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Protein

14-3-3 protein sigma

Gene

SFN

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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. When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway. May also regulate MDM2 autoubiquitination and degradation and thereby activate p53/TP53.1 Publication
p53-regulated inhibitor of G2/M progression.1 Publication

GO - Molecular functioni

  • cadherin binding Source: BHF-UCL
  • identical protein binding Source: IntAct
  • phosphoprotein binding Source: Ensembl
  • protein domain specific binding Source: InterPro
  • protein kinase binding Source: Ensembl
  • protein kinase C inhibitor activity Source: ProtInc

GO - Biological processi

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-5625740. RHO GTPases activate PKNs.
R-HSA-5628897. TP53 Regulates Metabolic Genes.
R-HSA-6804114. TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest.
R-HSA-75035. Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex.
SignaLinkiP31947.
SIGNORiP31947.

Names & Taxonomyi

Protein namesi
Recommended name:
14-3-3 protein sigma
Alternative name(s):
Epithelial cell marker protein 1
Stratifin
Gene namesi
Name:SFN
Synonyms:HME1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000175793.11.
HGNCiHGNC:10773. SFN.

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, Nucleus, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi2810.
OpenTargetsiENSG00000175793.
PharmGKBiPA177.

Chemistry databases

ChEMBLiCHEMBL1909482.

Polymorphism and mutation databases

BioMutaiSFN.
DMDMi398953.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000586431 – 24814-3-3 protein sigmaAdd BLAST248

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei5PhosphoserineCombined sources1
Modified residuei74PhosphoserineCombined sources1
Modified residuei248PhosphoserineCombined sources1

Post-translational modificationi

Ubiquitinated. Ubiquitination by RFFL induces proteasomal degradation and indirectly regulates p53/TP53 activation.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP31947.
MaxQBiP31947.
PaxDbiP31947.
PeptideAtlasiP31947.
PRIDEiP31947.
TopDownProteomicsiP31947-1. [P31947-1]
P31947-2. [P31947-2]

2D gel databases

OGPiP31947.
SWISS-2DPAGEiP31947.

PTM databases

iPTMnetiP31947.
PhosphoSitePlusiP31947.
SwissPalmiP31947.

Expressioni

Tissue specificityi

Present mainly in tissues enriched in stratified squamous keratinizing epithelium.

Gene expression databases

BgeeiENSG00000175793.
CleanExiHS_SFN.
GenevisibleiP31947. HS.

Organism-specific databases

HPAiCAB006268.
CAB040552.
HPA011105.

Interactioni

Subunit structurei

Homodimer. Interacts with KRT17 and SAMSN1 (By similarity). Found in a complex with XPO7, EIF4A1, ARHGAP1, VPS26A, VPS29 and VPS35. Interacts with GAB2. Interacts with SRPK2. Interacts with COPS6. Interacts with RFWD2; this interaction leads to proteasomal degradation. Interacts with the 'Thr-369' phosphorylated form of DAPK2 (PubMed:26047703). Interacts with PI4KB (PubMed:23572552). Interacts with SLITRK1 (PubMed:19640509).By similarity9 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei56Interaction with phosphoserine on interacting protein1
Sitei129Interaction with phosphoserine on interacting protein1

Binary interactionsi

Show more details

GO - Molecular functioni

  • cadherin binding Source: BHF-UCL
  • identical protein binding Source: IntAct
  • phosphoprotein binding Source: Ensembl
  • protein domain specific binding Source: InterPro
  • protein kinase binding Source: Ensembl

Protein-protein interaction databases

BioGridi109072. 258 interactors.
DIPiDIP-29861N.
ELMiP31947.
IntActiP31947. 168 interactors.
MINTiMINT-108060.
STRINGi9606.ENSP00000340989.

Chemistry databases

BindingDBiP31947.

Structurei

Secondary structure

1248
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi3 – 15Combined sources13
Helixi19 – 31Combined sources13
Helixi38 – 69Combined sources32
Helixi80 – 104Combined sources25
Helixi107 – 110Combined sources4
Helixi114 – 134Combined sources21
Beta strandi137 – 139Combined sources3
Helixi140 – 161Combined sources22
Helixi167 – 182Combined sources16
Helixi187 – 204Combined sources18
Helixi205 – 207Combined sources3
Helixi210 – 230Combined sources21

