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)

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. 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 Ref.9 Ref.10 Ref.11 Ref.12
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 anti-apoptosis Traceable author statement. Source: UniProtKB cell surface receptor linked signaling pathway Traceable author statement. Source: ProtInc cellular component movement Traceable author statement. Source: ProtInc inflammatory response Traceable author statement. Source: ProtInc keratinocyte differentiation Inferred from direct assay. Source: UniProtKB lipid metabolic process Traceable author statement. Source: ProtInc peptide cross-linking Inferred from direct assay. Source: UniProtKB positive regulation of vesicle fusion Inferred from direct assay. Source: UniProtKB
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. Source: UniProtKB nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	calcium ion binding Traceable author statement. Source: ProtInc calcium-dependent phospholipid binding Inferred from direct assay. Source: UniProtKB phospholipase A2 inhibitor activity Inferred from electronic annotation. Source: UniProtKB-KW 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
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 Ref.10

Modified residue

24

1

Phosphothreonine

Modified residue

27

1

Phosphoserine; by PKC Ref.5

Modified residue

39

1

Phosphotyrosine Ref.11 Ref.12

Modified residue

161

1

N6-acetyllysine Ref.13

Modified residue

207

1

Phosphotyrosine Ref.9 Ref.11 Ref.12

Modified residue

239

1

N6-acetyllysine Ref.13

Modified residue

250

1

N6-acetyllysine Ref.13

Modified residue

281

1

N6-acetyllysine Ref.13

Modified residue

312

1

N6-acetyllysine Ref.13

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: 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 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: 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: Cervix carcinoma.
[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. Tissue: Lung carcinoma.
[12]	"An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells." Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A., Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D., Wiley H.S., Qian W.-J. J. Proteome Res. 8:3852-3861(2009) [PubMed: 19534553] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-39 AND TYR-207, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[13]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-161; LYS-239; LYS-250; LYS-281 AND LYS-312, MASS SPECTROMETRY.
[14]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]	"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).
[16]	"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

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.

SMR

P04083. Positions 2-344.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-32875N.

IntAct

P04083. 13 interactions.

MINT

MINT-1212274.

STRING

P04083.

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.

PHCI-2DPAGE

P04083.

REPRODUCTION-2DPAGE

IPI00218918.
P04083.

UCD-2DPAGE

P04083.

Proteomic databases

PeptideAtlas

P04083.

PRIDE

P04083.

Protocols and materials databases

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.

H-InvDB

HIX0008100.

HGNC

HGNC:533. ANXA1.

HPA

CAB013023.
CAB035987.
HPA011271.
HPA011272.

MIM

151690. gene.

neXtProt

NX_P04083.

PharmGKB

PA24823.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG18218.

HOGENOM

HBG745057.

HOVERGEN

HBG061815.

InParanoid

P04083.

OMA

VFQKYSK.

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

InterPro

IPR001464. Annexin.
IPR018502. Annexin_repeat.
IPR018252. Annexin_repeat_CS.
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.

SMART

SM00335. ANX. 4 hits.
[Graphical view]

SUPFAM

SSF47874. Annexin. 1 hit.

PROSITE

PS00223. ANNEXIN. 4 hits.
[Graphical view]

ProtoNet

Search...

Other

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.

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:	January 25, 2012
This is version 159 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.