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Protein

Annexin A1

Gene

ANXA1

Organism
Bos taurus (Bovine)
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 (By similarity). 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 similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi59 – 591Calcium 1; via carbonyl oxygenBy similarity
Metal bindingi60 – 601Calcium 1; via carbonyl oxygenBy similarity
Metal bindingi62 – 621Calcium 1By similarity
Metal bindingi97 – 971Calcium 2; via carbonyl oxygenBy similarity
Metal bindingi100 – 1001Calcium 2; via carbonyl oxygenBy similarity
Metal bindingi105 – 1051Calcium 2By similarity
Metal bindingi127 – 1271Calcium 3; via carbonyl oxygenBy similarity
Metal bindingi129 – 1291Calcium 3; via carbonyl oxygenBy similarity
Metal bindingi131 – 1311Calcium 3; via carbonyl oxygenBy similarity
Metal bindingi132 – 1321Calcium 4; via carbonyl oxygenBy similarity
Metal bindingi134 – 1341Calcium 4By similarity
Metal bindingi171 – 1711Calcium 3By similarity
Metal bindingi210 – 2101Calcium 5; via carbonyl oxygenBy similarity
Metal bindingi213 – 2131Calcium 5; via carbonyl oxygenBy similarity
Metal bindingi215 – 2151Calcium 5; via carbonyl oxygenBy similarity
Metal bindingi253 – 2531Calcium 6By similarity
Metal bindingi255 – 2551Calcium 5By similarity
Metal bindingi256 – 2561Calcium 6; via carbonyl oxygenBy similarity
Metal bindingi261 – 2611Calcium 6By similarity
Metal bindingi286 – 2861Calcium 7; via carbonyl oxygenBy similarity
Metal bindingi288 – 2881Calcium 7; via carbonyl oxygenBy similarity
Metal bindingi290 – 2901Calcium 7; via carbonyl oxygenBy similarity
Metal bindingi328 – 3281Calcium 8; via carbonyl oxygenBy similarity
Metal bindingi330 – 3301Calcium 7By similarity
Metal bindingi331 – 3311Calcium 8; via carbonyl oxygenBy similarity
Metal bindingi336 – 3361Calcium 8By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Phospholipase A2 inhibitor

Keywords - Biological processi

Adaptive immunity, Immunity, Inflammatory response, Innate immunity

Keywords - Ligandi

Calcium, 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
Phospholipase A2 inhibitory protein
p35
Gene namesi
Name:ANXA1
Synonyms:ANX1
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Unplaced

Subcellular locationi

  • Nucleus By similarity
  • Cytoplasm 1 Publication
  • Cell projectioncilium 1 Publication
  • Basolateral cell membrane By similarity
  • Lateral cell membrane By similarity
  • Cell membrane By similarity; Peripheral membrane protein By similarity
  • Apical cell membrane By similarity
  • Membrane By similarity; Peripheral membrane protein By similarity
  • Endosome membrane By similarity; Peripheral membrane protein By similarity
  • Secreted By similarity
  • Secretedextracellular space By similarity
  • Cell membrane By similarity; Peripheral membrane protein By similarity; Extracellular side By similarity
  • Early endosome By similarity
  • Cytoplasmic vesicle membrane By similarity; Peripheral membrane protein By similarity
  • Secretedexosome By similarity
  • Cytoplasmic vesiclesecretory vesicle lumen By similarity
  • Cell projectionphagocytic cup By similarity

  • Note: Colocalizes with actin fibers at phagocytic cups. Secreted, at least in part via exosomes and other secretory vesicles. Detected in exosomes and other extracellular vesicles. Secretion is increased in response to wounding and inflammation (By similarity). Detected in gelatinase granules in resting neutrophils. Neutrophil adhesion to endothelial cells stimulates secretion via gelatinase granules, but foreign particle phagocytosis has no effect. Displays calcium-dependent binding to phospholipid membranes (By similarity).By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 346345Annexin A1PRO_0000067457Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineBy similarity
Modified residuei5 – 51Phosphoserine; by TRPM7By similarity
Cross-linki19 – 19Isoglutamyl lysine isopeptide (Gln-Lys) (interchain with K-?)By similarity
Modified residuei21 – 211Phosphotyrosine; by EGFRBy similarity
Modified residuei34 – 341PhosphoserineBy similarity
Modified residuei37 – 371PhosphoserineBy similarity
Modified residuei41 – 411PhosphothreonineBy similarity
Modified residuei58 – 581N6-acetyllysineBy similarity
Modified residuei136 – 1361PhosphothreonineBy similarity
Cross-linki214 – 214Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity
Cross-linki214 – 214Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei239 – 2391N6-acetyllysineBy similarity
Modified residuei312 – 3121N6-acetyllysineBy similarity
Disulfide bondi324 ↔ 343By similarity
Cross-linki332 – 332Glycyl 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

PaxDbiP46193.
PeptideAtlasiP46193.
PRIDEiP46193.

PTM databases

iPTMnetiP46193.

Expressioni

Tissue specificityi

Detected on surface epithelia and mucosal glands in nasal cavity, trachea, bronchi and bronchioles. Detected in blood vessel endothelial cells. Detected in neutrophils (at protein level).1 Publication

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

IntActiP46193. 1 interaction.
STRINGi9913.ENSBTAP00000021256.