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1YWTX-ray2.40A/B1-248[»]
1YZ5X-ray2.80A/B1-248[»]
3IQJX-ray1.15A1-231[»]
3IQUX-ray1.05A1-231[»]
3IQVX-ray1.20A1-231[»]
3LW1X-ray1.28A1-248[»]
3MHRX-ray1.15A1-231[»]
3O8IX-ray2.00A1-231[»]
3P1NX-ray1.40A1-231[»]
3P1OX-ray1.90A1-231[»]
3P1PX-ray1.95A1-231[»]
3P1QX-ray1.70A1-231[»]
3P1RX-ray1.70A1-231[»]
3P1SX-ray1.65A1-231[»]
3SMKX-ray2.10A1-231[»]
3SMLX-ray1.90A1-231[»]
3SMMX-ray2.00A1-231[»]
3SMNX-ray2.00A1-231[»]
3SMOX-ray1.80A1-231[»]
3SP5X-ray1.80A1-231[»]
3SPRX-ray1.99A1-231[»]
3T0LX-ray1.60A1-231[»]
3T0MX-ray1.62A1-231[»]
3U9XX-ray1.80A1-231[»]
3UX0X-ray1.75A1-231[»]
4DATX-ray1.40A1-231[»]
4DAUX-ray2.00A1-231[»]
4DHMX-ray1.70A1-231[»]
4DHNX-ray1.80A1-231[»]
4DHOX-ray1.70A1-231[»]
4DHPX-ray1.75A1-231[»]
4DHQX-ray1.75A1-231[»]
4DHRX-ray1.40A1-231[»]
4DHSX-ray1.74A1-231[»]
4DHTX-ray1.80A1-231[»]
4DHUX-ray1.67A1-231[»]
4FL5X-ray1.90A/B1-231[»]
4FR3X-ray1.90A1-231[»]
4IEAX-ray1.70A1-231[»]
4JC3X-ray2.05A1-231[»]
4JDDX-ray2.10A1-231[»]
4QLIX-ray1.45A1-231[»]
4Y32X-ray1.70A/B1-231[»]
4Y3BX-ray1.80A/B1-231[»]
4Y5IX-ray1.40A/B1-231[»]
5BTVX-ray1.70A1-231[»]
5HF3X-ray1.80A1-231[»]
5LTWX-ray4.50A/B/E/F/I/J1-231[»]
5LU1X-ray2.40A/B/E/F1-231[»]
5LU2X-ray2.50A/B1-231[»]
5MY9X-ray1.33A1-231[»]
5MYCX-ray1.46A1-231[»]
5N5RX-ray1.80A1-231[»]
5N5TX-ray1.80A1-231[»]
5N5WX-ray1.37A1-231[»]
5N75X-ray1.80A1-231[»]
5OEGX-ray3.15A1-231[»]
5OEHX-ray2.35A1-231[»]
ProteinModelPortaliP31947.
SMRiP31947.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP31947.

Family & Domainsi

Sequence similaritiesi

Belongs to the 14-3-3 family.Curated

Phylogenomic databases

eggNOGiKOG0841. Eukaryota.
COG5040. LUCA.
GeneTreeiENSGT00760000119116.
HOGENOMiHOG000240379.
HOVERGENiHBG050423.
InParanoidiP31947.
KOiK06644.
OMAiSIEQKGN.
OrthoDBiEOG091G0VKY.
PhylomeDBiP31947.
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: P31947-1) [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
MERASLIQKA KLAEQAERYE DMAAFMKGAV EKGEELSCEE RNLLSVAYKN
60 70 80 90 100
VVGGQRAAWR VLSSIEQKSN EEGSEEKGPE VREYREKVET ELQGVCDTVL
110 120 130 140 150
GLLDSHLIKE AGDAESRVFY LKMKGDYYRY LAEVATGDDK KRIIDSARSA
160 170 180 190 200
YQEAMDISKK EMPPTNPIRL GLALNFSVFH YEIANSPEEA ISLAKTTFDE
210 220 230 240
AMADLHTLSE DSYKDSTLIM QLLRDNLTLW TADNAGEEGG EAPQEPQS
Length:248
Mass (Da):27,774
Last modified:July 1, 1993 - v1
Checksum:i7F4B44E3AA59ECE6
GO
Isoform 2 (identifier: P31947-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     85-116: Missing.

Note: No experimental confirmation available.
Show »
Length:216
Mass (Da):24,336
Checksum:i14CBC2F26014D926
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti77K → M in CAG46703 (Ref. 4) Curated1
Sequence conflicti120Y → H in AAA59546 (PubMed:8515476).Curated1
Sequence conflicti242A → V in AAA59546 (PubMed:8515476).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_048095155M → I. Corresponds to variant dbSNP:rs11542705Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_02176885 – 116Missing in isoform 2. 1 PublicationAdd BLAST32

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M93010 mRNA. Translation: AAA59546.1.
X57348 mRNA. Translation: CAA40623.1.
AF029081 Genomic DNA. Translation: AAC52029.1.
AF029082 mRNA. Translation: AAC52030.1.
CR541905 mRNA. Translation: CAG46703.1.
CR541926 mRNA. Translation: CAG46724.1.
AL034380 Genomic DNA. Translation: CAB92118.1.
BC000329 mRNA. Translation: AAH00329.1.
BC000995 mRNA. Translation: AAH00995.1.
BC001550 mRNA. Translation: AAH01550.1.
BC002995 mRNA. Translation: AAH02995.1.
BC023552 mRNA. Translation: AAH23552.1.
CCDSiCCDS288.1. [P31947-1]
PIRiS34753.
S38956.
RefSeqiNP_006133.1. NM_006142.3. [P31947-1]
UniGeneiHs.523718.

Genome annotation databases

EnsembliENST00000339276; ENSP00000340989; ENSG00000175793. [P31947-1]
GeneIDi2810.
KEGGihsa:2810.
UCSCiuc001bnc.2. human. [P31947-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry namei1433S_HUMAN
AccessioniPrimary (citable) accession number: P31947
Secondary accession number(s): Q6FH30, Q6FH51, Q96DH0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 1, 1993
Last modified: October 25, 2017
This is version 189 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 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families