DOCK6_HUMAN
ID DOCK6_HUMAN Reviewed; 2047 AA.
AC Q96HP0; A6H8X5; Q7Z7P4; Q9P2F2;
DT 03-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 3.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Dedicator of cytokinesis protein 6;
GN Name=DOCK6; Synonyms=KIAA1395;
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 [LARGE SCALE MRNA], TISSUE SPECIFICITY, AND VARIANT
RP ARG-665.
RC TISSUE=Brain;
RX PubMed=10718198; DOI=10.1093/dnares/7.1.65;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVI. The
RT complete sequences of 150 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:65-73(2000).
RN [2]
RP SEQUENCE REVISION.
RA Ohara O., Nagase T., Kikuno R.;
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-665.
RC TISSUE=Kidney, and Spleen;
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 [5]
RP NOMENCLATURE.
RX PubMed=12432077; DOI=10.1242/jcs.00219;
RA Cote J.-F., Vuori K.;
RT "Identification of an evolutionarily conserved superfamily of DOCK180-
RT related proteins with guanine nucleotide exchange activity.";
RL J. Cell Sci. 115:4901-4913(2002).
RN [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17196961; DOI=10.1016/j.yexcr.2006.11.017;
RA Miyamoto Y., Yamauchi J., Sanbe A., Tanoue A.;
RT "Dock6, a Dock-C subfamily guanine nucleotide exchanger, has the dual
RT specificity for Rac1 and Cdc42 and regulates neurite outgrowth.";
RL Exp. Cell Res. 313:791-804(2007).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [9]
RP INVOLVEMENT IN AOS2.
RX PubMed=21820096; DOI=10.1016/j.ajhg.2011.07.009;
RA Shaheen R., Faqeih E., Sunker A., Morsy H., Al-Sheddi T., Shamseldin H.E.,
RA Adly N., Hashem M., Alkuraya F.S.;
RT "Recessive mutations in DOCK6, encoding the guanidine nucleotide exchange
RT factor DOCK6, lead to abnormal actin cytoskeleton organization and Adams-
RT Oliver syndrome.";
RL Am. J. Hum. Genet. 89:328-333(2011).
RN [10]
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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-872; SER-880; SER-1308 AND
RP SER-2036, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1308, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Acts as guanine nucleotide exchange factor (GEF) for CDC42
CC and RAC1 small GTPases. Through its activation of CDC42 and RAC1, may
CC regulate neurite outgrowth (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:17196961}.
CC -!- INTERACTION:
CC Q96HP0; O75427: LRCH4; NbExp=2; IntAct=EBI-4401295, EBI-718707;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17196961}.
CC Cytoplasm, perinuclear region {ECO:0000269|PubMed:17196961}.
CC Note=Mainly located near the cell surface.
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed at low level in spleen,
CC cerebellum, hippocampus and in substantia nigra.
CC {ECO:0000269|PubMed:10718198}.
CC -!- DOMAIN: The DOCKER domain may mediate some GEF activity. {ECO:0000250}.
CC -!- DISEASE: Adams-Oliver syndrome 2 (AOS2) [MIM:614219]: A disorder
CC characterized by the congenital absence of skin (aplasia cutis
CC congenita) in combination with transverse limb defects. Aplasia cutis
CC congenita can be located anywhere on the body, but in the vast majority
CC of the cases, it is present on the posterior parietal region where it
CC is often associated with an underlying defect of the parietal bones.
CC Limb abnormalities are typically limb truncation defects affecting the
CC distal phalanges or entire digits (true ectrodactyly). Only rarely,
CC metatarsals/metacarpals or more proximal limb structures are also
CC affected. Apart from transverse limb defects, syndactyly, most commonly
CC of second and third toes, can also be observed. The clinical features
CC are highly variable and can also include cardiovascular malformations,
CC brain abnormalities and vascular defects such as cutis marmorata and
CC dilated scalp veins. {ECO:0000269|PubMed:21820096}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the DOCK family. {ECO:0000255|PROSITE-
CC ProRule:PRU00983}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH08335.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA92633.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB037816; BAA92633.2; ALT_INIT; mRNA.
DR EMBL; AC009000; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC011472; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC008335; AAH08335.2; ALT_INIT; mRNA.
DR EMBL; BC051330; AAH51330.1; -; mRNA.
DR EMBL; BC146786; AAI46787.1; -; mRNA.
DR CCDS; CCDS45975.1; -.
DR RefSeq; NP_065863.2; NM_020812.3.
DR AlphaFoldDB; Q96HP0; -.
DR SMR; Q96HP0; -.
DR BioGRID; 121625; 61.
DR IntAct; Q96HP0; 34.
DR STRING; 9606.ENSP00000294618; -.
DR iPTMnet; Q96HP0; -.
DR PhosphoSitePlus; Q96HP0; -.
DR BioMuta; DOCK6; -.
DR DMDM; 296439370; -.
DR EPD; Q96HP0; -.
DR jPOST; Q96HP0; -.
DR MassIVE; Q96HP0; -.
DR MaxQB; Q96HP0; -.
