TCL1A_HUMAN
ID TCL1A_HUMAN Reviewed; 114 AA.
AC P56279; Q6IBK7;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 1.
DT 03-AUG-2022, entry version 192.
DE RecName: Full=T-cell leukemia/lymphoma protein 1A;
DE AltName: Full=Oncogene TCL-1;
DE Short=Oncogene TCL1;
DE AltName: Full=Protein p14 TCL1;
GN Name=TCL1A; Synonyms=TCL1;
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].
RX PubMed=7809072; DOI=10.1073/pnas.91.26.12530;
RA Virgilio L., Narducci M.G., Isobe M., Billips L.G., Cooper M.D.,
RA Croce C.M., Russo G.;
RT "Identification of the TCL1 gene involved in T-cell malignancies.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:12530-12534(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=B-cell, and Lymph;
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 [4]
RP CHARACTERIZATION, AND SUBCELLULAR LOCATION.
RX PubMed=7987816;
RA Fu T.-B., Virgilio L., Narducci M.G., Facchiano A., Russo G., Croce C.M.;
RT "Characterization and localization of the TCL-1 oncogene product.";
RL Cancer Res. 54:6297-6301(1994).
RN [5]
RP FUNCTION, AND INTERACTION WITH AKT1 AND AKT2.
RX PubMed=10983986; DOI=10.1016/s1097-2765(00)00039-3;
RA Laine J., Kuenstle G., Obata T., Sha M., Noguchi M.;
RT "The protooncogene TCL1 is an Akt kinase coactivator.";
RL Mol. Cell 6:395-407(2000).
RN [6]
RP FUNCTION, AND INTERACTION WITH AKT1.
RX PubMed=10716693; DOI=10.1073/pnas.97.7.3028;
RA Pekarsky Y., Koval A., Hallas C., Bichi R., Tresini M., Malstrom S.,
RA Russo G., Tsichlis P., Croce C.M.;
RT "Tcl1 enhances Akt kinase activity and mediates its nuclear
RT translocation.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:3028-3033(2000).
RN [7]
RP FUNCTION, AND INTERACTION WITH AKT3.
RX PubMed=11707444; DOI=10.1074/jbc.m107069200;
RA Laine J., Kuenstle G., Obata T., Noguchi M.;
RT "Differential regulation of Akt kinase isoforms by the members of the TCL1
RT oncogene family.";
RL J. Biol. Chem. 277:3743-3751(2002).
RN [8]
RP FUNCTION, INTERACTION WITH AKT1; AKT2 AND AKT3, AND MUTAGENESIS OF ASP-16;
RP LYS-30; 36-PRO--THR-38; GLN-46; ILE-74 AND MET-106.
RX PubMed=11839817; DOI=10.1128/mcb.22.5.1513-1525.2002;
RA Kuenstle G., Laine J., Pierron G., Kagami S., Nakajima H., Hoh F.,
RA Roumestand C., Stern M.H., Noguchi M.;
RT "Identification of Akt association and oligomerization domains of the Akt
RT kinase coactivator TCL1.";
RL Mol. Cell. Biol. 22:1513-1525(2002).
RN [9]
RP INTERACTION WITH PNPT1.
RX PubMed=16934922; DOI=10.1016/j.canlet.2006.07.006;
RA French S.W., Dawson D.W., Chen H.-W., Rainey R.N., Sievers S.A.,
RA Balatoni C.E., Wong L., Troke J.J., Nguyen M.T.N., Koehler C.M.,
RA Teitell M.A.;
RT "The TCL1 oncoprotein binds the RNase PH domains of the PNPase
RT exoribonuclease without affecting its RNA degrading activity.";
RL Cancer Lett. 248:198-210(2007).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
RX PubMed=9519406; DOI=10.1016/s0969-2126(98)00017-3;
RA Hoh F., Yang Y.-S., Guignard L., Padilla A., Stern M.-H., Lhoste J.-M.,
RA van Tilbourgh H.;
RT "Crystal structure of p14TCL1, an oncogene product involved in T-cell
RT prolymphocytic leukemia, reveals a novel beta-barrel topology.";
RL Structure 6:147-155(1998).
CC -!- FUNCTION: Enhances the phosphorylation and activation of AKT1, AKT2 and
CC AKT3. Promotes nuclear translocation of AKT1. Enhances cell
CC proliferation, stabilizes mitochondrial membrane potential and promotes
CC cell survival. {ECO:0000269|PubMed:10716693,
CC ECO:0000269|PubMed:10983986, ECO:0000269|PubMed:11707444,
CC ECO:0000269|PubMed:11839817}.
