GenomeNet

Database: UniProt
Entry: RYK_HUMAN
LinkDB: RYK_HUMAN
Original site: RYK_HUMAN 
ID   RYK_HUMAN               Reviewed;         607 AA.
AC   P34925; A0A087WUK1; A0A096LNL3; Q04696;
DT   01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT   28-MAR-2018, sequence version 3.
DT   28-MAR-2018, entry version 169.
DE   RecName: Full=Tyrosine-protein kinase RYK {ECO:0000305};
DE            EC=2.7.10.1 {ECO:0000255|PROSITE-ProRule:PRU00159};
DE   Flags: Precursor;
GN   Name=RYK {ECO:0000312|HGNC:HGNC:10481}; Synonyms=JTK5A;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=8386829;
RA   Stacker S.A., Hovens C.M., Vitali A., Pritchard M.A., Baker E.,
RA   Sutherland G.R., Wilks A.F.;
RT   "Molecular cloning and chromosomal localisation of the human homologue
RT   of a receptor related to tyrosine kinases (RYK).";
RL   Oncogene 8:1347-1356(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RX   PubMed=8390040;
RA   Tamagnone L., Partanen J., Armstrong E., Lasota J., Ohgami K.,
RA   Tazunoki T., Laforgia S., Huebner K., Alitalo K.;
RT   "The human ryk cDNA sequence predicts a protein containing two
RT   putative transmembrane segments and a tyrosine kinase catalytic
RT   domain.";
RL   Oncogene 8:2009-2014(1993).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16641997; DOI=10.1038/nature04728;
RA   Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA   Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA   Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA   Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA   Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA   Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA   Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA   Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA   Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA   Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA   Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA   Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA   Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA   Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA   Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA   Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA   Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA   Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA   Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA   Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA   Gibbs R.A.;
RT   "The DNA sequence, annotation and analysis of human chromosome 3.";
RL   Nature 440:1194-1198(2006).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 46-607 (ISOFORM 1).
RC   TISSUE=Ovary;
RX   PubMed=8726462;
RA   Wang X.C., Katso R., Butler R., Hanby A.M., Poulsom R., Jones T.,
RA   Sheer D., Ganesan T.S.;
RT   "H-RYK, an unusual receptor kinase: isolation and analysis of
RT   expression in ovarian cancer.";
RL   Mol. Med. 2:189-203(1996).
RN   [5]
RP   MUTAGENESIS OF LYS-364; ASN-484 AND ALA-485.
RX   PubMed=10454588; DOI=10.1128/MCB.19.9.6427;
RA   Katso R.M., Russell R.B., Ganesan T.S.;
RT   "Functional analysis of H-Ryk, an atypical member of the receptor
RT   tyrosine kinase family.";
RL   Mol. Cell. Biol. 19:6427-6440(1999).
RN   [6]
RP   FUNCTION, AND INTERACTION WITH DVL1.
RX   PubMed=15454084; DOI=10.1016/j.cell.2004.09.019;
RA   Lu W., Yamamoto V., Ortega B., Baltimore D.;
RT   "Mammalian Ryk is a Wnt coreceptor required for stimulation of neurite
RT   outgrowth.";
RL   Cell 119:97-108(2004).
RN   [7]
RP   CLEAVAGE BY PRESENILIN.
RX   PubMed=16116452; DOI=10.1038/nn1520;
RA   Liu Y., Shi J., Lu C.C., Wang Z.B., Lyuksyutova A.I., Song X.J.,
RA   Zou Y.;
RT   "Ryk-mediated Wnt repulsion regulates posterior-directed growth of
RT   corticospinal tract.";
RL   Nat. Neurosci. 8:1151-1159(2005).
RN   [8]
RP   VARIANTS [LARGE SCALE ANALYSIS] ASN-99; CYS-227 AND ILE-243.
RX   PubMed=17344846; DOI=10.1038/nature05610;
RA   Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C.,
RA   Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
RA   O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
RA   Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
RA   Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
RA   Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
RA   Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
RA   West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
RA   Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
RA   DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
RA   Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
RA   Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
RT   "Patterns of somatic mutation in human cancer genomes.";
RL   Nature 446:153-158(2007).
CC   -!- FUNCTION: May be a coreceptor along with FZD8 of Wnt proteins,
CC       such as WNT1, WNT3, WNT3A and WNT5A. Involved in neuron
CC       differentiation, axon guidance, corpus callosum establishment and
CC       neurite outgrowth. In response to WNT3 stimulation, receptor C-
CC       terminal cleavage occurs in its transmembrane region and allows
CC       the C-terminal intracellular product to translocate from the
CC       cytoplasm to the nucleus where it plays a crucial role in neuronal
CC       development. {ECO:0000269|PubMed:15454084}.