DR PaxDb; Q96HP0; -.
DR PeptideAtlas; Q96HP0; -.
DR PRIDE; Q96HP0; -.
DR ProteomicsDB; 76771; -.
DR Antibodypedia; 69705; 43 antibodies from 13 providers.
DR DNASU; 57572; -.
DR Ensembl; ENST00000294618.12; ENSP00000294618.6; ENSG00000130158.14.
DR GeneID; 57572; -.
DR KEGG; hsa:57572; -.
DR MANE-Select; ENST00000294618.12; ENSP00000294618.6; NM_020812.4; NP_065863.2.
DR UCSC; uc002mqs.6; human.
DR CTD; 57572; -.
DR DisGeNET; 57572; -.
DR GeneCards; DOCK6; -.
DR GeneReviews; DOCK6; -.
DR HGNC; HGNC:19189; DOCK6.
DR HPA; ENSG00000130158; Low tissue specificity.
DR MalaCards; DOCK6; -.
DR MIM; 614194; gene.
DR MIM; 614219; phenotype.
DR neXtProt; NX_Q96HP0; -.
DR OpenTargets; ENSG00000130158; -.
DR Orphanet; 974; Adams-Oliver syndrome.
DR PharmGKB; PA134913824; -.
DR VEuPathDB; HostDB:ENSG00000130158; -.
DR eggNOG; KOG1997; Eukaryota.
DR GeneTree; ENSGT00940000159313; -.
DR InParanoid; Q96HP0; -.
DR OMA; WEPQRVF; -.
DR OrthoDB; 20156at2759; -.
DR PhylomeDB; Q96HP0; -.
DR TreeFam; TF313629; -.
DR PathwayCommons; Q96HP0; -.
DR Reactome; R-HSA-9013148; CDC42 GTPase cycle.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR Reactome; R-HSA-983231; Factors involved in megakaryocyte development and platelet production.
DR SignaLink; Q96HP0; -.
DR BioGRID-ORCS; 57572; 45 hits in 1078 CRISPR screens.
DR ChiTaRS; DOCK6; human.
DR GeneWiki; Dock6; -.
DR GenomeRNAi; 57572; -.
DR Pharos; Q96HP0; Tbio.
DR PRO; PR:Q96HP0; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q96HP0; protein.
DR Bgee; ENSG00000130158; Expressed in colonic epithelium and 168 other tissues.
DR ExpressionAtlas; Q96HP0; baseline and differential.
DR Genevisible; Q96HP0; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IBA:GO_Central.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IBA:GO_Central.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IEA:InterPro.
DR CDD; cd08696; C2_Dock-C; 1.
DR Gene3D; 1.20.58.740; -; 1.
DR Gene3D; 1.25.40.410; -; 1.
DR Gene3D; 2.60.40.150; -; 1.
DR InterPro; IPR037808; C2_Dock-C.
DR InterPro; IPR027007; C2_DOCK-type_domain.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR026791; DOCK.
DR InterPro; IPR021816; DOCK_C/D_N.
DR InterPro; IPR043161; DOCK_C_lobe_A.
DR InterPro; IPR043162; DOCK_C_lobe_C.
DR InterPro; IPR027357; DOCKER_dom.
DR PANTHER; PTHR23317; PTHR23317; 2.
DR Pfam; PF06920; DHR-2; 1.
DR Pfam; PF14429; DOCK-C2; 1.
DR Pfam; PF11878; DUF3398; 1.
DR PROSITE; PS51650; C2_DOCK; 1.
DR PROSITE; PS51651; DOCKER; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Guanine-nucleotide releasing factor; Methylation;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..2047
FT /note="Dedicator of cytokinesis protein 6"
FT /id="PRO_0000189993"
FT DOMAIN 548..714
FT /note="C2 DOCK-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00983"
FT DOMAIN 1587..2023
FT /note="DOCKER"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00984"
FT REGION 20..42
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 136..190
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 213..254
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 410..444
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1068..1090
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2025..2047
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 20..34
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 144..178
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 239..254
