamp B., Toutain A., Laumonnier F.;
RT "Missense variants in DPYSL5 cause a neurodevelopmental disorder with
RT corpus callosum agenesis and cerebellar abnormalities.";
RL Am. J. Hum. Genet. 108:951-961(2021).
CC -!- FUNCTION: Involved in the negative regulation of dendrite outgrowth.
CC {ECO:0000269|PubMed:33894126}.
CC -!- SUBUNIT: Homotetramer, and heterotetramer with other DPYS-like
CC proteins. Interacts with DPYSL2, DPYSL3 and DPYSL4 (By similarity).
CC Interacts with MAP2 and TUBB3 (PubMed:33894126).
CC {ECO:0000250|UniProtKB:Q9EQF6, ECO:0000269|PubMed:33894126}.
CC -!- INTERACTION:
CC Q9BPU6; P55212: CASP6; NbExp=3; IntAct=EBI-724653, EBI-718729;
CC Q9BPU6; Q6P656: CFAP161; NbExp=3; IntAct=EBI-724653, EBI-11901329;
CC Q9BPU6; Q8NI60: COQ8A; NbExp=3; IntAct=EBI-724653, EBI-745535;
CC Q9BPU6; Q16555: DPYSL2; NbExp=14; IntAct=EBI-724653, EBI-1104711;
CC Q9BPU6; Q14195-2: DPYSL3; NbExp=3; IntAct=EBI-724653, EBI-10232496;
CC Q9BPU6; P22607: FGFR3; NbExp=3; IntAct=EBI-724653, EBI-348399;
CC Q9BPU6; Q14957: GRIN2C; NbExp=3; IntAct=EBI-724653, EBI-8285963;
CC Q9BPU6; P06396: GSN; NbExp=3; IntAct=EBI-724653, EBI-351506;
CC Q9BPU6; O00291: HIP1; NbExp=3; IntAct=EBI-724653, EBI-473886;
CC Q9BPU6; P04792: HSPB1; NbExp=3; IntAct=EBI-724653, EBI-352682;
CC Q9BPU6; P42858: HTT; NbExp=9; IntAct=EBI-724653, EBI-466029;
CC Q9BPU6; O60333-2: KIF1B; NbExp=3; IntAct=EBI-724653, EBI-10975473;
CC Q9BPU6; O14901: KLF11; NbExp=3; IntAct=EBI-724653, EBI-948266;
CC Q9BPU6; P13473-2: LAMP2; NbExp=3; IntAct=EBI-724653, EBI-21591415;
CC Q9BPU6; P28331-2: NDUFS1; NbExp=3; IntAct=EBI-724653, EBI-6190702;
CC Q9BPU6; O43933: PEX1; NbExp=3; IntAct=EBI-724653, EBI-988601;
CC Q9BPU6; O75400-2: PRPF40A; NbExp=3; IntAct=EBI-724653, EBI-5280197;
CC Q9BPU6; P62826: RAN; NbExp=3; IntAct=EBI-724653, EBI-286642;
CC Q9BPU6; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-724653, EBI-396669;
CC Q9BPU6; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-724653, EBI-741480;
CC Q9BPU6; O76024: WFS1; NbExp=3; IntAct=EBI-724653, EBI-720609;
CC Q9BPU6; Q9Y649; NbExp=3; IntAct=EBI-724653, EBI-25900580;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- DISEASE: Ritscher-Schinzel syndrome 4 (RTSC4) [MIM:619435]: An
CC autosomal dominant form of Ritscher-Schinzel syndrome, a developmental
CC malformation syndrome characterized by cerebellar brain anomalies
CC associated with global developmental delay and impaired intellectual
CC development, congenital heart defects, and craniofacial abnormalities.
CC {ECO:0000269|PubMed:33894126}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the metallo-dependent hydrolases superfamily.
CC Hydantoinase/dihydropyrimidinase family. {ECO:0000305}.
CC -!- CAUTION: Lacks most of the conserved residues that are essential for
CC binding the metal cofactor and hence for dihydropyrimidinase activity.
CC Its enzyme activity is therefore unsure. {ECO:0000305}.
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DR EMBL; AF264015; AAK16830.1; -; mRNA.
