TFEC_HUMAN
ID TFEC_HUMAN Reviewed; 347 AA.
AC O14948; B2R8X5; Q5H9U8; Q709A4; Q8N6J9;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Transcription factor EC;
DE Short=TFE-C;
DE AltName: Full=Class E basic helix-loop-helix protein 34;
DE Short=bHLHe34;
DE AltName: Full=Transcription factor EC-like;
DE Short=hTFEC-L;
GN Name=TFEC; Synonyms=BHLHE34, TCFEC, TFECL;
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]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RC TISSUE=Monocytic leukemia;
RX PubMed=9256061; DOI=10.1016/s0167-4781(97)00034-1;
RA Yasumoto K., Shibahara S.;
RT "Molecular cloning of cDNA encoding a human TFEC isoform, a newly
RT identified transcriptional regulator.";
RL Biochim. Biophys. Acta 1353:23-31(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Fetal kidney;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-104 (ISOFORM 4), AND TISSUE SPECIFICITY.
RX PubMed=15118077; DOI=10.1093/nar/gkh571;
RA Kuiper R.P., Schepens M., Thijssen J., Schoenmakers E.F.P.M.,
RA Geurts van Kessel A.;
RT "Regulation of the MiTF/TFE bHLH-LZ transcription factors through
RT restricted spatial expression and alternative splicing of functional
RT domains.";
RL Nucleic Acids Res. 32:2315-2322(2004).
RN [8]
RP FUNCTION, SUBUNIT, DNA-BINDING, SUBCELLULAR LOCATION, ALTERNATIVE SPLICING
RP (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY.
RX PubMed=11467950; DOI=10.1021/bi002847d;
RA Chung M.-C., Kim H.-K., Kawamoto S.;
RT "TFEC can function as a transcriptional activator of the nonmuscle myosin
RT II heavy chain-A gene in transfected cells.";
RL Biochemistry 40:8887-8897(2001).
RN [9]
RP VARIANT [LARGE SCALE ANALYSIS] VAL-146.
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: Transcriptional regulator that acts as a repressor or an
CC activator. Acts as a transcriptional repressor on minimal promoter
CC containing element F (that includes an E-box sequence). Binds to
CC element F in an E-box sequence-specific manner. Acts as a
CC transcriptional transactivator on the proximal promoter region of the
CC tartrate-resistant acid phosphatase (TRAP) E-box containing promoter
CC (By similarity). Collaborates with MITF in target gene activation (By
CC similarity). Acts as a transcriptional repressor on minimal promoter
CC containing mu E3 enhancer sequence (By similarity). Binds to mu E3 DNA
CC sequence of the immunoglobulin heavy-chain gene enhancer (By
CC similarity). Binds DNA in a homo- or heterodimeric form. {ECO:0000250,
CC ECO:0000269|PubMed:11467950, ECO:0000269|PubMed:9256061}.
CC -!- SUBUNIT: Homodimer. Forms heterodimers with TFE3. Forms heterodimers
CC with MITF (By similarity). Interacts with MITF (By similarity).
CC {ECO:0000250}.
CC -!- INTERACTION:
CC O14948; Q9H1M4: DEFB127; NbExp=3; IntAct=EBI-3916574, EBI-10305240;
CC O14948; Q9H115: NAPB; NbExp=3; IntAct=EBI-3916574, EBI-3921185;
CC O14948-3; Q9UBY5: LPAR3; NbExp=3; IntAct=EBI-12246506, EBI-12033434;
CC O14948-3; Q9NRQ5: SMCO4; NbExp=3; IntAct=EBI-12246506, EBI-8640191;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00981,
CC ECO:0000269|PubMed:11467950}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=TFEC-l, TFECL;
CC IsoId=O14948-1; Sequence=Displayed;
CC Name=2; Synonyms=TFEC-s;
CC IsoId=O14948-2; Sequence=VSP_030023;
CC Name=3;
CC IsoId=O14948-3; Sequence=VSP_030023, VSP_030025, VSP_030026;
CC Name=4; Synonyms=TFEC-C;
CC IsoId=O14948-4; Sequence=VSP_030022, VSP_030024;
CC -!- TISSUE SPECIFICITY: Expressed moderately in spleen, kidney, bone
CC marrow, small intestine and leukocytes. Expressed weakly in testis,
CC trachea and colon. {ECO:0000269|PubMed:11467950,
CC ECO:0000269|PubMed:15118077}.
