P04083 (ANXA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	ANXA1
Synonyms:	ANX1, LPC1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	346 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Calcium/phospholipid-binding protein which promotes membrane fusion and is involved in exocytosis. This protein regulates phospholipase A2 activity. It seems to bind from two to four calcium ions with high affinity.
Subunit structure	Homodimer in placenta (20%); linked by transglutamylation. Interacts with DYSF By similarity. Ref.7
Subcellular location	Nucleus By similarity. Cytoplasm By similarity. Cell projection › cilium By similarity. Basolateral cell membrane By similarity. Note: Found in the cilium, nucleus and basolateral cell membrane of ciliated cells in the tracheal endothelium By similarity. Found in the cytoplasm of type II pneumocytes and alveolar macrophages By similarity.
Domain	A pair of annexin repeats may form one binding site for calcium and phospholipid.
Post-translational modification	Phosphorylated by protein kinase C, epidermal growth factor receptor/kinase and TRPM7. Phosphorylation results in loss of the inhibitory activity. Ref.5 Ref.8
Sequence similarities	Belongs to the annexin family. Contains 4 annexin repeats.

Ontologies

Keywords
Cellular component	Cell membrane Cell projection Cilium Cytoplasm Membrane Nucleus
Domain	Annexin Repeat
Ligand	Calcium Calcium/phospholipid-binding
Molecular function	Phospholipase A2 inhibitor
PTM	Acetylation Isopeptide bond Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	alpha-beta T cell differentiation Inferred from sequence or structural similarity. Source: BHF-UCL arachidonic acid secretion Inferred from electronic annotation. Source: Compara cell cycle Inferred from electronic annotation. Source: Compara cell surface receptor signaling pathway Traceable author statement PubMed 10882119. Source: ProtInc cellular component movement Traceable author statement PubMed 10882119. Source: ProtInc cellular response to glucocorticoid stimulus Inferred from direct assay Ref.1. Source: BHF-UCL cellular response to hydrogen peroxide Inferred from electronic annotation. Source: Compara endocrine pancreas development Inferred from electronic annotation. Source: Compara estrous cycle phase Inferred from electronic annotation. Source: Compara gliogenesis Inferred from electronic annotation. Source: Compara hepatocyte differentiation Inferred from electronic annotation. Source: Compara inflammatory response Traceable author statement PubMed 10882119. Source: ProtInc insulin secretion Inferred from electronic annotation. Source: Compara keratinocyte differentiation Inferred from direct assay PubMed 10908733. Source: UniProtKB negative regulation of acute inflammatory response Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Traceable author statement PubMed 16130169. Source: UniProtKB negative regulation of protein secretion Inferred from electronic annotation. Source: Compara neutrophil clearance Inferred from mutant phenotype PubMed 21957127. Source: BHF-UCL peptide cross-linking Inferred from direct assay PubMed 10908733. Source: UniProtKB positive regulation of neutrophil apoptotic process Inferred from electronic annotation. Source: Compara positive regulation of prostaglandin biosynthetic process Inferred from electronic annotation. Source: Compara positive regulation of vesicle fusion Inferred from direct assay PubMed 2138016. Source: UniProtKB regulation of cell proliferation Inferred from electronic annotation. Source: Compara response to X-ray Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to estradiol stimulus Inferred from electronic annotation. Source: Compara response to interleukin-1 Inferred from electronic annotation. Source: Compara response to peptide hormone stimulus Inferred from electronic annotation. Source: Compara
Cellular_component	basolateral plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell cilium Inferred from electronic annotation. Source: UniProtKB-SubCell cornified envelope Inferred from direct assay PubMed 10908733. Source: UniProtKB cytoplasm Traceable author statement PubMed 16130169. Source: UniProtKB extracellular space Inferred from electronic annotation. Source: Compara extracellular vesicular exosome Inferred from direct assay PubMed 21362503. Source: UniProtKB mitochondrial membrane Inferred from electronic annotation. Source: Compara nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from direct assay. Source: HPA protein complex Inferred from electronic annotation. Source: Compara sarcolemma Inferred from electronic annotation. Source: Compara
Molecular_function	calcium ion binding Traceable author statement PubMed 2967291. Source: ProtInc calcium-dependent phospholipid binding Inferred from direct assay PubMed 2138016. Source: UniProtKB phospholipase A2 inhibitor activity Inferred from direct assay Ref.1. Source: BHF-UCL protein binding, bridging Inferred from direct assay PubMed 10908733. Source: UniProtKB receptor binding Traceable author statement PubMed 10882119. Source: ProtInc structural molecule activity Inferred from direct assay PubMed 10908733. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
IKBKG	Q9Y6K9	6	EBI-354007,EBI-81279
RIPK1	Q13546	5	EBI-354007,EBI-358507

