ID   DLEC1_HUMAN             Reviewed;        1755 AA.
AC   Q9Y238; Q9NSW0; Q9NTG5;
DT   25-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT   18-MAY-2010, sequence version 2.
DT   18-JUL-2018, entry version 127.
DE   RecName: Full=Deleted in lung and esophageal cancer protein 1;
DE   AltName: Full=Deleted in lung cancer protein 1;
DE            Short=DLC-1;
GN   Name=DLEC1 {ECO:0000312|EMBL:BAA77624.1};
GN   Synonyms=DLC1 {ECO:0000303|PubMed:10213508};
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] {ECO:0000305, ECO:0000312|EMBL:BAA77624.1}
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), ALTERNATIVE
RP   SPLICING, PUTATIVE FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP   AND INVOLVEMENT IN LUNG CANCER; ESOPHAGEAL CANCER AND RENAL CANCER.
RX   PubMed=10213508;
RA   Daigo Y., Nishiwaki T., Kawasoe T., Tamari M., Tsuchiya E.,
RA   Nakamura Y.;
RT   "Molecular cloning of a candidate tumor suppressor gene, DLC1, from
RT   chromosome 3p21.3.";
RL   Cancer Res. 59:1966-1972(1999).
RN   [2]
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 595-1755 (ISOFORM 2), AND
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1417-1755 (ISOFORM 3).
RC   TISSUE=Testis;
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.,
RA   Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA   Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [4]
RP   VARIANT [LARGE SCALE ANALYSIS] ARG-351.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA   Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA   Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA   Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA   Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal
RT   cancers.";
RL   Science 314:268-274(2006).
CC   -!- FUNCTION: May act as a tumor suppressor by inhibiting cell
CC       proliferation. {ECO:0000269|PubMed:10213508}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10213508}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC         Comment=At least six differentially spliced products may exist.
CC         {ECO:0000303|PubMed:10213508};
CC       Name=1 {ECO:0000303|PubMed:10213508};
CC         IsoId=Q9Y238-1; Sequence=Displayed;
CC         Note=No experimental confirmation available. {ECO:0000305};
CC       Name=2;
CC         IsoId=Q9Y238-2; Sequence=VSP_051847, VSP_051848, VSP_051849;
CC         Note=No experimental confirmation available. Levels of this
CC         splice isoform may be increased in cancer cell lines and primary
CC         cancers. {ECO:0000303|PubMed:10213508, ECO:0000305};
CC       Name=3; Synonyms=1S3 {ECO:0000303|PubMed:10213508};
CC         IsoId=Q9Y238-3; Sequence=VSP_051850;
CC         Note=Levels of this splice isoform are increased in cancer cell
CC         lines and primary cancers. {ECO:0000269|PubMed:10213508};
CC   -!- TISSUE SPECIFICITY: Expressed in all tissues examined. Expression
CC       is highest in prostate and testis. {ECO:0000269|PubMed:10213508}.
CC   -!- DISEASE: Note=DLEC1 silencing due to promoter methylation and
CC       aberrant transcription are implicated in the development of
CC       different cancers, including esophageal (ESCR), renal and lung
CC       cancers (LNCR).
CC   -!- DISEASE: Lung cancer (LNCR) [MIM:211980]: A common malignancy
CC       affecting tissues of the lung. The most common form of lung cancer
CC       is non-small cell lung cancer (NSCLC) that can be divided into 3
CC       major histologic subtypes: squamous cell carcinoma,
CC       adenocarcinoma, and large cell lung cancer. NSCLC is often
CC       diagnosed at an advanced stage and has a poor prognosis. Note=The
CC       gene represented in this entry may be involved in disease
CC       pathogenesis. DLEC1 silencing due to promoter methylation and
CC       aberrant transcription are implicated in the development of lung
CC       cancer.
