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UniProtKB - Q9UPZ9 (ICK_HUMAN)

Protein

Serine/threonine-protein kinase ICK

Gene

ICK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Required for ciliogenesis (PubMed:24797473). Phosphorylates KIF3A (By similarity). Involved in the control of ciliary length (PubMed:24853502). Regulates the ciliary localization of SHH pathway components as well as the localization of IFT components at ciliary tips (By similarity). May play a key role in the development of multiple organ systems and particularly in cardiac development (By similarity). Regulates intraflagellar transport (IFT) speed and negatively regulates cilium length in a cAMP and mTORC1 signaling-dependent manner and this regulation requires its kinase activity (By similarity).By similarity2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.2 Publications

Cofactori

Mg2+1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei33ATPPROSITE-ProRule annotation1 Publication1
Active sitei125Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi10 – 18ATPPROSITE-ProRule annotationBy similarity9

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionDevelopmental protein, Kinase, Serine/threonine-protein kinase, Transferase
Biological processCilium biogenesis/degradation
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

SignaLinkiQ9UPZ9
SIGNORiQ9UPZ9

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase ICK (EC:2.7.11.11 Publication)
Alternative name(s):
Intestinal cell kinase
Short name:
hICK
Laryngeal cancer kinase 2
Short name:
LCK2
MAK-related kinase
Short name:
MRK
Gene namesi
Name:ICK
Synonyms:KIAA0936
OrganismiHomo sapiens (Human)Imported
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000112144.15
HGNCiHGNC:21219 ICK
MIMi612325 gene
neXtProtiNX_Q9UPZ9

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell projection, Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Involvement in diseasei

Endocrine-cerebroosteodysplasia (ECO)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionPreviously unidentified neonatal lethal recessive disorder with multiple anomalies involving the endocrine, cerebral, and skeletal systems.
See also OMIM:612651
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_057994272R → Q in ECO; significantly impairs kinase activity; decreased localization at the ciliary tips; impaired ciliogenesis; results in abnormally elongated cilia; impairs mitosis, cell-cycle exit and radial neuroblast migration, while promoting apoptosis, when tested in a heterologous system; loss of nuclear localization. 4 PublicationsCorresponds to variant dbSNP:rs118203918EnsemblClinVar.1
Juvenile myoclonic epilepsy 10 (EJM10)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of juvenile myoclonic epilepsy, a subtype of idiopathic generalized epilepsy generally characterized by afebrile seizures with onset in adolescence (rather than in childhood) and myoclonic jerks, which usually occur after awakening and are triggered by sleep deprivation and fatigue. EJM10 is an autosomal dominant seizure disorder with variable manifestations, even within families. Affected individuals have febrile, myoclonic, tonic-clonic, or absence seizures, although several seizure types can occur in the same individual. Some patients have onset of seizures in the first years of life.
See also OMIM:617924
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_080554102I → L in EJM10; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs748539319Ensembl.1
Natural variantiVAR_080555220K → E in EJM10; impairs mitosis, cell-cycle exit and radial neuroblast migration, while promoting apoptosis, when tested in a heterologous system. 1 Publication1
Natural variantiVAR_080556305K → T in EJM10; impairs mitosis, cell-cycle exit and radial neuroblast migration, while promoting apoptosis, when tested in a heterologous system. 1 PublicationCorresponds to variant dbSNP:rs765078446EnsemblClinVar.1
Natural variantiVAR_080557369 – 373Missing in EJM10; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs201964851Ensembl.5
Natural variantiVAR_042005615A → T in EJM10; unknown pathological significance; impairs mitosis, cell-cycle exit and radial neuroblast migration, while promoting apoptosis, when tested in a heterologous system. 2 PublicationsCorresponds to variant dbSNP:rs55932059EnsemblClinVar.1
Natural variantiVAR_080558632Missing in EJM10; impairs mitosis, cell-cycle exit and radial neuroblast migration, while promoting apoptosis, when tested in a heterologous system. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi33K → R: Loss of activity and autophosphorylation; when associated with R-34; R-36 and R-38. 1 Publication1
Mutagenesisi34K → R: Loss of activity and autophosphorylation; when associated with R-33; R-36 and R-38. 1 Publication1
Mutagenesisi36K → R: Loss of activity and autophosphorylation; when associated with R-33; R-34 and R-38. 1 Publication1
Mutagenesisi38K → R: Loss of activity and autophosphorylation; when associated with R-33; R-34 and R-36. 1 Publication1
Mutagenesisi157T → A: Reduction of activity and loss of autophosphorylation. Loss of activity and autophosphorylation; when associated with F-159. 1 Publication1
Mutagenesisi159Y → F: Reduction of activity and loss of autophosphorylation. Loss of activity and autophosphorylation; when associated with A-157. 1 Publication1