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 413..437
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1071..1090
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 178
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VDR9"
FT MOD_RES 865
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q8VDR9"
FT MOD_RES 872
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 880
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 884
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VDR9"
FT MOD_RES 1308
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 2036
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 250
FT /note="P -> L (in dbSNP:rs12978266)"
FT /id="VAR_029830"
FT VARIANT 555
FT /note="P -> L (in dbSNP:rs12609039)"
FT /id="VAR_029831"
FT VARIANT 665
FT /note="G -> R (in dbSNP:rs17001264)"
FT /evidence="ECO:0000269|PubMed:10718198,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_029832"
FT VARIANT 826
FT /note="R -> C (in dbSNP:rs35881692)"
FT /id="VAR_057522"
FT VARIANT 1420
FT /note="V -> L (in dbSNP:rs8108071)"
FT /id="VAR_029833"
FT VARIANT 1442
FT /note="A -> T (in dbSNP:rs34243815)"
FT /id="VAR_057523"
SQ SEQUENCE 2047 AA; 229558 MW; 6370F02FFF80D070 CRC64;
MAASERRAFA HKINRTVAAE VRKQVSRERS GSPHSSRRCS SSLGVPLTEV VEPLDFEDVL
LSRPPDAEPG PLRDLVEFPA DDLELLLQPR ECRTTEPGIP KDEKLDAQVR AAVEMYIEDW
VIVHRRYQYL SAAYSPVTTD TQRERQKGLP RQVFEQDASG DERSGPEDSN DSRRGSGSPE
DTPRSSGASS IFDLRNLAAD SLLPSLLERA APEDVDRRNE TLRRQHRPPA LLTLYPAPDE
DEAVERCSRP EPPREHFGQR ILVKCLSLKF EIEIEPIFGI LALYDVREKK KISENFYFDL
NSDSMKGLLR AHGTHPAIST LARSAIFSVT YPSPDIFLVI KLEKVLQQGD ISECCEPYMV
LKEVDTAKNK EKLEKLRLAA EQFCTRLGRY RMPFAWTAVH LANIVSSAGQ LDRDSDSEGE
RRPAWTDRRR RGPQDRASSG DDACSFSGFR PATLTVTNFF KQEAERLSDE DLFKFLADMR
RPSSLLRRLR PVTAQLKIDI SPAPENPHFC LSPELLHIKP YPDPRGRPTK EILEFPAREV
YAPHTSYRNL LYVYPHSLNF SSRQGSVRNL AVRVQYMTGE DPSQALPVIF GKSSCSEFTR
EAFTPVVYHN KSPEFYEEFK LHLPACVTEN HHLLFTFYHV SCQPRPGTAL ETPVGFTWIP
LLQHGRLRTG PFCLPVSVDQ PPPSYSVLTP DVALPGMRWV DGHKGVFSVE LTAVSSVHPQ
DPYLDKFFTL VHVLEEGAFP FRLKDTVLSE GNVEQELRAS LAALRLASPE PLVAFSHHVL
DKLVRLVIRP PIISGQIVNL GRGAFEAMAH VVSLVHRSLE AAQDARGHCP QLAAYVHYAF
RLPGTEPSLP DGAPPVTVQA ATLARGSGRP ASLYLARSKS ISSSNPDLAV APGSVDDEVS
RILASKLLHE ELALQWVVSS SAVREAILQH AWFFFQLMVK SMALHLLLGQ RLDTPRKLRF
PGRFLDDITA LVGSVGLEVI TRVHKDVELA EHLNASLAFF LSDLLSLVDR GFVFSLVRAH
YKQVATRLQS SPNPAALLTL RMEFTRILCS HEHYVTLNLP CCPLSPPASP SPSVSSTTSQ
SSTFSSQAPD PKVTSMFELS GPFRQQHFLA GLLLTELALA LEPEAEGAFL LHKKAISAVH
SLLCGHDTDP RYAEATVKAR VAELYLPLLS IARDTLPRLH DFAEGPGQRS RLASMLDSDT
EGEGDIAGTI NPSVAMAIAG GPLAPGSRAS ISQGPPTASR AGCALSAESS RTLLACVLWV
LKNTEPALLQ RWATDLTLPQ LGRLLDLLYL CLAAFEYKGK KAFERINSLT FKKSLDMKAR
LEEAILGTIG ARQEMVRRSR ERSPFGNPEN VRWRKSVTHW KQTSDRVDKT KDEMEHEALV
EGNLATEASL VVLDTLEIIV QTVMLSEARE SVLGAVLKVV LYSLGSAQSA LFLQHGLATQ
RALVSKFPEL LFEEDTELCA DLCLRLLRHC GSRISTIRTH ASASLYLLMR QNFEIGHNFA
RVKMQVTMSL SSLVGTTQNF SEEHLRRSLK TILTYAEEDM GLRDSTFAEQ VQDLMFNLHM
ILTDTVKMKE HQEDPEMLID LMYRIARGYQ GSPDLRLTWL QNMAGKHAEL GNHAEAAQCM
VHAAALVAEY LALLEDHRHL PVGCVSFQNI SSNVLEESAI SDDILSPDEE GFCSGKHFTE
LGLVGLLEQA AGYFTMGGLY EAVNEVYKNL IPILEAHRDY KKLAAVHGKL QEAFTKIMHQ
SSGWERVFGT YFRVGFYGAH FGDLDEQEFV YKEPSITKLA EISHRLEEFY TERFGDDVVE
IIKDSNPVDK SKLDSQKAYI QITYVEPYFD TYELKDRVTY FDRNYGLRTF LFCTPFTPDG
RAHGELPEQH KRKTLLSTDH AFPYIKTRIR VCHREETVLT PVEVAIEDMQ KKTRELAFAT
EQDPPDAKML QMVLQGSVGP TVNQGPLEVA QVFLAEIPED PKLFRHHNKL RLCFKDFCKK
CEDALRKNKA LIGPDQKEYH RELERNYCRL REALQPLLTQ RLPQLMAPTP PGLRNSLNRA
SFRKADL
