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UniProtKB - P63104 (1433Z_HUMAN)

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Protein

14-3-3 protein zeta/delta

Gene

YWHAZ

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.5 Publications

Caution

Was originally thought to have phospholipase A2 activity.1 Publication

GO - Molecular functioni

  • cadherin binding Source: BHF-UCL
  • identical protein binding Source: IntAct
  • ion channel binding Source: SynGO-UCL
  • protein domain specific binding Source: InterPro
  • protein kinase binding Source: UniProtKB
  • RNA binding Source: UniProtKB
  • transcription factor binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: ParkinsonsUK-UCL
View the complete GO annotation on QuickGO ...

GO - Biological processi

  • cytokine-mediated signaling pathway Source: Reactome
  • establishment of Golgi localization Source: UniProtKB
  • Golgi reassembly Source: UniProtKB
  • membrane organization Source: Reactome
  • negative regulation of apoptotic process Source: ProtInc
  • platelet activation Source: Reactome
  • positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway Source: Reactome
  • regulation of mRNA stability Source: Reactome
  • signal transduction Source: ProtInc
View the complete GO annotation on QuickGO ...

Enzyme and pathway databases

ReactomeiR-HSA-111447 Activation of BAD and translocation to mitochondria
R-HSA-1445148 Translocation of GLUT4 to the plasma membrane
R-HSA-3769402 Deactivation of the beta-catenin transactivating complex
R-HSA-392517 Rap1 signalling
R-HSA-430116 GP1b-IX-V activation signalling
R-HSA-450604 KSRP (KHSRP) binds and destabilizes mRNA
R-HSA-512988 Interleukin-3, 5 and GM-CSF signaling
R-HSA-5625740 RHO GTPases activate PKNs
R-HSA-5628897 TP53 Regulates Metabolic Genes
R-HSA-75035 Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex
SignaLinkiP63104
SIGNORiP63104

Protein family/group databases

MoonDBiP63104 Predicted
TCDBi8.A.98.1.2 the 14-3-3 protein (14-3-3) family

Names & Taxonomyi

Protein namesi
Recommended name:
14-3-3 protein zeta/delta
Alternative name(s):
Protein kinase C inhibitor protein 1
Short name:
KCIP-1
Gene namesi
Name:YWHAZ
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000164924.17
HGNCiHGNC:12855 YWHAZ
MIMi601288 gene
neXtProtiNX_P63104

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi49K → E: Loss of interaction with NOXA1. 1 Publication1
Mutagenesisi58S → A: Loss of sphingosine-activated PKA phosphorylation. Promotes homodimerization and heterodimerization with YWHAE. Enhanced transcriptional activity of P53. 2 Publications1
Mutagenesisi58S → E: Loss of homodimerization. Reduced dimerization with YWHAE. Significantly reduced interaction with P53. No enhancement of P53 transcriptional activity. 2 Publications1
Mutagenesisi184S → A: On DNA damage, loss of MAPK8-mediated phosphorylation. Loss of binding ABL1. Attenuates ABL1-mediated apoptosis. No loss of interaction with BAX under stress conditions. Inhibits translocation of BAX to mitochondria. 2 Publications1

Organism-specific databases

DisGeNETi7534
OpenTargetsiENSG00000164924
PharmGKBiPA37444

Polymorphism and mutation databases

BioMutaiYWHAZ
DMDMi52000887

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000586271 – 24514-3-3 protein zeta/deltaAdd BLAST245

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1 Publication1
Modified residuei3N6-acetyllysineCombined sources1
Modified residuei58Phosphoserine; by PKA and PKB/AKT14 Publications1
Modified residuei68N6-acetyllysineCombined sources1
Modified residuei184Phosphoserine; by MAPK82 Publications1
Modified residuei207PhosphoserineCombined sources1
Modified residuei210PhosphoserineBy similarity1
Modified residuei232Phosphothreonine; by CK1Combined sources1 Publication1

Post-translational modificationi

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. 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 similarity7 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP63104
MaxQBiP63104
PaxDbiP63104
PeptideAtlasiP63104
PRIDEiP63104
TopDownProteomicsiP63104-1 [P63104-1]

2D gel databases

DOSAC-COBS-2DPAGEiP63104
OGPiP63104
UCD-2DPAGEiP63104

PTM databases

iPTMnetiP63104
PhosphoSitePlusiP63104
SwissPalmiP63104

Expressioni

Gene expression databases

BgeeiENSG00000164924
ExpressionAtlasiP63104 baseline and differential
GenevisibleiP63104 HS

