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Protein

Protein S100-A12

Gene

S100A12

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi16 – 161Zinc or copper
Metal bindingi26 – 261Zinc or copper
Metal bindingi86 – 861Zinc or copper
Metal bindingi90 – 901Zinc or copper

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Calcium bindingi19 – 32141; low affinityPROSITE-ProRule annotationAdd
BLAST
Calcium bindingi62 – 73122; high affinityPROSITE-ProRule annotationAdd
BLAST

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

  • cytokine secretion Source: UniProtKB
  • defense response to bacterium Source: UniProtKB
  • defense response to fungus Source: UniProtKB
  • inflammatory response Source: ProtInc
  • innate immune response Source: UniProtKB
  • killing of cells of other organism Source: UniProtKB-KW
  • mast cell activation Source: UniProtKB
  • monocyte chemotaxis Source: UniProtKB
  • neutrophil chemotaxis Source: UniProtKB
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • positive regulation of inflammatory response Source: UniProtKB
  • positive regulation of MAP kinase activity Source: UniProtKB
  • positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • xenobiotic metabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Antibiotic, Antimicrobial, Fungicide

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity

Keywords - Ligandi

Calcium, Copper, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-1810476. RIP-mediated NFkB activation via ZBP1.
R-HSA-3134963. DEx/H-box helicases activate type I IFN and inflammatory cytokines production.
R-HSA-445989. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
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

HGNCiHGNC:10489. S100A12.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytoskeleton Source: UniProtKB
  • cytosol Source: UniProtKB
  • extracellular region Source: UniProtKB
  • nucleus Source: UniProtKB
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA34901.

Chemistry

DrugBankiDB01025. Amlexanox.
DB00768. Olopatadine.

Polymorphism and mutation databases

BioMutaiS100A12.
DMDMi2507565.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemoved4 Publications
Chaini2 – 9291Protein S100-A12PRO_0000045383Add
BLAST
Peptidei78 – 9215CalciterminPRO_0000004774Add
BLAST

Proteomic databases

PaxDbiP80511.
PeptideAtlasiP80511.
PRIDEiP80511.
TopDownProteomicsiP80511.

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.
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

  • RAGE receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi112191. 1 interaction.
IntActiP80511. 1 interaction.
MINTiMINT-239108.
STRINGi9606.ENSP00000357726.

Structurei

Secondary structure

1
92
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi3 – 1917Combined sources
Beta strandi21 – 244Combined sources
Beta strandi27 – 293Combined sources
Helixi30 – 4011Combined sources
Helixi42 – 476Combined sources
Helixi51 – 588Combined sources
Beta strandi61 – 644Combined sources
Beta strandi67 – 704Combined sources
Helixi71 – 8919Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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. Positions 2-92.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP80511.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini13 – 4836EF-hand 1PROSITE-ProRule annotationAdd
BLAST
Domaini49 – 8436EF-hand 2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni38 – 5316Hinge domainAdd
BLAST

Domaini

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

Sequence similaritiesi

Belongs to the S-100 family.Curated
Contains 2 EF-hand domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410JDIE. Eukaryota.
ENOG411177M. LUCA.
GeneTreeiENSGT00760000119034.
HOGENOMiHOG000246968.
HOVERGENiHBG001479.
InParanoidiP80511.
OMAiNTKDQAT.
OrthoDBiEOG091G12NB.
PhylomeDBiP80511.
TreeFamiTF332727.

Family and domain databases

Gene3Di1.10.238.10. 1 hit.
InterProiIPR011992. EF-hand-dom_pair.
IPR002048. EF_hand_dom.
IPR001751. S100/CaBP-9k_CS.
IPR013787. S100_Ca-bd_sub.
[Graphical view]
PfamiPF01023. S_100. 1 hit.
[Graphical view]
SMARTiSM01394. S_100. 1 hit.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
PROSITEiPS50222. EF_HAND_2. 1 hit.
PS00303. S100_CABP. 1 hit.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti7 – 71H → V AA sequence (PubMed:1860454).Curated
Sequence conflicti12 – 132VN → YS AA sequence (PubMed:1860454).Curated
Sequence conflicti16 – 161H → F AA sequence (PubMed:1860454).Curated

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. Translation: CAI19495.1.
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.

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. Translation: CAI19495.1.
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
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. Positions 2-92.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112191. 1 interaction.
IntActiP80511. 1 interaction.
MINTiMINT-239108.
STRINGi9606.ENSP00000357726.

Chemistry

DrugBankiDB01025. Amlexanox.
DB00768. Olopatadine.

Polymorphism and mutation databases

BioMutaiS100A12.
DMDMi2507565.

Proteomic databases

PaxDbiP80511.
PeptideAtlasiP80511.
PRIDEiP80511.
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.
GeneCardsiS100A12.
HGNCiHGNC:10489. S100A12.
HPAiCAB025872.
HPA002881.
MIMi603112. gene.
neXtProtiNX_P80511.
PharmGKBiPA34901.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410JDIE. Eukaryota.
ENOG411177M. LUCA.
GeneTreeiENSGT00760000119034.
HOGENOMiHOG000246968.
HOVERGENiHBG001479.
InParanoidiP80511.
OMAiNTKDQAT.
OrthoDBiEOG091G12NB.
PhylomeDBiP80511.
TreeFamiTF332727.

Enzyme and pathway databases

ReactomeiR-HSA-1810476. RIP-mediated NFkB activation via ZBP1.
R-HSA-3134963. DEx/H-box helicases activate type I IFN and inflammatory cytokines production.
R-HSA-445989. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
R-HSA-879415. Advanced glycosylation endproduct receptor signaling.
R-HSA-933542. TRAF6 mediated NF-kB activation.

Miscellaneous databases

EvolutionaryTraceiP80511.
GeneWikiiS100A12.
GenomeRNAii6283.
PROiP80511.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000163221.
CleanExiHS_S100A12.
GenevisibleiP80511. HS.

Family and domain databases

Gene3Di1.10.238.10. 1 hit.
InterProiIPR011992. EF-hand-dom_pair.
IPR002048. EF_hand_dom.
IPR001751. S100/CaBP-9k_CS.
IPR013787. S100_Ca-bd_sub.
[Graphical view]
PfamiPF01023. S_100. 1 hit.
[Graphical view]
SMARTiSM01394. S_100. 1 hit.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
PROSITEiPS50222. EF_HAND_2. 1 hit.
PS00303. S100_CABP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiS10AC_HUMAN
AccessioniPrimary (citable) accession number: P80511
Secondary accession number(s): P83219, Q5SY66, Q7M4R1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 23, 2007
Last modified: September 7, 2016
This is version 161 of the entry and version 2 of the sequence. [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. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.