Reviewed, UniProtKB/Swiss-Prot P61981 (1433G_HUMAN)

Names and origin

Protein names

Recommended name:
    14-3-3 protein gamma
Alternative name(s):
    Protein kinase C inhibitor protein 1
      Short name=KCIP-1
Cleaved into the following chain:
    1- Recommended name:
            14-3-3 protein gamma, N-terminally processed

Gene names

Name:

YWHAG

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	247 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 pathway. 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.
Subunit structure	Homodimer. Interacts with RAF1, SSH1 and CRTC2/TORC2. Interacts with ABL1 (phosphorylated form); the interaction retains it in the cytoplasm.
Subcellular location	Cytoplasm By similarity.
Tissue specificity	Highly expressed in brain, skeletal muscle, and heart. Ref.2
Post-translational modification	Phosphorylated by various PKC isozymes. Ref.1 Ref.6
Sequence similarities	Belongs to the 14-3-3 family.

Ontologies

Keywords
Cellular component	Cytoplasm
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	negative regulation of protein kinase activity Ref.1 Non-traceable author statement. Source: UniProtKB regulation of neuron differentiation Inferred from mutant phenotype. Source: UniProtKB regulation of signal transduction Ref.1 Ref.2 Non-traceable author statement. Source: UniProtKB regulation of synaptic plasticity Inferred from mutant phenotype. Source: UniProtKB
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	insulin-like growth factor receptor binding Inferred from physical interaction. Source: UniProtKB protein kinase C binding Ref.1 Inferred from physical interaction. Source: UniProtKB protein kinase C inhibitor activity Ref.1 Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ANKS1A	Q92625	1	EBI-359832,EBI-1048612
ARAF	P10398	1	EBI-359832,EBI-365961
BAIAP2	Q9UQB8	1	EBI-359832,EBI-525456
BRAF	P15056	1	EBI-359832,EBI-365980
C22orf9	Q6ICG6	1	EBI-359832,EBI-1053969
CDKN1B	P46527	1	EBI-359832,EBI-519280
CGN	Q9P2M7	1	EBI-359832,EBI-79537
CLASP1	Q7Z460	1	EBI-359832,EBI-913476
DENND4A	Q7Z401	1	EBI-359832,EBI-1046479
EDC3	Q96F86	1	EBI-359832,EBI-997311
EPB41L3	Q9Y2J2	1	EBI-359832,EBI-310986
ERC1	Q8IUD2	1	EBI-359832,EBI-1044755
FAM82A2	Q96TC7	1	EBI-359832,EBI-1056589
FRYL	O94915	1	EBI-359832,EBI-1104821
GBF1	Q92538	1	EBI-359832,EBI-359050
IGF1R	P08069	1	EBI-359832,EBI-475981
IRS2	Q9Y4H2	1	EBI-359832,EBI-1049582
KIF23	Q02241	1	EBI-359832,EBI-306852
KIF5B	P33176	1	EBI-359832,EBI-355878
KIF5C	O60282	1	EBI-359832,EBI-717170
KLC1	Q07866	1	EBI-359832,EBI-721019
KLC2	Q9H0B6	1	EBI-359832,EBI-726994
KLC4	Q9NSK0	1	EBI-359832,EBI-949319
KRT31	Q15323	1	EBI-359832,EBI-948001
KRT33B	Q14525	1	EBI-359832,EBI-1049638
KRT85	P78386	1	EBI-359832,EBI-1049371
LARP1	Q6PKG0	1	EBI-359832,EBI-1052114
LBR	Q14739	1	EBI-359832,EBI-1055147
LUC7L2	Q9Y383	1	EBI-359832,EBI-352851
MARK3	P27448	1	EBI-359832,EBI-707595
MLLT4	P55196	1	EBI-359832,EBI-365875
MPRIP	Q6WCQ1	1	EBI-359832,EBI-1022605
OSBPL3	Q9H4L5	1	EBI-359832,EBI-1051317
PAK4	O96013	1	EBI-359832,EBI-713738
PARD3	Q8TEW0	1	EBI-359832,EBI-81968
PI4KB	Q9UBF8	1	EBI-359832,EBI-1053214
PPFIBP1	Q86W92	1	EBI-359832,EBI-1045582
RABEP1	Q15276	1	EBI-359832,EBI-447043
RABGEF1	Q9UJ41	1	EBI-359832,EBI-913954
RACGAP1	Q9H0H5	1	EBI-359832,EBI-717233
RAF1	P04049	1	EBI-359832,EBI-365996
RAI14	Q9P0K7	1	EBI-359832,EBI-1023749
SAMD4B	Q5PRF9	1	EBI-359832,EBI-1047489
SHCBP1	Q8NEM2	1	EBI-359832,EBI-744700
SNRNP200	O75643	1	EBI-359832,EBI-1045395
SON	P18583	1	EBI-359832,EBI-1053513
SRRM2	Q9UQ35	1	EBI-359832,EBI-1050142
TJP2	Q9UDY2	1	EBI-359832,EBI-1042602

