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Deleted in lung and esophageal cancer protein 1 (Deleted in lung cancer protein 1) (DLC-1)

 DLEC1_HUMAN             Reviewed;        1755 AA.
Q9Y238; Q9NSW0; Q9NTG5;
25-OCT-2005, integrated into UniProtKB/Swiss-Prot.
18-MAY-2010, sequence version 2.
18-JUL-2018, entry version 127.
RecName: Full=Deleted in lung and esophageal cancer protein 1;
AltName: Full=Deleted in lung cancer protein 1;
Short=DLC-1;
Name=DLEC1 {ECO:0000312|EMBL:BAA77624.1};
Synonyms=DLC1 {ECO:0000303|PubMed:10213508};
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1] {ECO:0000305, ECO:0000312|EMBL:BAA77624.1}
NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), ALTERNATIVE
SPLICING, PUTATIVE FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
AND INVOLVEMENT IN LUNG CANCER; ESOPHAGEAL CANCER AND RENAL CANCER.
PubMed=10213508;
Daigo Y., Nishiwaki T., Kawasoe T., Tamari M., Tsuchiya E.,
Nakamura Y.;
"Molecular cloning of a candidate tumor suppressor gene, DLC1, from
chromosome 3p21.3.";
Cancer Res. 59:1966-1972(1999).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=16641997; DOI=10.1038/nature04728;
Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
Gibbs R.A.;
"The DNA sequence, annotation and analysis of human chromosome 3.";
Nature 440:1194-1198(2006).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 595-1755 (ISOFORM 2), AND
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1417-1755 (ISOFORM 3).
TISSUE=Testis;
PubMed=17974005; DOI=10.1186/1471-2164-8-399;
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
"The full-ORF clone resource of the German cDNA consortium.";
BMC Genomics 8:399-399(2007).
[4]
VARIANT [LARGE SCALE ANALYSIS] ARG-351.
PubMed=16959974; DOI=10.1126/science.1133427;
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
Vogelstein B., Kinzler K.W., Velculescu V.E.;
"The consensus coding sequences of human breast and colorectal
cancers.";
Science 314:268-274(2006).
-!- FUNCTION: May act as a tumor suppressor by inhibiting cell
proliferation. {ECO:0000269|PubMed:10213508}.
-!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10213508}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=3;
Comment=At least six differentially spliced products may exist.
{ECO:0000303|PubMed:10213508};
Name=1 {ECO:0000303|PubMed:10213508};
IsoId=Q9Y238-1; Sequence=Displayed;
Note=No experimental confirmation available. {ECO:0000305};
Name=2;
IsoId=Q9Y238-2; Sequence=VSP_051847, VSP_051848, VSP_051849;
Note=No experimental confirmation available. Levels of this
splice isoform may be increased in cancer cell lines and primary
cancers. {ECO:0000303|PubMed:10213508, ECO:0000305};
Name=3; Synonyms=1S3 {ECO:0000303|PubMed:10213508};
IsoId=Q9Y238-3; Sequence=VSP_051850;
Note=Levels of this splice isoform are increased in cancer cell
lines and primary cancers. {ECO:0000269|PubMed:10213508};
-!- TISSUE SPECIFICITY: Expressed in all tissues examined. Expression
is highest in prostate and testis. {ECO:0000269|PubMed:10213508}.
-!- DISEASE: Note=DLEC1 silencing due to promoter methylation and
aberrant transcription are implicated in the development of
different cancers, including esophageal (ESCR), renal and lung
cancers (LNCR).
-!- DISEASE: Lung cancer (LNCR) [MIM:211980]: A common malignancy
affecting tissues of the lung. The most common form of lung cancer
is non-small cell lung cancer (NSCLC) that can be divided into 3
major histologic subtypes: squamous cell carcinoma,
adenocarcinoma, and large cell lung cancer. NSCLC is often
diagnosed at an advanced stage and has a poor prognosis. Note=The
gene represented in this entry may be involved in disease
pathogenesis. DLEC1 silencing due to promoter methylation and
aberrant transcription are implicated in the development of lung
cancer.
-!- DISEASE: Esophageal cancer (ESCR) [MIM:133239]: A malignancy of
the esophagus. The most common types are esophageal squamous cell
carcinoma and adenocarcinoma. Cancer of the esophagus remains a
devastating disease because it is usually not detected until it
has progressed to an advanced incurable stage.
{ECO:0000269|PubMed:10213508}. Note=The gene represented in this
entry may be involved in disease pathogenesis. DLEC1 silencing due
to promoter methylation and aberrant transcription may be
implicated in the development of esophageal cancer.
-!- SEQUENCE CAUTION:
Sequence=CAB70676.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
Sequence=CAB70884.2; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
-----------------------------------------------------------------------
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EMBL; AB026898; BAA77624.1; -; Genomic_DNA.
EMBL; AB020522; BAA77247.1; -; mRNA.
EMBL; AC144536; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; AP006309; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; AL137706; CAB70884.2; ALT_INIT; Transcribed_RNA.
EMBL; AL137282; CAB70676.1; ALT_SEQ; mRNA.
CCDS; CCDS2672.2; -. [Q9Y238-1]
PIR; T46351; T46351.
PIR; T46406; T46406.
RefSeq; NP_001308082.1; NM_001321153.1.
