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

Names and origin

Protein names

Recommended name:
    14-3-3 protein sigma
Alternative name(s):
    Stratifin
    Epithelial cell marker protein 1

Gene names

Name:	SFN
Synonyms:	HME1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	248 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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 pathway. 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 By similarity. Found in a complex with XPO7, EIF4A1, ARHGAP1, VPS26A, VPS29, VPS35 and SFN.
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 keratinising 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
Gene Ontology (GO)
Biological process	DNA damage response, signal transduction resulting in induction of apoptosis Inferred from direct assay. Source: HGNC negative regulation of caspase activity Inferred from direct assay. Source: HGNC negative regulation of protein kinase activity Ref.2 Traceable author statement. Source: ProtInc release of cytochrome c from mitochondria Inferred from direct assay. Source: HGNC
Cellular component	cytoplasm Traceable author statement. Source: ProtInc extracellular space Ref.2 Traceable author statement. Source: ProtInc nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein domain specific binding Inferred from electronic annotation. Source: InterPro protein kinase C inhibitor activity Ref.2 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ABL1	P00519	1	EBI-476295,EBI-375543
HNRNPD	Q14103-3	1	EBI-476295,EBI-432539
HNRNPD	Q14103-4	3	EBI-476295,EBI-432545
PLK4	O00444	1	EBI-476295,EBI-746202

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

64

1

Phosphoserine By similarity

Modified residue

216

1

Phosphoserine By similarity

Modified residue

248

1

Phosphoserine Ref.9 Ref.10 Ref.11

Natural variations

Alternative sequence

85 – 116

32

Missing in isoform 2.

VSP_021768

Natural variant

155

1

M → I: dbSNP rs11542705.

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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248

Helix Strand Turn

Details...

Helix

3 – 15

13

Helix

19 – 31

13

Helix

38 – 66

29

Helix

67 – 69

3

Helix

80 – 104

25

Turn

105 – 107

3

Beta strand

108 – 110

3

Helix

114 – 133

20

Helix

137 – 161

25

Helix

167 – 182

16

Helix

187 – 202

16

Helix

205 – 207

3

Turn

210 – 212

3

Helix

213 – 229

17

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. 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: 1390337] [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: 8515476] [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: 9659898] [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: 16710414] [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: 15489334] [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: 1286667] [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: 15282546] [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: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-248, MASS SPECTROMETRY. Tissue: Epithelium.
[10]	"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: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-248, MASS SPECTROMETRY.
[11]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-248, MASS SPECTROMETRY.
[12]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[13]	"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: 15731107] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH PHOSPHOSERINE PEPTIDE.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

UniGene

Hs.523718

3D structure databases

PDBPDBe

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	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P31947. 18 interactions.

PTM databases

PhosphoSite

P31947.

2-D gel databases

SWISS-2DPAGE

P31947.

Aarhus/Ghent-2DPAGE

9109. IEF.

Cornea-2DPAGE

P31947.

OGP

P31947.

Proteomic databases

PeptideAtlas

P31947.

PRIDE

P31947.

Genome annotation databases

Ensembl

ENSG00000175793. Homo sapiens. [Contig view]

GeneID

2810.

KEGG

hsa:2810.

UCSC

uc001bnc.1. human.

Organism-specific databases

GeneCards

GC01P027062.

H-InvDB

HIX0000327.

HGNC

HGNC:10773. SFN.

HPA

CAB006268.
HPA011105.

MIM

601290. gene.

PharmGKB

PA177.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P31947.

HOVERGEN

P31947.

OMA

P31947. FMKSAVE.

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.

Gene expression databases

ArrayExpress

P31947.

Bgee

P31947.

CleanEx

HS_SFN.

GermOnline

ENSG00000175793. Homo sapiens.

Family and domain databases

InterPro

IPR000308. 14-3-3.
[Graphical view]

Gene3D

G3DSA:1.20.190.20. 14-3-3. 1 hit.

PANTHER

PTHR18860. 14-3-3. 1 hit.

Pfam

PF00244. 14-3-3. 1 hit.
[Graphical view]

PIRSF

PIRSF000868. 14-3-3. 1 hit.

PRINTS

PR00305. 1433ZETA.

ProDom

PD000600. 14-3-3. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00101. 14_3_3. 1 hit.
[Graphical view]

PROSITE

PS00796. 1433_1. 1 hit.
PS00797. 1433_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

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:	July 7, 2009
This is version 97 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)