UniProtKB - P80511 (S10AC_HUMAN)
Protein S100-A12
S100A12
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 pro-inflammatory 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 pro-inflammatory 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 PublicationsSites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 16 | Copper; via tele nitrogenCombined sources1 Publication | 1 | |
Metal bindingi | 16 | Zinc; via tele nitrogenCombined sources1 Publication | 1 | |
Metal bindingi | 19 | Calcium 1; via carbonyl oxygen; low affinityCombined sources2 Publications | 1 | |
Metal bindingi | 22 | Calcium 1; via carbonyl oxygen; low affinityCombined sources2 Publications | 1 | |
Metal bindingi | 24 | Calcium 1; via carbonyl oxygen; low affinityCombined sources2 Publications | 1 | |
Metal bindingi | 26 | CopperCombined sources1 Publication | 1 | |
Metal bindingi | 26 | ZincCombined sources1 Publication | 1 | |
Metal bindingi | 27 | Calcium 1; via carbonyl oxygen; low affinityCombined sources2 Publications | 1 | |
Metal bindingi | 32 | Calcium 1; low affinityCombined sources2 Publications | 1 | |
Metal bindingi | 62 | Calcium 2; high affinityCombined sources2 Publications | 1 | |
Metal bindingi | 64 | Calcium 2; high affinityCombined sources2 Publications | 1 | |
Metal bindingi | 66 | Calcium 2; high affinityCombined sources2 Publications | 1 | |
Metal bindingi | 68 | Calcium 2; via carbonyl oxygen; high affinityCombined sources2 Publications | 1 | |
Metal bindingi | 73 | Calcium 2; high affinityCombined sources2 Publications | 1 | |
Metal bindingi | 86 | Copper; via tele nitrogenCombined sources1 Publication | 1 | |
Metal bindingi | 86 | Zinc; via tele nitrogenCombined sources1 Publication | 1 | |
Metal bindingi | 90 | Copper; via tele nitrogenCombined sources1 Publication | 1 | |
Metal bindingi | 90 | Zinc; via tele nitrogenCombined sources1 Publication | 1 |
GO - Molecular functioni
- calcium-dependent protein binding Source: GO_Central
- calcium ion binding Source: GO_Central
- copper ion binding Source: UniProtKB
- RAGE receptor binding Source: UniProtKB
- zinc ion binding Source: UniProtKB
GO - Biological processi
- antimicrobial humoral immune response mediated by antimicrobial peptide 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 another organism Source: UniProtKB
- 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
Keywordsi
Molecular function | Antibiotic, Antimicrobial, Fungicide |
Biological process | Immunity, Inflammatory response, Innate immunity |
Ligand | Calcium, Copper, Metal-binding, Zinc |
Enzyme and pathway databases
PathwayCommonsi | P80511 |
Reactomei | R-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 |
SignaLinki | P80511 |
Names & Taxonomyi
Protein namesi | Recommended name: Protein S100-A12Alternative 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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:10489, S100A12 |
MIMi | 603112, gene |
neXtProti | NX_P80511 |
VEuPathDBi | HostDB:ENSG00000163221 |
Subcellular locationi
Plasma membrane
- Cell membrane 1 Publication; Peripheral membrane protein 1 Publication
Cytoskeleton
- cytoskeleton 1 Publication
Cytoplasm and Cytosol
- Cytoplasm 1 Publication
Extracellular region or secreted
- Secreted 1 Publication
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.
