Reviewed, UniProtKB/Swiss-Prot P56279 (TCL1A_HUMAN)

Names and origin

Protein names

Recommended name:
    T-cell leukemia/lymphoma protein 1A
Alternative name(s):
    Protein p14 TCL1
    Oncogene TCL1
      Short name=TCL-1

Gene names

Name:	TCL1A
Synonyms:	TCL1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	114 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Enhances the phosphorylation and activation of AKT1, AKT2 and AKT3. Promotes nuclear translocation of AKT1. Enhances cell proliferation, stabilizes mitochondrial membrane potential and promotes cell survival. Ref.5 Ref.6 Ref.7 Ref.8
Subunit structure	Homodimer. Interacts with AKT1, AKT2 and AKT3 (via PH domain). Interacts with PNPT1; the interaction has no effect on PNPT1 exonuclease activity. Ref.5 Ref.6 Ref.7 Ref.8 Ref.9
Subcellular location	Cytoplasm By similarity. Nucleus By similarity. Microsome. Endoplasmic reticulum. Note: Microsomal fraction. Ref.4
Tissue specificity	Restricted in the T-cell lineage to immature thymocytes and activated peripheral lymphocytes. Preferentially expressed early in T- and B-lymphocyte differentiation.
Involvement in disease	Chromosomal aberrations activating TCL1A are found in chronic T-cell leukemias (T-CLL). Translocation t(14;14)(q11;q32); translocation t(7;14)(q35;q32); inversion inv(14)(q11;q32) that involves the T-cell receptor alpha/delta locuses.
Sequence similarities	Belongs to the TCL1 family.

Ontologies

Keywords
Cellular component	Cytoplasm Endoplasmic reticulum Microsome Nucleus
Coding sequence diversity	Chromosomal rearrangement Polymorphism
Disease	Proto-oncogene
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	multicellular organismal development Ref.1 Traceable author statement. Source: ProtInc
Cellular component	endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-SubCell microsome Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein binding Ref.7 Inferred from physical interaction. Source: GDB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 114

114

T-cell leukemia/lymphoma protein 1A

PRO_0000184488

Natural variations

Natural variant

56

1

V → I: dbSNP rs17093294.

VAR_053718

Experimental info

Mutagenesis

16

1

D → G: Greatly reduced binding to AKT1, AKT2 and AKT3. Abolishes nuclear transport of AKT1. Ref.8

Mutagenesis

30

1

K → M: Slightly reduced binding to AKT2. Ref.8

Mutagenesis

36 – 38

3

PLT → AAA: Unable to homodimerize but has no effect on interaction with AKT1, AKT2 or AKT3. Ref.8

Mutagenesis

46

1

Q → R: Slightly increased binding to AKT2. Ref.8

Mutagenesis

74

1

I → V: Greatly reduced binding to AKT2. Abolishes nuclear transport of AKT1. Ref.8

Mutagenesis

106

1

M → V: Slightly increased binding to AKT2. Ref.8

Sequence conflict

106

1

M → V in CAG33077. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

114

Helix Strand Turn

Details...

