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P06703 (S10A6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 150. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein S100-A6
Alternative name(s):
Calcyclin
Growth factor-inducible protein 2A9
MLN 4
Prolactin receptor-associated protein
Short name=PRA
S100 calcium-binding protein A6
Gene names
Name:S100A6
Synonyms:CACY
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length90 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May function as calcium sensor and modulator, contributing to cellular calcium signaling. May function by interacting with other proteins, such as TPR-containing proteins, and indirectly play a role in many physiological processes such as the reorganization of the actin cytoskeleton and in cell motility. Binds 2 calcium ions. Calcium binding is cooperative. Ref.18

Subunit structure

Homodimer; head to tail assembly of 2 subunits. Interacts with CACYBP in a calcium-dependent manner. Interacts with ANXA2 and ANXA11 (via N-terminus). Interacts with SUGT1. Interacts with TP53; has higher affinity for TP53 that is phosphorylated on its N-terminal domain, and lower affinity for TP53 that is phosphorylated on its C-terminal domain. Interacts with tropomyosin. Interacts with FKBP4. Interacts with PPP5C (via TPR repeats); the interaction is calcium-dependent and modulates PPP5C activity. Ref.11 Ref.13 Ref.14 Ref.16 Ref.18 Ref.19

Subcellular location

Nucleus envelope. Cytoplasm. Cell membrane; Peripheral membrane protein; Cytoplasmic side Ref.12 Ref.13 Ref.18.

Induction

Preferentially expressed when quiescent fibroblasts are stimulated to proliferate. It is inducible by growth factors and overexpressed in acute myeloid leukemias.

Post-translational modification

The N-terminus is blocked.

Miscellaneous

This protein co-purified with the prolactin receptor.

Sequence similarities

Belongs to the S-100 family.

Contains 2 EF-hand domains.

Ontologies

Keywords
   Cellular componentCell membrane
Cytoplasm
Membrane
Nucleus
   Coding sequence diversityPolymorphism
   DomainRepeat
   LigandCalcium
Metal-binding
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processaxonogenesis

Non-traceable author statement PubMed 12152788. Source: UniProtKB

positive regulation of fibroblast proliferation

Non-traceable author statement PubMed 12577318. Source: UniProtKB

signal transduction

Traceable author statement PubMed 16130169. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 10913138Ref.12. Source: UniProtKB

cytosol

Inferred from direct assay Ref.13. Source: UniProtKB

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867PubMed 19199708PubMed 23376485. Source: UniProt

extrinsic component of cytoplasmic side of plasma membrane

Inferred from direct assay Ref.13. Source: UniProtKB

nuclear envelope

Inferred from direct assay Ref.12PubMed 12805373. Source: UniProtKB

nucleus

Inferred from direct assay PubMed 10913138. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from direct assay PubMed 12118070. Source: UniProtKB

ruffle

Inferred from direct assay PubMed 10913138. Source: UniProtKB

   Molecular_functionS100 protein binding

Inferred from physical interaction PubMed 10913138. Source: UniProtKB

calcium ion binding

Inferred from direct assay Ref.19. Source: UniProtKB

calcium-dependent protein binding

Inferred from direct assay PubMed 10913138. Source: UniProtKB

ion transmembrane transporter activity

Inferred from electronic annotation. Source: Ensembl

protein binding

Inferred from physical interaction PubMed 12577318Ref.13. Source: UniProtKB

protein homodimerization activity

Inferred from direct assay PubMed 10913138. Source: UniProtKB

tropomyosin binding

Inferred from direct assay Ref.13. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 9090Protein S100-A6
PRO_0000143984

Regions

Domain12 – 4736EF-hand 1
Domain48 – 8336EF-hand 2
Calcium binding20 – 33141 Ref.19
Calcium binding61 – 72122 Ref.19

Amino acid modifications

Modified residue401N6-acetyllysine Ref.15
Modified residue471N6-acetyllysine; alternate By similarity
Modified residue471N6-succinyllysine; alternate By similarity

Natural variations

Natural variant271H → R.
Corresponds to variant rs11974 [ dbSNP | Ensembl ].
VAR_011982
Natural variant691N → S.
Corresponds to variant rs1802581 [ dbSNP | Ensembl ].
VAR_011983
Natural variant831I → T.
Corresponds to variant rs1802582 [ dbSNP | Ensembl ].
VAR_011984
Natural variant901G → D.
Corresponds to variant rs2228293 [ dbSNP | Ensembl ].
VAR_029281

Secondary structure

.................. 90
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P06703 [UniParc].