RefSeq; NP_031361.2; NM_007335.3. [Q9Y238-1]
RefSeq; NP_031363.2; NM_007337.3. [Q9Y238-3]
UniGene; Hs.714499; -.
ProteinModelPortal; Q9Y238; -.
STRING; 9606.ENSP00000308597; -.
iPTMnet; Q9Y238; -.
PhosphoSitePlus; Q9Y238; -.
BioMuta; DLEC1; -.
DMDM; 296434480; -.
PaxDb; Q9Y238; -.
PeptideAtlas; Q9Y238; -.
PRIDE; Q9Y238; -.
ProteomicsDB; 85633; -.
ProteomicsDB; 85634; -. [Q9Y238-2]
ProteomicsDB; 85635; -. [Q9Y238-3]
DNASU; 9940; -.
Ensembl; ENST00000308059; ENSP00000308597; ENSG00000008226. [Q9Y238-1]
Ensembl; ENST00000346219; ENSP00000315914; ENSG00000008226. [Q9Y238-3]
GeneID; 9940; -.
KEGG; hsa:9940; -.
UCSC; uc003cho.2; human. [Q9Y238-1]
CTD; 9940; -.
DisGeNET; 9940; -.
EuPathDB; HostDB:ENSG00000008226.19; -.
GeneCards; DLEC1; -.
H-InvDB; HIX0003176; -.
HGNC; HGNC:2899; DLEC1.
HPA; HPA019077; -.
MalaCards; DLEC1; -.
MIM; 133239; phenotype.
MIM; 211980; phenotype.
MIM; 604050; gene.
neXtProt; NX_Q9Y238; -.
OpenTargets; ENSG00000008226; -.
PharmGKB; PA27353; -.
eggNOG; ENOG410IFYS; Eukaryota.
eggNOG; ENOG410YKY2; LUCA.
GeneTree; ENSGT00390000006098; -.
HOGENOM; HOG000168427; -.
HOVERGEN; HBG081444; -.
InParanoid; Q9Y238; -.
OMA; IPVHMAV; -.
OrthoDB; EOG091G0I43; -.
PhylomeDB; Q9Y238; -.
TreeFam; TF340616; -.
ChiTaRS; DLEC1; human.
GenomeRNAi; 9940; -.
PRO; PR:Q9Y238; -.
Proteomes; UP000005640; Chromosome 3.
Bgee; ENSG00000008226; -.
CleanEx; HS_DLC1; -.
CleanEx; HS_DLEC1; -.
ExpressionAtlas; Q9Y238; baseline and differential.
Genevisible; Q9Y238; HS.
GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
GO; GO:0005829; C:cytosol; IDA:HPA.
GO; GO:0008285; P:negative regulation of cell proliferation; TAS:ProtInc.
Gene3D; 2.60.40.10; -; 7.
InterPro; IPR033304; DLEC1.
InterPro; IPR013783; Ig-like_fold.
PANTHER; PTHR23053:SF12; PTHR23053:SF12; 1.
2: Evidence at transcript level;
Alternative splicing; Complete proteome; Cytoplasm; Polymorphism;
Reference proteome; Tumor suppressor.
CHAIN 1 1755 Deleted in lung and esophageal cancer
protein 1.
/FTId=PRO_0000079929.
VAR_SEQ 704 704 E -> MARLRGGRIPAMPQPSPGQPAGTQWCFQGTVFALQ
(in isoform 2).
{ECO:0000303|PubMed:17974005}.
/FTId=VSP_051847.
VAR_SEQ 856 885 GPALIINVSALQFGLLRLGQKATNSIQIRN -> PFSLVCS
AWGRKPQTPSRSGTSASSQPHGA (in isoform 2).
{ECO:0000303|PubMed:17974005}.
/FTId=VSP_051848.
VAR_SEQ 886 1755 Missing (in isoform 2).
{ECO:0000303|PubMed:17974005}.
/FTId=VSP_051849.
VAR_SEQ 1675 1755 QQEPAKAAVAFRVSPNSGLLEARSANAPPTSIALQVFFTAR
SSELYESTMVVEGVLGEKSCTLRLRGQGSYDERYMLPHQP
-> VVSCTSPRWWWKVCSVRSPAPCGSGAKAPMMRDTCCLT
SPEAPPQPSAPGPSWRKNIAQGLGAALQHKDTDLGTWGPLG
SSWNGRTPFHNGLSLGPHDMSSELT (in isoform 3).
{ECO:0000303|PubMed:17974005}.
/FTId=VSP_051850.
VARIANT 79 79 L -> R (in dbSNP:rs7625806).
/FTId=VAR_056860.
VARIANT 192 192 S -> F (in dbSNP:rs34012183).
/FTId=VAR_056861.
VARIANT 351 351 P -> R (in a breast cancer sample;
somatic mutation).
{ECO:0000269|PubMed:16959974}.
/FTId=VAR_035908.
VARIANT 1022 1022 K -> N (in dbSNP:rs36012922).
/FTId=VAR_056862.
VARIANT 1150 1150 N -> D (in dbSNP:rs9840172).
/FTId=VAR_056863.
VARIANT 1227 1227 L -> P (in dbSNP:rs9810085).
/FTId=VAR_056864.
CONFLICT 704 704 E -> M (in Ref. 2; CAB70884).
{ECO:0000305}.
CONFLICT 1442 1442 G -> R (in Ref. 1; BAA77624/BAA77247).
{ECO:0000305}.
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


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