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Protein

Protein S100-A12

Gene

S100A12

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi16Zinc or copper1
Metal bindingi26Zinc or copper1
Metal bindingi86Zinc or copper1
Metal bindingi90Zinc or copper1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi19 – 321; low affinityPROSITE-ProRule annotationAdd BLAST14
Calcium bindingi62 – 732; high affinityPROSITE-ProRule annotationAdd BLAST12

GO - Molecular functioni

  • calcium ion binding Source: UniProtKB
  • copper ion binding Source: UniProtKB
  • RAGE receptor binding Source: UniProtKB
  • zinc ion binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionAntibiotic, Antimicrobial, Fungicide
Biological processImmunity, Inflammatory response, Innate immunity
LigandCalcium, Copper, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-445989 TAK1 activates NFkB by phosphorylation and activation of IKKs complex
R-HSA-6798695 Neutrophil degranulation
R-HSA-879415 Advanced glycosylation endproduct receptor signaling
R-HSA-933542 TRAF6 mediated NF-kB activation

Names & Taxonomyi

Protein namesi
Recommended 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:
Gene namesi
Name:S100A12
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000163221.8
HGNCiHGNC:10489 S100A12
MIMi603112 gene
neXtProtiNX_P80511

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi6283
OpenTargetsiENSG00000163221
PharmGKBiPA34901

Chemistry databases

DrugBankiDB01025 Amlexanox
DB00768 Olopatadine

Polymorphism and mutation databases

BioMutaiS100A12
DMDMi2507565

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved4 Publications
ChainiPRO_00000453832 – 92Protein S100-A12Add BLAST91
PeptideiPRO_000000477478 – 92CalciterminAdd BLAST15

Proteomic databases

PaxDbiP80511
PeptideAtlasiP80511
PRIDEiP80511
ProteomicsDBi57687
TopDownProteomicsiP80511

PTM databases

iPTMnetiP80511
PhosphoSitePlusiP80511

Expressioni

Tissue specificityi

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.

Gene expression databases

BgeeiENSG00000163221 Expressed in 151 organ(s), highest expression level in bone marrow
CleanExiHS_S100A12
GenevisibleiP80511 HS

Organism-specific databases

HPAiCAB025872
HPA002881

Interactioni

Subunit structurei

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.2 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112191, 1 interactor
IntActiP80511, 1 interactor
STRINGi9606.ENSP00000357726

Structurei

Secondary structure

192
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP80511
SMRiP80511
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP80511

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini13 – 48EF-hand 1PROSITE-ProRule annotationAdd BLAST36
Domaini49 – 84EF-hand 2PROSITE-ProRule annotationAdd BLAST36

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni38 – 53Hinge domainAdd BLAST16

Domaini

The hinge domain contributes significantly to its chemotactic properties.1 Publication

Sequence similaritiesi

Belongs to the S-100 family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410JDIE Eukaryota
ENOG411177M LUCA
GeneTreeiENSGT00910000144230
HOGENOMiHOG000246968
HOVERGENiHBG001479
InParanoidiP80511
OMAiNTKDQAT
OrthoDBiEOG091G12NB
PhylomeDBiP80511
TreeFamiTF332727

Family and domain databases

InterProiView protein in InterPro
IPR011992 EF-hand-dom_pair
IPR002048 EF_hand_dom
IPR001751 S100/CaBP-9k_CS
IPR013787 S100_Ca-bd_sub
PfamiView protein in Pfam
PF01023 S_100, 1 hit
SMARTiView protein in SMART
SM01394 S_100, 1 hit
SUPFAMiSSF47473 SSF47473, 1 hit
PROSITEiView protein in PROSITE
PS50222 EF_HAND_2, 1 hit
PS00303 S100_CABP, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P80511-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MTKLEEHLEG IVNIFHQYSV RKGHFDTLSK GELKQLLTKE LANTIKNIKD
60 70 80 90
KAVIDEIFQG LDANQDEQVD FQEFISLVAI ALKAAHYHTH KE
Length:92
Mass (Da):10,575
Last modified:January 23, 2007 - v2
Checksum:i52AF75A31BDC222A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti7H → V AA sequence (PubMed:1860454).Curated1
Sequence conflicti12 – 13VN → YS AA sequence (PubMed:1860454).Curated2
Sequence conflicti16H → F AA sequence (PubMed:1860454).Curated1

