P63101 (1433Z_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Alternative name(s):
Protein kinase C inhibitor protein 1
Short name=KCIP-1
SEZ-2

Gene names

Name:

Ywhaz

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

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.
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 and ARHGEF2. Interacts with CDK16 and with WEE1 (C-terminal). Interacts with MLF1 (phosphorylated form); the interaction retains it in the cytoplasm. Interacts with BSPRY. Interacts with Thr-phosphorylated ITGB2 By similarity. Interacts with Pseudomonas aeruginosa exoS (unphosphorylated form). Interacts with BAX; the interaction occurs in the cytoplasm. Under stress conditions, MAPK8-mediated phosphorylation releases BAX to mitochondria. Interacts with phosphorylated RAF1; the interaction is inhibited when YWHAZ is phosphorylated on Thr-232. 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 By similarity. It may also prevent thiol-dependent inactivation By similarity. Interacts with AKT1; the interaction phosphorylates YWHAZ and modulates dimerization By similarity. Interacts with GAB2 By similarity. Interacts with SAMSN1. Interacts with BCL2L11 and TLK2. Ref.3 Ref.4 Ref.9 Ref.10 Ref.11 Ref.12
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. Ref.8
Sequence similarities	Belongs to the 14-3-3 family.

Ontologies

Keywords
Cellular component	Cytoplasm
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	histamine secretion by mast cell Inferred from electronic annotation. Source: Compara protein targeting Inferred from direct assay PubMed 12446771. Source: MGI protein targeting to mitochondrion Inferred from electronic annotation. Source: Compara regulation of cell death Inferred from genetic interaction PubMed 19451227. Source: MGI
Cellular_component	cell leading edge Inferred from electronic annotation. Source: Compara melanosome Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrion Inferred from direct assay PubMed 14651853. Source: MGI nucleus Inferred from direct assay PubMed 15615787. Source: MGI perinuclear region of cytoplasm Inferred from electronic annotation. Source: Compara postsynaptic density Inferred from electronic annotation. Source: Compara protein complex Inferred from electronic annotation. Source: Compara
Molecular_function	protein domain specific binding Inferred from direct assay Ref.10. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Lrrk2	Q5S006	4	EBI-354751,EBI-2693710
Mlf1	Q9QWV4	2	EBI-354751,EBI-354765