CC   -!- DISEASE: Esophageal cancer (ESCR) [MIM:133239]: A malignancy of
CC       the esophagus. The most common types are esophageal squamous cell
CC       carcinoma and adenocarcinoma. Cancer of the esophagus remains a
CC       devastating disease because it is usually not detected until it
CC       has progressed to an advanced incurable stage.
CC       {ECO:0000269|PubMed:10213508}. Note=The gene represented in this
CC       entry may be involved in disease pathogenesis. DLEC1 silencing due
CC       to promoter methylation and aberrant transcription may be
CC       implicated in the development of esophageal cancer.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAB70676.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
CC       Sequence=CAB70884.2; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
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DR   EMBL; AB026898; BAA77624.1; -; Genomic_DNA.
DR   EMBL; AB020522; BAA77247.1; -; mRNA.
DR   EMBL; AC144536; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AP006309; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL137706; CAB70884.2; ALT_INIT; Transcribed_RNA.
DR   EMBL; AL137282; CAB70676.1; ALT_SEQ; mRNA.
DR   CCDS; CCDS2672.2; -. [Q9Y238-1]
DR   PIR; T46351; T46351.
DR   PIR; T46406; T46406.
DR   RefSeq; NP_001308082.1; NM_001321153.1.
DR   RefSeq; NP_031361.2; NM_007335.3. [Q9Y238-1]
DR   RefSeq; NP_031363.2; NM_007337.3. [Q9Y238-3]
DR   UniGene; Hs.714499; -.
DR   ProteinModelPortal; Q9Y238; -.
DR   STRING; 9606.ENSP00000308597; -.
DR   iPTMnet; Q9Y238; -.
DR   PhosphoSitePlus; Q9Y238; -.
DR   BioMuta; DLEC1; -.
DR   DMDM; 296434480; -.
DR   PaxDb; Q9Y238; -.
DR   PeptideAtlas; Q9Y238; -.
DR   PRIDE; Q9Y238; -.
DR   ProteomicsDB; 85633; -.
DR   ProteomicsDB; 85634; -. [Q9Y238-2]
DR   ProteomicsDB; 85635; -. [Q9Y238-3]
DR   DNASU; 9940; -.
DR   Ensembl; ENST00000308059; ENSP00000308597; ENSG00000008226. [Q9Y238-1]
DR   Ensembl; ENST00000346219; ENSP00000315914; ENSG00000008226. [Q9Y238-3]
DR   GeneID; 9940; -.
DR   KEGG; hsa:9940; -.
DR   UCSC; uc003cho.2; human. [Q9Y238-1]
DR   CTD; 9940; -.
DR   DisGeNET; 9940; -.
DR   EuPathDB; HostDB:ENSG00000008226.19; -.
DR   GeneCards; DLEC1; -.
DR   H-InvDB; HIX0003176; -.
DR   HGNC; HGNC:2899; DLEC1.
DR   HPA; HPA019077; -.
DR   MalaCards; DLEC1; -.
DR   MIM; 133239; phenotype.
DR   MIM; 211980; phenotype.
DR   MIM; 604050; gene.
DR   neXtProt; NX_Q9Y238; -.
DR   OpenTargets; ENSG00000008226; -.
DR   PharmGKB; PA27353; -.
DR   eggNOG; ENOG410IFYS; Eukaryota.
DR   eggNOG; ENOG410YKY2; LUCA.
DR   GeneTree; ENSGT00390000006098; -.
DR   HOGENOM; HOG000168427; -.
DR   HOVERGEN; HBG081444; -.
DR   InParanoid; Q9Y238; -.
DR   OMA; IPVHMAV; -.
DR   OrthoDB; EOG091G0I43; -.
DR   PhylomeDB; Q9Y238; -.
DR   TreeFam; TF340616; -.
DR   ChiTaRS; DLEC1; human.
DR   GenomeRNAi; 9940; -.
DR   PRO; PR:Q9Y238; -.
DR   Proteomes; UP000005640; Chromosome 3.
DR   Bgee; ENSG00000008226; -.
DR   CleanEx; HS_DLC1; -.
