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P80511 (S10AC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 143. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein S100-A12
Alternative name(s):
CGRP
Calcium-binding protein in amniotic fluid 1
Short name=CAAF1
Calgranulin-C
Short name=CAGC
Extracellular newly identified RAGE-binding protein
Short name=EN-RAGE
Migration inhibitory factor-related protein 6
Short name=MRP-6
Short name=p6
Neutrophil S100 protein
S100 calcium-binding protein A12

Cleaved into the following chain:

  1. Calcitermin
Gene names
Name:S100A12
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length92 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

S100A12 is a calcium-, zinc- and copper-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. Its proinflammatory activity involves recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration. Acts as an alarmin or a danger associated molecular pattern (DAMP) molecule and stimulates innate immune cells via binding to receptor for advanced glycation endproducts (AGER). Binding to AGER activates the MAP-kinase and NF-kappa-B signaling pathways leading to production of proinflammatory cytokines and up-regulation of cell adhesion molecules ICAM1 and VCAM1. Acts as a monocyte and mast cell chemoattractant. Can stimulate mast cell degranulation and activation which generates chemokines, histamine and cytokines inducing further leukocyte recruitment to the sites of inflammation. Can inhibit the activity of matrix metalloproteinases; MMP2, MMP3 and MMP9 by chelating Zn2+ from their active sites. Possesses filariacidal and filariastatic activity. Calcitermin possesses antifungal activity against C.albicans and is also active against E.coli and P.aeruginosa but not L.monocytogenes and S.aureus. Ref.9 Ref.12 Ref.13 Ref.16

Subunit structure

Homodimer. Homooligomer (tetramer or hexamer) in the presence of calcium, zinc and copper ions. Interacts with AGER and both calcium and zinc are essential for the interaction. Interacts with CACYBP in a calcium-dependent manner. Ref.10 Ref.16

Subcellular location

Secreted. Cytoplasm. Cytoplasmcytoskeleton. Cell membrane; Peripheral membrane protein. Note: Predominantly localized in the cytoplasm. Upon elevation of the intracellular calcium level, translocated from the cytoplasm to the cytoskeleton and the cell membrane. Upon neutrophil activation is secreted via a microtubule-mediated, alternative pathway. Ref.19

Tissue specificity

Predominantly expressed by neutrophils, monocytes and activated macrophages. Expressed by eosinophils and macrophages in asthmatic airways in regions where mast cells accumulate. Found in high concentrations in the serum of patients suffering from various inflammatory disorders, such as rheumatoid arthritis, psoriatic arthritis, Crohn's disease, ulcerative colitis, and Kawasaki disease.

Domain

The hinge domain contributes significantly to its chemotactic properties. Ref.13

Sequence similarities

Belongs to the S-101 family.

Contains 2 EF-hand domains.

Mass spectrometry

Molecular mass is 10444 Da from positions 2 - 92. Determined by ESI. Ref.9

Molecular mass is 1688.9 Da from positions 78 - 92. Determined by MALDI. Ref.9

Ontologies

Keywords
   Biological processImmunity
Inflammatory response
Innate immunity
   Cellular componentCell membrane
Cytoplasm
Cytoskeleton
Membrane
Secreted
   DomainRepeat
   LigandCalcium
Copper
Metal-binding
Zinc
   Molecular functionAntibiotic
Antimicrobial
Fungicide
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcytokine secretion