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_0000058628
Sites
	Site	56	1	Interaction with phosphoserine on interacting protein By similarity
	Site	127	1	Interaction with phosphoserine on interacting protein By similarity
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 Ref.8
	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	78	1	M → V in BAA11751. Ref.4
	Sequence conflict	139	1	K → R in BAE36724. Ref.5
	Sequence conflict	218 – 219	2	MQ → IE in BAA13421. Ref.2
	Sequence conflict	236	1	E → D in BAA11751. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P63101 [UniParc]. Last modified September 13, 2004. Version 1. Checksum: 2164DF3793B45B7A	FASTA	245	27,771
	10 20 30 40 50 60 MDKNELVQKA KLAEQAERYD DMAACMKSVT EQGAELSNEE RNLLSVAYKN VVGARRSSWR 70 80 90 100 110 120 VVSSIEQKTE GAEKKQQMAR EYREKIETEL RDICNDVLSL LEKFLIPNAS QPESKVFYLK 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]	"Molecular characterization of seizure-related genes isolated by differential screening." Kajiwara K., Nagawawa H., Shimizu-Nishikawa K., Ookura T., Kimura M., Sugaya E. Biochem. Biophys. Res. Commun. 219:795-799(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: C57BL/6. Tissue: Brain.
[2]	"14-3-3 family members play an important role in tumorigenic transformation of NIH 3T3 cells and retinoic acid-mediated F9 cell differentiation." Takihara Y., Irie K., Nomura M., Motaleb M., Matsumoto K., Shimada K. Submitted (SEP-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: 129/Sv.
[3]	"The Cdk-like protein PCTAIRE-1 from mouse brain associates with p11 and 14-3-3 proteins." Sladeczek F., Camonis J.H., Burnol A.-F., Le Bouffant F. Mol. Gen. Genet. 254:571-577(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH CDK16.
[4]	"14-3-3 zeta protein binds to the carboxyl half of mouse wee1 kinase." Honda R., Ohba Y., Yasuda H. Biochem. Biophys. Res. Commun. 230:262-265(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH WEE1.
[5]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Blastocyst, Bone marrow macrophage, Egg, Embryonic kidney and Thymus.
[6]	"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]. Strain: C57BL/6. Tissue: Brain.
[7]	Lubec G., Kang S.U., Klug S., Friebe K., Yang J.W., Zigmond M., Sunyer B., Chen W.-Q. Submitted (JAN-2009) to UniProtKB Cited for: PROTEIN SEQUENCE OF 12-55; 61-68; 84-115; 128-167 AND 194-245, MASS SPECTROMETRY. Strain: C57BL/6 and OF1. Tissue: Brain and Hippocampus.
[8]	"A novel sphingosine-dependent protein kinase (SDK1) specifically phosphorylates certain isoforms of 14-3-3 protein." Megidish T., Cooper J., Zhang L., Fu H., Hakomori S. J. Biol. Chem. 273:21834-21845(1998) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-58.
[9]	"Nuclear localization of protein kinase U-alpha is regulated by 14-3-3." Zhang S., Xing H., Muslin A.J. J. Biol. Chem. 274:24865-24872(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TLK2.
[10]	"MADM, a novel adaptor protein that mediates phosphorylation of the 14-3-3 binding site of myeloid leukemia factor 1." Lim R., Winteringham L.N., Williams J.H., McCulloch R.K., Ingley E., Tiao J.Y.-H., Lalonde J.-P., Tsai S., Tilbrook P.A., Sun Y., Wu X., Morris S.W., Klinken S.P. J. Biol. Chem. 277:40997-41008(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MLF1.
[11]	"SLy2 targets the nuclear SAP30/HDAC1 complex." Brandt S., Ellwanger K., Beuter-Gunia C., Schuster M., Hausser A., Schmitz I., Beer-Hammer S. Int. J. Biochem. Cell Biol. 42:1472-1481(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SAMSN1.
[12]	"Identification of a novel Bcl-2-interacting mediator of cell death (Bim) E3 ligase, tripartite motif-containing protein 2 (TRIM2), and its role in rapid ischemic tolerance-induced neuroprotection." Thompson S., Pearson A.N., Ashley M.D., Jessick V., Murphy B.M., Gafken P., Henshall D.C., Morris K.T., Simon R.P., Meller R. J. Biol. Chem. 286:19331-19339(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BCL2L11.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D78647 mRNA. Translation: BAA11464.1. D87660 mRNA. Translation: BAA13421.1. U79231 mRNA. Translation: AAC53254.1. D83037 mRNA. Translation: BAA11751.1. AK083368 mRNA. Translation: BAC38887.1. AK145657 mRNA. Translation: BAE26570.1. AK146800 mRNA. Translation: BAE27442.1. AK150381 mRNA. Translation: BAE29512.1. AK151900 mRNA. Translation: BAE30783.1. AK162099 mRNA. Translation: BAE36724.1. AK167128 mRNA. Translation: BAE39275.1. BC050891 mRNA. Translation: AAH50891.1. BC089334 mRNA. Translation: AAH89334.1.
IPI	IPI00116498.
PIR	JC5384.
RefSeq	NP_001240734.1. NM_001253805.1. NP_001240735.1. NM_001253806.1. NP_035870.1. NM_011740.3.
UniGene	Mm.3360. Mm.465895.
3D structure databases
ProteinModelPortal	P63101.
SMR	P63101. Positions 1-230.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-31894N.
IntAct	P63101. 149 interactions.
MINT	MINT-101845.
PTM databases
PhosphoSite	P63101.
2D gel databases
REPRODUCTION-2DPAGE	P63101.
UCD-2DPAGE	P63101.
Proteomic databases
PaxDb	P63101.
PRIDE	P63101.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000022894; ENSMUSP00000022894; ENSMUSG00000022285. ENSMUST00000110361; ENSMUSP00000105990; ENSMUSG00000022285. ENSMUST00000110362; ENSMUSP00000105991; ENSMUSG00000022285.
GeneID	22631.
KEGG	mmu:22631.
UCSC	uc007vmz.2. mouse.
Organism-specific databases
CTD	7534.
MGI	MGI:109484. Ywhaz.
Phylogenomic databases
eggNOG	COG5040.
GeneTree	ENSGT00690000101832.
HOGENOM	HOG000240379.
HOVERGEN	HBG050423.
InParanoid	P63101.
KO	K16197.
OMA	VMDKNEL.
OrthoDB	EOG4N30PR.
Enzyme and pathway databases
Reactome	REACT_147847. Translocation of Glut4 to the Plasma Membrane.
Gene expression databases
ArrayExpress	P63101.
Bgee	P63101.
Genevestigator	P63101.
GermOnline	ENSMUSG00000022285. Mus musculus.
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	YWHAZ. mouse.
NextBio	303003.
SOURCE	Search...

Entry information

Entry name

1433Z_MOUSE

Accession

Primary (citable) accession number: P63101
Secondary accession number(s): P35215 , P70197, P97286, Q3TSF1, Q5EBQ1

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 13, 2004
Last sequence update:	September 13, 2004
Last modified:	May 1, 2013
This is version 99 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program