P63103 (1433Z_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
14-3-3 protein zeta/delta

Alternative name(s):
Factor activating exoenzyme S
Short name=FAS
Protein kinase C inhibitor protein 1
Short name=KCIP-1

Gene names

Name:

YWHAZ

Organism

Bos taurus (Bovine) [Reference proteome]

Taxonomic identifier

9913 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

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. Activates the ADP-ribosyltransferase (exoS) activity of bacterial origin. Ref.4
Subunit structure	Homodimer. Heterodimerizes with YWHAE By similarity. Homo- and hetero-dimerization is inhibited by phosphorylation on Ser-58 By similarity. Interacts with FOXO4, NOXA1, SSH1 ARHGEF2, CDK16 and BSPRY. Interacts with WEE1 (C-terminal). Interacts with MLF1 (phosphorylated form); the interaction retains it in the cytoplasm. Interacts with BAX; the interaction occurs in the cytoplasm. Under stress conditions, MAPK8-mediated phosphorylation releases BAX to mitochondria. Interacts with TP53; the interaction enhances p53 transcriptional activity. The Ser-58 phosphorylated form inhibits this interaction and p53 transcriptional activity. Interacts with ABL1 (phosphorylated form); the interaction retains ABL1 in the cytoplasm. Interacts with PKA-phosphorylated AANAT; the interaction modulates AANAT enzymatic activity by increasing affinity for arylalkylamines and acetyl-CoA and protecting the enzyme from dephosphorylation and proteasomal degradation. It may also prevent thiol-dependent inactivation By similarity. Interacts with AKT1; the interaction phosphorylates YWHAZ and modulates dimerization By similarity. Interacts with GAB2. Interacts with BCL2L11, SAMSN1 and TLK2 By similarity. Interacts with phosphorylated RAF1; the interaction is inhibited when YWHAZ is phosphorylated on Thr-232. Interacts with Thr-phosphorylated ITGB2. Ref.6 Ref.7
Subcellular location	Cytoplasm. Melanosome. Note: Located to stage I to stage IV melanosomes By similarity.
Post-translational modification	The delta, brain-specific form differs from the zeta form in being phosphorylated By similarity. Phosphorylation on Ser-184 by MAPK8; promotes dissociation of BAX and translocation of BAX to mitochondria. Phosphorylation on Thr-232; inhibits binding of RAF1 By similarity. Phosphorylated on Ser-58 by PKA and protein kinase C delta type catalytic subunit in a sphingosine-dependent fashion. Phosphorylation on Ser-58 by PKA; disrupts homodimerization and heterodimerization with YHAE and TP53 By similarity.
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	protein targeting Inferred from electronic annotation. Source: Compara regulation of cell death Inferred from electronic annotation. Source: Compara
Cellular_component	melanosome Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrion Inferred from electronic annotation. Source: Compara nucleus Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 245

245

14-3-3 protein zeta/delta

PRO_0000058626

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 By similarity

Modified residue

3

1

N6-acetyllysine By similarity

Modified residue

58

1

Phosphoserine; by PKA By similarity

Modified residue

68

1

N6-acetyllysine By similarity

Modified residue

184

1

Phosphoserine By similarity

Modified residue

207

1

Phosphoserine By similarity

Modified residue

232

1

Phosphothreonine; by CK1 By similarity

Experimental info

Sequence conflict

25

1

C → A AA sequence Ref.1

Secondary structure

1

.

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.

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.

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245

Helix Strand Turn

Details...