Traceable author statement Ref.14. Source: UniProtKB

defense response to bacterium

Traceable author statement Ref.14. Source: UniProtKB

defense response to fungus

Inferred from direct assay Ref.9. Source: UniProtKB

inflammatory response

Traceable author statement Ref.5. Source: ProtInc

innate immune response

Traceable author statement Ref.14. Source: UniProtKB

killing of cells of other organism

Inferred from electronic annotation. Source: UniProtKB-KW

mast cell activation

Traceable author statement Ref.14. Source: UniProtKB

monocyte chemotaxis

Traceable author statement Ref.14. Source: UniProtKB

neutrophil chemotaxis

Traceable author statement Ref.14. Source: UniProtKB

positive regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from direct assay PubMed 15033494. Source: UniProtKB

positive regulation of MAP kinase activity

Traceable author statement Ref.14. Source: UniProtKB

positive regulation of NF-kappaB transcription factor activity

Traceable author statement Ref.14. Source: UniProtKB

positive regulation of inflammatory response

Traceable author statement Ref.14. Source: UniProtKB

xenobiotic metabolic process

Inferred from direct assay Ref.9. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 15033494. Source: UniProtKB

cytoskeleton

Traceable author statement Ref.14. Source: UniProtKB

cytosol

Traceable author statement Ref.14. Source: UniProtKB

extracellular region

Traceable author statement Ref.14. Source: UniProtKB

nucleus

Inferred from direct assay PubMed 15033494. Source: UniProtKB

plasma membrane

Traceable author statement Ref.14. Source: UniProtKB

   Molecular_functionRAGE receptor binding

Inferred from direct assay Ref.16. Source: UniProtKB

calcium ion binding

Traceable author statement Ref.14. Source: UniProtKB

copper ion binding

Traceable author statement Ref.14. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.16. Source: UniProtKB

zinc ion binding

Traceable author statement Ref.9Ref.14. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.5 Ref.6 Ref.7 Ref.8
Chain2 – 9291Protein S100-A12
PRO_0000045383
Peptide78 – 9215Calcitermin Ref.9
PRO_0000004774

Regions

Domain13 – 4836EF-hand 1
Domain49 – 8436EF-hand 2
Calcium binding19 – 32141; low affinity By similarity
Calcium binding62 – 73122; high affinity By similarity
Region38 – 5316Hinge domain

Sites

Metal binding161Zinc or copper
Metal binding261Zinc or copper
Metal binding861Zinc or copper
Metal binding901Zinc or copper

Experimental info

Sequence conflict71H → V AA sequence Ref.8
Sequence conflict12 – 132VN → YS AA sequence Ref.8
Sequence conflict161H → F AA sequence Ref.8

Secondary structure

................. 92
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P80511 [UniParc].

Last modified January 23, 2007. Version 2.
Checksum: 52AF75A31BDC222A

FASTA9210,575
        10         20         30         40         50         60 
MTKLEEHLEG IVNIFHQYSV RKGHFDTLSK GELKQLLTKE LANTIKNIKD KAVIDEIFQG 

