P31947 (1433S_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
14-3-3 protein sigma

Alternative name(s):
Epithelial cell marker protein 1
Stratifin

Gene names

Name:	SFN
Synonyms:	HME1

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	248 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. When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway By similarity. p53-regulated inhibitor of G2/M progression.
Subunit structure	Homodimer. Interacts with KRT17 and SAMSN1 By similarity. Found in a complex with XPO7, EIF4A1, ARHGAP1, VPS26A, VPS29, VPS35 and SFN. Interacts with GAB2. Interacts with SRPK2. Interacts with COPS6. Interacts with RFWD2; this interaction leads to proteasomal degradation. Ref.8 Ref.10 Ref.13 Ref.16
Subcellular location	Cytoplasm. Nucleus By similarity. Secreted. Note: May be secreted by a non-classical secretory pathway.
Tissue specificity	Present mainly in tissues enriched in stratified squamous keratinizing epithelium.
Sequence similarities	Belongs to the 14-3-3 family.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus Secreted
Coding sequence diversity	Alternative splicing Polymorphism
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	intrinsic apoptotic signaling pathway in response to DNA damage Inferred from direct assay PubMed 11574543. Source: HGNC keratinocyte differentiation Inferred from electronic annotation. Source: Compara keratinocyte proliferation Inferred from electronic annotation. Source: Compara negative regulation of cell proliferation Inferred from electronic annotation. Source: Compara negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from direct assay PubMed 11574543. Source: HGNC positive regulation of cell growth Inferred from electronic annotation. Source: Compara positive regulation of protein export from nucleus Inferred from electronic annotation. Source: Compara regulation of cyclin-dependent protein serine/threonine kinase activity Inferred from electronic annotation. Source: Compara release of cytochrome c from mitochondria Inferred from direct assay PubMed 11574543. Source: HGNC skin development Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasm Inferred from direct assay. Source: HPA extracellular space Traceable author statement Ref.2. Source: ProtInc nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	protein kinase C inhibitor activity Traceable author statement Ref.2. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ABL1	P00519	2	EBI-476295,EBI-375543
COPS6	Q7L5N1	7	EBI-476295,EBI-486838
HNRNPD	Q14103-4	7	EBI-476295,EBI-432545
PLK4	O00444	2	EBI-476295,EBI-746202
RFWD2	Q8NHY2	6	EBI-476295,EBI-1176214

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P31947-1)

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.

Isoform 2 (identifier: P31947-2)

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

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 248

248

14-3-3 protein sigma

PRO_0000058643

Sites

Site

56

1

Interaction with phosphoserine on interacting protein

Site

129

1

Interaction with phosphoserine on interacting protein

Amino acid modifications

Modified residue

5

1

Phosphoserine Ref.14

Modified residue

64

1

Phosphoserine By similarity

Modified residue

216

1

Phosphoserine By similarity

Modified residue

248

1

Phosphoserine Ref.9 Ref.11 Ref.12 Ref.14

Natural variations

Alternative sequence

85 – 116

32

Missing in isoform 2.

VSP_021768

Natural variant

155

1

M → I.
Corresponds to variant rs11542705 [ dbSNP | Ensembl ].

VAR_048095

Experimental info

Sequence conflict

77

1

K → M in CAG46703. Ref.4

Sequence conflict

120

1

Y → H in AAA59546. Ref.2

Sequence conflict

242

1

A → V in AAA59546. Ref.2

Secondary structure

1

.

.

.

.

.

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.

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.

.

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.

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248

Helix Strand Turn

Details...

