Q04917 (1433F_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
14-3-3 protein eta

Alternative name(s):
Protein AS1

Gene names

Name:	YWHAH
Synonyms:	YWHA1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	246 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
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.13
Subunit structure	Homodimer By similarity. Interacts with many nuclear hormone receptors and cofactors including AR, ESR1, ESR2, MC2R, NR3C1, NRIP1, PPARBP and THRA. Interacts with ABL1 (phosphorylated form); the interaction retains it in the cytoplasm. Interacts with RGNEF and CDK16 By similarity. Weakly interacts with CDKN1B. Interacts with GAB2. Interacts with KCNK18 in a phosphorylation-dependent manner. Interacts with SAMSN1 By similarity. Interacts with the 'Ser-241' phosphorylated form of PDPK1. Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.19
Tissue specificity	Expressed mainly in the brain and present in other tissues albeit at lower levels.
Sequence similarities	Belongs to the 14-3-3 family.

Ontologies

Keywords
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	glucocorticoid catabolic process Inferred from direct assay. Source: UniProtKB glucocorticoid receptor signaling pathway Inferred from direct assay. Source: UniProtKB intracellular protein transport Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of dendrite morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription, DNA-dependent Inferred from direct assay. Source: UniProtKB regulation of synaptic plasticity Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	enzyme binding Inferred from physical interaction. Source: BHF-UCL glucocorticoid receptor binding Inferred from physical interaction. Source: UniProtKB insulin-like growth factor receptor binding Inferred from sequence or structural similarity. Source: UniProtKB protein domain specific binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDK14	O94921	3	EBI-306940,EBI-1043945
GREM1	O60565	5	EBI-306940,EBI-944395
MARK4	Q96L34	4	EBI-306940,EBI-302319
PARD3	Q8TEW0	6	EBI-306940,EBI-81968
PARD6A	Q9NPB6	2	EBI-306940,EBI-81876
PARD6B	Q9BYG5	2	EBI-306940,EBI-295391
PARD6G	Q9BYG4	2	EBI-306940,EBI-295417
PRKCI	P41743	3	EBI-306940,EBI-286199
RAF1	P04049	2	EBI-306940,EBI-365996

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.10 Ref.11

Chain

2 – 246

245

14-3-3 protein eta

PRO_0000058623

Sites

Site

57

1

Interaction with phosphoserine on interacting protein

Site

132

1

Interaction with phosphoserine on interacting protein

Amino acid modifications

Modified residue

2

1

N-acetylglycine Ref.11

Modified residue

25

1

Phosphoserine Ref.17

Modified residue

117

1

Phosphotyrosine By similarity

Experimental info

Sequence conflict

144

1

N → T in CAA40620. Ref.9

Sequence conflict

157

1

A → G in AAA35483. Ref.1

Sequence conflict

237

1

Q → L in AAA35483. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

246

Helix Strand Turn

Details...