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 247

247

14-3-3 protein gamma

PRO_0000367907

Initiator methionine

1

1

Removed; alternate Ref.6 Ref.7 Ref.8 Ref.10

Chain

2 – 247

246

14-3-3 protein gamma, N-terminally processed

PRO_0000058606

Sites

Site

57

1

Interaction with phosphoserine on interacting protein

Site

132

1

Interaction with phosphoserine on interacting protein

Amino acid modifications

Modified residue

1

1

N-acetylmethionine; in 14-3-3 protein gamma; alternate; partial Ref.6

Modified residue

2

1

N-acetylvaline; in 14-3-3 protein gamma, N-terminally processed; partial Ref.6 Ref.8 Ref.10

Modified residue

2

1

N-acetylvaline; partial Ref.6 Ref.8 Ref.10

Modified residue

117

1

Phosphotyrosine By similarity

Modified residue

145

1

Phosphothreonine Ref.6

Experimental info

Sequence conflict

4

1

R → P in AAD48408. Ref.1

Sequence conflict

19

1

R → G in AAD48408. Ref.1

Sequence conflict

78

1

Missing in AAD48408. Ref.1

Sequence conflict

89

1

I → V in AAD48408. Ref.1

Sequence conflict

104

1

L → V in AAD48408. Ref.1

Sequence conflict

109

1

I → Y in AAD48408. Ref.1

Sequence conflict

119 – 122

4

SKVF → RKDL in AAD48408. Ref.1

Sequence conflict

144 – 145

2

AT → GD in AAD48408. Ref.1

Sequence conflict

157 – 158

2

AH → R in AAD48408. Ref.1

Sequence conflict

200 – 202

3

AFD → EFE in AAD48408. Ref.1

Sequence conflict

214

1

D → E in AAD48408. Ref.1

Sequence conflict

240

1

D → DH in AAD48408. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

247

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

208 – 210

3

Turn

213 – 215

3

Helix

216 – 233

18

Sequences

	Sequence		Length	Mass (Da)
	P61981-1 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: B0D16C6DE1F4455D	FASTA	247	28,303
	10 20 30 40 50 60 MVDREQLVQK ARLAEQAERY DDMAAAMKNV TELNEPLSNE ERNLLSVAYK NVVGARRSSW 70 80 90 100 110 120 RVISSIEQKT SADGNEKKIE MVRAYREKIE KELEAVCQDV LSLLDNYLIK NCSETQYESK 130 140 150 160 170 180 VFYLKMKGDY YRYLAEVATG EKRATVVESS EKAYSEAHEI SKEHMQPTHP IRLGLALNYS 190 200 210 220 230 240 VFYYEIQNAP EQACHLAKTA FDDAIAELDT LNEDSYKDST LIMQLLRDNL TLWTSDQQDD DGGEGNN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"14-3-3gamma interacts with and is phosphorylated by multiple protein kinase C isoforms in PDGF-stimulated human vascular smooth muscle cells." Autieri M.V., Carbone C.J. DNA Cell Biol. 18:555-564(1999) [PubMed: 10433554] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PHOSPHORYLATION, INTERACTION WITH RAF1. Tissue: Vascular smooth muscle.
[2]	"Cloning, expression, and chromosomal mapping of the human 14-3-3gamma gene (YWHAG) to 7q11.23." Horie M., Suzuki M., Takahashi E., Tanigami A. Genomics 60:241-243(1999) [PubMed: 10486217] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Fetal brain.
[3]	"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].
[4]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed: 12853948] [Abstract] 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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Endometrial tumor.
[6]	Bienvenut W.V., Boldt K., von Kriegsheim A.F., Zebisch A., Kolch W. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 1-10; 13-56; 62-69; 133-172 AND 199-227, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT MET-1 AND VAL-2, PHOSPHORYLATION AT THR-145, MASS SPECTROMETRY. Tissue: Colon carcinoma and Hepatoma.
[7]	"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 2-12. Tissue: Platelet.
