Reviewed, UniProtKB/Swiss-Prot P04083 (ANXA1_HUMAN)

Names and origin

Protein names

Recommended name:
    Annexin A1
Alternative name(s):
    Annexin-1
    Annexin I
    Lipocortin I
    Calpactin II
    Chromobindin-9
    p35
    Phospholipase A2 inhibitory protein

Gene names

Name:	ANXA1
Synonyms:	ANX1, LPC1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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.
Subcellular location	NucleusBy similarity. CytoplasmBy similarity. Cell projection › ciliumBy similarity. Basolateral cell membraneBy 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.
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 Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	anti-apoptosis Traceable author statement. Source: UniProtKB cell motion Traceable author statement. Source: ProtInc cell surface receptor linked signal transduction Traceable author statement. Source: ProtInc inflammatory response Traceable author statement. Source: ProtInc keratinocyte differentiation Inferred from direct assay. Source: UniProtKB lipid metabolic process Ref.1 Traceable author statement. Source: ProtInc peptide cross-linking Inferred from direct assay. Source: UniProtKB
Cellular component	cornified envelope Inferred from direct assay. Source: UniProtKB cytoplasm Traceable author statement. Source: UniProtKB
Molecular function	calcium ion binding Traceable author statement. Source: ProtInc phospholipase inhibitor activity Ref.1 Traceable author statement. Source: ProtInc phospholipid binding Traceable author statement. Source: ProtInc protein binding, bridging Inferred from direct assay. Source: UniProtKB receptor binding Traceable author statement. Source: ProtInc structural molecule activity Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DLG3	Q92796	1	EBI-354007,EBI-80440
PPM1B	O75688	1	EBI-354007,EBI-1047039

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 346

345

Annexin A1

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

Modified residue

5

1

Phosphoserine; by TRPM7

Modified residue

21

1

Phosphotyrosine; by EGFR

Modified residue

24

1

Phosphothreonine

Modified residue

27

1

Phosphoserine; by PKC

Modified residue

39

1

Phosphotyrosine

Modified residue

207

1

Phosphotyrosine

Cross-link

19

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

Secondary structure

1

.

.

.

346

Helix Strand Turn

Details...

Helix

3 – 10

8

Sequences

	Sequence		Length	Mass (Da)
	P04083-1 [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: 2936963] [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: 1832554] [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: 8425544] [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: 15489334] [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: 2457390] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, PHOSPHORYLATION AT TYR-21 AND SER-27.
[6]	"Characterization by tandem mass spectrometry of structural modifications in proteins." Biemann K., Scoble H.A. Science 237:992-998(1987) [PubMed: 3303336] [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: 2532504] [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: 15485879] [Abstract] Cited for: PHOSPHORYLATION AT SER-5 BY TRPM7.
[9]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-207, MASS SPECTROMETRY.
[10]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-21, MASS SPECTROMETRY. Tissue: Epithelium.
[11]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-39 AND TYR-207, MASS SPECTROMETRY.
[12]	"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: 8453382] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
[13]	"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: 9915835] [Abstract] Cited for: STRUCTURE BY NMR OF 41-113.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

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

PIR

LUHU. A03080.

RefSeq

NP_000691.1.

UniGene

Hs.494173

3D structure databases

PDBMSD

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	1-12	[»]

SMR

P04083. Positions 2-344.

ModBase

Search...

Protein-protein interaction databases

IntAct

P04083.

PTM databases

PhosphoSite

P04083.

2-D gel databases

DOSAC-COBS-2DPAGE

P04083.

PHCI-2DPAGE

P04083.

REPRODUCTION-2DPAGE

IPI00218918.
P04083.

Proteomic databases

PeptideAtlas

P04083.

Genome annotation databases

Ensembl

ENSG00000135046. Homo sapiens. [Contig view]

GeneID

301.

KEGG

hsa:301.

Organism-specific databases

H-InvDB

HIX0008100.

HGNC

HGNC:533. ANXA1.

HPA

CAB013023.
HPA011271.
HPA011272.

MIM

151690. gene.

PharmGKB

PA24823.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

P04083.

HOVERGEN

P04083.

Gene expression databases

ArrayExpress

P04083.

CleanEx

HS_ANXA1.

GermOnline

ENSG00000135046. Homo sapiens.

Family and domain databases

InterPro

IPR001464. Annexin.
IPR002388. AnnexinI.
[Graphical view]

Gene3D

G3DSA:1.10.220.10. Annexin. 4 hits.

PANTHER

PTHR10502. Annexin. 1 hit.

Pfam

PF00191. Annexin. 4 hits.
[Graphical view]

PRINTS

PR00196. ANNEXIN.
PR00197. ANNEXINI.

ProDom

PD000143. Annexin. 4 hits.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00335. ANX. 4 hits.
[Graphical view]

PROSITE

PS00223. ANNEXIN. 4 hits.
[Graphical view]

BLOCKS

Search...

Other Resources

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.

LinkHub

P04083.

SOURCE

Search...

ProtoNet

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:	September 2, 2008
This is version 121 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)