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   26-FEB-2020, entry version 137.
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; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1] {ECO:0000305, ECO:0000312|EMBL:BAA77624.1}
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), ALTERNATIVE SPLICING,
RP   PUTATIVE FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP   INVOLVEMENT IN LUNG CANCER; ESOPHAGEAL CANCER AND RENAL CANCER.
RX   PubMed=10213508;
RA   Daigo Y., Nishiwaki T., Kawasoe T., Tamari M., Tsuchiya E., 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., Buhay C.J.,
RA   Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA   Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA   Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA   Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA   Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA   Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA   Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA   Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA   Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA   Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA   Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA   Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA   Palmeiri A., 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., Zhang X.,
RA   Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA   Naylor S.L., Yang H., Olson M., Weinstock G., 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., 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   [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., Buckhaults P.,
RA   Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA   Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA   Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA   Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal 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       Name=2;
CC         IsoId=Q9Y238-2; Sequence=VSP_051847, VSP_051848, VSP_051849;
CC       Name=3; Synonyms=1S3 {ECO:0000303|PubMed:10213508};
CC         IsoId=Q9Y238-3; Sequence=VSP_051850;
CC   -!- TISSUE SPECIFICITY: Expressed in all tissues examined. Expression is
CC       highest in prostate and testis. {ECO:0000269|PubMed:10213508}.
CC   -!- DISEASE: Note=DLEC1 silencing due to promoter methylation and aberrant
CC       transcription are implicated in the development of different cancers,
CC       including esophageal (ESCR), renal and lung cancers (LNCR).
CC   -!- DISEASE: Lung cancer (LNCR) [MIM:211980]: A common malignancy affecting
CC       tissues of the lung. The most common form of lung cancer is non-small
CC       cell lung cancer (NSCLC) that can be divided into 3 major histologic
CC       subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung
CC       cancer. NSCLC is often diagnosed at an advanced stage and has a poor
CC       prognosis. Note=The gene represented in this entry may be involved in
CC       disease 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 the
CC       esophagus. The most common types are esophageal squamous cell carcinoma
CC       and adenocarcinoma. Cancer of the esophagus remains a devastating
CC       disease because it is usually not detected until it has progressed to
CC       an advanced incurable stage. {ECO:0000269|PubMed:10213508}. Note=The
CC       gene represented in this entry may be involved in disease pathogenesis.
CC       DLEC1 silencing due to promoter methylation and aberrant transcription
CC       may be implicated in the development of esophageal cancer.
CC   -!- MISCELLANEOUS: [Isoform 2]: Levels of this splice isoform may be
CC       increased in cancer cell lines and primary cancers.
CC       {ECO:0000303|PubMed:10213508, ECO:0000305}.
CC   -!- MISCELLANEOUS: [Isoform 3]: Levels of this splice isoform are increased
CC       in cancer cell lines and primary cancers.
CC       {ECO:0000269|PubMed:10213508}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAB70676.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
CC       Sequence=CAB70884.2; Type=Erroneous initiation; Note=Truncated N-terminus.; 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   BioGrid; 115266; 1.
DR   IntAct; Q9Y238; 2.
DR   STRING; 9606.ENSP00000308597; -.
DR   iPTMnet; Q9Y238; -.
DR   PhosphoSitePlus; Q9Y238; -.
DR   BioMuta; DLEC1; -.
DR   DMDM; 296434480; -.
DR   jPOST; Q9Y238; -.
DR   MassIVE; Q9Y238; -.
DR   PaxDb; Q9Y238; -.
DR   PeptideAtlas; Q9Y238; -.
DR   PRIDE; Q9Y238; -.
DR   ProteomicsDB; 85633; -. [Q9Y238-1]
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   GeneCards; DLEC1; -.
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   Orphanet; 99977; Squamous cell carcinoma of the esophagus.
DR   PharmGKB; PA27353; -.
DR   eggNOG; ENOG410IFYS; Eukaryota.
DR   eggNOG; ENOG410YKY2; LUCA.
DR   GeneTree; ENSGT00390000006098; -.
DR   HOGENOM; CLU_003422_0_0_1; -.
DR   InParanoid; Q9Y238; -.
DR   OMA; YWDSLIC; -.
DR   OrthoDB; 373519at2759; -.
DR   PhylomeDB; Q9Y238; -.
DR   TreeFam; TF340616; -.
DR   ChiTaRS; DLEC1; human.
DR   GenomeRNAi; 9940; -.
DR   Pharos; Q9Y238; Tbio.
DR   PRO; PR:Q9Y238; -.
DR   Proteomes; UP000005640; Chromosome 3.
DR   RNAct; Q9Y238; protein.
DR   Bgee; ENSG00000008226; Expressed in right uterine tube and 124 other tissues.
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 population proliferation; TAS:ProtInc.
DR   Gene3D; 2.60.40.10; -; 7.
DR   InterPro; IPR033304; DLEC1.
DR   InterPro; IPR013783; Ig-like_fold.
DR   PANTHER; PTHR46348; PTHR46348; 1.
PE   2: Evidence at transcript level;
KW   Alternative splicing; Cytoplasm; Polymorphism; Reference proteome;
KW   Tumor suppressor.
FT   CHAIN           1..1755
FT                   /note="Deleted in lung and esophageal cancer protein 1"
FT                   /id="PRO_0000079929"
FT   VAR_SEQ         704
FT                   /note="E -> MARLRGGRIPAMPQPSPGQPAGTQWCFQGTVFALQ (in isoform
FT                   2)"
FT                   /evidence="ECO:0000303|PubMed:17974005"
FT                   /id="VSP_051847"
FT   VAR_SEQ         856..885
FT                   /note="GPALIINVSALQFGLLRLGQKATNSIQIRN -> PFSLVCSAWGRKPQTPSR
FT                   SGTSASSQPHGA (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:17974005"
FT                   /id="VSP_051848"
FT   VAR_SEQ         886..1755
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:17974005"
FT                   /id="VSP_051849"
FT   VAR_SEQ         1675..1755
FT                   /note="QQEPAKAAVAFRVSPNSGLLEARSANAPPTSIALQVFFTARSSELYESTMVV
FT                   EGVLGEKSCTLRLRGQGSYDERYMLPHQP -> VVSCTSPRWWWKVCSVRSPAPCGSGA
FT                   KAPMMRDTCCLTSPEAPPQPSAPGPSWRKNIAQGLGAALQHKDTDLGTWGPLGSSWNGR
FT                   TPFHNGLSLGPHDMSSELT (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:17974005"
FT                   /id="VSP_051850"
FT   VARIANT         79
FT                   /note="L -> R (in dbSNP:rs7625806)"
FT                   /id="VAR_056860"
FT   VARIANT         192
FT                   /note="S -> F (in dbSNP:rs34012183)"
FT                   /id="VAR_056861"
FT   VARIANT         351
FT                   /note="P -> R (in a breast cancer sample; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_035908"
FT   VARIANT         1022
FT                   /note="K -> N (in dbSNP:rs36012922)"
FT                   /id="VAR_056862"
FT   VARIANT         1150
FT                   /note="N -> D (in dbSNP:rs9840172)"
FT                   /id="VAR_056863"
FT   VARIANT         1227
FT                   /note="L -> P (in dbSNP:rs9810085)"
FT                   /id="VAR_056864"
FT   CONFLICT        704
FT                   /note="E -> M (in Ref. 2; CAB70884)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1442
FT                   /note="G -> R (in Ref. 1; BAA77624/BAA77247)"
FT                   /evidence="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
//