        70         80         90 
LDANQDEQVD FQEFISLVAI ALKAAHYHTH KE 

« Hide

References

« Hide 'large scale' references
[1]"Human CAAF1 gene -- molecular cloning, gene structure, and chromosome mapping."
Yamamura T., Hitomi J., Nagasaki K., Suzuki M., Takahashi E., Saito S., Tsukada T., Yamaguchi K.
Biochem. Biophys. Res. Commun. 221:356-360(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[2]"Characterization of the human S100A12 (calgranulin C, p6, CAAF1, CGRP) gene, a new member of the S100 gene cluster on chromosome 1q21."
Wicki R., Marenholz I., Mischke D., Schaefer B.W., Heizmann C.W.
Cell Calcium 20:459-464(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[3]"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].
[4]"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: Blood.
[5]"Host-parasite interaction in human onchocerciasis: identification and sequence analysis of a novel human calgranulin."
Marti T., Erttmann K.D., Gallin M.Y.
Biochem. Biophys. Res. Commun. 221:454-458(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-92.
[6]"Amino acid sequence determination of human S100A12 (P6, calgranulin C, CGRP, CAAF1) by tandem mass spectrometry."
Ilg E.C., Troxler H., Buergisser D.M., Kuster T., Markert M., Guignard F., Hunziker P., Birchler N., Heizmann C.W.
Biochem. Biophys. Res. Commun. 225:146-150(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-92.
Tissue: Neutrophil.
[7]"Identification and characterization of a novel human neutrophil protein related to the S100 family."
Guignard F., Mauel J., Markert M.
Biochem. J. 309:395-401(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-21.
[8]"Identification, isolation, and partial characterization of a 7.5-kDa surfactant-associated protein."
Singh G., Katyal S.L., Brown W.E., Kennedy A.L., Wong-Chong M.-L., Gottron S.A.
Exp. Lung Res. 17:559-567(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-16.
[9]"Calcitermin, a novel antimicrobial peptide isolated from human airway secretions."
Cole A.M., Kim Y.-H., Tahk S., Hong T., Weis P., Waring A.J., Ganz T.
FEBS Lett. 504:5-10(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 78-92, FUNCTION AS AN ANTIMICROBIAL PROTEIN, MASS SPECTROMETRY.
Tissue: Nasal mucus.
[10]"CacyBP/SIP, a calcyclin and Siah-1-interacting protein, binds EF-hand proteins of the S100 family."
Filipek A., Jastrzebska B., Nowotny M., Kuznicki J.
J. Biol. Chem. 277:28848-28852(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CACYBP.
[11]"Multiple structural states of S100A12: A key to its functional diversity."
Moroz O.V., Dodson G.G., Wilson K.S., Lukanidin E., Bronstein I.B.
Microsc. Res. Tech. 60:581-592(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[12]"S100A12 provokes mast cell activation: a potential amplification pathway in asthma and innate immunity."
Yang Z., Yan W.X., Cai H., Tedla N., Armishaw C., Di Girolamo N., Wang H.W., Hampartzoumian T., Simpson J.L., Gibson P.G., Hunt J., Hart P., Hughes J.M., Perry M.A., Alewood P.F., Geczy C.L.
J. Allergy Clin. Immunol. 119:106-114(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[13]"Mast cell and monocyte recruitment by S100A12 and its hinge domain."
Yan W.X., Armishaw C., Goyette J., Yang Z., Cai H., Alewood P., Geczy C.L.
J. Biol. Chem. 283:13035-13043(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DOMAIN HINGE.
[14]"Human S100A12: a novel key player in inflammation?"
Pietzsch J., Hoppmann S.
Amino Acids 36:381-389(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[15]"Anti-infective protective properties of S100 calgranulins."
Hsu K., Champaiboon C., Guenther B.D., Sorenson B.S., Khammanivong A., Ross K.F., Geczy C.L., Herzberg M.C.
Antiinflamm. Antiallergy Agents Med. Chem. 8:290-305(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[16]"Both Ca2+ and Zn2+ are essential for S100A12 protein oligomerization and function."
Moroz O.V., Burkitt W., Wittkowski H., He W., Ianoul A., Novitskaya V., Xie J., Polyakova O., Lednev I.K., Shekhtman A., Derrick P.J., Bjoerk P., Foell D., Bronstein I.B.
BMC Biochem. 10:11-11(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, INTERACTION WITH AGER.
[17]"S100 Calgranulins in inflammatory arthritis."
Perera C., McNeil H.P., Geczy C.L.
Immunol. Cell Biol. 88:41-49(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[18]"Inflammation-associated S100 proteins: new mechanisms that regulate function."
Goyette J., Geczy C.L.
Amino Acids 41:821-842(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[19]"The role of S100A12 as a systemic marker of inflammation."
Meijer B., Gearry R.B., Day A.S.
Int. J. Inflamm. 2012:907078-907078(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW, SUBCELLULAR LOCATION.
[20]"The three-dimensional structure of human S100A12."
Moroz O.V., Antson A.A., Murshudov G.N., Maitland N.J., Dodson G.G., Wilson K.S., Skibshoj I., Lukanidin E.M., Bronstein I.B.
Acta Crystallogr. D 57:20-29(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS).
[21]"Structure of the human S100A12-copper complex: implications for host-parasite defence."
Moroz O.V., Antson A.A., Grist S.J., Maitland N.J., Dodson G.G., Wilson K.S., Lukanidin E., Bronstein I.B.
Acta Crystallogr. D 59:859-867(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.19 ANGSTROMS), COPPER-BINDING.
[22]"The crystal structures of human S100A12 in apo form and in complex with zinc: new insights into S100A12 oligomerisation."
Moroz O.V., Blagova E.V., Wilkinson A.J., Wilson K.S., Bronstein I.B.
J. Mol. Biol. 391:536-551(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.88 ANGSTROMS) OF 2-92, ZINC-BINDING.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D49549 mRNA. Translation: BAA08497.1.
D83657 Genomic DNA. Translation: BAA12030.1.
D83664 mRNA. Translation: BAA12036.1.
X97859 mRNA. Translation: CAA66453.1.
X98289, X98290 Genomic DNA. Translation: CAB94792.1.
AL591704 Genomic DNA. Translation: CAI19495.1.
BC070294 mRNA. Translation: AAH70294.1.
CCDSCCDS1037.1.
PIRA61522.
JC4712.
RefSeqNP_005612.1. NM_005621.1.
UniGeneHs.19413.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1E8AX-ray1.95A/B2-92[»]
1GQMX-ray2.70A/B/C/D/E/F/G/H/I/J/K/L2-92[»]
1ODBX-ray2.19A/B/C/D/E/F2-92[»]
2M9GNMR-A/B1-92[»]
2WC8X-ray1.88A/B/C/D2-92[»]
2WCBX-ray1.73A/B2-92[»]
2WCEX-ray1.77A/B2-92[»]
2WCFX-ray2.78A/B/C/D/E/F2-92[»]
ProteinModelPortalP80511.
SMRP80511. Positions 2-92.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112191. 1 interaction.
IntActP80511. 1 interaction.
MINTMINT-239108.
STRING9606.ENSP00000357726.