DR   CleanEx; HS_DLEC1; -.
DR   ExpressionAtlas; Q9Y238; baseline and differential.
DR   Genevisible; Q9Y238; HS.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0008285; P:negative regulation of cell proliferation; TAS:ProtInc.
DR   Gene3D; 2.60.40.10; -; 7.
DR   InterPro; IPR033304; DLEC1.
DR   InterPro; IPR013783; Ig-like_fold.
DR   PANTHER; PTHR23053:SF12; PTHR23053:SF12; 1.
PE   2: Evidence at transcript level;
KW   Alternative splicing; Complete proteome; Cytoplasm; Polymorphism;
KW   Reference proteome; Tumor suppressor.
FT   CHAIN         1   1755       Deleted in lung and esophageal cancer
FT                                protein 1.
FT                                /FTId=PRO_0000079929.
FT   VAR_SEQ     704    704       E -> MARLRGGRIPAMPQPSPGQPAGTQWCFQGTVFALQ
FT                                (in isoform 2).
FT                                {ECO:0000303|PubMed:17974005}.
FT                                /FTId=VSP_051847.
FT   VAR_SEQ     856    885       GPALIINVSALQFGLLRLGQKATNSIQIRN -> PFSLVCS
FT                                AWGRKPQTPSRSGTSASSQPHGA (in isoform 2).
FT                                {ECO:0000303|PubMed:17974005}.
FT                                /FTId=VSP_051848.
FT   VAR_SEQ     886   1755       Missing (in isoform 2).
FT                                {ECO:0000303|PubMed:17974005}.
FT                                /FTId=VSP_051849.
FT   VAR_SEQ    1675   1755       QQEPAKAAVAFRVSPNSGLLEARSANAPPTSIALQVFFTAR
FT                                SSELYESTMVVEGVLGEKSCTLRLRGQGSYDERYMLPHQP
FT                                -> VVSCTSPRWWWKVCSVRSPAPCGSGAKAPMMRDTCCLT
FT                                SPEAPPQPSAPGPSWRKNIAQGLGAALQHKDTDLGTWGPLG
FT                                SSWNGRTPFHNGLSLGPHDMSSELT (in isoform 3).
FT                                {ECO:0000303|PubMed:17974005}.
FT                                /FTId=VSP_051850.
FT   VARIANT      79     79       L -> R (in dbSNP:rs7625806).
FT                                /FTId=VAR_056860.
FT   VARIANT     192    192       S -> F (in dbSNP:rs34012183).
FT                                /FTId=VAR_056861.
FT   VARIANT     351    351       P -> R (in a breast cancer sample;
FT                                somatic mutation).
FT                                {ECO:0000269|PubMed:16959974}.
FT                                /FTId=VAR_035908.
FT   VARIANT    1022   1022       K -> N (in dbSNP:rs36012922).
FT                                /FTId=VAR_056862.
FT   VARIANT    1150   1150       N -> D (in dbSNP:rs9840172).
FT                                /FTId=VAR_056863.
FT   VARIANT    1227   1227       L -> P (in dbSNP:rs9810085).
FT                                /FTId=VAR_056864.
FT   CONFLICT    704    704       E -> M (in Ref. 2; CAB70884).
FT                                {ECO:0000305}.
FT   CONFLICT   1442   1442       G -> R (in Ref. 1; BAA77624/BAA77247).
FT                                {ECO:0000305}.