CC   -!- CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a
CC       [protein]-L-tyrosine phosphate. {ECO:0000255|PROSITE-
CC       ProRule:PRU10028}.
CC   -!- SUBUNIT: Interacts with DVL1 (via PDZ domain).
CC       {ECO:0000269|PubMed:15454084}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250}; Single-pass type I
CC       membrane protein {ECO:0000250}. Nucleus {ECO:0000250}. Cytoplasm
CC       {ECO:0000250}. Note=In cells that have undergone neuronal
CC       differentiation, the C-terminal cleaved part is translocated from
CC       the cytoplasm to the nucleus. {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P34925-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P34925-2; Sequence=VSP_005009;
CC         Note=No experimental confirmation available.;
CC   -!- TISSUE SPECIFICITY: Observed in all the tissues examined.
CC   -!- DOMAIN: The extracellular WIF domain is responsible for Wnt
CC       binding. {ECO:0000250}.
CC   -!- PTM: Proteolytically cleaved, in part by presenilin, in response
CC       to WNT3 stimulation. Cleavage occurs during neuronal
CC       differentiation. {ECO:0000269|PubMed:16116452}.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC       kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC   -!- CAUTION: According to some authors, has impaired kinase activity.
CC       {ECO:0000305|PubMed:10454588}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAB26341.1; Type=Frameshift; Positions=Several; Evidence={ECO:0000305};
CC       Sequence=CAA65406.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
DR   EMBL; S59184; AAB26341.1; ALT_FRAME; mRNA.
DR   EMBL; X69970; CAA49591.1; -; mRNA.
DR   EMBL; AC096967; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC107310; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC108742; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AMYH02007719; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; X96588; CAA65406.1; ALT_INIT; mRNA.
DR   PIR; I37560; I37560.
DR   RefSeq; NP_001005861.1; NM_001005861.2.
DR   RefSeq; NP_002949.2; NM_002958.3.
DR   UniGene; Hs.654562; -.
DR   ProteinModelPortal; P34925; -.
DR   SMR; P34925; -.
DR   BioGrid; 112171; 86.
DR   IntAct; P34925; 1.
DR   STRING; 9606.ENSP00000296084; -.
DR   iPTMnet; P34925; -.
DR   PhosphoSitePlus; P34925; -.
DR   BioMuta; RYK; -.
DR   DMDM; 1710811; -.
DR   PaxDb; P34925; -.
DR   PeptideAtlas; P34925; -.
DR   PRIDE; P34925; -.
DR   DNASU; 6259; -.
DR   Ensembl; ENST00000296084; ENSP00000296084; ENSG00000163785.
DR   GeneID; 6259; -.
DR   KEGG; hsa:6259; -.
DR   UCSC; uc032sdg.2; human.
DR   UCSC; uc032sdh.1; human.
DR   CTD; 6259; -.
DR   DisGeNET; 6259; -.
DR   EuPathDB; HostDB:ENSG00000163785.12; -.
DR   GeneCards; RYK; -.
DR   HGNC; HGNC:10481; RYK.
DR   HPA; HPA045503; -.
DR   MIM; 600524; gene.
DR   neXtProt; NX_P34925; -.
DR   OpenTargets; ENSG00000163785; -.
DR   PharmGKB; PA34894; -.
DR   eggNOG; KOG1024; Eukaryota.
DR   eggNOG; ENOG410XSKI; LUCA.
DR   GeneTree; ENSGT00810000125384; -.
DR   HOGENOM; HOG000236284; -.
DR   HOVERGEN; HBG047417; -.
DR   InParanoid; P34925; -.
DR   KO; K05128; -.
DR   OMA; EYKLGFQ; -.
DR   OrthoDB; EOG091G0353; -.
DR   PhylomeDB; P34925; -.
DR   TreeFam; TF317402; -.
DR   BRENDA; 2.7.10.1; 2681.
DR   Reactome; R-HSA-201681; TCF dependent signaling in response to WNT.
DR   Reactome; R-HSA-4086400; PCP/CE pathway.
DR   SignaLink; P34925; -.
DR   SIGNOR; P34925; -.
DR   ChiTaRS; RYK; human.
DR   GeneWiki; Related_to_receptor_tyrosine_kinase; -.
DR   GenomeRNAi; 6259; -.
DR   PRO; PR:P34925; -.
DR   Proteomes; UP000005640; Chromosome 3.
DR   Proteomes; UP000005640; Unplaced.
DR   Bgee; ENSG00000163785; -.
DR   CleanEx; HS_RYK; -.