Organism-specific databases

HPAiCAB005065

Interactioni

Subunit structurei

Interacts with CDK16 and BSPRY (By similarity). Interacts with WEE1 (C-terminal). Interacts with SAMSN1 (By similarity). Interacts with MLF1 (phosphorylated form); the interaction retains it in the cytoplasm (By similarity). Interacts with Thr-phosphorylated ITGB2 (By similarity). Interacts with BCL2L11 (By similarity). Homodimer. Heterodimerizes with YWHAE. Homo- and hetero-dimerization is inhibited by phosphorylation on Ser-58. Interacts with FOXO4, NOXA1, SSH1 and ARHGEF2. 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. It may also prevent thiol-dependent inactivation. Interacts with AKT1; the interaction phosphorylates YWHAZ and modulates dimerization. Interacts with GAB2 and TLK2. Interacts with the 'Thr-369' phosphorylated form of DAPK2 (PubMed:26047703). Interacts with PI4KB, TBC1D22A and TBC1D22B (PubMed:23572552). Interacts with ZFP36L1 (via phosphorylated form); this interaction occurs in a p38 MAPK- and AKT-signaling pathways (By similarity). Interacts with SLITRK1 (PubMed:19640509).By similarity21 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei56Interaction with phosphoserine on interacting proteinBy similarity1
Sitei127Interaction with phosphoserine on interacting proteinBy similarity1

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-347088,EBI-347088
AANATQ294953EBI-347088,EBI-446413From Ovis aries.
ABL1P005193EBI-347088,EBI-375543
ACTBP607093EBI-347088,EBI-353944
ADAM22Q9P0K15EBI-347088,EBI-1567236
ADAM22Q9P0K1-33EBI-347088,EBI-1567267
ARAFP103985EBI-347088,EBI-365961
ARHGEF2Q929742EBI-347088,EBI-302405
ATP5F1AP257054EBI-347088,EBI-351437
ATP5F1BP065762EBI-347088,EBI-356231
ATXN1P542535EBI-347088,EBI-930964
BADQ929345EBI-347088,EBI-700771
BadQ613373EBI-347088,EBI-400328From Mus musculus.
BRAFP150566EBI-347088,EBI-365980
BspryQ6P6S33EBI-347088,EBI-8615392From Rattus norvegicus.
CALM3P621582EBI-347088,EBI-397435
CBX4O00257-32EBI-347088,EBI-4392727
CDC25AP303042EBI-347088,EBI-747671
CDC25BP303058EBI-347088,EBI-1051746
CDK17Q005372EBI-347088,EBI-624648
CDK18Q070022EBI-347088,EBI-746238
CFL1P235283EBI-347088,EBI-352733
CPS1P313272EBI-347088,EBI-536811
CSNK1A1P678284EBI-347088,EBI-7540603From Oryctolagus cuniculus.
DFFAO002732EBI-347088,EBI-727171
EDC3Q96F862EBI-347088,EBI-997311
EEF1A1P681042EBI-347088,EBI-352162
EGFRP005335EBI-347088,EBI-297353
ENO1P067333EBI-347088,EBI-353877
EPB41L3Q9Y2J22EBI-347088,EBI-310986
exoSQ514512EBI-347088,EBI-1030357From Pseudomonas aeruginosa.
FOXO3O435242EBI-347088,EBI-1644164
FSCN1Q166583EBI-347088,EBI-351076
GCH1P307934EBI-347088,EBI-958183
GSK3BP498414EBI-347088,EBI-373586
Hap1P54256-24EBI-347088,EBI-994554From a different organism.
HDAC4P565245EBI-347088,EBI-308629
HDAC5Q9UQL62EBI-347088,EBI-715576
HDAC7Q8WUI43EBI-347088,EBI-1048378
HIST1H2AMP0C0S82EBI-347088,EBI-1390628
HIST1H3DP684313EBI-347088,EBI-79722
HIST2H4BP628053EBI-347088,EBI-302023
HNRNPCP079102EBI-347088,EBI-357966
HSPB1P047924EBI-347088,EBI-352682
IL9RQ011135EBI-347088,EBI-3910754
IRS2Q9Y4H22EBI-347088,EBI-1049582
KIF23Q022415EBI-347088,EBI-306852
KIF5BP331763EBI-347088,EBI-355878
KLC2Q9H0B62EBI-347088,EBI-726994
KLC4Q9NSK02EBI-347088,EBI-949319
KRT18P057833EBI-347088,EBI-297888
LARP1Q6PKG03EBI-347088,EBI-1052114
LMNAP025452EBI-347088,EBI-351935
LRRK2Q5S0079EBI-347088,EBI-5323863
MAP3K20Q9NYL24EBI-347088,EBI-602273
MAP3K5Q996834EBI-347088,EBI-476263
MAPTP106368EBI-347088,EBI-366182
MAPTP10636-39EBI-347088,EBI-7145070
MAPTP291722EBI-347088,EBI-7291149From Bos taurus.
MARK2Q7KZI76EBI-347088,EBI-516560
MARK3P2744810EBI-347088,EBI-707595
MYCBP2O755922EBI-347088,EBI-1043774
NADKO955442EBI-347088,EBI-743949
NCLP193382EBI-347088,EBI-346967
NOLC1Q149782EBI-347088,EBI-396155
NPM1P067482EBI-347088,EBI-78579
PABPC4Q133102EBI-347088,EBI-372844
PAK4O960133EBI-347088,EBI-713738
PARD3Q8TEW04EBI-347088,EBI-81968
PPP1R3DO956853EBI-347088,EBI-1045661
PRKCEQ021565EBI-347088,EBI-706254
PRLRP164713EBI-347088,EBI-476182
PRMT5O147443EBI-347088,EBI-351098
PTPN3P260453EBI-347088,EBI-1047946
RAF1P0404916EBI-347088,EBI-365996
RAI14Q9P0K72EBI-347088,EBI-1023749
RALGPS2Q86X272EBI-347088,EBI-1050841
REPS2Q8NFH8-22EBI-347088,EBI-8029141
RND3P6158711EBI-347088,EBI-1111534
Rnd3P615883EBI-347088,EBI-6930266From Mus musculus.
RPS3P233962EBI-347088,EBI-351193
SAMD4BQ5PRF92EBI-347088,EBI-1047489
SFNP319472EBI-347088,EBI-476295
SIK1P570594EBI-347088,EBI-1181640
SIK3Q9Y2K25EBI-347088,EBI-1181460
SORBS2O948752EBI-347088,EBI-311323
STK11Q158316EBI-347088,EBI-306838
STK25O005062EBI-347088,EBI-618295
TGFBR1P368974EBI-347088,EBI-1027557
TJP2Q9UDY22EBI-347088,EBI-1042602
TP53P046372EBI-347088,EBI-366083
TP53BP2Q136252EBI-347088,EBI-77642
TPD52L1Q168903EBI-347088,EBI-717470
TRA2BP629952EBI-347088,EBI-725485
TSC2P4981510EBI-347088,EBI-396587
TUBA1AQ71U364EBI-347088,EBI-302552
USP8P408183EBI-347088,EBI-1050865
VCPP550722EBI-347088,EBI-355164
VIMP086702EBI-347088,EBI-353844
VIMP841985EBI-347088,EBI-457639From Chlorocebus aethiops.
WEE1P302913EBI-347088,EBI-914695
XPO1O149802EBI-347088,EBI-355867
YAP1P469378EBI-347088,EBI-1044059
YWHAEP622586EBI-347088,EBI-356498

