P33764 (S10A3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein S100-A3

Alternative name(s):
Protein S-100E
S100 calcium-binding protein A3

Gene names

Name:	S100A3
Synonyms:	S100E

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	101 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Binds both calcium and zinc. May be involved in calcium-dependent cuticle cell differentiation, hair shaft and hair cuticular barrier formation. Ref.9
Subunit structure	Homodimer and homotetramer for the citrullinated form. Ref.9
Subcellular location	Cytoplasm Ref.9.
Tissue specificity	Skin specific, specifically expressed at the inner endocuticle of hair fibers. Ref.8
Post-translational modification	More than half of the arginine residues undergo citrullination by PAD1 and PAD2. Arg-51 is specifically citrullinated by PAD3 and promotes tetramerization.
Sequence similarities	Belongs to the S-100 family. Contains 2 EF-hand domains.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Domain	Repeat
Ligand	Calcium Metal-binding Zinc
PTM	Acetylation Citrullination Disulfide bond
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 101

100

Protein S100-A3

PRO_0000143972

Regions

Domain

12 – 47

36

EF-hand 1

Domain

50 – 85

36

EF-hand 2

Calcium binding

20 – 33

14

1; low affinity Potential

Calcium binding

63 – 74

12

2; high affinity Potential

Sites

Metal binding

83

1

Zinc

Metal binding

86

1

Zinc

Metal binding

87

1

Zinc

Metal binding

93

1

Zinc

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.8

Modified residue

51

1

Citrulline; by PAD3

Disulfide bond

30 ↔ 68

Ref.11

Disulfide bond

81 ↔ 99

Ref.11

Natural variations

Natural variant

3

1

R → K.
Corresponds to variant rs36022742 [ dbSNP | Ensembl ].

VAR_061047

Experimental info

Mutagenesis

30

1

C → A: Abolishes calcium binding; when associated with Ala-68. Ref.11

Mutagenesis

68

1

C → A: Abolishes calcium binding; when associated with Ala-30. Ref.11

Mutagenesis

81

1

C → A: Increases affinity for calcium; when associated with Ala-99. Ref.11

Mutagenesis

99

1

C → A: Increases affinity for calcium; when associated with Ala-81. Ref.11

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

101

Helix Strand Turn

Details...

Helix

4 – 20

17

Beta strand

22 – 24

3

Beta strand

28 – 30

3

Helix

31 – 41

11

Turn

42 – 44

3

Turn

49 – 51

3

Helix

52 – 64

13

Turn

65 – 67

3

Beta strand

68 – 71

4

Helix

72 – 86

15

Helix

88 – 90

3

Sequences

	Sequence		Length	Mass (Da)
	P33764 [UniParc]. Last modified February 1, 1994. Version 1. Checksum: ABCAF4B7E5F2E0A1	FASTA	101	11,713
	10 20 30 40 50 60 MARPLEQAVA AIVCTFQEYA GRCGDKYKLC QAELKELLQK ELATWTPTEF RECDYNKFMS 70 80 90 100 VLDTNKDCEV DFVEYVRSLA CLCLYCHEYF KDCPSEPPCS Q