DR   ExpressionAtlas; A0A096LNL3; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR   GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR   GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; ISS:ParkinsonsUK-UCL.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:1904929; F:coreceptor activity involved in Wnt signaling pathway, planar cell polarity pathway; TAS:ParkinsonsUK-UCL.
DR   GO; GO:0005109; F:frizzled binding; ISS:ParkinsonsUK-UCL.
DR   GO; GO:0016301; F:kinase activity; IEA:UniProtKB-KW.
DR   GO; GO:0004888; F:transmembrane signaling receptor activity; IDA:UniProtKB.
DR   GO; GO:0042813; F:Wnt-activated receptor activity; ISS:ParkinsonsUK-UCL.
DR   GO; GO:0017147; F:Wnt-protein binding; ISS:ParkinsonsUK-UCL.
DR   GO; GO:0007411; P:axon guidance; ISS:UniProtKB.
DR   GO; GO:0007409; P:axonogenesis; ISS:ParkinsonsUK-UCL.
DR   GO; GO:0060070; P:canonical Wnt signaling pathway; NAS:ParkinsonsUK-UCL.
DR   GO; GO:0033278; P:cell proliferation in midbrain; ISS:ParkinsonsUK-UCL.
DR   GO; GO:0036518; P:chemorepulsion of dopaminergic neuron axon; ISS:ParkinsonsUK-UCL.
DR   GO; GO:0071679; P:commissural neuron axon guidance; ISS:ParkinsonsUK-UCL.
DR   GO; GO:0022038; P:corpus callosum development; ISS:UniProtKB.
DR   GO; GO:1904948; P:midbrain dopaminergic neuron differentiation; ISS:ParkinsonsUK-UCL.
DR   GO; GO:0022008; P:neurogenesis; NAS:ParkinsonsUK-UCL.
DR   GO; GO:0030182; P:neuron differentiation; ISS:UniProtKB.
DR   GO; GO:0031175; P:neuron projection development; ISS:UniProtKB.
DR   GO; GO:0035567; P:non-canonical Wnt signaling pathway; NAS:ParkinsonsUK-UCL.
DR   GO; GO:1904938; P:planar cell polarity pathway involved in axon guidance; ISS:ParkinsonsUK-UCL.
DR   GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:UniProtKB.
DR   GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR   GO; GO:0007416; P:synapse assembly; NAS:ParkinsonsUK-UCL.
DR   GO; GO:0016055; P:Wnt signaling pathway; TAS:Reactome.
DR   GO; GO:1904953; P:Wnt signaling pathway involved in midbrain dopaminergic neuron differentiation; ISS:ParkinsonsUK-UCL.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR   InterPro; IPR008266; Tyr_kinase_AS.
DR   InterPro; IPR003306; WIF.
DR   Pfam; PF07714; Pkinase_Tyr; 1.
DR   Pfam; PF02019; WIF; 1.
DR   PRINTS; PR00109; TYRKINASE.
DR   ProDom; PD013948; WIF; 1.
DR   SMART; SM00469; WIF; 1.
DR   SUPFAM; SSF56112; SSF56112; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR   PROSITE; PS50814; WIF; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; ATP-binding; Complete proteome; Cytoplasm;
KW   Disulfide bond; Glycoprotein; Kinase; Membrane; Nucleotide-binding;
KW   Nucleus; Phosphoprotein; Polymorphism; Receptor; Reference proteome;
KW   Signal; Transferase; Transmembrane; Transmembrane helix;
KW   Tyrosine-protein kinase; Wnt signaling pathway.
FT   SIGNAL        1     25       {ECO:0000255}.
FT   CHAIN        26    607       Tyrosine-protein kinase RYK.
FT                                /FTId=PRO_0000024464.
FT   TOPO_DOM     26    227       Extracellular. {ECO:0000255}.
FT   TRANSMEM    228    248       Helical. {ECO:0000255}.
FT   TOPO_DOM    249    607       Cytoplasmic. {ECO:0000255}.
FT   DOMAIN       66    194       WIF. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00222}.
FT   DOMAIN      330    603       Protein kinase. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00159}.
FT   NP_BIND     336    344       ATP. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00159}.
FT   COMPBIAS     24     53       Pro-rich. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00015}.
FT   ACT_SITE    465    465       Proton acceptor. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00159}.
FT   BINDING     364    364       ATP. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00159}.
FT   MOD_RES     495    495       Phosphotyrosine; by autocatalysis.
FT                                {ECO:0000250}.
FT   CARBOHYD    139    139       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    174    174       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    178    178       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    182    182       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    209    209       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID    159    194       {ECO:0000255|PROSITE-ProRule:PRU00222}.