GO - Molecular functioni

  • cadherin binding Source: BHF-UCL
  • identical protein binding Source: IntAct
  • ion channel binding Source: SynGO-UCL
  • protein domain specific binding Source: InterPro
  • protein kinase binding Source: UniProtKB
  • transcription factor binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: ParkinsonsUK-UCL
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi113366, 399 interactors
ComplexPortaliCPX-1147 FOXO3-YWHAZ complex
CORUMiP63104
DIPiDIP-563N
ELMiP63104
IntActiP63104, 616 interactors
MINTiP63104
STRINGi9606.ENSP00000309503

Structurei

Secondary structure

1245
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi3 – 15Combined sources13
Helixi19 – 31Combined sources13
Helixi38 – 67Combined sources30
Turni69 – 71Combined sources3
Helixi76 – 103Combined sources28
Helixi105 – 108Combined sources4
Helixi112 – 131Combined sources20
Helixi135 – 159Combined sources25
Helixi165 – 180Combined sources16
Helixi185 – 200Combined sources16
Helixi201 – 205Combined sources5
Turni208 – 210Combined sources3
Helixi211 – 228Combined sources18

3D structure databases

ProteinModelPortaliP63104
SMRiP63104
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP63104

Family & Domainsi

Sequence similaritiesi

Belongs to the 14-3-3 family.Curated

Phylogenomic databases

eggNOGiKOG0841 Eukaryota
COG5040 LUCA
GeneTreeiENSGT00760000119116
HOGENOMiHOG000240379
HOVERGENiHBG050423
InParanoidiP63104
KOiK16197
PhylomeDBiP63104
TreeFamiTF102003