Helix

4 – 16

13

Helix

20 – 31

12

Helix

39 – 73

35

Helix

76 – 106

31

Turn

107 – 111

5

Helix

117 – 137

21

Helix

140 – 164

25

Helix

170 – 185

16

Helix

190 – 206

17

Helix

207 – 210

4

Turn

213 – 215

3

Helix

216 – 234

19

Sequences

	Sequence		Length	Mass (Da)
	Q04917 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: D70FBC100C45D6E5	FASTA	246	28,219
	10 20 30 40 50 60 MGDREQLLQR ARLAEQAERY DDMASAMKAV TELNEPLSNE DRNLLSVAYK NVVGARRSSW 70 80 90 100 110 120 RVISSIEQKT MADGNEKKLE KVKAYREKIE KELETVCNDV LSLLDKFLIK NCNDFQYESK 130 140 150 160 170 180 VFYLKMKGDY YRYLAEVASG EKKNSVVEAS EAAYKEAFEI SKEQMQPTHP IRLGLALNFS 190 200 210 220 230 240 VFYYEIQNAP EQACLLAKQA FDDAIAELDT LNEDSYKDST LIMQLLRDNL TLWTSDQQDE EAGEGN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The human and bovine 14-3-3 eta protein mRNAs are highly conserved in both their translated and untranslated regions." Swanson K.D., Dhar M.S., Joshi J.G. Biochim. Biophys. Acta 1216:145-148(1993) [PubMed: 8218406] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	"cDNA cloning and chromosome assignment of the gene for human brain 14-3-3 protein eta chain." Ichimura-Ohshima Y., Morii K., Ichimura T., Araki K., Takahashi Y., Isobe T., Minoshima S., Fukuyama R., Shimizu N., Kuwano R. J. Neurosci. Res. 31:600-605(1992) [PubMed: 1578511] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Brain.
[3]	Leffers H., Tommerup N., Celis J.E. Submitted (MAR-1994) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"The effect on methamphetamine on the mRNA level for 14.3.3 eta chain in the human cultured cells." Muratake T., Hayashi S., Ichimura Y., Morii K., Kuwano R., Ichikawa T., Kumanishi T., Isobe T., Watanabe M., Kondo H. Mol. Neurobiol. 11:223-230(1995) [PubMed: 8561965] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"Structural organization and chromosomal assignment of the human 14-3-3 eta chain gene (YWHAH)." Muratake T., Hayashi S., Ichikawa T., Kumanishi T., Ichimura Y., Kuwano R., Isobe T., Wang Y., Minoshima S., Shimizu N., Takahashi Y. Genomics 36:63-69(1996) [PubMed: 8812417] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"A genome annotation-driven approach to cloning the human ORFeome." Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I. Genome Biol. 5:R84.1-R84.11(2004) [PubMed: 15461802] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]	"The DNA sequence of human chromosome 22." Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H. Nature 402:489-495(1999) [PubMed: 10591208] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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: Lymph.
[9]	"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: 8515476] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 27-225. Tissue: Keratinocyte.
[10]	"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: 12665801] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-10. Tissue: Platelet.
[11]	Bienvenut W.V. Submitted (AUG-2005) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-10; 29-50; 62-69; 126-132; 144-155; 163-172 AND 218-227, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT GLY-2, MASS SPECTROMETRY. Tissue: Platelet.
[12]	"Regulation of glucocorticoid receptor activity by 14-3-3-dependent intracellular relocalization of the corepressor RIP140." Zilliacus J., Holter E., Wakui H., Tazawa H., Treuter E., Gustafsson J.-A. Mol. Endocrinol. 15:501-511(2001) [PubMed: 11266503] [Abstract] Cited for: INTERACTION WITH AR; ESR1; ESR2; MC2R; NRIP1; NR3C1; PPARBP AND THRA.
[13]	"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: 12177059] [Abstract] Cited for: FUNCTION, INTERACTION WITH PDPK1.
[14]	"Phosphorylation of p27Kip1 at threonine 198 by p90 ribosomal protein S6 kinases promotes its binding to 14-3-3 and cytoplasmic localization." Fujita N., Sato S., Tsuruo T. J. Biol. Chem. 278:49254-49260(2003) [PubMed: 14504289] [Abstract] Cited for: INTERACTION WITH CDKN1B.
[15]	"JNK phosphorylation of 14-3-3 proteins regulates nuclear targeting of c-Abl in the apoptotic response to DNA damage." Yoshida K., Yamaguchi T., Natsume T., Kufe D., Miki Y. Nat. Cell Biol. 7:278-285(2005) [PubMed: 15696159] [Abstract] Cited for: INTERACTION WITH ABL1, MASS SPECTROMETRY.
[16]	"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: 19172738] [Abstract] Cited for: INTERACTION WITH GAB2.
[17]	"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: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-25, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[18]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[19]	"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: 17085597] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS), MASS SPECTROMETRY, INTERACTION WITH PHOSPHOSERINE MOTIFS, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L20422 mRNA. Translation: AAA35483.1.
X80536 Genomic DNA. Translation: CAA56676.1.
X78138 mRNA. Translation: CAA55017.1.
X57345 mRNA. Translation: CAA40620.1.
D78577 Genomic DNA. Translation: BAA11418.1.
S80794 mRNA. Translation: AAB36036.1.
CR456612 mRNA. Translation: CAG30498.1.
Z82248 Genomic DNA. Translation: CAB05112.1.
BC003047 mRNA. Translation: AAH03047.1.

IPI

IPI00216319.

PIR

S34756.
S38509.
S38532.

RefSeq

NP_003396.1. NM_003405.3.

UniGene

Hs.226755.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2C63	X-ray	2.15	A/B/C/D	1-246	[»]
2C74	X-ray	2.70	A/B	1-246	[»]

ProteinModelPortal

Q04917.

SMR

Q04917. Positions 3-235.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-27566N.

IntAct

Q04917. 108 interactions.

MINT

MINT-124456.

STRING

Q04917.

PTM databases

PhosphoSite

Q04917.

Polymorphism databases

DMDM

1345593.

Proteomic databases

PeptideAtlas

Q04917.

PRIDE

Q04917.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000248975; ENSP00000248975; ENSG00000128245.

GeneID

7533.

KEGG

hsa:7533.

UCSC

uc003alz.1. human.

Organism-specific databases

CTD

7533.

GeneCards

GC22P032340.

H-InvDB

HIX0016401.

HGNC

HGNC:12853. YWHAH.

HPA

CAB025918.

MIM

113508. gene.

neXtProt

NX_Q04917.

PharmGKB

PA37442.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HBG611720.

HOVERGEN

HBG050423.

InParanoid

Q04917.

OMA

KYLIKNC.

OrthoDB

EOG48PMM0.

PhylomeDB

Q04917.

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.

Gene expression databases

ArrayExpress

Q04917.

Bgee

Q04917.

CleanEx

HS_YWHAH.

Genevestigator

Q04917.

GermOnline

ENSG00000128245. Homo sapiens.

Family and domain databases

InterPro

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

Gene3D

G3DSA:1.20.190.20. 14-3-3. 1 hit.

KO

K06630.

PANTHER

PTHR18860. 14-3-3. 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

NextBio

29471.

SOURCE

Search...

Entry information

Entry name

1433F_HUMAN

Accession

Primary (citable) accession number: Q04917

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1993
Last sequence update:	January 23, 2007
Last modified:	January 25, 2012
This is version 133 of the entry and version 4 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.