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Protein

Annexin A1

Gene

ANXA1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 (PubMed:8425544). Plays a role in glucocorticoid-mediated down-regulation of the early phase of the inflammatory response (By similarity). Promotes resolution of inflammation and wound healing (PubMed:25664854). Functions at least in part by activating the formyl peptide receptors and downstream signaling cascades (PubMed:15187149, PubMed:25664854). Promotes chemotaxis of granulocytes and monocytes via activation of the formyl peptide receptors (PubMed:15187149). 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 (PubMed:17008549). Promotes the differentiation of T-cells into Th1 cells and negatively regulates differentiation into Th2 cells (PubMed:17008549). Has no effect on unstimulated T cells (PubMed:17008549). Promotes rearrangement of the actin cytoskeleton, cell polarization and cell migration (PubMed:15187149). Negatively regulates hormone exocytosis via activation of the formyl peptide receptors and reorganization of the actin cytoskeleton (PubMed:19625660). Has high affinity for Ca2+ and can bind up to eight Ca2+ ions (By similarity). Displays Ca2+-dependent binding to phospholipid membranes (PubMed:2532504, PubMed:8557678). 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 similarity8 Publications

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:2936963, PubMed:8425544). Inhibition of phospholipase activity is mediated via its phospholipid binding activity that limits the access of phospholipase to its substrates.Curated2 Publications

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

Enzyme and pathway databases

ReactomeiR-HSA-416476 G alpha (q) signalling events
R-HSA-418594 G alpha (i) signalling events
R-HSA-444473 Formyl peptide receptors bind formyl peptides and many other ligands
R-HSA-445355 Smooth Muscle Contraction
R-HSA-6785807 Interleukin-4 and Interleukin-13 signaling
SignaLinkiP04083
SIGNORiP04083

Protein family/group databases

TCDBi1.A.31.1.3 the annexin (annexin) family

Names & Taxonomyi

Protein namesi
Recommended name:
Annexin A1
Alternative name(s):
Annexin I
Annexin-1
Calpactin II
Calpactin-2
Chromobindin-9
Lipocortin I1 Publication
Phospholipase A2 inhibitory protein
p35
Gene namesi
Name:ANXA1
Synonyms:ANX1, LPC1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000135046.13
HGNCiHGNC:533 ANXA1
MIMi151690 gene
neXtProtiNX_P04083

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

Pathology & Biotechi

Pharmaceutical usei

Peptides based on the N-terminal sequence might be used for the treatment of inflammation, e.g. in chronic bowel diseases and in rheumatoid arthritis.Curated

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi27S → A: Abolishes secretion and modulation of exocytosis. 1 Publication1
Mutagenesisi34S → A: No effect on secretion and modulation of exocytosis. 1 Publication1
Mutagenesisi45S → A: Abolishes secretion and nearly abolishes modulation of exocytosis. 1 Publication1

Organism-specific databases

DisGeNETi301
OpenTargetsiENSG00000135046
PharmGKBiPA24823

Chemistry databases

DrugBankiDB00288 Amcinonide
DB01234 Dexamethasone
DB00741 Hydrocortisone

Polymorphism and mutation databases

BioMutaiANXA1
DMDMi113944

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00000674602 – 346Annexin A1Add BLAST345

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanine1 Publication1
Modified residuei5Phosphoserine; by TRPM71 Publication1
Cross-linki19Isoglutamyl lysine isopeptide (Gln-Lys) (interchain with K-?)
Modified residuei21Phosphotyrosine; by EGFR1 Publication1
Modified residuei27Phosphoserine; by PKC1 Publication1
Modified residuei34PhosphoserineCombined sources1
Modified residuei37PhosphoserineCombined sources1
Modified residuei41PhosphothreonineCombined sources1
Modified residuei58N6-acetyllysineBy similarity1
Modified residuei136PhosphothreonineCombined sources1
Cross-linki214Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternateCombined sources
Cross-linki214Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei239N6-acetyllysineCombined sources1
Cross-linki257Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity
Modified residuei312N6-acetyllysineCombined sources1
Disulfide bondi324 ↔ 343By similarity
Cross-linki332Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)Combined sources

Post-translational modificationi

Phosphorylated by protein kinase C, EGFR and TRPM7 (PubMed:2457390, PubMed:15485879). Phosphorylated in response to EGF treatment (PubMed:2532504).3 Publications
Sumoylated.By similarity

