DLEC1_HUMAN
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 03-AUG-2022, entry version 148.
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).
RN [5]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH ALPHA-TUBULIN; BETA-TUBULIN;
RP BBS2; BBS4; BBS5; MKKS; TCP1; CCT2; CCT3; CCT4; CCT5 AND CCT7.
RX PubMed=33144677; DOI=10.1038/s41598-020-75957-y;
RA Okitsu Y., Nagano M., Yamagata T., Ito C., Toshimori K., Dohra H.,
RA Fujii W., Yogo K.;
RT "Dlec1 is required for spermatogenesis and male fertility in mice.";
RL Sci. Rep. 10:18883-18883(2020).
CC -!- FUNCTION: Essential for spermatogenesis and male fertility (By
CC similarity). May play an important role in sperm head and tail
CC formation (By similarity). May act as a tumor suppressor by inhibiting
CC cell proliferation. {ECO:0000250|UniProtKB:Q8BLA1,
CC ECO:0000269|PubMed:10213508}.
CC -!- SUBUNIT: Interacts with alpha- and beta-tubulin (PubMed:33144677).
CC Interacts with BBS2, BBS4, BBS5, MKKS, TCP1, CCT2, CCT3, CCT4, CCT5 and
CC CCT7 (PubMed:33144677). {ECO:0000269|PubMed:33144677}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10213508,
CC ECO:0000269|PubMed:33144677}.
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 AlphaFoldDB; Q9Y238; -.
DR BioGRID; 115266; 12.
DR IntAct; Q9Y238; 2.
DR STRING; 9606.ENSP00000308597; -.
DR iPTMnet; Q9Y238; -.
DR PhosphoSitePlus; Q9Y238; -.
DR BioMuta; DLEC1; -.
DR DMDM; 296434480; -.
DR EPD; 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 Antibodypedia; 6364; 180 antibodies from 24 providers.
DR DNASU; 9940; -.
DR Ensembl; ENST00000308059.11; ENSP00000308597.6; ENSG00000008226.20. [Q9Y238-1]
DR Ensembl; ENST00000346219.7; ENSP00000315914.5; ENSG00000008226.20. [Q9Y238-3]
DR GeneID; 9940; -.
DR KEGG; hsa:9940; -.
DR MANE-Select; ENST00000308059.11; ENSP00000308597.6; NM_007335.4; NP_031361.2.
DR UCSC; uc003cho.2; human. [Q9Y238-1]
DR CTD; 9940; -.
DR DisGeNET; 9940; -.
DR GeneCards; DLEC1; -.
DR HGNC; HGNC:2899; DLEC1.
DR HPA; ENSG00000008226; Tissue enhanced (choroid plexus, fallopian tube, testis).
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 VEuPathDB; HostDB:ENSG00000008226; -.
DR eggNOG; ENOG502QQQ5; Eukaryota.
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 PathwayCommons; Q9Y238; -.
DR SignaLink; Q9Y238; -.
DR BioGRID-ORCS; 9940; 9 hits in 1062 CRISPR screens.
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 142 other tissues.
DR ExpressionAtlas; Q9Y238; baseline and differential.
DR Genevisible; Q9Y238; HS.
DR GO; GO:0005929; C:cilium; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0043014; F:alpha-tubulin binding; IDA:UniProtKB.
DR GO; GO:0048487; F:beta-tubulin binding; IDA:UniProtKB.
DR GO; GO:0015631; F:tubulin binding; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0002357; P:defense response to tumor cell; IMP:ARUK-UCL.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; TAS:ProtInc.
DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB.
DR Gene3D; 2.60.40.10; -; 7.
DR InterPro; IPR033304; DLEC1.
DR InterPro; IPR013783; Ig-like_fold.
DR PANTHER; PTHR46348; PTHR46348; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Differentiation; Reference proteome;
KW Spermatogenesis; Tumor suppressor.
FT CHAIN 1..1755
FT /note="Deleted in lung and esophageal cancer protein 1"
FT /id="PRO_0000079929"
FT REGION 1..39
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1339..1360
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1529..1553
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 12..39
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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