Structurei

3D structure databases

ProteinModelPortaliP46193.
SMRiP46193. Positions 2-344.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati51 – 11161Annexin 1Add
BLAST
Repeati123 – 18361Annexin 2Add
BLAST
Repeati207 – 26761Annexin 3Add
BLAST
Repeati282 – 34261Annexin 4Add
BLAST

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
Contains 4 annexin repeats.Curated

Keywords - Domaini

Annexin, Repeat

Phylogenomic databases

eggNOGiKOG0819. Eukaryota.
ENOG410XPUN. LUCA.
HOGENOMiHOG000158803.
HOVERGENiHBG061815.
InParanoidiP46193.
KOiK17091.

Family and domain databases

Gene3Di1.10.220.10. 4 hits.
InterProiIPR001464. Annexin.
IPR018502. Annexin_repeat.
IPR018252. Annexin_repeat_CS.
IPR002388. AnnexinI.
[Graphical view]
PANTHERiPTHR10502:SF17. PTHR10502:SF17. 1 hit.
PfamiPF00191. Annexin. 4 hits.
[Graphical view]
PRINTSiPR00196. ANNEXIN.
PR00197. ANNEXINI.
SMARTiSM00335. ANX. 4 hits.
[Graphical view]
PROSITEiPS00223. ANNEXIN. 4 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P46193-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAMVSEFLKQ AWFIENEEQE YIKTVKGSKG GPGSAVSPYP TFNPSSDVEA
60 70 80 90 100
LHKAITVKGV DEATIIEILT KRNNAQRQQI KAAYLQEKGK PLDEVLKKAL
110 120 130 140 150
LGHLEEVVLA LLKTPAQFDA EELRAAMKGL GTDEDTLNEI LASRTNREIR
160 170 180 190 200
EINRVYREEL KRDLAKDIAS DTSGDYEKAL LSLAKGDRSE ELAVNDDLAD
210 220 230 240 250
SDARALYEAG ERRKGTDVNV FITILTTRSY PHLRRVFQKY SKYSKHDMNK
260 270 280 290 300
VLDLELKGDI EKCLTVIVKC ATSQPMFFAE KLHQAMKGIG TRHKTLIRIM
310 320 330 340
VSRSEIDMND IKACYQKLYG ISLCQAILDE TKGDYEKILV ALCGRD
Length:346
Mass (Da):38,952
Last modified:May 30, 2006 - v2
Checksum:i09FA6CEF5F1AD9FB
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti58 – 581K → R in AAX46348 (PubMed:16305752).Curated
Sequence conflicti156 – 1561Y → H in CAA39971 (PubMed:7678738).Curated
Sequence conflicti182 – 1821S → A in CAA39971 (PubMed:7678738).Curated
Sequence conflicti222 – 2221I → T in CAA39971 (PubMed:7678738).Curated
Sequence conflicti265 – 2651T → I in AAX46348 (PubMed:16305752).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X56649 mRNA. Translation: CAA39971.1.
BT021501 mRNA. Translation: AAX46348.1.
BC103375 mRNA. Translation: AAI03376.1.
PIRiS28228.
RefSeqiNP_786978.2. NM_175784.3.
UniGeneiBt.16032.

Genome annotation databases

GeneIDi327662.
KEGGibta:327662.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X56649 mRNA. Translation: CAA39971.1.
BT021501 mRNA. Translation: AAX46348.1.
BC103375 mRNA. Translation: AAI03376.1.
PIRiS28228.
RefSeqiNP_786978.2. NM_175784.3.
UniGeneiBt.16032.

3D structure databases

ProteinModelPortaliP46193.
SMRiP46193. Positions 2-344.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP46193. 1 interaction.
STRINGi9913.ENSBTAP00000021256.

PTM databases

iPTMnetiP46193.

Proteomic databases

PaxDbiP46193.
PeptideAtlasiP46193.
PRIDEiP46193.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi327662.
KEGGibta:327662.

Organism-specific databases

CTDi301.

Phylogenomic databases

eggNOGiKOG0819. Eukaryota.
ENOG410XPUN. LUCA.
HOGENOMiHOG000158803.
HOVERGENiHBG061815.
InParanoidiP46193.
KOiK17091.

Family and domain databases

Gene3Di1.10.220.10. 4 hits.
InterProiIPR001464. Annexin.
IPR018502. Annexin_repeat.
IPR018252. Annexin_repeat_CS.
IPR002388. AnnexinI.
[Graphical view]
PANTHERiPTHR10502:SF17. PTHR10502:SF17. 1 hit.
PfamiPF00191. Annexin. 4 hits.
[Graphical view]
PRINTSiPR00196. ANNEXIN.
PR00197. ANNEXINI.
SMARTiSM00335. ANX. 4 hits.
[Graphical view]
PROSITEiPS00223. ANNEXIN. 4 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Epitope mapping of annexin I: antibodies that compete with phospholipids and calcium recognize amino acids 42-99."
    Ernst J.D.
    Biochem. J. 289:539-542(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Kidney.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  3. NIH - Mammalian Gene Collection (MGC) project
    Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: Crossbred X Angus.
    Tissue: Ileum.
  4. "Localization of annexins A1 and A2 in the respiratory tract of healthy calves and those experimentally infected with Mannheimia haemolytica."
    Senthilkumaran C., Hewson J., Ollivett T.L., Bienzle D., Lillie B.N., Clark M., Caswell J.L.
    Vet. Res. 46:6-6(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.

Entry informationi

Entry nameiANXA1_BOVIN
AccessioniPrimary (citable) accession number: P46193
Secondary accession number(s): Q3ZBF5, Q58DU6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: May 30, 2006
Last modified: July 6, 2016
This is version 122 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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). Inhibition of phospholipase activity is mediated via its phospholipid binding activity that limits the access of phospholipase to its substrates.By similarity

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.