Helix

3 – 15

13

Helix

19 – 31

13

Helix

38 – 69

32

Helix

80 – 104

25

Helix

107 – 110

4

Helix

114 – 134

21

Beta strand

137 – 139

3

Helix

140 – 161

22

Helix

167 – 182

16

Helix

187 – 204

18

Helix

205 – 207

3

Helix

210 – 230

21

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 1, 1993. Version 1. Checksum: 7F4B44E3AA59ECE6	FASTA	248	27,774
	10 20 30 40 50 60 MERASLIQKA KLAEQAERYE DMAAFMKGAV EKGEELSCEE RNLLSVAYKN VVGGQRAAWR 70 80 90 100 110 120 VLSSIEQKSN EEGSEEKGPE VREYREKVET ELQGVCDTVL GLLDSHLIKE AGDAESRVFY 130 140 150 160 170 180 LKMKGDYYRY LAEVATGDDK KRIIDSARSA YQEAMDISKK EMPPTNPIRL GLALNFSVFH 190 200 210 220 230 240 YEIANSPEEA ISLAKTTFDE AMADLHTLSE DSYKDSTLIM QLLRDNLTLW TADNAGEEGG EAPQEPQS
	Isoform 2 [UniParc]. Checksum: 14CBC2F26014D926	FASTA	216	24,336
	10 20 30 40 50 60 MERASLIQKA KLAEQAERYE DMAAFMKGAV EKGEELSCEE RNLLSVAYKN VVGGQRAAWR 70 80 90 100 110 120 VLSSIEQKSN EEGSEEKGPE VREYRVFYLK MKGDYYRYLA EVATGDDKKR IIDSARSAYQ 130 140 150 160 170 180 EAMDISKKEM PPTNPIRLGL ALNFSVFHYE IANSPEEAIS LAKTTFDEAM ADLHTLSEDS 190 200 210 YKDSTLIMQL LRDNLTLWTA DNAGEEGGEA PQEPQS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complementary DNA cloning of a novel epithelial cell marker protein, HME1, that may be down-regulated in neoplastic mammary cells." Prasad G.L., Valverius E.M., McDuffie E., Cooper H.L. Cell Growth Differ. 3:507-513(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Epithelium.
[2]	"Molecular cloning and expression of the transformation sensitive epithelial marker stratifin. A member of a protein family that has been involved in the protein kinase C signalling pathway." Leffers H., Madsen P., Rasmussen H.H., Honore B., Andersen A.H., Walbum E., Vandekerckhove J., Celis J.E. J. Mol. Biol. 231:982-998(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 19-25; 42-49; 118-122; 130-139; 149-159; 161-181; 196-199; 225-229 AND 231-239. Tissue: Keratinocyte.
[3]	"14-3-3 sigma is a p53-regulated inhibitor of G2/M progression." Hermeking H., Lengauer C., Polyak K., He T.-C., Zhang L., Thiagalingam S., Kinzler K.W., Vogelstein B. Mol. Cell 1:3-11(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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] (ISOFORMS 1 AND 2). Tissue: Cervix, Lung and Placenta.
[7]	"Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes." Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E., Vandekerckhove J. Electrophoresis 13:960-969(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 42-49 AND 118-122. Tissue: Keratinocyte.
[8]	"Exportin 7 defines a novel general nuclear export pathway." Mingot J.-M., Bohnsack M.T., Jaekle U., Goerlich D. EMBO J. 23:3227-3236(2004) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH XPO7; ARHGAP1; EIF4A1; VPS26A; VPS29 AND VPS35.
[9]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-248, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"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.
[11]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-248, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-248, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"Interaction of Akt-phosphorylated SRPK2 with 14-3-3 mediates cell cycle and cell death in neurons." Jang S.W., Liu X., Fu H., Rees H., Yepes M., Levey A., Ye K. J. Biol. Chem. 284:24512-24525(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SRPK2.
[14]	"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-5 AND SER-248, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[15]	"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].
[16]	"COP9 signalosome subunit 6 stabilizes COP1, which functions as an E3 ubiquitin ligase for 14-3-3sigma." Choi H.H., Gully C., Su C.H., Velazquez-Torres G., Chou P.C., Tseng C., Zhao R., Phan L., Shaiken T., Chen J., Yeung S.C., Lee M.H. Oncogene 30:4791-4801(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH COPS6 AND RFWD2.
[17]	"A structural basis for 14-3-3sigma functional specificity." Wilker E.W., Grant R.A., Artim S.C., Yaffe M.B. J. Biol. Chem. 280:18891-18898(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH PHOSPHOSERINE PEPTIDE.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00013890.
IPI00411765.

