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Protein

Annexin A1

Gene

ANXA1

Organism
Cavia cutleri (Guinea pig)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Plays important roles in the innate immune response as effector of glucocorticoid-mediated responses and regulator of the inflammatory process. Has anti-inflammatory activity. Plays a role in glucocorticoid-mediated down-regulation of the early phase of the inflammatory response. Promotes resolution of inflammation and wound healing (By similarity). Functions at least in part by activating the formyl peptide receptors and downstream signaling cascades. Promotes chemotaxis of granulocytes and monocytes via activation of the formyl peptide receptors (By similarity). Contributes to the adaptive immune response by enhancing signaling cascades that are triggered by T-cell activation, regulates differentiation and proliferation of activated T-cells. Promotes the differentiation of T-cells into Th1 cells and negatively regulates differentiation into Th2 cells (By similarity). Has no effect on unstimulated T-cells. Promotes rearrangement of the actin cytoskeleton, cell polarization and cell migration. Negatively regulates hormone exocytosis via activation of the formyl peptide receptors and reorganization of the actin cytoskeleton (By similarity). Has high affinity for Ca2+ and can bind up to eight Ca2+ ions (By similarity). Displays Ca2+-dependent binding to phospholipid membranes (PubMed:2962884). Plays a role in the formation of phagocytic cups and phagosomes. Plays a role in phagocytosis by mediating the Ca2+-dependent interaction between phagosomes and the actin cytoskeleton (By similarity).By similarity1 Publication

Miscellaneous

Was originally identified as calcium and phospholipid binding protein that displays Ca2+-dependent binding to phospholipid membranes and can promote membrane aggregation in vitro. Was initially identified as inhibitor of phospholipase A2 activity (in vitro) (PubMed:2962884). Inhibition of phospholipase activity is mediated via its phospholipid binding activity that limits the access of phospholipase to its substrates.By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi59Calcium 1; via carbonyl oxygenBy similarity1
Metal bindingi60Calcium 1; via carbonyl oxygenBy similarity1
Metal bindingi62Calcium 1By similarity1
Metal bindingi97Calcium 2; via carbonyl oxygenBy similarity1
Metal bindingi100Calcium 2; via carbonyl oxygenBy similarity1
Metal bindingi105Calcium 2By similarity1
Metal bindingi127Calcium 3; via carbonyl oxygenBy similarity1
Metal bindingi129Calcium 3; via carbonyl oxygenBy similarity1
Metal bindingi131Calcium 3; via carbonyl oxygenBy similarity1
Metal bindingi132Calcium 4; via carbonyl oxygenBy similarity1
Metal bindingi134Calcium 4By similarity1
Metal bindingi171Calcium 3By similarity1
Metal bindingi210Calcium 5; via carbonyl oxygenBy similarity1
Metal bindingi213Calcium 5; via carbonyl oxygenBy similarity1
Metal bindingi215Calcium 5; via carbonyl oxygenBy similarity1
Metal bindingi253Calcium 6By similarity1
Metal bindingi255Calcium 5By similarity1
Metal bindingi256Calcium 6; via carbonyl oxygenBy similarity1
Metal bindingi261Calcium 6By similarity1
Metal bindingi286Calcium 7; via carbonyl oxygenBy similarity1
Metal bindingi288Calcium 7; via carbonyl oxygenBy similarity1
Metal bindingi290Calcium 7; via carbonyl oxygenBy similarity1
Metal bindingi328Calcium 8; via carbonyl oxygenBy similarity1
Metal bindingi330Calcium 7By similarity1
Metal bindingi331Calcium 8; via carbonyl oxygenBy similarity1
Metal bindingi336Calcium 8By similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionPhospholipase A2 inhibitor
Biological processAdaptive immunity, Immunity, Inflammatory response, Innate immunity
LigandCalcium, Calcium/phospholipid-binding, Metal-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Annexin A1
Alternative name(s):
Annexin I
Annexin-1
Calpactin II
Calpactin-2
Chromobindin-9
Lipocortin I
Lipocortin-like 33 kDa protein
Phospholipase A2 inhibitory protein
p35
Gene namesi
Name:ANXA1
Synonyms:ANX1
OrganismiCavia cutleri (Guinea pig)
Taxonomic identifieri10144 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaHystricomorphaCaviidaeCavia

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, Cell projection, Cilium, Cytoplasm, Cytoplasmic vesicle, Endosome, Membrane, Nucleus, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000674581 – 346Annexin A1Add BLAST346