CC -!- SUBUNIT: Homodimer. Interacts with AKT1, AKT2 and AKT3 (via PH domain).
CC Interacts with PNPT1; the interaction has no effect on PNPT1
CC exonuclease activity. {ECO:0000269|PubMed:10716693,
CC ECO:0000269|PubMed:10983986, ECO:0000269|PubMed:11707444,
CC ECO:0000269|PubMed:11839817, ECO:0000269|PubMed:16934922}.
CC -!- INTERACTION:
CC P56279; A0A0S2Z3D6: AKT1; NbExp=3; IntAct=EBI-749995, EBI-16430470;
CC P56279; B0LPE5: AKT1; NbExp=3; IntAct=EBI-749995, EBI-10175397;
CC P56279; P31749: AKT1; NbExp=8; IntAct=EBI-749995, EBI-296087;
CC P56279; A2RRN7: CADPS; NbExp=6; IntAct=EBI-749995, EBI-10179719;
CC P56279; Q13137: CALCOCO2; NbExp=10; IntAct=EBI-749995, EBI-739580;
CC P56279; Q9H257: CARD9; NbExp=3; IntAct=EBI-749995, EBI-751319;
CC P56279; Q9H257-2: CARD9; NbExp=3; IntAct=EBI-749995, EBI-11530605;
CC P56279; Q8IYE1: CCDC13; NbExp=3; IntAct=EBI-749995, EBI-10961312;
CC P56279; Q53EZ4: CEP55; NbExp=6; IntAct=EBI-749995, EBI-747776;
CC P56279; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-749995, EBI-742054;
CC P56279; Q9Y6K1: DNMT3A; NbExp=10; IntAct=EBI-749995, EBI-923653;
CC P56279; Q09472: EP300; NbExp=4; IntAct=EBI-749995, EBI-447295;
CC P56279; Q96Q35: FLACC1; NbExp=3; IntAct=EBI-749995, EBI-750451;
CC P56279; P01100: FOS; NbExp=4; IntAct=EBI-749995, EBI-852851;
CC P56279; Q08379: GOLGA2; NbExp=8; IntAct=EBI-749995, EBI-618309;
CC P56279; Q0VD86: INCA1; NbExp=3; IntAct=EBI-749995, EBI-6509505;
CC P56279; P05412: JUN; NbExp=6; IntAct=EBI-749995, EBI-852823;
CC P56279; P17275: JUNB; NbExp=2; IntAct=EBI-749995, EBI-748062;
CC P56279; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-749995, EBI-739832;
CC P56279; P62310: LSM3; NbExp=6; IntAct=EBI-749995, EBI-348239;
CC P56279; P25963: NFKBIA; NbExp=3; IntAct=EBI-749995, EBI-307386;
CC P56279; Q8NI38: NFKBID; NbExp=3; IntAct=EBI-749995, EBI-10271199;
CC P56279; Q9GZT8: NIF3L1; NbExp=5; IntAct=EBI-749995, EBI-740897;
CC P56279; Q96HA8: NTAQ1; NbExp=5; IntAct=EBI-749995, EBI-741158;
CC P56279; Q96KQ4: PPP1R13B; NbExp=3; IntAct=EBI-749995, EBI-1105153;
CC P56279; Q9NRG1: PRTFDC1; NbExp=6; IntAct=EBI-749995, EBI-739759;
CC P56279; Q04864-2: REL; NbExp=3; IntAct=EBI-749995, EBI-10829018;
CC P56279; Q86VP1: TAX1BP1; NbExp=3; IntAct=EBI-749995, EBI-529518;
CC P56279; P15884: TCF4; NbExp=3; IntAct=EBI-749995, EBI-533224;
CC P56279; P56279: TCL1A; NbExp=4; IntAct=EBI-749995, EBI-749995;
CC P56279; Q96N21: TEPSIN; NbExp=3; IntAct=EBI-749995, EBI-11139477;
CC P56279; O95271: TNKS; NbExp=3; IntAct=EBI-749995, EBI-1105254;
CC P56279; Q13625-3: TP53BP2; NbExp=3; IntAct=EBI-749995, EBI-10175039;
CC P56279; Q13077: TRAF1; NbExp=8; IntAct=EBI-749995, EBI-359224;
CC P56279; Q12933: TRAF2; NbExp=3; IntAct=EBI-749995, EBI-355744;
CC P56279; Q96FX7: TRMT61A; NbExp=3; IntAct=EBI-749995, EBI-934042;
CC P56279; Q6PID6: TTC33; NbExp=7; IntAct=EBI-749995, EBI-2555404;
CC P56279; P40222: TXLNA; NbExp=6; IntAct=EBI-749995, EBI-359793;
CC P56279; Q8N3L3: TXLNB; NbExp=3; IntAct=EBI-749995, EBI-6116822;
CC P56279; O94967: WDR47; NbExp=3; IntAct=EBI-749995, EBI-723239;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC Microsome {ECO:0000269|PubMed:7987816}. Endoplasmic reticulum
CC {ECO:0000269|PubMed:7987816}. Note=Microsomal fraction.