Last modified January 1, 1988. Version 1.
Checksum: 860CBB1416ACBCA1

FASTA9010,180
        10         20         30         40         50         60 
MACPLDQAIG LLVAIFHKYS GREGDKHTLS KKELKELIQK ELTIGSKLQD AEIARLMEDL 

        70         80         90 
DRNKDQEVNF QEYVTFLGAL ALIYNEALKG 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning of the cDNA for a growth factor-inducible gene with strong homology to S-100, a calcium-binding protein."
Calabretta B., Battini R., Kaczmarek L., de Riel J.K., Baserga R.
J. Biol. Chem. 261:12628-12632(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Fibroblast.
[2]"Structural and functional analysis of a growth-regulated gene, the human calcyclin."
Ferrari S., Calabretta B., Deriel J.K., Battini R., Ghezzo F., Lauret E., Griffin C., Emanuel B.S., Gurrieri F., Baserga R.
J. Biol. Chem. 262:8325-8332(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Cloning and characterization of a cDNA encoding a highly conserved, putative calcium binding protein, identified by an anti-prolactin receptor antiserum."
Murphy L.C., Murphy L.J., Tsuyuki D., Duckworth M.L., Shiu R.P.C.
J. Biol. Chem. 263:2397-2401(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"Cloning of human calcyclin and calcyclin binding protein (CacyBP)."
Wu J., Liu W., Zhou Y., Zhao Z., Peng X., Yuan J., Qiang B.
Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]"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. expand/collapse author list , 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].
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"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].
Tissue: Brain and Placenta.
[9]"Calcyclin and calvasculin exist in human platelets."
Tomida Y., Terasawa M., Kobayashi R., Hidaka H.
Biochem. Biophys. Res. Commun. 189:1310-1316(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 27-31 AND 48-89.
Tissue: Platelet.
[10]"Identification of a cell cycle-dependent gene product as a sialic acid-binding protein."
Gabius H.J., Bardosi A., Gabius S., Hellmann K.P., Karas M., Kratzin H.
Biochem. Biophys. Res. Commun. 163:506-512(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 57-74.
[11]"Calcium-regulated interaction of Sgt1 with S100A6 (calcyclin) and other S100 proteins."
Nowotny M., Spiechowicz M., Jastrzebska B., Filipek A., Kitagawa K., Kuznicki J.
J. Biol. Chem. 278:26923-26928(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SUGT1.
[12]"Calcium- and cell cycle-dependent association of annexin 11 with the nuclear envelope."
Tomas A., Moss S.E.
J. Biol. Chem. 278:20210-20216(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[13]"S100A6 binds to annexin 2 in pancreatic cancer cells and promotes pancreatic cancer cell motility."
Nedjadi T., Kitteringham N., Campbell F., Jenkins R.E., Park B.K., Navarro P., Ashcroft F., Tepikin A., Neoptolemos J.P., Costello E.
Br. J. Cancer 101:1145-1154(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ANXA2; ANXA11 AND TROPOMYOSIN, SUBCELLULAR LOCATION.
[14]"Posttranslational modifications affect the interaction of S100 proteins with tumor suppressor p53."
van Dieck J., Teufel D.P., Jaulent A.M., Fernandez-Fernandez M.R., Rutherford T.J., Wyslouch-Cieszynska A., Fersht A.R.
J. Mol. Biol. 394:922-930(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TP53.
[15]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-40, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]"S100 proteins regulate the interaction of Hsp90 with cyclophilin 40 and FKBP52 through their tetratricopeptide repeats."
Shimamoto S., Kubota Y., Tokumitsu H., Kobayashi R.
FEBS Lett. 584:1119-1125(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FKBP4.
[17]"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].
[18]"S100 proteins modulate protein phosphatase 5 function: a link between CA2+ signal transduction and protein dephosphorylation."
Yamaguchi F., Umeda Y., Shimamoto S., Tsuchiya M., Tokumitsu H., Tokuda M., Kobayashi R.
J. Biol. Chem. 287:13787-13798(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PPP5C, SUBCELLULAR LOCATION.
[19]"Crystal structures of S100A6 in the Ca(2+)-free and Ca(2+)-bound states: the calcium sensor mechanism of S100 proteins revealed at atomic resolution."
Otterbein L.R., Kordowska J., Witte-Hoffmann C., Wang C.-L.A., Dominguez R.
Structure 10:557-567(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.15 ANGSTROMS), SUBUNIT, CALCIUM-BINDING.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M14300 mRNA. Translation: AAA35886.1.
J02763 Genomic DNA. Translation: AAA51905.1.
M18981 mRNA. Translation: AAA51906.1.
AY034480 Genomic DNA. Translation: AAK59702.1.
BT006965 mRNA. Translation: AAP35611.1.
BX470102 Genomic DNA. Translation: CAI14752.1.
CH471121 Genomic DNA. Translation: EAW53318.1.
CH471121 Genomic DNA. Translation: EAW53320.1.
CH471121 Genomic DNA. Translation: EAW53321.1.
CH471121 Genomic DNA. Translation: EAW53322.1.
CH471121 Genomic DNA. Translation: EAW53323.1.
CH471121 Genomic DNA. Translation: EAW53324.1.
CH471121 Genomic DNA. Translation: EAW53325.1.
CH471121 Genomic DNA. Translation: EAW53326.1.
BC001431 mRNA. Translation: AAH01431.1.
BC009017 mRNA. Translation: AAH09017.1.
CCDSCCDS1040.1.
PIRBCHUY. A28363.
RefSeqNP_055439.1. NM_014624.3.
UniGeneHs.275243.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1K8UX-ray1.15A1-90[»]
1K96X-ray1.44A1-90[»]
1K9KX-ray1.76A/B1-90[»]
1K9PX-ray1.90A1-90[»]
ProteinModelPortalP06703.
SMRP06703. Positions 2-90.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112185. 19 interactions.
IntActP06703. 10 interactions.
MINTMINT-3005220.
STRING9606.ENSP00000357708.