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Six S100 genes are clustered on human chromosome 1q21: identification of two genes coding for the two previously unreported calcium-binding proteins S100D and S100E." Engelkamp D., Schaefer B.W., Mattei M.-G., Erne P., Heizmann C.W. Proc. Natl. Acad. Sci. U.S.A. 90:6547-6551(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[2]	"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].
[3]	"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].
[4]	"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].
[5]	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].
[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]. Tissue: Lung.
[7]	"Probing the structure of the human Ca2+- and Zn2+-binding protein S100A3: spectroscopic investigations of its transition metal ion complexes, and three-dimensional structural model." Fritz G., Heizmann C.W., Kroneck P.M.H. Biochim. Biophys. Acta 1448:264-276(1998) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[8]	"Characterization of the cysteine-rich calcium-binding S100A3 protein from human hair cuticles." Kizawa K., Troxler H., Kleinert P., Inoue T., Toyoda M., Morohashi M., Heizmann C.W. Biochem. Biophys. Res. Commun. 299:857-862(2002) [PubMed] [Europe PMC] [Abstract] Cited for: REMOVAL OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, TISSUE SPECIFICITY.
[9]	"Specific citrullination causes assembly of a globular S100A3 homotetramer: a putative Ca2+ modulator matures human hair cuticle." Kizawa K., Takahara H., Troxler H., Kleinert P., Mochida U., Heizmann C.W. J. Biol. Chem. 283:5004-5013(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBUNIT, CITRULLINATION AT ARG-51, SUBCELLULAR LOCATION.
[10]	"Metal-free MIRAS phasing: structure of apo-S100A3." Mittl P.R., Fritz G., Sargent D.F., Richmond T.J., Heizmann C.W., Grutter M.G. Acta Crystallogr. D 58:1255-1261(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS).
[11]	"Refined crystal structures of human Ca(2+)/Zn(2+)-binding S100A3 protein characterized by two disulfide bridges." Unno M., Kawasaki T., Takahara H., Heizmann C.W., Kizawa K. J. Mol. Biol. 408:477-490(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS), DISULFIDE BONDS, ZINC-BINDING SITES, MUTAGENESIS OF CYS-30; CYS-68; CSY-81 AND CYS-99.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Z18948 mRNA. Translation: CAA79471.1.
Z18950 Genomic DNA. Translation: CAA79473.1.
BT006955 mRNA. Translation: AAP35601.1.
CR542163 mRNA. Translation: CAG46960.1.
CR542185 mRNA. Translation: CAG46982.1.
BX470102 Genomic DNA. Translation: CAI14755.1.
CH471121 Genomic DNA. Translation: EAW53306.1.
CH471121 Genomic DNA. Translation: EAW53307.1.
BC012893 mRNA. Translation: AAH12893.1.

IPI

IPI00016752.

PIR

C48219.
S70326.

RefSeq

NP_002951.1. NM_002960.1.

UniGene

Hs.557609.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1KSO	X-ray	1.70	A/B	1-101	[»]
3NSI	X-ray	2.15	A/B	1-101	[»]
3NSK	X-ray	1.55	A/B	1-101	[»]
3NSL	X-ray	1.50	A/B/C/D/E/F	2-101	[»]
3NSO	X-ray	1.45	A/B	1-101	[»]

ProteinModelPortal

P33764.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000357701.

Polymorphism databases

DMDM

464729.

Proteomic databases

PaxDb

P33764.

PeptideAtlas

P33764.

PRIDE

P33764.

Protocols and materials databases

DNASU

6274.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000368712; ENSP00000357701; ENSG00000188015.
ENST00000368713; ENSP00000357702; ENSG00000188015.

GeneID

6274.

KEGG

hsa:6274.

UCSC

uc001fca.1. human.

Organism-specific databases

CTD

6274.

GeneCards

GC01M153519.

H-InvDB

HIX0116376.

HGNC

HGNC:10493. S100A3.

HPA

HPA042674.

MIM

176992. gene.

neXtProt

NX_P33764.

PharmGKB

PA34905.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG40471.

HOGENOM

HOG000246968.

HOVERGEN

HBG001479.

InParanoid

P33764.

OMA

YFKDCPP.

OrthoDB

EOG43210N.

PhylomeDB

P33764.

Gene expression databases

Bgee

P33764.

CleanEx

HS_S100A3.

Genevestigator

P33764.

GermOnline

ENSG00000188015. Homo sapiens.

Family and domain databases

Gene3D

1.10.238.10. 1 hit.

InterPro

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

Pfam

PF01023. S_100. 1 hit.
[Graphical view]

PROSITE

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

ProtoNet

Search...

Other

EvolutionaryTrace

P33764.

GenomeRNAi

6274.

NextBio

24351.

SOURCE

Search...

Entry information

Entry name

S10A3_HUMAN

Accession

Primary (citable) accession number: P33764
Secondary accession number(s): D3DV51, Q6FGE4

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	February 1, 1994
Last modified:	May 1, 2013
This is version 125 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.