Cytoskeleton
- cytoskeleton Source: UniProtKB
Cytosol
- cytosol Source: UniProtKB
Extracellular region or secreted
- extracellular region Source: UniProtKB
- extracellular space Source: GO_Central
Nucleus
- nucleus Source: UniProtKB
Plasma Membrane
- plasma membrane Source: UniProtKB
Other locations
- cytoplasm Source: UniProtKB
- secretory granule lumen Source: Reactome
Keywords - Cellular componenti
Cell membrane, Cytoplasm, Cytoskeleton, Membrane, SecretedPathology & Biotechi
Organism-specific databases
DisGeNETi | 6283 |
OpenTargetsi | ENSG00000163221 |
PharmGKBi | PA34901 |
Miscellaneous databases
Pharosi | P80511, Tbio |
Chemistry databases
DrugBanki | DB01025, Amlexanox DB00768, Olopatadine |
Genetic variation databases
BioMutai | S100A12 |
DMDMi | 2507565 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | Removed4 Publications | |||
ChainiPRO_0000045383 | 2 – 92 | Protein S100-A12Add BLAST | 91 | |
PeptideiPRO_0000004774 | 78 – 92 | CalciterminAdd BLAST | 15 |
Proteomic databases
CPTACi | non-CPTAC-1154 |
jPOSTi | P80511 |
MassIVEi | P80511 |
PaxDbi | P80511 |
PeptideAtlasi | P80511 |
PRIDEi | P80511 |
ProteomicsDBi | 57687 |
TopDownProteomicsi | P80511 |
PTM databases
iPTMneti | P80511 |
PhosphoSitePlusi | P80511 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000163221, Expressed in bone marrow and 166 other tissues |
Genevisiblei | P80511, HS |
Organism-specific databases
HPAi | ENSG00000163221, Tissue enriched (bone) |
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 PublicationsBinary interactionsi
P80511
With | #Exp. | IntAct |
---|---|---|
AGER [Q15109] | 2 | EBI-2823305,EBI-1646426 |
itself | 6 | EBI-2823305,EBI-2823305 |
GO - Molecular functioni
- calcium-dependent protein binding Source: GO_Central
- RAGE receptor binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 112191, 3 interactors |
IntActi | P80511, 4 interactors |
STRINGi | 9606.ENSP00000357726 |
Miscellaneous databases
RNActi | P80511, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | P80511 |
BMRBi | P80511 |
SMRi | P80511 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P80511 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 13 – 48 | EF-hand 1CuratedAdd BLAST | 36 | |
Domaini | 49 – 84 | EF-hand 2PROSITE-ProRule annotationAdd BLAST | 36 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 38 – 53 | Hinge domainAdd BLAST | 16 |
Domaini
Sequence similaritiesi
Keywords - Domaini
RepeatPhylogenomic databases
eggNOGi | ENOG502SA01, Eukaryota |
GeneTreei | ENSGT00940000162189 |
HOGENOMi | CLU_138624_6_2_1 |
InParanoidi | P80511 |
OMAi | TKLEDHM |
OrthoDBi | 1521098at2759 |
PhylomeDBi | P80511 |
TreeFami | TF332727 |
Family and domain databases
InterProi | View protein in InterPro IPR011992, EF-hand-dom_pair IPR002048, EF_hand_dom IPR001751, S100/CaBP7/8-like_CS IPR013787, S100_Ca-bd_sub |
Pfami | View protein in Pfam PF01023, S_100, 1 hit |
SMARTi | View protein in SMART SM01394, S_100, 1 hit |
SUPFAMi | SSF47473, SSF47473, 1 hit |
PROSITEi | View protein in PROSITE PS50222, EF_HAND_2, 1 hit PS00303, S100_CABP, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MTKLEEHLEG IVNIFHQYSV RKGHFDTLSK GELKQLLTKE LANTIKNIKD
60 70 80 90
KAVIDEIFQG LDANQDEQVD FQEFISLVAI ALKAAHYHTH KE
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 7 | H → V AA sequence (PubMed:1860454).Curated | 1 | |
Sequence conflicti | 12 – 13 | VN → YS AA sequence (PubMed:1860454).Curated | 2 | |
Sequence conflicti | 16 | H → F AA sequence (PubMed:1860454).Curated | 1 |
Mass spectrometryi
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 |