SQ   SEQUENCE   1755 AA;  195684 MW;  CD4BDB5EEF24DF98 CRC64;
     METRSSKTRR SLASRTNECQ GTMWAPTSPP AGSSSPSQPT WKSSLYSSLA YSEAFHYSFA
     ARPRRLTQLA LAQRPEPQLL RLRPSSLRTQ DISHLLTGVF RNLYSAEVIG DEVSASLIKA
     RGSENERHEE FVDQLQQIRE LYKQRLDEFE MLERHITQAQ ARAIAENERV MSQAGVQDLE
     SLVRLPPVKS VSRWCIDSEL LRKHHLISPE DYYTDTVPFH SAPKGISLPG CSKLTFSCEK
     RSVQKKELNK KLEDSCRKKL AEFEDELDHT VDSLTWNLTP KAKERTREPL KKASQPRNKN
     WMNHLRVPQR ELDRLLLARM ESRNHFLKNP RFFPPNTRYG GKSLVFPPKK PAPIGEFQST
     EPEQSCADTP VFLAKPPIGF FTDYEIGPVY EMVIALQNTT TTSRYLRVLP PSTPYFALGL
     GMFPGKGGMV APGMTCQYIV QFFPDCLGDF DDFILVETQS AHTLLIPLQA RRPPPVLTLS
     PVLDCGYCLI GGVKMTRFIC KNVGFSVGRF CIMPKTSWPP LSFKAIATVG FVEQPPFGIL
     PSVFELAPGH AILVEVLFSP KSLGKAEQTF IIMCDNCQIK ELVTIGIGQL IALDLIYISG
     EKSQPDPGEL TDLTAQHFIR FEPENLRSTA RKQLIIRNAT HVELAFYWQI MKPNLQPLMP
     GETFSMDSIK CYPDKETAFS IMPRKGVLSP HTDHEFILSF SPHELRDFHS VLQMVLEEVP
     EPVSSEAESL GHSSYSVDDV IVLEIEVKGS VEPFQVLLEP YALIIPGENY IGINVKKAFK
     MWNNSKSPIR YLWGKISDCH IIEVEPGTGV IEPSEVGDFE LNFTGGVPGP TSQDLLCEIE
     DSPSPVVLHI EAVFKGPALI INVSALQFGL LRLGQKATNS IQIRNVSQLP ATWRMKESPV
     SLQERPEDVS PFDIEPSSGQ LHSLGECRVD ITLEALHCQH LETVLELEVE NGAWSYLPVY
     AEVQKPHVYL QSSQVEVRNL YLGVPTKTTI TLINGTLLPT QFHWGKLLGH QAEFCMVTVS
     PKHGLLGPSE ECQLKLELTA HTQEELTHLA LPCHVSGMKK PLVLGISGKP QGLQVAITIS
     KESSDCSTEQ WPGHPKELRL DFGSAVPLRT RVTRQLILTN RSPIRTRFSL KFEYFGSPQN
     SLSKKTSLPN MPPALLKTVR MQEHLAKREQ LDFMESMLSH GKGAAFFPHF SQGMLGPYQQ
     LCIDITGCAN MWGEYWDNLI CTVGDLLPEV IPVHMAAVGC PISSLRTTSY TIDQAQKEPA
     MRFGTQVSGG DTVTRTLRLN NSSPCDIRLD WETYVPEDKE DRLVELLVFY GPPFPLRDQA
     GNELVCPDTP EGGCLLWSPG PSSSSEFSHE TDSSVEGSSS ASNRVAQKLI SVILQAHEGV
     PSGHLYCISP KQVVVPAGGS STIYISFTPM VLSPEILHKV ECTGYALGFM SLDSKVEREI
     PGKRHRLQDF AVGPLKLDLH SYVRPAQLSV ELDYGGSMEF QCQASDLIPE QPCSGVLSEL
     VTTHHLKLTN TTEIPHYFRL MVSRPFSVSQ DGASQDHRAP GPGQKQECEE ETASADKQLV
     LQAQENMLVN VSFSLSLELL SYQKLPADQT LPGVDIQQSA SGEREMVFTQ NLLLEYTNQT
     TQVVPLRAVV AVPELQLSTS WVDFGTCFVS QQRVREVYLM NLSGCRSYWT MLMGQQEPAK
     AAVAFRVSPN SGLLEARSAN APPTSIALQV FFTARSSELY ESTMVVEGVL GEKSCTLRLR
     GQGSYDERYM LPHQP
//