P06703 (S10A6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	90 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May function as calcium sensor and contribute to cellular calcium signaling Potential. May function by interacting with other proteins and indirectly play a role in the reorganization of the actin cytoskeleton and in cell motility. Binds 2 calcium ions. Calcium binding is cooperative.
Subunit structure	Homodimer; head to tail assembly of 2 subunits. Interacts with CACYBP By similarity. 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. Ref.11 Ref.13 Ref.14 Ref.16 Ref.17
Subcellular location	Nucleus envelope. Cytoplasm. Cell membrane; Peripheral membrane protein; Cytoplasmic side Ref.12 Ref.13.
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 component	Cell membrane Cytoplasm Membrane Nucleus
Coding sequence diversity	Polymorphism
Domain	Repeat
Ligand	Calcium Metal-binding
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	axonogenesis Non-traceable author statement. Source: UniProtKB positive regulation of fibroblast proliferation Non-traceable author statement. Source: UniProtKB signal transduction Traceable author statement. Source: UniProtKB
Cellular component	cytosol Inferred from direct assay Ref.13. Source: UniProtKB extrinsic to internal side of plasma membrane Inferred from direct assay Ref.13. Source: UniProtKB nuclear envelope Inferred from direct assay Ref.12. Source: UniProtKB perinuclear region of cytoplasm Inferred from direct assay. Source: UniProtKB ruffle Inferred from direct assay. Source: UniProtKB
Molecular function	S100 beta binding Inferred from physical interaction. Source: UniProtKB calcium ion binding Inferred from direct assay Ref.17. Source: UniProtKB calcium-dependent protein binding Inferred from direct assay. Source: UniProtKB protein homodimerization activity Inferred from direct assay. Source: UniProtKB tropomyosin binding Inferred from direct assay Ref.13. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
S100B	P04271	5	EBI-352877,EBI-458391

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 90

90

Protein S100-A6

PRO_0000143984

Regions

Domain

12 – 47

36

EF-hand 1

Domain

48 – 83

36

EF-hand 2

Calcium binding

20 – 33

14

1 Ref.17

Calcium binding

61 – 72

12

2 Ref.17

Amino acid modifications

Modified residue

40

1

N6-acetyllysine Ref.15

Natural variations

Natural variant

27

1

H → R.
Corresponds to variant rs11974 [ dbSNP | Ensembl ].

VAR_011982

Natural variant

69

1

N → S.
Corresponds to variant rs1802581 [ dbSNP | Ensembl ].

VAR_011983

Natural variant

83

1

I → T.
Corresponds to variant rs1802582 [ dbSNP | Ensembl ].

VAR_011984

Natural variant

90

1

G → D.
Corresponds to variant rs2228293 [ dbSNP | Ensembl ].

VAR_029281

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

90

Helix Strand Turn

Details...

Helix

4 – 20

17

Beta strand

22 – 24

3

Beta strand

28 – 30

3

Helix

31 – 41

11

Helix

45 – 47

3

Helix

51 – 62

12

Turn

63 – 65

3

Beta strand

67 – 69

3

Helix

70 – 84

15

Helix

86 – 88

3

Sequences

	Sequence		Length	Mass (Da)
	P06703 [UniParc]. Last modified January 1, 1988. Version 1. Checksum: 860CBB1416ACBCA1	FASTA	90	10,180
	10 20 30 40 50 60 MACPLDQAIG LLVAIFHKYS GREGDKHTLS KKELKELIQK ELTIGSKLQD AEIARLMEDL 70 80 90 DRNKDQEVNF QEYVTFLGAL ALIYNEALKG

References

	« Hide 'large scale' referencesShow '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: 3755724] [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: 3036810] [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: 2448309] [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. , 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].
[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. , 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: 15489334] [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: 1482346] [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: 2775283] [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: 12746458] [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: 12601007] [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: 19724273] [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: 19819244] [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., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-40, MASS SPECTROMETRY.
[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: 20188096] [Abstract] Cited for: INTERACTION WITH FKBP4.
[17]	"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: 11937060] [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.

IPI

IPI00027463.

PIR

BCHUY. A28363.

RefSeq

NP_055439.1. NM_014624.3.

UniGene

Hs.275243.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1K8U	X-ray	1.15	A	1-90	[»]
1K96	X-ray	1.44	A	1-90	[»]
1K9K	X-ray	1.76	A/B	1-90	[»]
1K9P	X-ray	1.90	A	1-90	[»]

ProteinModelPortal

P06703.

SMR

P06703. Positions 2-90.

ModBase

Search...

Protein-protein interaction databases

IntAct

P06703. 4 interactions.

MINT

MINT-3005220.

STRING

P06703.

PTM databases

PhosphoSite

P06703.

Polymorphism databases

DMDM

116509.

2D gel databases

DOSAC-COBS-2DPAGE

P06703.

Proteomic databases

PeptideAtlas

P06703.

PRIDE

P06703.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000368719; ENSP00000357708; ENSG00000197956.
ENST00000368720; ENSP00000357709; ENSG00000197956.

GeneID

6277.

KEGG

hsa:6277.

UCSC

uc001fbw.1. human.

Organism-specific databases

CTD

6277.

GeneCards

GC01M153507.

H-InvDB

HIX0001080.

HGNC

HGNC:10496. S100A6.

HPA

CAB002601.
CAB040549.
HPA007575.

MIM

114110. gene.

neXtProt

NX_P06703.

PharmGKB

PA34908.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG21294.

GeneTree

ENSGT00600000084162.

HOGENOM

HBG716817.

HOVERGEN

HBG001479.

InParanoid

P06703.

OMA

VVNFQEY.

OrthoDB

EOG4MSD0W.

PhylomeDB

P06703.

Gene expression databases

ArrayExpress

P06703.

Bgee

P06703.

CleanEx

HS_S100A6.

Genevestigator

P06703.

GermOnline

ENSG00000197956. Homo sapiens.

Family and domain databases

InterPro

IPR011992. EF-hand-like_dom.
IPR018247. EF_Hand_1_Ca_BS.
IPR018249. EF_HAND_2.
IPR001751. S100/CaBP-9k_CS.
IPR013787. S100_Ca-bd_sub.
[Graphical view]

Gene3D

G3DSA:1.10.238.10. EF-Hand_type. 1 hit.

Pfam

PF01023. S_100. 1 hit.
[Graphical view]

PROSITE

PS00018. EF_HAND_1. 1 hit.
PS50222. EF_HAND_2. 1 hit.
PS00303. S100_CABP. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

24365.

SOURCE

Search...

Entry information

Entry name

S10A6_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 126 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.