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 346

345

Annexin A1

PRO_0000067460

Regions

Repeat

51 – 111

61

Annexin 1

Repeat

123 – 183

61

Annexin 2

Repeat

207 – 267

61

Annexin 3

Repeat

282 – 342

61

Annexin 4

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.6

Modified residue

5

1

Phosphoserine; by TRPM7 Ref.8

Modified residue

21

1

Phosphotyrosine; by EGFR Ref.5

Modified residue

24

1

Phosphothreonine

Modified residue

27

1

Phosphoserine; by PKC Ref.5

Modified residue

37

1

Phosphoserine Ref.11

Modified residue

239

1

N6-acetyllysine Ref.10

Modified residue

312

1

N6-acetyllysine Ref.10

Cross-link

19

Isoglutamyl lysine isopeptide (Gln-Lys) (interchain with K-?)

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

346

Helix Strand Turn

Details...

Helix

3 – 10

8

Helix

46 – 55

10

Beta strand

62 – 64

3

Helix

65 – 71

7

Helix

77 – 87

11

Helix

94 – 99

6

Helix

106 – 109

4

Helix

110 – 112

3

Sequences

	Sequence		Length	Mass (Da)
	P04083 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 14B42E1FA4178EC0	FASTA	346	38,714
	10 20 30 40 50 60 MAMVSEFLKQ AWFIENEEQE YVQTVKSSKG GPGSAVSPYP TFNPSSDVAA LHKAIMVKGV 70 80 90 100 110 120 DEATIIDILT KRNNAQRQQI KAAYLQETGK PLDETLKKAL TGHLEEVVLA LLKTPAQFDA 130 140 150 160 170 180 DELRAAMKGL GTDEDTLIEI LASRTNKEIR DINRVYREEL KRDLAKDITS DTSGDFRNAL 190 200 210 220 230 240 LSLAKGDRSE DFGVNEDLAD SDARALYEAG ERRKGTDVNV FNTILTTRSY PQLRRVFQKY 250 260 270 280 290 300 TKYSKHDMNK VLDLELKGDI EKCLTAIVKC ATSKPAFFAE KLHQAMKGVG TRHKALIRIM 310 320 330 340 VSRSEIDMND IKAFYQKMYG ISLCQAILDE TKGDYEKILV ALCGGN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression of human lipocortin, a phospholipase A2 inhibitor with potential anti-inflammatory activity." Wallner B.P., Mattaliano R.J., Hession C., Cate R.L., Tizard R., Sinclair L.K., Foeller C., Chow E.P., Browning J.L., Ramachandran K.L., Pepinsky R.B. Nature 320:77-81(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Correlation of gene and protein structure of rat and human lipocortin I." Kovacic R.T., Tizard R., Cate R.L., Frey A.Z., Wallner B.P. Biochemistry 30:9015-9021(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Structural characterization of a biologically active human lipocortin 1 expressed in Escherichia coli." Arcone R., Arpaia G., Ruoppolo M., Malorni A., Pucci P., Marino G., Ialenti A., di Rosa M., Ciliberto G. Eur. J. Biochem. 211:347-355(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Cervix and Lung.
[5]	"Location of sites in human lipocortin I that are phosphorylated by protein tyrosine kinases and protein kinases A and C." Varticovski L., Chahwala S.B., Whitman M., Cantley L., Schindler D., Chow E.P., Sinclair L.K., Pepinsky R.B. Biochemistry 27:3682-3690(1988) [PubMed] [Europe PMC] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, PHOSPHORYLATION AT TYR-21 BY EGFR AND SER-27 BY PKC.
[6]	"Characterization by tandem mass spectrometry of structural modifications in proteins." Biemann K., Scoble H.A. Science 237:992-998(1987) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION AT ALA-2, MASS SPECTROMETRY.
[7]	"A dimeric form of lipocortin-1 in human placenta." Pepinsky R.B., Sinclair L.K., Chow E.P., O'Brine-Greco B. Biochem. J. 263:97-103(1989) [PubMed] [Europe PMC] [Abstract] Cited for: DIMERIZATION.
[8]	"Phosphorylation of annexin I by TRPM7 channel-kinase." Dorovkov M.V., Ryazanov A.G. J. Biol. Chem. 279:50643-50646(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-5 BY TRPM7.
[9]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[10]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-239 AND LYS-312, MASS SPECTROMETRY.
[11]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]	"Crystal structure of human annexin I at 2.5-A resolution." Weng X., Luecke H., Song I.S., Kang D.S., Kim S.-H., Huber R. Protein Sci. 2:448-458(1993) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
[14]	"NMR solution structure of domain 1 of human annexin I shows an autonomous folding unit." Gao J., Li Y., Yan H. J. Biol. Chem. 274:2971-2977(1999) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 41-113.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X05908 mRNA. Translation: CAA29338.1.
BC001275 mRNA. Translation: AAH01275.1.
BC035993 mRNA. Translation: AAH35993.1.