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei5Phosphoserine; by TRPM7By similarity1
Cross-linki19Isoglutamyl lysine isopeptide (Gln-Lys) (interchain with K-?)By similarity
Modified residuei21Phosphotyrosine; by EGFRBy similarity1
Modified residuei27Phosphoserine; by PKCBy similarity1
Modified residuei34PhosphoserineBy similarity1
Modified residuei37PhosphoserineBy similarity1
Modified residuei58N6-acetyllysineBy similarity1
Modified residuei136PhosphothreonineBy similarity1
Cross-linki214Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity
Cross-linki214Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei239N6-acetyllysineBy similarity1
Modified residuei312N6-acetyllysineBy similarity1
Disulfide bondi324 ↔ 343By similarity
Cross-linki332Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity

Post-translational modificationi

Phosphorylated by protein kinase C, EGFR and TRPM7. Phosphorylated in response to EGF treatment.By similarity
Sumoylated.By similarity

Keywords - PTMi

Acetylation, Disulfide bond, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PRIDEiP14087.

Interactioni

Subunit structurei

Homodimer; non-covalently linked (By similarity). Homodimer; linked by transglutamylation. Homodimers linked by transglutamylation are observed in placenta, but not in other tissues. Interacts with S100A11. Heterotetramer, formed by two molecules each of S100A11 and ANXA1 (By similarity). Interacts with DYSF (By similarity). Interacts with EGFR (By similarity).By similarity

Protein-protein interaction databases

MINTiMINT-4996460.

Structurei

3D structure databases

ProteinModelPortaliP14087.
SMRiP14087.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati51 – 111Annexin 1Add BLAST61
Repeati123 – 183Annexin 2Add BLAST61
Repeati207 – 267Annexin 3Add BLAST61
Repeati282 – 342Annexin 4Add BLAST61

Domaini

The full-length protein can bind eight Ca2+ ions via the annexin repeats. Calcium binding causes a major conformation change that modifies dimer contacts and leads to surface exposure of the N-terminal phosphorylation sites; in the absence of Ca2+, these sites are buried in the interior of the protein core. The N-terminal region becomes disordered in response to calcium-binding.By similarity
The N-terminal 26 amino acids are sufficient for its extracellular functions in the regulation of inflammation and wound healing. Acylated peptides that contain the first 26 amino acids of the mature protein can activate signaling via the formyl peptide receptors.By similarity

Sequence similaritiesi

Belongs to the annexin family.Curated

Keywords - Domaini

Annexin, Repeat

Phylogenomic databases

HOVERGENiHBG061815.

Family and domain databases

Gene3Di1.10.220.10. 4 hits.
InterProiView protein in InterPro
IPR001464. Annexin.
IPR018502. Annexin_repeat.
IPR018252. Annexin_repeat_CS.
IPR037104. Annexin_sf.
IPR002388. ANX1.
PANTHERiPTHR10502:SF17. PTHR10502:SF17. 1 hit.
PfamiView protein in Pfam
PF00191. Annexin. 4 hits.
PRINTSiPR00196. ANNEXIN.
PR00197. ANNEXINI.
SMARTiView protein in SMART
SM00335. ANX. 4 hits.
PROSITEiView protein in PROSITE
PS00223. ANNEXIN. 4 hits.

Sequencei

Sequence statusi: Complete.

P14087-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSMVSEFLKQ AYFIDNQEQD YVKTVKSSKG GPGSAVSPYP SFDASSDVAA
60 70 80 90 100
LHKAITVKGV DEATIIDILT KRNNAQRQQI KAAYLQEKGK PLDEALKKAL
110 120 130 140 150
TGHLEEVVLA LLKTPAQLDA DELRAAMKGL GTDEDTLIEI LVSRKNREIK
160 170 180 190 200
EINRVYRDEL KRDLAKDITS DTSGDFQKAL LSLAKGDRCE DLSVNDDLAD
210 220 230 240 250
SDARALYEAG ERRKGTDVNV FITILTTRSY SHLRRVFQKY TKYSQHDMNK
260 270 280 290 300
ALDLELKGDI ENCLTAIVKC ATSTPAFFAE KLHLAMKGAG TRHKALIRIM
310 320 330 340
VSRSEIDMND IKVYYQKMYG ISLCQAILDE TKGDYEKILV ALCGGQ
Length:346
Mass (Da):38,555
Last modified:January 1, 1990 - v1
Checksum:i63A638C2A95CE954
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X14635 mRNA. Translation: CAA32783.1.

Similar proteinsi

Entry informationi

Entry nameiANXA1_CAVCU
AccessioniPrimary (citable) accession number: P14087
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: January 1, 1990
Last modified: October 25, 2017
This is version 116 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Direct protein sequencing

Documents

  1. SIMILARITY comments
    Index of protein domains and families