PIR

S34753.
S38956.

RefSeq

NP_006133.1. NM_006142.3.

UniGene

Hs.523718.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1YWT	X-ray	2.40	A/B	1-248	[»]
1YZ5	X-ray	2.80	A/B	1-248	[»]
3IQJ	X-ray	1.15	A	1-231	[»]
3IQU	X-ray	1.05	A	1-231	[»]
3IQV	X-ray	1.20	A	1-231	[»]
3LW1	X-ray	1.28	A	1-248	[»]
3MHR	X-ray	1.15	A	1-231	[»]
3O8I	X-ray	2.00	A	1-231	[»]
3P1N	X-ray	1.40	A	1-231	[»]
3P1O	X-ray	1.90	A	1-231	[»]
3P1P	X-ray	1.95	A	1-231	[»]
3P1Q	X-ray	1.70	A	1-231	[»]
3P1R	X-ray	1.70	A	1-231	[»]
3P1S	X-ray	1.65	A	1-231	[»]
3SMK	X-ray	2.10	A	1-231	[»]
3SML	X-ray	1.90	A	1-231	[»]
3SMM	X-ray	2.00	A	1-231	[»]
3SMN	X-ray	2.00	A	1-231	[»]
3SMO	X-ray	1.80	A	1-231	[»]
3SPR	X-ray	1.99	A	1-231	[»]
3T0L	X-ray	1.60	A	1-231	[»]
3T0M	X-ray	1.62	A	1-231	[»]
3U9X	X-ray	1.80	A	1-231	[»]
3UX0	X-ray	1.75	A	1-231	[»]
4DAT	X-ray	1.40	A	1-231	[»]
4DAU	X-ray	2.00	A	1-231	[»]
4HQW	X-ray	2.35	A	1-231	[»]
4HRU	X-ray	3.15	A	1-231	[»]

ProteinModelPortal

P31947.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29861N.

IntAct

P31947. 24 interactions.

MINT

MINT-108060.

STRING

9606.ENSP00000340989.

PTM databases

PhosphoSite

P31947.

Polymorphism databases

DMDM

398953.

2D gel databases

OGP

P31947.

SWISS-2DPAGE

P31947.

Proteomic databases

PaxDb

P31947.

PeptideAtlas

P31947.

PRIDE

P31947.

Protocols and materials databases

DNASU

2810.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000339276; ENSP00000340989; ENSG00000175793.

GeneID

2810.

KEGG

hsa:2810.

UCSC

uc001bnc.1. human.

Organism-specific databases

CTD

2810.

GeneCards

GC01P027189.

HGNC

HGNC:10773. SFN.

HPA

CAB006268.
CAB040552.
HPA011105.

MIM

601290. gene.

neXtProt

NX_P31947.

PharmGKB

PA177.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5040.

HOGENOM

HOG000240379.

HOVERGEN

HBG050423.

InParanoid

P31947.

KO

K06644.

OMA

AFMKSAV.

OrthoDB

EOG4XH00X.

PhylomeDB

P31947.

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.

Gene expression databases

Bgee

P31947.

CleanEx

HS_SFN.

Genevestigator

P31947.

GermOnline

ENSG00000175793. 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

P31947.

ChEMBL

CHEMBL1909482.

EvolutionaryTrace

P31947.

GenomeRNAi

2810.

NextBio

11071.

SOURCE

Search...

Entry information

Entry name

1433S_HUMAN

Accession

Primary (citable) accession number: P31947
Secondary accession number(s): Q6FH30, Q6FH51, Q96DH0

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1993
Last sequence update:	July 1, 1993
Last modified:	May 1, 2013
This is version 139 of the entry and version 1 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.