S10AC_BOVIN
ID S10AC_BOVIN Reviewed; 92 AA.
AC P79105; Q3T070; Q9TR16;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Protein S100-A12;
DE AltName: Full=Calcium-binding protein in amniotic fluid 1;
DE Short=CAAF1;
DE AltName: Full=Calgranulin-C;
DE Short=CAGC;
DE AltName: Full=Cornea-associated antigen;
DE Short=CO-AG;
DE AltName: Full=Extracellular newly identified RAGE-binding protein;
DE Short=EN-RAGE;
DE AltName: Full=RAGE-binding protein;
DE AltName: Full=S100 calcium-binding protein A12;
GN Name=S100A12; Synonyms=CAAF1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Esophagus;
RX PubMed=8718672; DOI=10.1242/jcs.109.4.805;
RA Hitomi J., Yamaguchi K., Kikuchi Y., Kimura T., Maruyama K., Nagasaki K.;
RT "A novel calcium-binding protein in amniotic fluid, CAAF1: its molecular
RT cloning and tissue distribution.";
RL J. Cell Sci. 109:805-815(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 1-51 AND 66-83, INTERACTION
RP WITH AGER, AND TISSUE SPECIFICITY.
RC TISSUE=Lung;
RX PubMed=10399917; DOI=10.1016/s0092-8674(00)80801-6;
RA Hofmann M.A., Drury S., Fu C., Qu W., Taguchi A., Lu Y., Avila C.,
RA Kambham N., Bierhaus A., Nawroth P., Neurath M.F., Slattery T., Beach D.,
RA McClary J., Nagashima M., Morser J., Stern D., Schmidt A.M.;
RT "RAGE mediates a novel proinflammatory axis: a central cell surface
RT receptor for S100/calgranulin polypeptides.";
RL Cell 97:889-901(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Liver;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP PROTEIN SEQUENCE OF 2-71.
RC TISSUE=Corneal stroma;
RX PubMed=8603881;
RA Liu S.H., Gottsch J.D.;
RT "Amino acid sequence of an immunogenic corneal stromal protein.";
RL Invest. Ophthalmol. Vis. Sci. 37:944-948(1996).
CC -!- FUNCTION: S100A12 is a calcium-, zinc- and copper-binding protein which
CC plays a prominent role in the regulation of inflammatory processes and
CC immune response. Its pro-inflammatory activity involves recruitment of
CC leukocytes, promotion of cytokine and chemokine production, and
CC regulation of leukocyte adhesion and migration. Acts as an alarmin or a
CC danger associated molecular pattern (DAMP) molecule and stimulates
CC innate immune cells via binding to receptor for advanced glycation
CC endproducts (AGER). Binding to AGER activates the MAP-kinase and NF-
CC kappa-B signaling pathways leading to production of pro-inflammatory
CC cytokines and up-regulation of cell adhesion molecules ICAM1 and VCAM1.
CC Acts as a monocyte and mast cell chemoattractant. Can stimulate mast
CC cell degranulation and activation which generates chemokines, histamine
CC and cytokines inducing further leukocyte recruitment to the sites of
CC inflammation. Can inhibit the activity of matrix metalloproteinases;
CC MMP2, MMP3 and MMP9 by chelating Zn(2+) from their active sites (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer. Homooligomer (tetramer or hexamer) in the presence
CC of calcium, zinc and copper ions. Interacts with AGER and both calcium
CC and zinc are essential for the interaction (By similarity). Interacts
CC with CACYBP in a calcium-dependent manner (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}. Cytoplasm {ECO:0000250}.
CC Cytoplasm, cytoskeleton {ECO:0000250}. Cell membrane {ECO:0000250};
CC Peripheral membrane protein {ECO:0000250}. Note=Predominantly localized
CC in the cytoplasm. Upon elevation of the intracellular calcium level,
CC translocated from the cytoplasm to the cytoskeleton and the cell
CC membrane. Upon neutrophil activation is secreted via a microtubule-
CC mediated, alternative pathway (By similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Up-regulated in stimulated inflammatory effector
CC cells. {ECO:0000269|PubMed:10399917}.
CC -!- DOMAIN: The hinge domain contributes significantly to its chemotactic
CC properties. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the S-100 family. {ECO:0000305}.
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DR EMBL; D49548; BAA08496.1; -; mRNA.