Beta strand

8 – 10

3

Beta strand

16 – 22

7

Beta strand

25 – 28

4

Beta strand

33 – 42

10

Turn

43 – 45

3

Beta strand

46 – 53

8

Helix

64 – 67

4

Beta strand

74 – 78

5

Beta strand

84 – 86

3

Beta strand

91 – 100

10

Beta strand

103 – 111

9

Sequences

	Sequence		Length	Mass (Da)
	P56279-1 [UniParc]. Last modified July 15, 1998. Version 1. Checksum: 90D55ABC97C36D04	FASTA	114	13,460
	10 20 30 40 50 60 MAECPTLGEA VTDHPDRLWA WEKFVYLDEK QHAWLPLTIE IKDRLQLRVL LRREDVVLGR 70 80 90 100 110 PMTPTQIGPS LLPIMWQLYP DGRYRSSDSS FWRLVYHIKI DGVEDMLLEL LPDD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of the TCL1 gene involved in T-cell malignancies." Virgilio L., Narducci M.G., Isobe M., Billips L.G., Cooper M.D., Croce C.M., Russo G. Proc. Natl. Acad. Sci. U.S.A. 91:12530-12534(1994) [PubMed: 7809072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: B-cell and Lymph.
[4]	"Characterization and localization of the TCL-1 oncogene product." Fu T.-B., Virgilio L., Narducci M.G., Facchiano A., Russo G., Croce C.M. Cancer Res. 54:6297-6301(1994) [PubMed: 7987816] [Abstract] Cited for: CHARACTERIZATION, SUBCELLULAR LOCATION.
[5]	"The protooncogene TCL1 is an Akt kinase coactivator." Laine J., Kuenstle G., Obata T., Sha M., Noguchi M. Mol. Cell 6:395-407(2000) [PubMed: 10983986] [Abstract] Cited for: FUNCTION, INTERACTION WITH AKT1 AND AKT2.
[6]	"Tcl1 enhances Akt kinase activity and mediates its nuclear translocation." Pekarsky Y., Koval A., Hallas C., Bichi R., Tresini M., Malstrom S., Russo G., Tsichlis P., Croce C.M. Proc. Natl. Acad. Sci. U.S.A. 97:3028-3033(2000) [PubMed: 10716693] [Abstract] Cited for: FUNCTION, INTERACTION WITH AKT1.
[7]	"Differential regulation of Akt kinase isoforms by the members of the TCL1 oncogene family." Laine J., Kuenstle G., Obata T., Noguchi M. J. Biol. Chem. 277:3743-3751(2002) [PubMed: 11707444] [Abstract] Cited for: FUNCTION, INTERACTION WITH AKT3.
[8]	"Identification of Akt association and oligomerization domains of the Akt kinase coactivator TCL1." Kuenstle G., Laine J., Pierron G., Kagami S., Nakajima H., Hoh F., Roumestand C., Stern M.H., Noguchi M. Mol. Cell. Biol. 22:1513-1525(2002) [PubMed: 11839817] [Abstract] Cited for: FUNCTION, INTERACTION WITH AKT1; AKT2 AND AKT3, MUTAGENESIS OF ASP-16; LYS-30; 36-PRO--THR-38; GLN-46; ILE-74 AND MET-106.
[9]	"The TCL1 oncoprotein binds the RNase PH domains of the PNPase exoribonuclease without affecting its RNA degrading activity." French S.W., Dawson D.W., Chen H.-W., Rainey R.N., Sievers S.A., Balatoni C.E., Wong L., Troke J.J., Nguyen M.T.N., Koehler C.M., Teitell M.A. Cancer Lett. 248:198-210(2007) [PubMed: 16934922] [Abstract] Cited for: INTERACTION WITH PNPT1.
[10]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[11]	"Crystal structure of p14TCL1, an oncogene product involved in T-cell prolymphocytic leukemia, reveals a novel beta-barrel topology." Hoh F., Yang Y.-S., Guignard L., Padilla A., Stern M.-H., Lhoste J.-M., van Tilbourgh H. Structure 6:147-155(1998) [PubMed: 9519406] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X82240 mRNA. Translation: CAA57708.1.
CR456796 mRNA. Translation: CAG33077.1.
BC003574 mRNA. Translation: AAH03574.1.
BC005831 mRNA. Translation: AAH05831.1.
BC014024 mRNA. Translation: AAH14024.1.

IPI

IPI00178749.

PIR

I38286.

RefSeq

NP_001092195.1.
NP_068801.1.

UniGene

Hs.2484

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1JSG	X-ray	2.50	A	1-114	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P56279. 1 interaction.

STRING

P56279.

Proteomic databases

PRIDE

P56279.

Genome annotation databases

Ensembl

ENST00000216612; ENSP00000216612; ENSG00000100721; Homo sapiens. [Genome view]
ENST00000402399; ENSP00000385036; ENSG00000100721; Homo sapiens. [Genome view]

GeneID

8115.

KEGG

hsa:8115.

UCSC

uc001yfb.2. human.

Organism-specific databases

CTD

8115.

GeneCards

GC14M095246.

H-InvDB

HIX0011943.

HGNC

HGNC:11648. TCL1A.

HPA

CAB004045.
HPA016604.

MIM

186960. gene.

Orphanet

86872. Leukemia, T-cell large granular lymphocyte.

PharmGKB

PA36400.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG20682.

HOGENOM

HBG279858.

HOVERGEN

P56279.

InParanoid

P56279.

OMA

HPDHLWI.

OrthoDB

EOG9T7BPB.

PhylomeDB

P56279.

Gene expression databases

ArrayExpress

P56279.

Bgee

P56279.

CleanEx

HS_TCL1A.

Genevestigator

P56279.

GermOnline

ENSG00000100721. Homo sapiens.

Family and domain databases

InterPro

IPR004832. TCL1_MTCP1.
[Graphical view]

Gene3D

G3DSA:2.40.15.10. TCL1_MTCP1. 1 hit.

Pfam

PF01840. TCL1_MTCP1. 1 hit.
[Graphical view]

ProDom

PD015575. TCL1_MTCP1. 1 hit.
[Graphical view] [Entries sharing at least one domain]

ProtoNet

Search...

Other Resources

NextBio

30770.

SOURCE

Search...

Entry information

Entry name

TCL1A_HUMAN

Accession

Primary (citable) accession number: P56279
Secondary accession number(s): Q6IBK7

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	July 15, 1998
Last modified:	January 19, 2010
This is version 89 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.