Family and domain databases

Gene3Di1.20.190.20, 1 hit
InterProiView protein in InterPro
IPR000308 14-3-3
IPR023409 14-3-3_CS
IPR036815 14-3-3_dom_sf
IPR023410 14-3-3_domain
PANTHERiPTHR18860 PTHR18860, 1 hit
PfamiView protein in Pfam
PF00244 14-3-3, 1 hit
PIRSFiPIRSF000868 14-3-3, 1 hit
PRINTSiPR00305 1433ZETA
SMARTiView protein in SMART
SM00101 14_3_3, 1 hit
SUPFAMiSSF48445 SSF48445, 1 hit
PROSITEiView protein in PROSITE
PS00796 1433_1, 1 hit
PS00797 1433_2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P63104-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MDKNELVQKA KLAEQAERYD DMAACMKSVT EQGAELSNEE RNLLSVAYKN 
        60         70         80         90        100
VVGARRSSWR VVSSIEQKTE GAEKKQQMAR EYREKIETEL RDICNDVLSL 
       110        120        130        140        150
LEKFLIPNAS QAESKVFYLK MKGDYYRYLA EVAAGDDKKG IVDQSQQAYQ 
       160        170        180        190        200
EAFEISKKEM QPTHPIRLGL ALNFSVFYYE ILNSPEKACS LAKTAFDEAI 
       210        220        230        240 
AELDTLSEES YKDSTLIMQL LRDNLTLWTS DTQGDEAEAG EGGEN
Length:245
Mass (Da):27,745
Last modified:September 13, 2004 - v1
Checksum:iD464DF2286BBFE60
GO
Isoform 2 (identifier: P63104-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-98: MDKNELVQKA...ELRDICNDVL → MSQPCRKLWRHNYETSSCIEFLK

Note: No experimental confirmation available.
Show »
Length:170
Mass (Da):19,333
Checksum:iBE97CE3F0A74C75C
GO

Sequence cautioni

The sequence AAH51814 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAH73141 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti22M → V in AAH68456 (PubMed:15489334).Curated1
Sequence conflicti136D → G in BAH12451 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0475051 – 98MDKNE…CNDVL → MSQPCRKLWRHNYETSSCIE FLK in isoform 2. 1 PublicationAdd BLAST98

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M86400 mRNA Translation: AAA36446.1
U28964 mRNA Translation: AAC52052.1
AK289945 mRNA Translation: BAF82634.1
AK296902 mRNA Translation: BAH12451.1
CH471060 Genomic DNA Translation: EAW91823.1
BC003623 mRNA Translation: AAH03623.3
BC051814 mRNA Translation: AAH51814.1 Different initiation.
BC063824 mRNA Translation: AAH63824.2
BC068456 mRNA Translation: AAH68456.2
BC072426 mRNA Translation: AAH72426.2
BC073141 mRNA Translation: AAH73141.1 Different initiation.
BC083508 mRNA Translation: AAH83508.2
BC099904 mRNA Translation: AAH99904.1
BC101483 mRNA Translation: AAI01484.1
BC108281 mRNA Translation: AAI08282.1
BC111951 mRNA Translation: AAI11952.1
CCDSiCCDS6290.1 [P63104-1]
PIRiA38246 PSHUAM
RefSeqiNP_001129171.1, NM_001135699.1 [P63104-1]
NP_001129172.1, NM_001135700.1 [P63104-1]
NP_001129173.1, NM_001135701.1 [P63104-1]
NP_001129174.1, NM_001135702.1 [P63104-1]
NP_003397.1, NM_003406.3 [P63104-1]
NP_663723.1, NM_145690.2 [P63104-1]
XP_005251118.1, XM_005251061.3 [P63104-1]
XP_005251120.1, XM_005251063.3 [P63104-1]
XP_016869299.1, XM_017013810.1 [P63104-1]
XP_016869300.1, XM_017013811.1 [P63104-1]
UniGeneiHs.492407

Genome annotation databases

EnsembliENST00000353245; ENSP00000309503; ENSG00000164924 [P63104-1]
ENST00000395951; ENSP00000379281; ENSG00000164924 [P63104-1]
ENST00000395953; ENSP00000379283; ENSG00000164924 [P63104-1]
ENST00000395956; ENSP00000379286; ENSG00000164924 [P63104-1]
ENST00000395957; ENSP00000379287; ENSG00000164924 [P63104-1]
ENST00000395958; ENSP00000379288; ENSG00000164924 [P63104-1]
ENST00000419477; ENSP00000395114; ENSG00000164924 [P63104-1]
ENST00000457309; ENSP00000398599; ENSG00000164924 [P63104-1]
ENST00000522542; ENSP00000430072; ENSG00000164924 [P63104-2]
GeneIDi7534
KEGGihsa:7534
UCSCiuc003yjv.3 human [P63104-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry namei1433Z_HUMAN
AccessioniPrimary (citable) accession number: P63104
Secondary accession number(s): A8K1N0
, B7Z465, P29213, P29312, Q32P43, Q5XJ08, Q6GPI2, Q6IN74, Q6NUR9, Q6P3U9, Q86V33
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 13, 2004
Last sequence update: September 13, 2004
Last modified: July 18, 2018
This is version 175 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

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