Keywords - Diseasei

Disease mutation, Epilepsy

Organism-specific databases

DisGeNETi22858
MalaCardsiICK
MIMi612651 phenotype
617924 phenotype
OpenTargetsiENSG00000112144
Orphaneti199332 Endocrine-cerebro-osteodysplasia syndrome
PharmGKBiPA134894544

Chemistry databases

ChEMBLiCHEMBL1163126

Polymorphism and mutation databases

BioMutaiICK
DMDMi48428273

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000860071 – 632Serine/threonine-protein kinase ICKAdd BLAST632

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei157Phosphothreonine1 Publication1
Modified residuei159Phosphotyrosine1 Publication1
Modified residuei161PhosphoserineBy similarity1

Post-translational modificationi

Autophosphorylated on serine and threonine residues. Phosphorylation at Thr-157 increases kinase activity.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9UPZ9
PaxDbiQ9UPZ9
PeptideAtlasiQ9UPZ9
PRIDEiQ9UPZ9
ProteomicsDBi85480
85481 [Q9UPZ9-2]

PTM databases

iPTMnetiQ9UPZ9
PhosphoSitePlusiQ9UPZ9

Expressioni

Tissue specificityi

Expressed in heart, brain, placenta, pancreas, thymus, prostate, testis, ovary, small intestine and colon, with highest levels in placenta and testis. Not detected in spleen. Also expressed in many cancer cell lines.2 Publications

Gene expression databases

BgeeiENSG00000112144 Expressed in 216 organ(s), highest expression level in nasal cavity mucosa
CleanExiHS_ICK
ExpressionAtlasiQ9UPZ9 baseline and differential
GenevisibleiQ9UPZ9 HS

Organism-specific databases

HPAiHPA000791
HPA001113

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
HSP90AB1P082382EBI-6381479,EBI-352572

Protein-protein interaction databases

BioGridi116527, 41 interactors
IntActiQ9UPZ9, 10 interactors
MINTiQ9UPZ9
STRINGi9606.ENSP00000263043

Chemistry databases

BindingDBiQ9UPZ9

Structurei

3D structure databases

ProteinModelPortaliQ9UPZ9
SMRiQ9UPZ9
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini4 – 284Protein kinasePROSITE-ProRule annotationCuratedAdd BLAST281

Sequence similaritiesi

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.Curated

Phylogenomic databases

eggNOGiKOG0661 Eukaryota
ENOG410XPBB LUCA
GeneTreeiENSGT00650000093283
HOVERGENiHBG014652
InParanoidiQ9UPZ9
KOiK08828
OMAiFHTQPRS
OrthoDBiEOG091G0DU3
PhylomeDBiQ9UPZ9
TreeFamiTF328769

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 11 Publication (identifier: Q9UPZ9-1) [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
MNRYTTIRQL GDGTYGSVLL GRSIESGELI AIKKMKRKFY SWEECMNLRE 
        60         70         80         90        100
VKSLKKLNHA NVVKLKEVIR ENDHLYFIFE YMKENLYQLI KERNKLFPES 
       110        120        130        140        150
AIRNIMYQIL QGLAFIHKHG FFHRDLKPEN LLCMGPELVK IADFGLAREI 
       160        170        180        190        200
RSKPPYTDYV STRWYRAPEV LLRSTNYSSP IDVWAVGCIM AEVYTLRPLF 
       210        220        230        240        250
PGASEIDTIF KICQVLGTPK KTDWPEGYQL SSAMNFRWPQ CVPNNLKTLI 
       260        270        280        290        300
PNASSEAVQL LRDMLQWDPK KRPTASQALR YPYFQVGHPL GSTTQNLQDS 
       310        320        330        340        350
EKPQKGILEK AGPPPYIKPV PPAQPPAKPH TRISSRQHQA SQPPLHLTYP 
       360        370        380        390        400
YKAEVSRTDH PSHLQEDKPS PLLFPSLHNK HPQSKITAGL EHKNGEIKPK 
       410        420        430        440        450
SRRRWGLISR STKDSDDWAD LDDLDFSPSL SRIDLKNKKR QSDDTLCRFE 
       460        470        480        490        500
SVLDLKPSEP VGTGNSAPTQ TSYQRRDTPT LRSAAKQHYL KHSRYLPGIS 
       510        520        530        540        550
IRNGILSNPG KEFIPPNPWS SSGLSGKSSG TMSVISKVNS VGSSSTSSSG 
       560        570        580        590        600
LTGNYVPSFL KKEIGSAMQR VHLAPIPDPS PGYSSLKAMR PHPGRPFFHT 
       610        620        630 
QPRSTPGLIP RPPAAQPVHG RTDWASKYAS RR
Length:632
Mass (Da):71,427
Last modified:May 1, 2000 - v1
Checksum:iF4C22C6CCD5878D2
GO
Isoform 2Curated (identifier: Q9UPZ9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     278-292: ALRYPYFQVGHPLGS → VFFHFLVITFISNSE
     293-632: Missing.