CC -!- SIMILARITY: Belongs to the MiT/TFE family. {ECO:0000305}.
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DR EMBL; D43945; BAA21908.1; -; mRNA.
DR EMBL; AK313546; BAG36322.1; -; mRNA.
DR EMBL; CR933605; CAI45926.1; -; mRNA.
DR EMBL; CH236947; EAL24366.1; -; Genomic_DNA.
DR EMBL; CH471070; EAW83491.1; -; Genomic_DNA.
DR EMBL; CH471070; EAW83492.1; -; Genomic_DNA.
DR EMBL; BC029891; AAH29891.1; -; mRNA.
DR EMBL; AJ608795; CAE77680.1; -; mRNA.
DR CCDS; CCDS34738.1; -. [O14948-2]
DR CCDS; CCDS5762.1; -. [O14948-1]
DR CCDS; CCDS59076.1; -. [O14948-4]
DR RefSeq; NP_001018068.1; NM_001018058.2. [O14948-2]
DR RefSeq; NP_001231512.1; NM_001244583.1. [O14948-4]
DR RefSeq; NP_036384.1; NM_012252.3. [O14948-1]
DR RefSeq; XP_016867364.1; XM_017011875.1. [O14948-1]
DR AlphaFoldDB; O14948; -.
DR SMR; O14948; -.
DR BioGRID; 116478; 14.
DR IntAct; O14948; 8.
DR STRING; 9606.ENSP00000265440; -.
DR iPTMnet; O14948; -.
DR PhosphoSitePlus; O14948; -.
DR BioMuta; TFEC; -.
DR EPD; O14948; -.
DR jPOST; O14948; -.
DR MassIVE; O14948; -.
DR MaxQB; O14948; -.
DR PaxDb; O14948; -.
DR PeptideAtlas; O14948; -.
DR PRIDE; O14948; -.
DR ProteomicsDB; 48328; -. [O14948-1]
DR ProteomicsDB; 48329; -. [O14948-2]
DR ProteomicsDB; 48330; -. [O14948-3]
DR ProteomicsDB; 48331; -. [O14948-4]
DR Antibodypedia; 31571; 234 antibodies from 30 providers.
DR DNASU; 22797; -.
DR Ensembl; ENST00000265440.12; ENSP00000265440.7; ENSG00000105967.16. [O14948-1]
DR Ensembl; ENST00000320239.11; ENSP00000318676.7; ENSG00000105967.16. [O14948-2]
DR Ensembl; ENST00000393485.5; ENSP00000377125.1; ENSG00000105967.16. [O14948-3]
DR Ensembl; ENST00000457268.5; ENSP00000387650.1; ENSG00000105967.16. [O14948-4]
DR GeneID; 22797; -.
DR KEGG; hsa:22797; -.
DR MANE-Select; ENST00000265440.12; ENSP00000265440.7; NM_012252.4; NP_036384.1.
DR UCSC; uc003vhj.3; human. [O14948-1]
DR CTD; 22797; -.
DR DisGeNET; 22797; -.
DR GeneCards; TFEC; -.
DR HGNC; HGNC:11754; TFEC.
DR HPA; ENSG00000105967; Tissue enhanced (bone marrow, kidney, lymphoid tissue).
DR MIM; 604732; gene.
DR neXtProt; NX_O14948; -.
DR OpenTargets; ENSG00000105967; -.
DR PharmGKB; PA36469; -.