CC -!- TISSUE SPECIFICITY: Restricted in the T-cell lineage to immature
CC thymocytes and activated peripheral lymphocytes. Preferentially
CC expressed early in T- and B-lymphocyte differentiation.
CC -!- DISEASE: Note=Chromosomal aberrations activating TCL1A are found in
CC chronic T-cell leukemias (T-CLL). Translocation t(14;14)(q11;q32);
CC translocation t(7;14)(q35;q32); inversion inv(14)(q11;q32) that
CC involves the T-cell receptor alpha/delta loci.
CC -!- SIMILARITY: Belongs to the TCL1 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/TCL1ID66.html";
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DR EMBL; X82240; CAA57708.1; -; mRNA.
DR EMBL; CR456796; CAG33077.1; -; mRNA.
DR EMBL; BC003574; AAH03574.1; -; mRNA.
DR EMBL; BC005831; AAH05831.1; -; mRNA.
DR EMBL; BC014024; AAH14024.1; -; mRNA.
DR CCDS; CCDS9941.1; -.
DR PIR; I38286; I38286.
DR RefSeq; NP_001092195.1; NM_001098725.1.
DR RefSeq; NP_068801.1; NM_021966.2.
DR RefSeq; XP_016877165.1; XM_017021676.1.
DR RefSeq; XP_016877166.1; XM_017021677.1.
DR PDB; 1JSG; X-ray; 2.50 A; A=1-114.
DR PDBsum; 1JSG; -.
DR AlphaFoldDB; P56279; -.
DR SMR; P56279; -.
DR BioGRID; 113783; 61.
DR CORUM; P56279; -.
DR DIP; DIP-60787N; -.
DR IntAct; P56279; 42.
DR MINT; P56279; -.
DR STRING; 9606.ENSP00000385036; -.
DR iPTMnet; P56279; -.
DR PhosphoSitePlus; P56279; -.
DR BioMuta; TCL1A; -.
DR MassIVE; P56279; -.
DR MaxQB; P56279; -.
DR PaxDb; P56279; -.
DR PeptideAtlas; P56279; -.
DR PRIDE; P56279; -.
DR ProteomicsDB; 56910; -.
DR Antibodypedia; 65; 434 antibodies from 40 providers.
DR DNASU; 8115; -.
DR Ensembl; ENST00000402399.6; ENSP00000385036.1; ENSG00000100721.11.
DR Ensembl; ENST00000554012.5; ENSP00000451506.1; ENSG00000100721.11.
DR Ensembl; ENST00000555202.1; ENSP00000450496.1; ENSG00000100721.11.
DR Ensembl; ENST00000556450.5; ENSP00000450701.1; ENSG00000100721.11.
DR GeneID; 8115; -.
DR KEGG; hsa:8115; -.
DR MANE-Select; ENST00000402399.6; ENSP00000385036.1; NM_021966.3; NP_068801.1.
DR UCSC; uc001yfb.5; human.
DR CTD; 8115; -.
DR DisGeNET; 8115; -.
DR GeneCards; TCL1A; -.
DR HGNC; HGNC:11648; TCL1A.
DR HPA; ENSG00000100721; Tissue enriched (lymphoid).
DR MalaCards; TCL1A; -.
DR MIM; 186960; gene.
DR neXtProt; NX_P56279; -.
DR OpenTargets; ENSG00000100721; -.
DR Orphanet; 99861; Precursor T-cell acute lymphoblastic leukemia.
DR PharmGKB; PA36400; -.
DR VEuPathDB; HostDB:ENSG00000100721; -.
DR eggNOG; ENOG502TDVJ; Eukaryota.
DR GeneTree; ENSGT00390000006885; -.
DR HOGENOM; CLU_168379_0_1_1; -.
DR InParanoid; P56279; -.
DR OMA; LWIWERS; -.
DR OrthoDB; 1496659at2759; -.
