P27348 (1433T_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
14-3-3 protein theta

Alternative name(s):
14-3-3 protein T-cell
14-3-3 protein tau
Protein HS1

Gene names

Name:

YWHAQ

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	245 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negatively regulates the kinase activity of PDPK1. Ref.12
Subunit structure	Homodimer. Interacts with CDK16 By similarity. Interacts with SSH1. Interacts with CDKN1B ('Thr-198' phosphorylated form); the interaction translocates CDKN1B to the cytoplasm. Interacts with GAB2. Interacts with the 'Ser-241' phosphorylated form of PDPK1. Ref.11 Ref.12 Ref.13 Ref.15 Ref.23
Subcellular location	Cytoplasm. Note: In neurons, axonally transported to the nerve terminals.
Tissue specificity	Abundantly expressed in brain, heart and pancreas, and at lower levels in kidney and placenta. Up-regulated in the lumbar spinal cord from patients with sporadic amyotrophic lateral sclerosis (ALS) compared with controls, with highest levels of expression in individuals with predominant lower motor neuron involvement. Ref.10
Post-translational modification	Ser-232 is probably phosphorylated by CK1. Ref.9
Sequence similarities	Belongs to the 14-3-3 family.

Ontologies

Keywords
Cellular component	Cytoplasm
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cellular membrane organization Traceable author statement. Source: Reactome intrinsic apoptotic signaling pathway Traceable author statement. Source: Reactome negative regulation of transcription, DNA-dependent Inferred from direct assay PubMed 15163635. Source: BHF-UCL positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway Traceable author statement. Source: Reactome protein targeting Inferred from electronic annotation. Source: Compara small GTPase mediated signal transduction Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasmic vesicle membrane Traceable author statement. Source: Reactome cytosol Traceable author statement. Source: Reactome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ADAM22	Q9P0K1-3	2	EBI-359854,EBI-1567267
ARRB1	P49407	3	EBI-359854,EBI-743313
ARRB2	P32121	3	EBI-359854,EBI-714559
CDK14	O94921	3	EBI-359854,EBI-1043945
EGFR	P00533	4	EBI-359854,EBI-297353
FSHR	P23945	3	EBI-359854,EBI-848239
KANK1	Q14678	2	EBI-359854,EBI-2556221
KANK1	Q14678-2	3	EBI-359854,EBI-6173812
LRRK2	Q5S007	3	EBI-359854,EBI-5323863

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 245

245

14-3-3 protein theta

PRO_0000058636

Sites

Site

56

1

Interaction with phosphoserine on interacting protein

Site

127

1

Interaction with phosphoserine on interacting protein

Amino acid modifications

Modified residue

1

1

N-acetylmethionine Ref.7 Ref.19

Modified residue

3

1

N6-acetyllysine Ref.19

Modified residue

49

1

N6-acetyllysine Ref.19

Modified residue

68

1

N6-acetyllysine Ref.19

Modified residue

115

1

N6-acetyllysine Ref.19

Modified residue

232

1

Phosphoserine Ref.9 Ref.17

Experimental info

Sequence conflict

136

1

D → N in AAV38817. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

245

Helix Strand Turn

Details...