Mass spectrometryi

Molecular mass is 10444 Da from positions 2 - 92. Determined by ESI. 1 Publication
Molecular mass is 1688.9 Da from positions 78 - 92. Determined by MALDI. 1 Publication

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 No translation available.
BC070294 mRNA Translation: AAH70294.1
CCDSiCCDS1037.1
PIRiA61522
JC4712
RefSeqiNP_005612.1, NM_005621.1
UniGeneiHs.19413

Genome annotation databases

EnsembliENST00000368737; ENSP00000357726; ENSG00000163221
GeneIDi6283
KEGGihsa:6283
UCSCiuc001fbr.2 human

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 No translation available.
BC070294 mRNA Translation: AAH70294.1
CCDSiCCDS1037.1
PIRiA61522
JC4712
RefSeqiNP_005612.1, NM_005621.1
UniGeneiHs.19413

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
ProteinModelPortaliP80511
SMRiP80511
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112191, 1 interactor
IntActiP80511, 1 interactor
STRINGi9606.ENSP00000357726

Chemistry databases

DrugBankiDB01025 Amlexanox
DB00768 Olopatadine

PTM databases

iPTMnetiP80511
PhosphoSitePlusiP80511

Polymorphism and mutation databases

BioMutaiS100A12
DMDMi2507565

Proteomic databases

PaxDbiP80511
PeptideAtlasiP80511
PRIDEiP80511
ProteomicsDBi57687
TopDownProteomicsiP80511

Protocols and materials databases

DNASUi6283
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000368737; ENSP00000357726; ENSG00000163221
GeneIDi6283
KEGGihsa:6283
UCSCiuc001fbr.2 human

Organism-specific databases

CTDi6283
DisGeNETi6283
EuPathDBiHostDB:ENSG00000163221.8
GeneCardsiS100A12
HGNCiHGNC:10489 S100A12
HPAiCAB025872
HPA002881
MIMi603112 gene
neXtProtiNX_P80511
OpenTargetsiENSG00000163221
PharmGKBiPA34901
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410JDIE Eukaryota
ENOG411177M LUCA
GeneTreeiENSGT00910000144230
HOGENOMiHOG000246968
HOVERGENiHBG001479
InParanoidiP80511
OMAiNTKDQAT
OrthoDBiEOG091G12NB
PhylomeDBiP80511
TreeFamiTF332727

Enzyme and pathway databases

ReactomeiR-HSA-445989 TAK1 activates NFkB by phosphorylation and activation of IKKs complex
R-HSA-6798695 Neutrophil degranulation
R-HSA-879415 Advanced glycosylation endproduct receptor signaling
R-HSA-933542 TRAF6 mediated NF-kB activation

Miscellaneous databases

EvolutionaryTraceiP80511
GeneWikiiS100A12
GenomeRNAii6283
PROiPR:P80511
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000163221 Expressed in 151 organ(s), highest expression level in bone marrow
CleanExiHS_S100A12
GenevisibleiP80511 HS

Family and domain databases

InterProiView protein in InterPro
IPR011992 EF-hand-dom_pair
IPR002048 EF_hand_dom
IPR001751 S100/CaBP-9k_CS
IPR013787 S100_Ca-bd_sub
PfamiView protein in Pfam
PF01023 S_100, 1 hit
SMARTiView protein in SMART
SM01394 S_100, 1 hit
SUPFAMiSSF47473 SSF47473, 1 hit
PROSITEiView protein in PROSITE
PS50222 EF_HAND_2, 1 hit
PS00303 S100_CABP, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiS10AC_HUMAN
AccessioniPrimary (citable) accession number: P80511
Secondary accession number(s): P83219, Q5SY66, Q7M4R1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 23, 2007
Last modified: September 12, 2018
This is version 173 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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