Keywords - PTMi

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

Proteomic databases

EPDiP04083
PaxDbiP04083
PeptideAtlasiP04083
PRIDEiP04083
ProteomicsDBi51649

2D gel databases

DOSAC-COBS-2DPAGEiP04083
REPRODUCTION-2DPAGEiIPI00218918
P04083
UCD-2DPAGEiP04083

PTM databases

iPTMnetiP04083
PhosphoSitePlusiP04083
SwissPalmiP04083

Expressioni

Tissue specificityi

Detected in resting neutrophils (PubMed:10772777). Detected in peripheral blood T-cells (PubMed:17008549). Detected in extracellular vesicles in blood serum from patients with inflammatory bowel disease, but not in serum from healthy donors (PubMed:25664854). Detected in placenta (at protein level) (PubMed:2532504). Detected in liver.2 Publications

Gene expression databases

BgeeiENSG00000135046 Expressed in 229 organ(s), highest expression level in mouth mucosa
CleanExiHS_ANXA1
ExpressionAtlasiP04083 baseline and differential
GenevisibleiP04083 HS

Organism-specific databases

HPAiCAB013023
CAB035987
CAB058693
HPA011271
HPA011272

Interactioni

Subunit structurei

Homodimer; non-covalently linked (By similarity). Homodimer; linked by transglutamylation (PubMed:2532504). Homodimers linked by transglutamylation are observed in placenta, but not in other tissues (PubMed:2532504). Interacts with S100A11 (PubMed:8557678, PubMed:10673436). Heterotetramer, formed by two molecules each of S100A11 and ANXA1 (PubMed:10673436). Interacts with DYSF (By similarity). Interacts with EGFR (By similarity).By similarity3 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi106798, 101 interactors
DIPiDIP-32875N
IntActiP04083, 76 interactors
MINTiP04083
STRINGi9606.ENSP00000257497

Structurei

Secondary structure

1346
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP04083
SMRiP04083
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP04083

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 (PubMed:25664854). Acylated peptides that contain the first 26 amino acids of the mature protein can activate signaling via the formyl peptide receptors (PubMed:15187149, PubMed:25664854).2 Publications

Sequence similaritiesi

Belongs to the annexin family.Curated

Keywords - Domaini

Annexin, Repeat

Phylogenomic databases

eggNOGiKOG0819 Eukaryota
ENOG410XPUN LUCA
GeneTreeiENSGT00760000118972
HOGENOMiHOG000158803
HOVERGENiHBG061815
InParanoidiP04083
KOiK17091
OMAiGTRHKTL
OrthoDBiEOG091G0H6H
PhylomeDBiP04083
TreeFamiTF105452

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

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

P04083-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MAMVSEFLKQ AWFIENEEQE YVQTVKSSKG GPGSAVSPYP TFNPSSDVAA
60 70 80 90 100
LHKAIMVKGV DEATIIDILT KRNNAQRQQI KAAYLQETGK PLDETLKKAL
110 120 130 140 150
TGHLEEVVLA LLKTPAQFDA DELRAAMKGL GTDEDTLIEI LASRTNKEIR
160 170 180 190 200
DINRVYREEL KRDLAKDITS DTSGDFRNAL LSLAKGDRSE DFGVNEDLAD
210 220 230 240 250
SDARALYEAG ERRKGTDVNV FNTILTTRSY PQLRRVFQKY TKYSKHDMNK
260 270 280 290 300
VLDLELKGDI EKCLTAIVKC ATSKPAFFAE KLHQAMKGVG TRHKALIRIM
310 320 330 340
VSRSEIDMND IKAFYQKMYG ISLCQAILDE TKGDYEKILV ALCGGN
Length:346
Mass (Da):38,714
Last modified:January 23, 2007 - v2
Checksum:i14B42E1FA4178EC0
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q5T3N1Q5T3N1_HUMAN
Annexin
ANXA1
204Annotation score:
Q5T3N0Q5T3N0_HUMAN
Annexin
ANXA1
115Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti118F → L in BAG70088 (PubMed:19054851).Curated1
Sequence conflicti118F → L in BAG70215 (PubMed:19054851).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X05908 mRNA Translation: CAA29338.1
AB451274 mRNA Translation: BAG70088.1
AB451401 mRNA Translation: BAG70215.1
BC001275 mRNA Translation: AAH01275.1
BC035993 mRNA Translation: AAH35993.1
CCDSiCCDS6645.1
PIRiA03080 LUHU
RefSeqiNP_000691.1, NM_000700.2
XP_011516911.1, XM_011518609.1
UniGeneiHs.494173