Note: No experimental confirmation available.Curated
Show »
Length:292
Mass (Da):34,071
Checksum:iAB4CA7370E16F983
GO

Sequence cautioni

The sequence BAA76780 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti48L → Q in AAF37278 (PubMed:10699974).Curated1
Sequence conflicti119H → L in AAF37278 (PubMed:10699974).Curated1
Sequence conflicti310K → R in AAF37278 (PubMed:10699974).Curated1
Sequence conflicti598 – 599FH → LD in AAF37278 (PubMed:10699974).Curated2
Sequence conflicti629A → P in AAF37278 (PubMed:10699974).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05393198P → L. Corresponds to variant dbSNP:rs1493105Ensembl.1
Natural variantiVAR_080554102I → L in EJM10; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs748539319Ensembl.1
Natural variantiVAR_042001115F → Y in a renal clear cell carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_080555220K → E in EJM10; impairs mitosis, cell-cycle exit and radial neuroblast migration, while promoting apoptosis, when tested in a heterologous system. 1 Publication1
Natural variantiVAR_057994272R → Q in ECO; significantly impairs kinase activity; decreased localization at the ciliary tips; impaired ciliogenesis; results in abnormally elongated cilia; impairs mitosis, cell-cycle exit and radial neuroblast migration, while promoting apoptosis, when tested in a heterologous system; loss of nuclear localization. 4 PublicationsCorresponds to variant dbSNP:rs118203918EnsemblClinVar.1
Natural variantiVAR_080556305K → T in EJM10; impairs mitosis, cell-cycle exit and radial neuroblast migration, while promoting apoptosis, when tested in a heterologous system. 1 PublicationCorresponds to variant dbSNP:rs765078446EnsemblClinVar.1
Natural variantiVAR_042002320V → I2 PublicationsCorresponds to variant dbSNP:rs33936662Ensembl.1
Natural variantiVAR_080557369 – 373Missing in EJM10; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs201964851Ensembl.5
Natural variantiVAR_042003471T → K1 PublicationCorresponds to variant dbSNP:rs56164633Ensembl.1
Natural variantiVAR_042004476R → Q1 PublicationCorresponds to variant dbSNP:rs55895113Ensembl.1
Natural variantiVAR_042005615A → T in EJM10; unknown pathological significance; impairs mitosis, cell-cycle exit and radial neuroblast migration, while promoting apoptosis, when tested in a heterologous system. 2 PublicationsCorresponds to variant dbSNP:rs55932059EnsemblClinVar.1
Natural variantiVAR_080558632Missing in EJM10; impairs mitosis, cell-cycle exit and radial neuroblast migration, while promoting apoptosis, when tested in a heterologous system. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_050752278 – 292ALRYP…HPLGS → VFFHFLVITFISNSE in isoform 2. 1 PublicationAdd BLAST15
Alternative sequenceiVSP_050753293 – 632Missing in isoform 2. 1 PublicationAdd BLAST340

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF225919 mRNA Translation: AAF37278.1
AF152469 mRNA Translation: AAG43364.1
AB023153 mRNA Translation: BAA76780.2 Different initiation.
AL031178 Genomic DNA No translation available.
AL162581 Genomic DNA No translation available.
CH471081 Genomic DNA Translation: EAX04400.1
BC035807 mRNA Translation: AAH35807.1
BC136420 mRNA Translation: AAI36421.1
BC136421 mRNA Translation: AAI36422.1
BC152464 mRNA Translation: AAI52465.1
CCDSiCCDS4949.1 [Q9UPZ9-1]
RefSeqiNP_055735.1, NM_014920.3 [Q9UPZ9-1]
NP_057597.2, NM_016513.4 [Q9UPZ9-1]
XP_016865977.1, XM_017010488.1 [Q9UPZ9-1]
XP_016865978.1, XM_017010489.1 [Q9UPZ9-1]
XP_016865979.1, XM_017010490.1 [Q9UPZ9-1]
XP_016865980.1, XM_017010491.1 [Q9UPZ9-1]
XP_016865981.1, XM_017010492.1 [Q9UPZ9-1]
UniGeneiHs.417022