[8]	Bienvenut W.V., Claeys D. Submitted (NOV-2005) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-10; 13-19; 29-42; 62-69; 133-143 AND 218-227, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT VAL-2, MASS SPECTROMETRY. Tissue: Platelet.
[9]	Lubec G., Vishwanath V., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 92-110; 199-217 AND 228-247, MASS SPECTROMETRY. Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
[10]	"Proteomics-based target identification: bengamides as a new class of methionine aminopeptidase inhibitors." Towbin H., Bair K.W., DeCaprio J.A., Eck M.J., Kim S., Kinder F.R., Morollo A., Mueller D.R., Schindler P., Song H.K., van Oostrum J., Versace R.W., Voshol H., Wood J., Zabludoff S., Phillips P.E. J. Biol. Chem. 278:52964-52971(2003) [PubMed: 14534293] [Abstract] Cited for: CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT VAL-2, MASS SPECTROMETRY.
[11]	"The CREB coactivator TORC2 functions as a calcium- and cAMP-sensitive coincidence detector." Screaton R.A., Conkright M.D., Katoh Y., Best J.L., Canettieri G., Jeffries S., Guzman E., Niessen S., Yates J.R. III, Takemori H., Okamoto M., Montminy M. Cell 119:61-74(2004) [PubMed: 15454081] [Abstract] Cited for: INTERACTION WITH CRTC2.
[12]	"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: 15159416] [Abstract] Cited for: INTERACTION WITH SSH1.
[13]	"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.
[14]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[15]	"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 (2.55 ANGSTROMS), MASS SPECTROMETRY, INTERACTION WITH PHOSPHOSERINE MOTIFS, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF142498 mRNA. Translation: AAD48408.1.
AB024334 mRNA. Translation: BAA85184.1.
CR541904 mRNA. Translation: CAG46702.1.
CR541925 mRNA. Translation: CAG46723.1.
AC006388 Genomic DNA. No translation available.
BC020963 mRNA. Translation: AAH20963.1.

IPI

IPI00220642.

RefSeq

NP_036611.2.

UniGene

Hs.520974

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2B05	X-ray	2.55	A/B/C/D/E/F	2-246	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P61981. 181 interactions.

PTM databases

PhosphoSite

P61981.

2-D gel databases

Cornea-2DPAGE

P61981.

REPRODUCTION-2DPAGE

IPI00220642.

Proteomic databases

PeptideAtlas

P61981.

PRIDE

P61981.

Genome annotation databases

Ensembl

ENSG00000170027. Homo sapiens. [Contig view]

GeneID

7532.

KEGG

hsa:7532.

Organism-specific databases

GeneCards

GC07M075794.

H-InvDB

HIX0006789.

HGNC

HGNC:12852. YWHAG.

HPA

CAB013274.
CAB018389.

MIM

605356. gene.

PharmGKB

PA37441.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P61981.

HOVERGEN

P61981.

OMA

P61981. CSETQHE.

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

P61981.

Bgee

P61981.

CleanEx

HS_YWHAG.

GermOnline

ENSG00000170027. Homo sapiens.

Family and domain databases

InterPro

IPR000308. 14-3-3.
[Graphical view]

Gene3D

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

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.

ProDom

PD000600. 14-3-3. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

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

PROSITE

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

ProtoNet

Search...

Other Resources

NextBio

29467.

SOURCE

Search...

Entry information

Entry name

1433G_HUMAN

Accession

Primary (citable) accession number: P61981
Secondary accession number(s): O70457 , P35214, Q6FH52, Q9UDP2, Q9UN99

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 7, 2004
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 66 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)