DR PhylomeDB; P56279; -.
DR TreeFam; TF337903; -.
DR PathwayCommons; P56279; -.
DR SignaLink; P56279; -.
DR SIGNOR; P56279; -.
DR BioGRID-ORCS; 8115; 8 hits in 1069 CRISPR screens.
DR ChiTaRS; TCL1A; human.
DR EvolutionaryTrace; P56279; -.
DR GeneWiki; TCL1A; -.
DR GenomeRNAi; 8115; -.
DR Pharos; P56279; Tbio.
DR PRO; PR:P56279; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; P56279; protein.
DR Bgee; ENSG00000100721; Expressed in oocyte and 123 other tissues.
DR ExpressionAtlas; P56279; baseline and differential.
DR Genevisible; P56279; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0032991; C:protein-containing complex; IMP:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; IMP:UniProtKB.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IDA:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0010918; P:positive regulation of mitochondrial membrane potential; IDA:UniProtKB.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IMP:UniProtKB.
DR GO; GO:0071902; P:positive regulation of protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; IDA:UniProtKB.
DR Gene3D; 2.40.15.10; -; 1.
DR InterPro; IPR004832; TCL1_MTCP1.
DR InterPro; IPR036672; TCL1_MTCP1_sf.
DR PANTHER; PTHR14060; PTHR14060; 1.
DR Pfam; PF01840; TCL1_MTCP1; 1.
DR SUPFAM; SSF50904; SSF50904; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Chromosomal rearrangement; Cytoplasm; Endoplasmic reticulum;
KW Microsome; Nucleus; Proto-oncogene; Reference proteome.
FT CHAIN 1..114
FT /note="T-cell leukemia/lymphoma protein 1A"
FT /id="PRO_0000184488"
FT VARIANT 56
FT /note="V -> I (in dbSNP:rs17093294)"
FT /id="VAR_053718"
FT MUTAGEN 16
FT /note="D->G: Greatly reduced binding to AKT1, AKT2 and
FT AKT3. Abolishes nuclear transport of AKT1."
FT /evidence="ECO:0000269|PubMed:11839817"
FT MUTAGEN 30
FT /note="K->M: Slightly reduced binding to AKT2."
FT /evidence="ECO:0000269|PubMed:11839817"
FT MUTAGEN 36..38
FT /note="PLT->AAA: Unable to homodimerize but has no effect
FT on interaction with AKT1, AKT2 or AKT3."
FT /evidence="ECO:0000269|PubMed:11839817"
FT MUTAGEN 46
FT /note="Q->R: Slightly increased binding to AKT2."
FT /evidence="ECO:0000269|PubMed:11839817"
FT MUTAGEN 74
FT /note="I->V: Greatly reduced binding to AKT2. Abolishes
FT nuclear transport of AKT1."
FT /evidence="ECO:0000269|PubMed:11839817"
FT MUTAGEN 106
FT /note="M->V: Slightly increased binding to AKT2."
FT /evidence="ECO:0000269|PubMed:11839817"
FT CONFLICT 106
FT /note="M -> V (in Ref. 2; CAG33077)"
FT /evidence="ECO:0000305"
FT STRAND 8..10
FT /evidence="ECO:0007829|PDB:1JSG"
FT STRAND 16..22
FT /evidence="ECO:0007829|PDB:1JSG"
FT STRAND 25..28
FT /evidence="ECO:0007829|PDB:1JSG"
FT STRAND 33..42
FT /evidence="ECO:0007829|PDB:1JSG"
FT TURN 43..45
FT /evidence="ECO:0007829|PDB:1JSG"
FT STRAND 46..53
FT /evidence="ECO:0007829|PDB:1JSG"
FT HELIX 64..67
FT /evidence="ECO:0007829|PDB:1JSG"
FT STRAND 74..78
FT /evidence="ECO:0007829|PDB:1JSG"
FT STRAND 84..86
FT /evidence="ECO:0007829|PDB:1JSG"
FT STRAND 91..100
FT /evidence="ECO:0007829|PDB:1JSG"
FT STRAND 103..111
FT /evidence="ECO:0007829|PDB:1JSG"
SQ SEQUENCE 114 AA; 13460 MW; 90D55ABC97C36D04 CRC64;
MAECPTLGEA VTDHPDRLWA WEKFVYLDEK QHAWLPLTIE IKDRLQLRVL LRREDVVLGR
PMTPTQIGPS LLPIMWQLYP DGRYRSSDSS FWRLVYHIKI DGVEDMLLEL LPDD