Genome annotation databases

EnsembliENST00000350082; ENSP00000263043; ENSG00000112144 [Q9UPZ9-1]
ENST00000356971; ENSP00000349458; ENSG00000112144 [Q9UPZ9-1]
GeneIDi22858
KEGGihsa:22858
UCSCiuc003pbh.3 human [Q9UPZ9-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF225919 mRNA Translation: AAF37278.1
AF152469 mRNA Translation: AAG43364.1
AB023153 mRNA Translation: BAA76780.2 Different initiation.
AL031178 Genomic DNA No translation available.
AL162581 Genomic DNA No translation available.
CH471081 Genomic DNA Translation: EAX04400.1
BC035807 mRNA Translation: AAH35807.1
BC136420 mRNA Translation: AAI36421.1
BC136421 mRNA Translation: AAI36422.1
BC152464 mRNA Translation: AAI52465.1
CCDSiCCDS4949.1 [Q9UPZ9-1]
RefSeqiNP_055735.1, NM_014920.3 [Q9UPZ9-1]
NP_057597.2, NM_016513.4 [Q9UPZ9-1]
XP_016865977.1, XM_017010488.1 [Q9UPZ9-1]
XP_016865978.1, XM_017010489.1 [Q9UPZ9-1]
XP_016865979.1, XM_017010490.1 [Q9UPZ9-1]
XP_016865980.1, XM_017010491.1 [Q9UPZ9-1]
XP_016865981.1, XM_017010492.1 [Q9UPZ9-1]
UniGeneiHs.417022

3D structure databases

ProteinModelPortaliQ9UPZ9
SMRiQ9UPZ9
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116527, 41 interactors
IntActiQ9UPZ9, 10 interactors
MINTiQ9UPZ9
STRINGi9606.ENSP00000263043

Chemistry databases

BindingDBiQ9UPZ9
ChEMBLiCHEMBL1163126

PTM databases

iPTMnetiQ9UPZ9
PhosphoSitePlusiQ9UPZ9

Polymorphism and mutation databases

BioMutaiICK
DMDMi48428273

Proteomic databases

EPDiQ9UPZ9
PaxDbiQ9UPZ9
PeptideAtlasiQ9UPZ9
PRIDEiQ9UPZ9
ProteomicsDBi85480
85481 [Q9UPZ9-2]

Protocols and materials databases

DNASUi22858
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000350082; ENSP00000263043; ENSG00000112144 [Q9UPZ9-1]
ENST00000356971; ENSP00000349458; ENSG00000112144 [Q9UPZ9-1]
GeneIDi22858
KEGGihsa:22858
UCSCiuc003pbh.3 human [Q9UPZ9-1]

Organism-specific databases

CTDi22858
DisGeNETi22858
EuPathDBiHostDB:ENSG00000112144.15
GeneCardsiICK
HGNCiHGNC:21219 ICK
HPAiHPA000791
HPA001113
MalaCardsiICK
MIMi612325 gene
612651 phenotype
617924 phenotype
neXtProtiNX_Q9UPZ9
OpenTargetsiENSG00000112144
Orphaneti199332 Endocrine-cerebro-osteodysplasia syndrome
PharmGKBiPA134894544
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0661 Eukaryota
ENOG410XPBB LUCA
GeneTreeiENSGT00650000093283
HOVERGENiHBG014652
InParanoidiQ9UPZ9
KOiK08828
OMAiFHTQPRS
OrthoDBiEOG091G0DU3
PhylomeDBiQ9UPZ9
TreeFamiTF328769

Enzyme and pathway databases

SignaLinkiQ9UPZ9
SIGNORiQ9UPZ9

Miscellaneous databases

ChiTaRSiICK human
GeneWikiiICK_(gene)
GenomeRNAii22858
PROiPR:Q9UPZ9
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000112144 Expressed in 216 organ(s), highest expression level in nasal cavity mucosa
CleanExiHS_ICK
ExpressionAtlasiQ9UPZ9 baseline and differential
GenevisibleiQ9UPZ9 HS

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiICK_HUMAN
AccessioniPrimary (citable) accession number: Q9UPZ9
Secondary accession number(s): A7MD41
, O75985, Q5THL2, Q8IYH8, Q9BX17, Q9NYX3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 7, 2004
Last sequence update: May 1, 2000
Last modified: September 12, 2018
This is version 161 of the entry and version 1 of the sequence. See 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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

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