Helix

3 – 15

13

Helix

19 – 31

13

Helix

38 – 68

31

Helix

75 – 103

29

Turn

104 – 108

5

Helix

112 – 132

21

Helix

135 – 159

25

Helix

165 – 180

16

Helix

185 – 201

17

Turn

202 – 205

4

Helix

208 – 227

20

Sequences

	Sequence		Length	Mass (Da)
	P27348 [UniParc]. Last modified August 1, 1992. Version 1. Checksum: 175534325E9E37C4	FASTA	245	27,764
	10 20 30 40 50 60 MEKTELIQKA KLAEQAERYD DMATCMKAVT EQGAELSNEE RNLLSVAYKN VVGGRRSAWR 70 80 90 100 110 120 VISSIEQKTD TSDKKLQLIK DYREKVESEL RSICTTVLEL LDKYLIANAT NPESKVFYLK 130 140 150 160 170 180 MKGDYFRYLA EVACGDDRKQ TIDNSQGAYQ EAFDISKKEM QPTHPIRLGL ALNFSVFYYE 190 200 210 220 230 240 ILNNPELACT LAKTAFDEAI AELDTLNEDS YKDSTLIMQL LRDNLTLWTS DSAGEECDAA EGAEN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structure of a human protein kinase regulator protein." Nielsen P.J. Biochim. Biophys. Acta 1088:425-428(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: T-cell.
[2]	"Molecular cloning and expression of the transformation sensitive epithelial marker stratifin. A member of a protein family that has been involved in the protein kinase C signalling pathway." Leffers H., Madsen P., Rasmussen H.H., Honore B., Andersen A.H., Walbum E., Vandekerckhove J., Celis J.E. J. Mol. Biol. 231:982-998(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Keratinocyte.
[3]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta, Skin and Uterus.
[6]	"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides." Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J. Nat. Biotechnol. 21:566-569(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-18. Tissue: Platelet.
[7]	Bienvenut W.V., Dhillon A.S., Kolch W. Submitted (FEB-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 1-9; 28-49; 61-68; 104-115; 139-167 AND 213-222, ACETYLATION AT MET-1, MASS SPECTROMETRY. Tissue: B-cell lymphoma and Hepatoma.
[8]	Yu W., Gibbs R.A. Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 73-245. Tissue: Brain.
[9]	"14-3-3 is phosphorylated by casein kinase I on residue 233. Phosphorylation at this site in vivo regulates Raf/14-3-3 interaction." Dubois T., Rommel C., Howell S., Steinhussen U., Soneji Y., Morrice N., Moelling K., Aitken A. J. Biol. Chem. 272:28882-28888(1997) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-232, MASS SPECTROMETRY.
[10]	"A 14-3-3 mRNA is up-regulated in amyotrophic lateral sclerosis spinal cord." Malaspina A., Kaushik N., de Belleroche J. J. Neurochem. 75:2511-2520(2000) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[11]	"Akt-dependent phosphorylation of p27Kip1 promotes binding to 14-3-3 and cytoplasmic localization." Fujita N., Sato S., Katayama K., Tsuruo T. J. Biol. Chem. 277:28706-28713(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CDKN1B.
[12]	"Regulation of kinase activity of 3-phosphoinositide-dependent protein kinase-1 by binding to 14-3-3." Sato S., Fujita N., Tsuruo T. J. Biol. Chem. 277:39360-39367(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH PDPK1.
[13]	"A pathway of neuregulin-induced activation of cofilin-phosphatase Slingshot and cofilin in lamellipodia." Nagata-Ohashi K., Ohta Y., Goto K., Chiba S., Mori R., Nishita M., Ohashi K., Kousaka K., Iwamatsu A., Niwa R., Uemura T., Mizuno K. J. Cell Biol. 165:465-471(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SSH1.
[14]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[15]	"Phosphorylation-dependent binding of 14-3-3 terminates signalling by the Gab2 docking protein." Brummer T., Larance M., Herrera Abreu M.T., Lyons R.J., Timpson P., Emmerich C.H., Fleuren E.D.G., Lehrbach G.M., Schramek D., Guilhaus M., James D.E., Daly R.J. EMBO J. 27:2305-2316(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GAB2.
[16]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[17]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-232, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[18]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Leukemic T-cell.
[19]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1; LYS-3; LYS-49; LYS-68 AND LYS-115, MASS SPECTROMETRY.
[20]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[21]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[22]	"Structure of a 14-3-3 protein and implications for coordination of multiple signalling pathways." Xiao B., Smerdon S.J., Jones D.H., Dodson G.G., Soneji Y., Aitken A., Gamblin S.J. Nature 376:188-191(1995) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS).
[23]	"Structural basis for protein-protein interactions in the 14-3-3 protein family." Yang X., Lee W.H., Sobott F., Papagrigoriou E., Robinson C.V., Grossmann J.G., Sundstroem M., Doyle D.A., Elkins J.M. Proc. Natl. Acad. Sci. U.S.A. 103:17237-17242(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1-234, MASS SPECTROMETRY, INTERACTION WITH PHOSPHOSERINE MOTIFS, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X56468 mRNA. Translation: CAA39840.1.
X57347 mRNA. Translation: CAA40622.1.
BT020014 mRNA. Translation: AAV38817.1.
CH471053 Genomic DNA. Translation: EAX00977.1.
CH471053 Genomic DNA. Translation: EAX00979.1.
BC050601 mRNA. Translation: AAH50601.1.
BC056867 mRNA. Translation: AAH56867.1.
BC093019 mRNA. Translation: AAH93019.1.
AF070556 mRNA. Translation: AAC28640.1.