Genome annotation databases

EnsembliENST00000257497; ENSP00000257497; ENSG00000135046
ENST00000376911; ENSP00000366109; ENSG00000135046
GeneIDi301
KEGGihsa:301

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X05908 mRNA Translation: CAA29338.1
AB451274 mRNA Translation: BAG70088.1
AB451401 mRNA Translation: BAG70215.1
BC001275 mRNA Translation: AAH01275.1
BC035993 mRNA Translation: AAH35993.1
CCDSiCCDS6645.1
PIRiA03080 LUHU
RefSeqiNP_000691.1, NM_000700.2
XP_011516911.1, XM_011518609.1
UniGeneiHs.494173

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AINX-ray2.50A33-346[»]
1BO9NMR-A41-113[»]
1QLSX-ray2.30D2-12[»]
5VFWNMR-A2-26[»]
ProteinModelPortaliP04083
SMRiP04083
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106798, 101 interactors
DIPiDIP-32875N
IntActiP04083, 76 interactors
MINTiP04083
STRINGi9606.ENSP00000257497

Chemistry databases

DrugBankiDB00288 Amcinonide
DB01234 Dexamethasone
DB00741 Hydrocortisone

Protein family/group databases

TCDBi1.A.31.1.3 the annexin (annexin) family

PTM databases

iPTMnetiP04083
PhosphoSitePlusiP04083
SwissPalmiP04083

Polymorphism and mutation databases

BioMutaiANXA1
DMDMi113944

2D gel databases

DOSAC-COBS-2DPAGEiP04083
REPRODUCTION-2DPAGEiIPI00218918
P04083
UCD-2DPAGEiP04083

Proteomic databases

EPDiP04083
PaxDbiP04083
PeptideAtlasiP04083
PRIDEiP04083
ProteomicsDBi51649

Protocols and materials databases

DNASUi301
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000257497; ENSP00000257497; ENSG00000135046
ENST00000376911; ENSP00000366109; ENSG00000135046
GeneIDi301
KEGGihsa:301

Organism-specific databases

CTDi301
DisGeNETi301
EuPathDBiHostDB:ENSG00000135046.13
GeneCardsiANXA1
HGNCiHGNC:533 ANXA1
HPAiCAB013023
CAB035987
CAB058693
HPA011271
HPA011272
MIMi151690 gene
neXtProtiNX_P04083
OpenTargetsiENSG00000135046
PharmGKBiPA24823
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0819 Eukaryota
ENOG410XPUN LUCA
GeneTreeiENSGT00760000118972
HOGENOMiHOG000158803
HOVERGENiHBG061815
InParanoidiP04083
KOiK17091
OMAiGTRHKTL
OrthoDBiEOG091G0H6H
PhylomeDBiP04083
TreeFamiTF105452

Enzyme and pathway databases

ReactomeiR-HSA-416476 G alpha (q) signalling events
R-HSA-418594 G alpha (i) signalling events
R-HSA-444473 Formyl peptide receptors bind formyl peptides and many other ligands
R-HSA-445355 Smooth Muscle Contraction
R-HSA-6785807 Interleukin-4 and Interleukin-13 signaling
SignaLinkiP04083
SIGNORiP04083

Miscellaneous databases

ChiTaRSiANXA1 human
EvolutionaryTraceiP04083
GeneWikiiAnnexin_A1
GenomeRNAii301
PROiPR:P04083
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000135046 Expressed in 229 organ(s), highest expression level in mouth mucosa
CleanExiHS_ANXA1
ExpressionAtlasiP04083 baseline and differential
GenevisibleiP04083 HS

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
ProtoNetiSearch...

Entry informationi

Entry nameiANXA1_HUMAN
AccessioniPrimary (citable) accession number: P04083
Secondary accession number(s): B5BU38
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1986
Last sequence update: January 23, 2007
Last modified: October 10, 2018
This is version 234 of the entry and version 2 of the sequence. See 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, Pharmaceutical, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. SIMILARITY comments
    Index of protein domains and families
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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