DR EMBL; AJ251275; CAB95124.1; -; mRNA.
DR EMBL; AF157634; AAF80348.1; -; mRNA.
DR EMBL; BT006871; AAP35517.1; -; mRNA.
DR EMBL; BC002874; AAH02874.1; -; mRNA.
DR EMBL; AL713706; CAD28503.1; -; mRNA.
DR CCDS; CCDS1730.1; -.
DR RefSeq; NP_001240652.1; NM_001253723.1.
DR RefSeq; NP_001240653.1; NM_001253724.1.
DR RefSeq; NP_064519.2; NM_020134.3.
DR PDB; 4B90; X-ray; 2.20 A; A/B=1-564.
DR PDB; 4B91; X-ray; 1.70 A; A/B=1-483.
DR PDB; 4B92; X-ray; 2.90 A; A/B=1-483.
DR PDBsum; 4B90; -.
DR PDBsum; 4B91; -.
DR PDBsum; 4B92; -.
DR AlphaFoldDB; Q9BPU6; -.
DR SMR; Q9BPU6; -.
DR BioGRID; 121226; 47.
DR IntAct; Q9BPU6; 41.
DR STRING; 9606.ENSP00000288699; -.
DR MEROPS; M38.978; -.
DR GlyGen; Q9BPU6; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9BPU6; -.
DR PhosphoSitePlus; Q9BPU6; -.
DR SwissPalm; Q9BPU6; -.
DR BioMuta; DPYSL5; -.
DR DMDM; 20137929; -.
DR UCD-2DPAGE; Q9BPU6; -.
DR EPD; Q9BPU6; -.
DR jPOST; Q9BPU6; -.
DR MassIVE; Q9BPU6; -.
DR MaxQB; Q9BPU6; -.
DR PaxDb; Q9BPU6; -.
DR PeptideAtlas; Q9BPU6; -.
DR PRIDE; Q9BPU6; -.
DR ProteomicsDB; 78573; -.
DR Antibodypedia; 28026; 240 antibodies from 28 providers.
DR DNASU; 56896; -.
DR Ensembl; ENST00000288699.11; ENSP00000288699.6; ENSG00000157851.17.
DR Ensembl; ENST00000401478.5; ENSP00000385549.1; ENSG00000157851.17.
DR Ensembl; ENST00000614712.4; ENSP00000481305.1; ENSG00000157851.17.
DR GeneID; 56896; -.
DR KEGG; hsa:56896; -.
DR MANE-Select; ENST00000288699.11; ENSP00000288699.6; NM_020134.4; NP_064519.2.
DR UCSC; uc002rhu.4; human.
DR CTD; 56896; -.
DR DisGeNET; 56896; -.
DR GeneCards; DPYSL5; -.
DR HGNC; HGNC:20637; DPYSL5.
DR HPA; ENSG00000157851; Tissue enriched (brain).
DR MIM; 608383; gene.
DR MIM; 619435; phenotype.
DR neXtProt; NX_Q9BPU6; -.
DR OpenTargets; ENSG00000157851; -.
DR Orphanet; 528084; Non-specific syndromic intellectual disability.
DR PharmGKB; PA134927413; -.
DR VEuPathDB; HostDB:ENSG00000157851; -.
DR eggNOG; KOG2584; Eukaryota.
DR GeneTree; ENSGT01030000234527; -.
DR HOGENOM; CLU_015572_2_2_1; -.
DR InParanoid; Q9BPU6; -.
DR OMA; THAHFRD; -.
DR OrthoDB; 719800at2759; -.
DR PhylomeDB; Q9BPU6; -.
DR TreeFam; TF314706; -.
DR PathwayCommons; Q9BPU6; -.
DR Reactome; R-HSA-399956; CRMPs in Sema3A signaling.
DR SignaLink; Q9BPU6; -.
DR SIGNOR; Q9BPU6; -.
DR BioGRID-ORCS; 56896; 12 hits in 1071 CRISPR screens.
DR ChiTaRS; DPYSL5; human.
DR GeneWiki; DPYSL5; -.
DR GenomeRNAi; 56896; -.
DR Pharos; Q9BPU6; Tbio.