PTM databases

PhosphoSiteP06703.

Polymorphism databases

DMDM116509.

2D gel databases

DOSAC-COBS-2DPAGEP06703.

Proteomic databases

MaxQBP06703.
PaxDbP06703.
PeptideAtlasP06703.
PRIDEP06703.

Protocols and materials databases

DNASU6277.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000368719; ENSP00000357708; ENSG00000197956.
ENST00000368720; ENSP00000357709; ENSG00000197956.
ENST00000496817; ENSP00000473589; ENSG00000197956.
GeneID6277.
KEGGhsa:6277.
UCSCuc001fbw.1. human.

Organism-specific databases

CTD6277.
GeneCardsGC01M153507.
HGNCHGNC:10496. S100A6.
HPACAB002601.
CAB040549.
HPA007575.
MIM114110. gene.
neXtProtNX_P06703.
PharmGKBPA34908.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG40006.
HOGENOMHOG000246968.
HOVERGENHBG001479.
InParanoidP06703.
OMACHLIRIS.
OrthoDBEOG78WKVD.
PhylomeDBP06703.
TreeFamTF332727.

Gene expression databases

BgeeP06703.
CleanExHS_S100A6.
GenevestigatorP06703.

Family and domain databases

Gene3D1.10.238.10. 1 hit.
InterProIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR001751. S100/CaBP-9k_CS.
IPR013787. S100_Ca-bd_sub.
[Graphical view]
PfamPF01023. S_100. 1 hit.
[Graphical view]
PROSITEPS00018. EF_HAND_1. 1 hit.
PS50222. EF_HAND_2. 1 hit.
PS00303. S100_CABP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSS100A6. human.
EvolutionaryTraceP06703.
GeneWikiS100A6.
GenomeRNAi6277.
NextBio24365.
PROP06703.
SOURCESearch...

Entry information

Entry nameS10A6_HUMAN
AccessionPrimary (citable) accession number: P06703
Secondary accession number(s): D3DV39, Q5RHS4
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: January 1, 1988
Last modified: July 9, 2014
This is version 150 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM