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

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

Gene names

Name:

YWHAG

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	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 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. Ref.15
Subunit structure	Homodimer. Interacts with SAMSN1 By similarity. Interacts with RAF1, SSH1 and CRTC2/TORC2. Interacts with ABL1 (phosphorylated form); the interaction retains it in the cytoplasm. Interacts with GAB2. Interacts with MDM4 (phosphorylated); negatively regulates MDM4 activity toward TP53. Interacts with PKA-phosphorylated AANAT. Ref.1 Ref.10 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.20
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 Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	G2/M transition of mitotic cell cycle Traceable author statement. Source: Reactome protein targeting Inferred from electronic annotation. Source: Compara regulation of neuron differentiation Inferred from mutant phenotype PubMed 11824616. Source: UniProtKB regulation of signal transduction Non-traceable author statement Ref.1Ref.2. Source: UniProtKB regulation of synaptic plasticity Inferred from mutant phenotype PubMed 11824616. Source: UniProtKB
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	protein kinase C inhibitor activity Non-traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
KANK1	Q14678-2	3	EBI-359832,EBI-6173812
LRRK2	Q5S007	2	EBI-359832,EBI-5323863
MARK2	Q7KZI7	2	EBI-359832,EBI-516560
MARK3	P27448	2	EBI-359832,EBI-707595
YWHAE	P62258	4	EBI-359832,EBI-356498

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.11

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.11

Modified residue

2

1

N-acetylvaline; partial Ref.6 Ref.8 Ref.11

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 – 70

32

Helix

79 – 106

28

Helix

108 – 111

4

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 – 233

18

Sequences

	Sequence		Length	Mass (Da)
	P61981 [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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]	"Role of a pineal cAMP-operated arylalkylamine N-acetyltransferase/14-3-3-binding switch in melatonin synthesis." Ganguly S., Gastel J.A., Weller J.L., Schwartz C., Jaffe H., Namboodiri M.A., Coon S.L., Hickman A.B., Rollag M., Obsil T., Beauverger P., Ferry G., Boutin J.A., Klein D.C. Proc. Natl. Acad. Sci. U.S.A. 98:8083-8088(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH AANAT.
[11]	"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] [Europe PMC] [Abstract] Cited for: CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT VAL-2, MASS SPECTROMETRY.
[12]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CRTC2.
[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]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ABL1, MASS SPECTROMETRY.
[15]	"14-3-3gamma binds to MDMX that is phosphorylated by UV-activated Chk1, resulting in p53 activation." Jin Y., Dai M.S., Lu S.Z., Xu Y., Luo Z., Zhao Y., Lu H. EMBO J. 25:1207-1218(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN TP53 ACTIVATION, INTERACTION WITH MDM4.
[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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Leukemic T-cell.
[18]	"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.
[19]	"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].
[20]	"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 (2.55 ANGSTROMS), MASS SPECTROMETRY, INTERACTION WITH PHOSPHOSERINE MOTIFS, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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. NM_012479.3.

UniGene

Hs.706016.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2B05	X-ray	2.55	A/B/C/D/E/F	2-246	[»]
3UZD	X-ray	1.86	A	1-247	[»]
4E2E	X-ray	2.25	A	1-247	[»]

ProteinModelPortal

P61981.

ModBase

Search...

Protein-protein interaction databases

IntAct

P61981. 67 interactions.

MINT

MINT-248956.

STRING

9606.ENSP00000306330.

PTM databases

PhosphoSite

P61981.

Polymorphism databases

DMDM

48428721.

2D gel databases

REPRODUCTION-2DPAGE

IPI00220642.

Proteomic databases

PaxDb

P61981.

PeptideAtlas

P61981.

PRIDE

P61981.

Protocols and materials databases

DNASU

7532.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000307630; ENSP00000306330; ENSG00000170027.

GeneID

7532.

KEGG

hsa:7532.

UCSC

uc011kgj.1. human.

Organism-specific databases

CTD

7532.

GeneCards

GC07M075956.

HGNC

HGNC:12852. YWHAG.

HPA

CAB013274.
CAB018389.
HPA026918.

MIM

605356. gene.

neXtProt

NX_P61981.

PharmGKB

PA37441.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5040.

HOGENOM

HOG000240379.

HOVERGEN

HBG050423.

InParanoid

P61981.

KO

K16198.

OMA

CSETQHE.

OrthoDB

EOG48PMM0.

PhylomeDB

P61981.

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.
REACT_115566. Cell Cycle.

Gene expression databases

ArrayExpress

P61981.

Bgee

P61981.

CleanEx

HS_YWHAG.

Genevestigator

P61981.

GermOnline

ENSG00000170027. 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

BindingDB

P61981.

ChEMBL

CHEMBL1293296.

ChiTaRS

YWHAG. human.

EvolutionaryTrace

P61981.

GenomeRNAi

7532.

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:	May 1, 2013
This is version 108 of the entry and version 2 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.