DR PRO; PR:Q9BPU6; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9BPU6; protein.
DR Bgee; ENSG00000157851; Expressed in cortical plate and 100 other tissues.
DR ExpressionAtlas; Q9BPU6; baseline and differential.
DR Genevisible; Q9BPU6; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0032991; C:protein-containing complex; IEA:Ensembl.
DR GO; GO:0016810; F:hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds; IEA:InterPro.
DR GO; GO:0008017; F:microtubule binding; IEA:InterPro.
DR GO; GO:0007411; P:axon guidance; TAS:ProtInc.
DR GO; GO:0050774; P:negative regulation of dendrite morphogenesis; IMP:UniProtKB.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR CDD; cd01314; D-HYD; 1.
DR Gene3D; 2.30.40.10; -; 1.
DR InterPro; IPR006680; Amidohydro-rel.
DR InterPro; IPR030626; DRP5.
DR InterPro; IPR011778; Hydantoinase/dihydroPyrase.
DR InterPro; IPR011059; Metal-dep_hydrolase_composite.
DR InterPro; IPR032466; Metal_Hydrolase.
DR PANTHER; PTHR11647:SF58; PTHR11647:SF58; 1.
DR Pfam; PF01979; Amidohydro_1; 1.
DR SUPFAM; SSF51338; SSF51338; 2.
DR SUPFAM; SSF51556; SSF51556; 1.
DR TIGRFAMs; TIGR02033; D-hydantoinase; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Direct protein sequencing; Disease variant;
KW Methylation; Phosphoprotein; Reference proteome.
FT CHAIN 1..564
FT /note="Dihydropyrimidinase-related protein 5"
FT /id="PRO_0000165924"
FT MOD_RES 509
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9EQF6"
FT MOD_RES 514
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9EQF6"
FT MOD_RES 532
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9EQF6"
FT MOD_RES 538
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9EQF6"
FT MOD_RES 559
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q9EQF6"
FT VARIANT 41
FT /note="E -> K (in RTSC4; reduced inhibition of dendrite
FT development in transfected primary neurons; decreased
FT interaction with MAP2; decreased interaction with TUBB3)"
FT /evidence="ECO:0000269|PubMed:33894126"
FT /id="VAR_086051"
FT VARIANT 47
FT /note="G -> R (in RTSC4; reduced inhibition of dendrite
FT development in transfected primary neurons; decreased
FT interaction with MAP2; decreased interaction with TUBB3)"
FT /evidence="ECO:0000269|PubMed:33894126"
FT /id="VAR_086052"
FT CONFLICT 380
FT /note="N -> S (in Ref. 2; CAB95124)"
FT /evidence="ECO:0000305"
FT CONFLICT 382
FT /note="A -> S (in Ref. 3; AAF80348)"
FT /evidence="ECO:0000305"
FT CONFLICT 399
FT /note="D -> H (in Ref. 3; AAF80348)"
FT /evidence="ECO:0000305"
FT STRAND 9..14
FT /evidence="ECO:0007829|PDB:4B91"
FT STRAND 16..18
FT /evidence="ECO:0007829|PDB:4B91"
FT STRAND 23..25
FT /evidence="ECO:0007829|PDB:4B91"
FT STRAND 27..31
FT /evidence="ECO:0007829|PDB:4B91"
FT STRAND 34..41
FT /evidence="ECO:0007829|PDB:4B91"
FT STRAND 49..52