DR EMBL; AF011757; AAB65423.1; -; mRNA.
DR EMBL; BC102542; AAI02543.1; -; mRNA.
DR RefSeq; NP_777076.1; NM_174651.3.
DR RefSeq; XP_005203669.1; XM_005203612.2.
DR RefSeq; XP_005203670.1; XM_005203613.1.
DR AlphaFoldDB; P79105; -.
DR SMR; P79105; -.
DR BioGRID; 159720; 6.
DR STRING; 9913.ENSBTAP00000056088; -.
DR PaxDb; P79105; -.
DR PeptideAtlas; P79105; -.
DR PRIDE; P79105; -.
DR Ensembl; ENSBTAT00000063314; ENSBTAP00000056088; ENSBTAG00000012638.
DR GeneID; 282467; -.
DR KEGG; bta:282467; -.
DR CTD; 6283; -.
DR VEuPathDB; HostDB:ENSBTAG00000012638; -.
DR VGNC; VGNC:59189; S100A12.
DR eggNOG; ENOG502SA01; Eukaryota.
DR GeneTree; ENSGT00940000162189; -.
DR HOGENOM; CLU_138624_6_2_1; -.
DR InParanoid; P79105; -.
DR OMA; CIEGECE; -.
DR OrthoDB; 1521098at2759; -.
DR Reactome; R-BTA-6798695; Neutrophil degranulation.
DR Proteomes; UP000009136; Chromosome 3.
DR Bgee; ENSBTAG00000012638; Expressed in anterior segment of eyeball and 102 other tissues.
DR ExpressionAtlas; P79105; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central.
DR GO; GO:0048306; F:calcium-dependent protein binding; IBA:GO_Central.
DR GO; GO:0050786; F:RAGE receptor binding; IBA:GO_Central.
DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IBA:GO_Central.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0043303; P:mast cell degranulation; IDA:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IBA:GO_Central.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR001751; S100/CaBP7/8-like_CS.
DR InterPro; IPR013787; S100_Ca-bd_sub.
DR Pfam; PF00036; EF-hand_1; 1.
DR Pfam; PF01023; S_100; 1.
DR SMART; SM00054; EFh; 1.
DR SMART; SM01394; S_100; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR PROSITE; PS00018; EF_HAND_1; 1.
DR PROSITE; PS50222; EF_HAND_2; 1.
DR PROSITE; PS00303; S100_CABP; 1.
PE 1: Evidence at protein level;
KW Calcium; Cell membrane; Copper; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; Immunity; Inflammatory response;
KW Innate immunity; Membrane; Metal-binding; Reference proteome; Repeat;
KW Secreted; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:8603881"
FT CHAIN 2..92
FT /note="Protein S100-A12"
FT /id="PRO_0000144015"
FT DOMAIN 13..48
FT /note="EF-hand 1"
FT /evidence="ECO:0000305"
FT DOMAIN 49..84
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 38..53
FT /note="Hinge domain"
FT /evidence="ECO:0000250"
FT BINDING 16
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000250|UniProtKB:P80511"
FT BINDING 16
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P80511"
FT BINDING 19
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /ligand_note="low affinity"
FT /evidence="ECO:0000250|UniProtKB:P80511"
FT BINDING 24
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /ligand_note="low affinity"
FT /evidence="ECO:0000250|UniProtKB:P80511"
FT BINDING 26
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000250|UniProtKB:P80511"
FT BINDING 26
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P80511"
FT BINDING 27
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /ligand_note="low affinity"
FT /evidence="ECO:0000250|UniProtKB:P80511"
FT BINDING 32
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /ligand_note="low affinity"
FT /evidence="ECO:0000250|UniProtKB:P80511"
FT BINDING 62
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 64
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 66
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 73
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 86
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000250|UniProtKB:P80511"
FT BINDING 86
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P80511"
FT BINDING 90
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000250|UniProtKB:P80511"
FT BINDING 90
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P80511"
FT CONFLICT 31
FT /note="R -> Y (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 37
FT /note="I -> G (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 66
FT /note="D -> K (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 70
FT /note="S -> V (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 92 AA; 10685 MW; 060233882D7C901F CRC64;
MTKLEDHLEG IINIFHQYSV RVGHFDTLNK RELKQLITKE LPKTLQNTKD QPTIDKIFQD
LDADKDGAVS FEEFVVLVSR VLKTAHIDIH KE