CCDSi | CCDS1037.1 |
PIRi | A61522 JC4712 |
RefSeqi | NP_005612.1, NM_005621.1 |
Genome annotation databases
Ensembli | ENST00000368737.5; ENSP00000357726.3; ENSG00000163221.9 |
GeneIDi | 6283 |
KEGGi | hsa:6283 |
MANE-Selecti | ENST00000368737.5; ENSP00000357726.3; NM_005621.2; NP_005612.1 |
UCSCi | uc001fbr.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 |
CCDSi | CCDS1037.1 |
PIRi | A61522 JC4712 |
RefSeqi | NP_005612.1, NM_005621.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1E8A | X-ray | 1.95 | A/B | 2-92 | [»] | |
1GQM | X-ray | 2.70 | A/B/C/D/E/F/G/H/I/J/K/L | 2-92 | [»] | |
1ODB | X-ray | 2.19 | A/B/C/D/E/F | 2-92 | [»] | |
2M9G | NMR | - | A/B | 1-92 | [»] | |
2WC8 | X-ray | 1.88 | A/B/C/D | 2-92 | [»] | |
2WCB | X-ray | 1.73 | A/B | 2-92 | [»] | |
2WCE | X-ray | 1.77 | A/B | 2-92 | [»] | |
2WCF | X-ray | 2.78 | A/B/C/D/E/F | 2-92 | [»] | |
AlphaFoldDBi | P80511 | |||||
BMRBi | P80511 | |||||
SMRi | P80511 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 112191, 3 interactors |
IntActi | P80511, 4 interactors |
STRINGi | 9606.ENSP00000357726 |
Chemistry databases
DrugBanki | DB01025, Amlexanox DB00768, Olopatadine |
PTM databases
iPTMneti | P80511 |
PhosphoSitePlusi | P80511 |
Genetic variation databases
BioMutai | S100A12 |
DMDMi | 2507565 |
Proteomic databases
CPTACi | non-CPTAC-1154 |
jPOSTi | P80511 |
MassIVEi | P80511 |
PaxDbi | P80511 |
PeptideAtlasi | P80511 |
PRIDEi | P80511 |
ProteomicsDBi | 57687 |
TopDownProteomicsi | P80511 |
Protocols and materials databases
Antibodypediai | 1076, 345 antibodies from 30 providers |
CPTCi | P80511, 1 antibody |
DNASUi | 6283 |
Genome annotation databases
Ensembli | ENST00000368737.5; ENSP00000357726.3; ENSG00000163221.9 |
GeneIDi | 6283 |
KEGGi | hsa:6283 |
MANE-Selecti | ENST00000368737.5; ENSP00000357726.3; NM_005621.2; NP_005612.1 |
UCSCi | uc001fbr.2, human |
Organism-specific databases
CTDi | 6283 |
DisGeNETi | 6283 |
GeneCardsi | S100A12 |
HGNCi | HGNC:10489, S100A12 |
HPAi | ENSG00000163221, Tissue enriched (bone) |
MIMi | 603112, gene |
neXtProti | NX_P80511 |
OpenTargetsi | ENSG00000163221 |
PharmGKBi | PA34901 |
VEuPathDBi | HostDB:ENSG00000163221 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502SA01, Eukaryota |
GeneTreei | ENSGT00940000162189 |
HOGENOMi | CLU_138624_6_2_1 |
InParanoidi | P80511 |
OMAi | TKLEDHM |
OrthoDBi | 1521098at2759 |
PhylomeDBi | P80511 |
TreeFami | TF332727 |
Enzyme and pathway databases
PathwayCommonsi | P80511 |
Reactomei | R-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 |
SignaLinki | P80511 |
Miscellaneous databases
BioGRID-ORCSi | 6283, 13 hits in 1076 CRISPR screens |
EvolutionaryTracei | P80511 |
GeneWikii | S100A12 |
GenomeRNAii | 6283 |
Pharosi | P80511, Tbio |
PROi | PR:P80511 |
RNActi | P80511, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000163221, Expressed in bone marrow and 166 other tissues |
Genevisiblei | P80511, HS |
Family and domain databases
InterProi | View protein in InterPro IPR011992, EF-hand-dom_pair IPR002048, EF_hand_dom IPR001751, S100/CaBP7/8-like_CS IPR013787, S100_Ca-bd_sub |
Pfami | View protein in Pfam PF01023, S_100, 1 hit |
SMARTi | View protein in SMART SM01394, S_100, 1 hit |
SUPFAMi | SSF47473, SSF47473, 1 hit |
PROSITEi | View protein in PROSITE PS50222, EF_HAND_2, 1 hit PS00303, S100_CABP, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | S10AC_HUMAN | |
Accessioni | P80511Primary (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: | May 25, 2022 | |
This is version 193 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families