FT   VAR_SEQ     297    297       S -> SSLG (in isoform 2).
FT                                {ECO:0000303|PubMed:8390040}.
FT                                /FTId=VSP_005009.
FT   VARIANT      99     99       S -> N. {ECO:0000269|PubMed:17344846}.
FT                                /FTId=VAR_041800.
FT   VARIANT     227    227       R -> C. {ECO:0000269|PubMed:17344846}.
FT                                /FTId=VAR_041801.
FT   VARIANT     243    243       V -> I (in an ovarian mucinous carcinoma
FT                                sample; somatic mutation).
FT                                {ECO:0000269|PubMed:17344846}.
FT                                /FTId=VAR_041802.
FT   MUTAGEN     364    364       K->A: No induction of the MAPK pathway.
FT                                {ECO:0000269|PubMed:10454588}.
FT   MUTAGEN     484    484       N->F: Gain of an autophosphorylation
FT                                activity. Gain of an autophosphorylation
FT                                activity; when associated with A-359.
FT                                Gain of an autophosphorylation activity;
FT                                when associated with G-334 and G-482.
FT                                {ECO:0000269|PubMed:10454588}.
FT   MUTAGEN     485    485       A->G: Gain of an autophosphorylation
FT                                activity. Gain of an autophosphorylation
FT                                activity; when associated with G-334 and
FT                                F-481. {ECO:0000269|PubMed:10454588}.
FT   CONFLICT     26     26       P -> R (in Ref. 1; AAB26341).
FT                                {ECO:0000305}.
FT   CONFLICT     33     33       L -> V (in Ref. 1; AAB26341).
FT                                {ECO:0000305}.
FT   CONFLICT     99     99       S -> N (in Ref. 1; AAB26341, 2; CAA49591
FT                                and 4; CAA65406). {ECO:0000305}.
FT   CONFLICT    254    254       S -> N (in Ref. 1; AAB26341 and 4;
FT                                CAA65406). {ECO:0000305}.
FT   CONFLICT    319    319       K -> E (in Ref. 2; CAA49591).
FT                                {ECO:0000305}.
FT   CONFLICT    358    358       E -> K (in Ref. 4; CAA65406).
FT                                {ECO:0000305}.
FT   CONFLICT    440    440       Q -> H (in Ref. 2; CAA49591).
FT                                {ECO:0000305}.
FT   CONFLICT    446    446       A -> P (in Ref. 2; CAA49591).
FT                                {ECO:0000305}.
FT   CONFLICT    531    531       T -> NS (in Ref. 1; AAB26341).
FT                                {ECO:0000305}.
FT   CONFLICT    544    544       V -> TL (in Ref. 1; AAB26341).
FT                                {ECO:0000305}.
FT   CONFLICT    566    566       N -> T (in Ref. 1; AAB26341).
FT                                {ECO:0000305}.
FT   CONFLICT    588    588       K -> R (in Ref. 1; AAB26341).
FT                                {ECO:0000305}.
SQ   SEQUENCE   607 AA;  67815 MW;  3AFAE21A2680F400 CRC64;
     MRGAARLGRP GRSCLPGARG LRAPPPPPLL LLLALLPLLP APGAAAAPAP RPPELQSASA
     GPSVSLYLSE DEVRRLIGLD AELYYVRNDL ISHYALSFSL LVPSETNFLH FTWHAKSKVE
     YKLGFQVDNV LAMDMPQVNI SVQGEVPRTL SVFRVELSCT GKVDSEVMIL MQLNLTVNSS
     KNFTVLNFKR RKMCYKKLEE VKTSALDKNT SRTIYDPVHA APTTSTRVFY ISVGVCCAVI
     FLVAIILAVL HLHSMKRIEL DDSISASSSS QGLSQPSTQT TQYLRADTPN NATPITSYPT
     LRIEKNDLRS VTLLEAKGKV KDIAISRERI TLKDVLQEGT FGRIFHGILI DEKDPNKEKQ
     AFVKTVKDQA SEIQVTMMLT ESCKLRGLHH RNLLPITHVC IEEGEKPMVI LPYMNWGNLK
     LFLRQCKLVE ANNPQAISQQ DLVHMAIQIA CGMSYLARRE VIHKDLAARN CVIDDTLQVK
     ITDNALSRDL FPMDYHCLGD NENRPVRWMA LESLVNNEFS SASDVWAFGV TLWELMTLGQ
     TPYVDIDPFE MAAYLKDGYR IAQPINCPDE LFAVMACCWA LDPEERPKFQ QLVQCLTEFH
     AALGAYV
//
DBGET integrated database retrieval system