Helix

3 – 15

13

Helix

19 – 30

12

Turn

31 – 33

3

Helix

38 – 67

30

Helix

74 – 103

30

Turn

104 – 107

4

Helix

112 – 115

4

Helix

117 – 131

15

Helix

137 – 156

20

Turn

157 – 159

3

Helix

165 – 180

16

Helix

185 – 201

17

Turn

202 – 205

4

Turn

208 – 210

3

Helix

211 – 226

16

Sequences

	Sequence		Length	Mass (Da)
	P63103 [UniParc]. Last modified September 13, 2004. Version 1. Checksum: D464DF2286BBFE60	FASTA	245	27,745
	10 20 30 40 50 60 MDKNELVQKA KLAEQAERYD DMAACMKSVT EQGAELSNEE RNLLSVAYKN VVGARRSSWR 70 80 90 100 110 120 VVSSIEQKTE GAEKKQQMAR EYREKIETEL RDICNDVLSL LEKFLIPNAS QAESKVFYLK 130 140 150 160 170 180 MKGDYYRYLA EVAAGDDKKG IVDQSQQAYQ EAFEISKKEM QPTHPIRLGL ALNFSVFYYE 190 200 210 220 230 240 ILNSPEKACS LAKTAFDEAI AELDTLSEES YKDSTLIMQL LRDNLTLWTS DTQGDEAEAG EGGEN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Activation of protein kinase C by the 14-3-3 proteins homologous with Exo1 protein that stimulates calcium-dependent exocytosis." Isobe T., Hiyane Y., Ichimura T., Okuyama T., Takahashi N., Nakajo S., Nakaya K. FEBS Lett. 308:121-124(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE. Tissue: Brain.
[2]	"The eukaryotic host factor that activates exoenzyme S of Pseudomonas aeruginosa is a member of the 14-3-3 protein family." Fu H., Coburn J., Collier R.J. Proc. Natl. Acad. Sci. U.S.A. 90:2320-2324(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 104-115; 140-157 AND 194-212. Tissue: Brain.
[3]	NIH - Mammalian Gene Collection (MGC) project Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: Crossbred X Angus. Tissue: Ileum.
[4]	"Activation of protein kinase C by purified bovine brain 14-3-3: comparison with tyrosine hydroxylase activation." Tanji M., Horwitz R., Rosenfeld G., Waymire J.C. J. Neurochem. 63:1908-1916(1994) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[5]	"Crystal structure of the zeta isoform of the 14-3-3 protein." Liu D., Blenkowska J., Petosa C., Collier R.J., Fu H., Liddington R. Nature 376:191-194(1995) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
[6]	"14-3-3zeta binds a phosphorylated Raf peptide and an unphosphorylated peptide via its conserved amphipathic groove." Petosa C., Masters S.C., Bankston L.A., Pohl J., Wang B., Fu H., Liddington R.C. J. Biol. Chem. 273:16305-16310(1998) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.35 ANGSTROMS) IN COMPLEX WITH PHOSPHORYLATED RAF1, INTERACTION WITH PHOSPHOSERINE PEPTIDE, SUBUNIT.
[7]	"Beta2 integrin phosphorylation on Thr758 acts as a molecular switch to regulate 14-3-3 and filamin binding." Takala H., Nurminen E., Nurmi S.M., Aatonen M., Strandin T., Takatalo M., Kiema T., Gahmberg C.G., Ylaenne J., Fagerholm S.C. Blood 112:1853-1862(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH PHOSPHORYLATED ITGB2, INTERACTION WITH PHOSPHORYLATED ITGB2.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L07955 mRNA. Translation: AAA30514.1.
BC102382 mRNA. Translation: AAI02383.1.

IPI

IPI00703110.

PIR

A47389.
S65013.

RefSeq

NP_777239.1. NM_174814.2.

UniGene

Bt.111451.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1A37	X-ray	3.60	A/B	1-245	[»]
1A38	X-ray	3.35	A/B	1-245	[»]
1A4O	X-ray	2.80	A/B/C/D	1-245	[»]
2V7D	X-ray	2.50	A/B/C/D	1-245	[»]

ProteinModelPortal

P63103.

ModBase

Search...

Protein-protein interaction databases

IntAct

P63103. 1 interaction.

MINT

MINT-99823.

STRING

9913.ENSBTAP00000000289.

Proteomic databases

PaxDb

P63103.

PRIDE

P63103.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSBTAT00000000289; ENSBTAP00000000289; ENSBTAG00000000236.

GeneID

287022.

KEGG

bta:287022.

Organism-specific databases

CTD

7534.

Phylogenomic databases

eggNOG

COG5040.

GeneTree

ENSGT00690000101832.

HOGENOM

HOG000240379.

HOVERGEN

HBG050423.

InParanoid

P63103.

KO

K16197.

OMA

VMDKNEL.

OrthoDB

EOG4N30PR.

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

EvolutionaryTrace

P63103.

NextBio

20806544.

Entry information

Entry name

1433Z_BOVIN

Accession

Primary (citable) accession number: P63103
Secondary accession number(s): P29213, P29312, Q3ZCF9

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 13, 2004
Last sequence update:	September 13, 2004
Last modified:	May 1, 2013
This is version 85 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program