DR VEuPathDB; HostDB:ENSG00000105967; -.
DR eggNOG; KOG1318; Eukaryota.
DR GeneTree; ENSGT00940000159404; -.
DR HOGENOM; CLU_031638_0_0_1; -.
DR InParanoid; O14948; -.
DR OMA; HQIVNQT; -.
DR OrthoDB; 1211990at2759; -.
DR PhylomeDB; O14948; -.
DR TreeFam; TF317174; -.
DR PathwayCommons; O14948; -.
DR SignaLink; O14948; -.
DR SIGNOR; O14948; -.
DR BioGRID-ORCS; 22797; 23 hits in 1093 CRISPR screens.
DR ChiTaRS; TFEC; human.
DR GeneWiki; TFEC; -.
DR GenomeRNAi; 22797; -.
DR Pharos; O14948; Tbio.
DR PRO; PR:O14948; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; O14948; protein.
DR Bgee; ENSG00000105967; Expressed in monocyte and 128 other tissues.
DR ExpressionAtlas; O14948; baseline and differential.
DR Genevisible; O14948; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; TAS:GO_Central.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:GO_Central.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0034605; P:cellular response to heat; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:GO_Central.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:GO_Central.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR021802; MiT/TFE_C.
DR InterPro; IPR024101; TFEC.
DR PANTHER; PTHR45776:SF1; PTHR45776:SF1; 1.
DR Pfam; PF11851; DUF3371; 1.
DR Pfam; PF00010; HLH; 1.
DR SMART; SM00353; HLH; 1.
DR SUPFAM; SSF47459; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
PE 1: Evidence at protein level;
KW Activator; Alternative splicing; DNA-binding; Nucleus; Reference proteome;
KW Repressor; Transcription; Transcription regulation.
FT CHAIN 1..347
FT /note="Transcription factor EC"
FT /id="PRO_0000313564"
FT DOMAIN 139..192
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 1..119
FT /note="Necessary for transcriptional transactivation"
FT REGION 271..347
FT /note="Necessary for transcriptional transactivation"
FT REGION 319..347
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 319..335
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..67
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15118077"
FT /id="VSP_030022"
FT VAR_SEQ 61..89
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_030023"
FT VAR_SEQ 68..89
FT /note="IIGMESSFKEEGADSPLLMQRT -> MMKEKEKTIAIVKVIDTSKLKL (in
FT isoform 4)"
FT /evidence="ECO:0000303|PubMed:15118077"
FT /id="VSP_030024"
FT VAR_SEQ 222..226
FT /note="ELEIQ -> VFIRM (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_030025"
FT VAR_SEQ 227..347
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_030026"
FT VARIANT 6
FT /note="Q -> H (in dbSNP:rs35695387)"
FT /id="VAR_037661"
FT VARIANT 100
FT /note="G -> S (in dbSNP:rs35170691)"
FT /id="VAR_037662"
FT VARIANT 146
FT /note="L -> V (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_037663"
SQ SEQUENCE 347 AA; 38788 MW; A29B4C4A1C88A985 CRC64;
MTLDHQIINP TLKWSQPAVP SGGPLVQHAH TTLDSDAGLT ENPLTKLLAI GKEDDNAQWH
MEDVIEDIIG MESSFKEEGA DSPLLMQRTL SGSILDVYSG EQGISPINMG LTSASCPSSL
PMKREITETD TRALAKERQK KDNHNLIERR RRYNINYRIK ELGTLIPKSN DPDMRWNKGT
ILKASVEYIK WLQKEQQRAR ELEHRQKKLE QANRRLLLRI QELEIQARTH GLPTLASLGT
VDLGAHVTKQ QSHPEQNSVD YCQQLTVSQG PSPELCDQAI AFSDPLSYFT DLSFSAALKE
EQRLDGMLLD DTISPFGTDP LLSATSPAVS KESSRRSSFS SDDGDEL