FT /evidence="ECO:0007829|PDB:4B91"
FT STRAND 57..60
FT /evidence="ECO:0007829|PDB:4B91"
FT STRAND 62..67
FT /evidence="ECO:0007829|PDB:4B91"
FT HELIX 82..91
FT /evidence="ECO:0007829|PDB:4B91"
FT STRAND 94..101
FT /evidence="ECO:0007829|PDB:4B91"
FT HELIX 109..120
FT /evidence="ECO:0007829|PDB:4B91"
FT TURN 121..123
FT /evidence="ECO:0007829|PDB:4B91"
FT STRAND 125..133
FT /evidence="ECO:0007829|PDB:4B91"
FT HELIX 139..151
FT /evidence="ECO:0007829|PDB:4B91"
FT STRAND 156..161
FT /evidence="ECO:0007829|PDB:4B91"
FT TURN 164..166
FT /evidence="ECO:0007829|PDB:4B91"
FT HELIX 171..183
FT /evidence="ECO:0007829|PDB:4B91"
FT STRAND 187..191
FT /evidence="ECO:0007829|PDB:4B91"
FT HELIX 195..207
FT /evidence="ECO:0007829|PDB:4B91"
FT HELIX 215..218
FT /evidence="ECO:0007829|PDB:4B91"
FT HELIX 223..239
FT /evidence="ECO:0007829|PDB:4B91"
FT STRAND 243..245
FT /evidence="ECO:0007829|PDB:4B91"
FT HELIX 251..262
FT /evidence="ECO:0007829|PDB:4B91"
FT STRAND 267..272
FT /evidence="ECO:0007829|PDB:4B91"
FT HELIX 273..277
FT /evidence="ECO:0007829|PDB:4B91"
FT HELIX 280..284
FT /evidence="ECO:0007829|PDB:4B91"
FT HELIX 288..292
FT /evidence="ECO:0007829|PDB:4B91"
FT HELIX 306..315
FT /evidence="ECO:0007829|PDB:4B91"
FT STRAND 321..323
FT /evidence="ECO:0007829|PDB:4B91"
FT HELIX 331..334
FT /evidence="ECO:0007829|PDB:4B91"
FT HELIX 335..337
FT /evidence="ECO:0007829|PDB:4B91"
FT HELIX 341..343
FT /evidence="ECO:0007829|PDB:4B91"
FT TURN 351..353
FT /evidence="ECO:0007829|PDB:4B91"
FT HELIX 354..362
FT /evidence="ECO:0007829|PDB:4B91"
FT TURN 363..366
FT /evidence="ECO:0007829|PDB:4B91"
FT HELIX 370..377
FT /evidence="ECO:0007829|PDB:4B91"
FT HELIX 379..384
FT /evidence="ECO:0007829|PDB:4B91"
FT TURN 388..390
FT /evidence="ECO:0007829|PDB:4B91"
FT STRAND 402..406
FT /evidence="ECO:0007829|PDB:4B91"
FT HELIX 415..417
FT /evidence="ECO:0007829|PDB:4B91"
FT STRAND 420..423
FT /evidence="ECO:0007829|PDB:4B91"
FT TURN 426..429
FT /evidence="ECO:0007829|PDB:4B91"
FT STRAND 435..441
FT /evidence="ECO:0007829|PDB:4B91"
FT STRAND 444..448
FT /evidence="ECO:0007829|PDB:4B91"
FT HELIX 469..478
FT /evidence="ECO:0007829|PDB:4B91"
SQ SEQUENCE 564 AA; 61421 MW; FF9DD1D44C599928 CRC64;
MLANSASVRI LIKGGKVVND DCTHEADVYI ENGIIQQVGR ELMIPGGAKV IDATGKLVIP
GGIDTSTHFH QTFMNATCVD DFYHGTKAAL VGGTTMIIGH VLPDKETSLV DAYEKCRGLA
DPKVCCDYAL HVGITWWAPK VKAEMETLVR EKGVNSFQMF MTYKDLYMLR DSELYQVLHA
CKDIGAIARV HAENGELVAE GAKEALDLGI TGPEGIEISR PEELEAEATH RVITIANRTH
CPIYLVNVSS ISAGDVIAAA KMQGKVVLAE TTTAHATLTG LHYYHQDWSH AAAYVTVPPL
RLDTNTSTYL MSLLANDTLN IVASDHRPFT TKQKAMGKED FTKIPHGVSG VQDRMSVIWE
RGVVGGKMDE NRFVAVTSSN AAKLLNLYPR KGRIIPGADA DVVVWDPEAT KTISASTQVQ
GGDFNLYENM RCHGVPLVTI SRGRVVYENG VFMCAEGTGK FCPLRSFPDT VYKKLVQREK
TLKVRGVDRT PYLGDVAVVV HPGKKEMGTP LADTPTRPVT RHGGMRDLHE SSFSLSGSQI
DDHVPKRASA RILAPPGGRS SGIW