IPI

IPI00218918.

PIR

LUHU. A03080.

RefSeq

NP_000691.1. NM_000700.1.

UniGene

Hs.494173.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AIN	X-ray	2.50	A	33-346	[»]
1BO9	NMR	-	A	41-113	[»]
1QLS	X-ray	2.30	D	2-12	[»]

ProteinModelPortal

P04083.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-32875N.

IntAct

P04083. 17 interactions.

MINT

MINT-1212274.

STRING

9606.ENSP00000257497.

Protein family/group databases

TCDB

1.A.31.1.3. annexin family.

PTM databases

PhosphoSite

P04083.

Polymorphism databases

DMDM

113944.

2D gel databases

DOSAC-COBS-2DPAGE

P04083.

REPRODUCTION-2DPAGE

IPI00218918.
P04083.

UCD-2DPAGE

P04083.

Proteomic databases

PaxDb

P04083.

PeptideAtlas

P04083.

PRIDE

P04083.

Protocols and materials databases

DNASU

301.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000257497; ENSP00000257497; ENSG00000135046.
ENST00000376911; ENSP00000366109; ENSG00000135046.

GeneID

301.

KEGG

hsa:301.

UCSC

uc004ajf.1. human.

Organism-specific databases

CTD

301.

GeneCards

GC09P075766.

HGNC

HGNC:533. ANXA1.

HPA

CAB013023.
CAB035987.
CAB058693.
HPA011271.
HPA011272.

MIM

151690. gene.

neXtProt

NX_P04083.

PharmGKB

PA24823.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG282829.

HOGENOM

HOG000158803.

HOVERGEN

HBG061815.

InParanoid

P04083.

OMA

GTRHKTL.

OrthoDB

EOG48WC2C.

PhylomeDB

P04083.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P04083.

Bgee

P04083.

CleanEx

HS_ANXA1.

Genevestigator

P04083.

GermOnline

ENSG00000135046. Homo sapiens.

Family and domain databases

Gene3D

1.10.220.10. 4 hits.

InterPro

IPR001464. Annexin.
IPR018502. Annexin_repeat.
IPR018252. Annexin_repeat_CS.
IPR002388. AnnexinI.
[Graphical view]

PANTHER

PTHR10502. PTHR10502. 1 hit.

Pfam

PF00191. Annexin. 4 hits.
[Graphical view]

PRINTS

PR00196. ANNEXIN.
PR00197. ANNEXINI.

SMART

SM00335. ANX. 4 hits.
[Graphical view]

SUPFAM

SSF47874. Annexin. 1 hit.

PROSITE

PS00223. ANNEXIN. 4 hits.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

ANXA1. human.

DrugBank

DB00240. Alclometasone.
DB00288. Amcinonide.
DB00394. Beclomethasone.
DB00443. Betamethasone.
DB01013. Clobetasol.
DB00838. Clocortolone.
DB01260. Desonide.
DB00547. Desoximetasone.
DB01234. Dexamethasone.
DB00223. Diflorasone.
DB00663. Flumethasone Pivalate.
DB00596. Halobetasol Propionate.
DB00769. Hydrocortamate.
DB00741. Hydrocortisone.
DB00873. Loteprednol Etabonate.
DB00959. Methylprednisolone.
DB00764. Mometasone.
DB01130. Prednicarbate.
DB00635. Prednisone.
DB00896. Rimexolone.
DB00620. Triamcinolone.

EvolutionaryTrace

P04083.

GenomeRNAi

301.

NextBio

1213.

SOURCE

Search...

Entry information

Entry name

ANXA1_HUMAN

Accession

Primary (citable) accession number: P04083

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1986
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 174 of the entry and version 2 of the sequence. [Complete history]

Entry status

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.