Chemistry

DrugBankDB01025. Amlexanox.

PTM databases

PhosphoSiteP80511.

Polymorphism databases

DMDM2507565.

Proteomic databases

PaxDbP80511.
PRIDEP80511.

Protocols and materials databases

DNASU6283.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000368737; ENSP00000357726; ENSG00000163221.
GeneID6283.
KEGGhsa:6283.
UCSCuc001fbr.1. human.

Organism-specific databases

CTD6283.
GeneCardsGC01M153346.
HGNCHGNC:10489. S100A12.
HPACAB025872.
HPA002881.
MIM603112. gene.
neXtProtNX_P80511.
PharmGKBPA34901.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG87949.
HOGENOMHOG000246968.
HOVERGENHBG001479.
InParanoidP80511.
OMAHYHTHKE.
OrthoDBEOG7M3J2R.
PhylomeDBP80511.
TreeFamTF332727.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

BgeeP80511.
CleanExHS_S100A12.
GenevestigatorP80511.

Family and domain databases

Gene3D1.10.238.10. 1 hit.
InterProIPR011992. EF-hand-dom_pair.
IPR002048. EF_hand_dom.
IPR001751. S100/CaBP-9k_CS.
IPR013787. S100_Ca-bd_sub.
[Graphical view]
PfamPF01023. S_100. 1 hit.
[Graphical view]
PROSITEPS50222. EF_HAND_2. 1 hit.
PS00303. S100_CABP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP80511.
GeneWikiS100A12.
GenomeRNAi6283.
NextBio24389.
PROP80511.
SOURCESearch...

Entry information

Entry nameS10AC_HUMAN
AccessionPrimary (citable) accession number: P80511
Secondary accession number(s): P83219, Q5SY66, Q7M4R1
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 143 of the entry and version 2 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 chromosome 1

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