IPI

IPI00018146.

PIR

S15076.

RefSeq

NP_006817.1. NM_006826.2.

UniGene

Hs.74405.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2BTP	X-ray	2.80	A/B	1-234	[»]

ProteinModelPortal

P27348.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-27584N.

IntAct

P27348. 40 interactions.

MINT

MINT-121282.

STRING

9606.ENSP00000238081.

PTM databases

PhosphoSite

P27348.

Polymorphism databases

DMDM

112690.

2D gel databases

OGP

P27348.

REPRODUCTION-2DPAGE

IPI00018146.

Proteomic databases

PaxDb

P27348.

PeptideAtlas

P27348.

PRIDE

P27348.

Protocols and materials databases

DNASU

10971.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000238081; ENSP00000238081; ENSG00000134308.
ENST00000381844; ENSP00000371267; ENSG00000134308.

GeneID

10971.

KEGG

hsa:10971.

UCSC

uc002qzx.3. human.

Organism-specific databases

CTD

10971.

GeneCards

GC02M009724.

H-InvDB

HIX0077146.

HGNC

HGNC:12854. YWHAQ.

HPA

CAB010286.
HPA007925.

MIM

609009. gene.

neXtProt

NX_P27348.

PharmGKB

PA37443.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5040.

HOGENOM

HOG000240379.

HOVERGEN

HBG050423.

InParanoid

P27348.

KO

K16197.

OMA

AMEKTEL.

OrthoDB

EOG480HXJ.

PhylomeDB

P27348.

Enzyme and pathway databases

Pathway_Interaction_DB

a6b1_a6b4_integrin_pathway. a6b1 and a6b4 Integrin signaling.
pi3kciaktpathway. Class I PI3K signaling events mediated by Akt.
foxopathway. FoxO family signaling.
insulin_glucose_pathway. Insulin-mediated glucose transport.
p38_mk2pathway. p38 signaling mediated by MAPKAP kinases.
nfat_3pathway. Role of Calcineurin-dependent NFAT signaling in lymphocytes.
pi3kplctrkpathway. Trk receptor signaling mediated by PI3K and PLC-gamma.

Reactome

REACT_11123. Membrane Trafficking.

SignaLink

P27348.

Gene expression databases

ArrayExpress

P27348.

Bgee

P27348.

CleanEx

HS_YWHAQ.

Genevestigator

P27348.

GermOnline

ENSG00000134308. Homo sapiens.

Family and domain databases

Gene3D

1.20.190.20. 1 hit.

InterPro

IPR000308. 14-3-3.
IPR023409. 14-3-3_CS.
IPR023410. 14-3-3_domain.
[Graphical view]

PANTHER

PTHR18860. PTHR18860. 1 hit.

Pfam

PF00244. 14-3-3. 1 hit.
[Graphical view]

PIRSF

PIRSF000868. 14-3-3. 1 hit.

PRINTS

PR00305. 1433ZETA.

SMART

SM00101. 14_3_3. 1 hit.
[Graphical view]

SUPFAM

SSF48445. 14-3-3. 1 hit.

PROSITE

PS00796. 1433_1. 1 hit.
PS00797. 1433_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

YWHAQ. human.

EvolutionaryTrace

P27348.

GenomeRNAi

10971.

NextBio

41686.

PMAP-CutDB

P27348.

SOURCE

Search...

Entry information

Entry name

1433T_HUMAN

Accession

Primary (citable) accession number: P27348
Secondary accession number(s): D6W4Z5 , Q567U5, Q5TZU8, Q9UP48

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	August 1, 1992
Last modified:	May 29, 2013
This is version 145 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.