P07355 (ANXA2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Annexin A2

Alternative name(s):
Annexin II
Annexin-2
Calpactin I heavy chain
Calpactin-1 heavy chain
Chromobindin-8
Lipocortin II
Placental anticoagulant protein IV
Short name=PAP-IV
Protein I
p36

Gene names

Name:	ANXA2
Synonyms:	ANX2, ANX2L4, CAL1H, LPC2D

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	339 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-regulated membrane-binding protein whose affinity for calcium is greatly enhanced by anionic phospholipids. It binds two calcium ions with high affinity. May be involved in heat-stress response.
Subunit structure	Heterotetramer containing 2 light chains of S100A10/p11 and 2 heavy chains of ANXA2/p36. Interacts with ATP1B1 and DYSF By similarity. Interacts with human cytomegalovirus (HCMV). Interacts with COCH. Ref.10 Ref.17
Subcellular location	Secreted › extracellular space › extracellular matrix › basement membrane. Melanosome. Note: In the lamina beneath the plasma membrane. Identified by mass spectrometry in melanosome fractions from stage I to stage IV. Translocated from the cytoplasm to the cell surface through a Golgi-independent mechanism. Ref.15
Domain	A pair of annexin repeats may form one binding site for calcium and phospholipid.
Post-translational modification	Phosphorylation of Tyr-24 enhances heat stress-induced translocation to the cell surface. ISGylated. Ref.14
Miscellaneous	It may cross-link plasma membrane phospholipids with actin and the cytoskeleton and be involved with exocytosis.
Sequence similarities	Belongs to the annexin family. Contains 4 annexin repeats.
Sequence caution	The sequence AAH66955.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Basement membrane Extracellular matrix Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Annexin Repeat
Ligand	Calcium Calcium/phospholipid-binding
PTM	Acetylation Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis Inferred from expression pattern PubMed 11866539. Source: UniProtKB body fluid secretion Inferred from electronic annotation. Source: Compara cellular response to acid Inferred from electronic annotation. Source: Compara collagen fibril organization Inferred from electronic annotation. Source: Compara fibrinolysis Inferred from electronic annotation. Source: Compara positive regulation of binding Inferred from electronic annotation. Source: Compara positive regulation of vesicle fusion Inferred from direct assay PubMed 2138016. Source: UniProtKB skeletal system development Traceable author statement PubMed 7961821. Source: ProtInc
Cellular_component	Schmidt-Lanterman incisure Inferred from electronic annotation. Source: Compara basement membrane Inferred from electronic annotation. Source: UniProtKB-SubCell early endosome Inferred from electronic annotation. Source: Compara extracellular vesicular exosome Inferred from direct assay PubMed 21362503. Source: UniProtKB extrinsic to plasma membrane Inferred from electronic annotation. Source: Compara lipid particle Inferred from direct assay PubMed 14741744. Source: UniProtKB melanosome Inferred from electronic annotation. Source: UniProtKB-SubCell midbody Inferred from direct assay PubMed 15166316. Source: UniProtKB myelin sheath adaxonal region Inferred from electronic annotation. Source: Compara perinuclear region of cytoplasm Inferred from electronic annotation. Source: Compara plasma membrane Traceable author statement PubMed 10809787. Source: ProtInc protein complex Inferred from electronic annotation. Source: Compara sarcolemma Inferred from electronic annotation. Source: Compara
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro calcium-dependent phospholipid binding Inferred from direct assay PubMed 2138016. Source: UniProtKB phosphatidylinositol-4,5-bisphosphate binding Inferred from electronic annotation. Source: Compara phospholipase inhibitor activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MLH1	P40692	7	EBI-352622,EBI-744248

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P07355-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P07355-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MGRQLAGCGDAGKKASFKM

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.7

Chain

2 – 339

338

Annexin A2

PRO_0000067470

Regions

Repeat

42 – 102

61

Annexin 1

Repeat

114 – 174

61

Annexin 2

Repeat

199 – 259

61

Annexin 3

Repeat

274 – 334

61

Annexin 4

Region

2 – 24

23

S100A10-binding site Potential

Amino acid modifications

Modified residue

2

1

N-acetylserine Ref.7

Modified residue

24

1

Phosphotyrosine; by SRC Ref.13

Modified residue

26

1

Phosphoserine; by PKC Ref.12

Natural variations

Alternative sequence

1

1

M → MGRQLAGCGDAGKKASFKM in isoform 2.

VSP_038091

Natural variant

98

1

V → L. Ref.6

VAR_012982

Experimental info

Mutagenesis

24

1

Y → A: Abolishes heat stress-induced cell surface localization. Ref.13

Sequence conflict

29

1

A → P AA sequence Ref.9

Sequence conflict

166

1

D → G in CAE45704. Ref.4

Sequence conflict

293

1

V → A in AAH23990. Ref.6

Secondary structure

1

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339

Helix Strand Turn

Details...

Helix

3 – 9

7

Helix

35 – 47

13

Helix

53 – 60

8

Helix

65 – 79

15

Helix

83 – 90

8

Helix

93 – 103

11

Helix

106 – 117

12

Beta strand

120 – 122

3

Helix

125 – 134

10

Helix

137 – 151

15

Helix

155 – 161

7

Helix

165 – 175

11

Helix

188 – 200

13

Turn

201 – 204

4

Beta strand

205 – 207

3

Helix

210 – 219

10

Helix

222 – 232

11

Turn

233 – 235

3

Helix

240 – 247

8

Helix

250 – 264

15

Helix

266 – 278

13

Beta strand

279 – 282

4

Helix

285 – 295

11

Turn

296 – 298

3

Helix

300 – 311

12

Helix

315 – 322

8

Helix

325 – 335

11

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 5126E1337A0CBEA1	FASTA	339	38,604
	10 20 30 40 50 60 MSTVHEILCK LSLEGDHSTP PSAYGSVKAY TNFDAERDAL NIETAIKTKG VDEVTIVNIL 70 80 90 100 110 120 TNRSNAQRQD IAFAYQRRTK KELASALKSA LSGHLETVIL GLLKTPAQYD ASELKASMKG 130 140 150 160 170 180 LGTDEDSLIE IICSRTNQEL QEINRVYKEM YKTDLEKDII SDTSGDFRKL MVALAKGRRA 190 200 210 220 230 240 EDGSVIDYEL IDQDARDLYD AGVKRKGTDV PKWISIMTER SVPHLQKVFD RYKSYSPYDM 250 260 270 280 290 300 LESIRKEVKG DLENAFLNLV QCIQNKPLYF ADRLYDSMKG KGTRDKVLIR IMVSRSEVDM 310 320 330 LKIRSEFKRK YGKSLYYYIQ QDTKGDYQKA LLYLCGGDD
	Isoform 2 [UniParc]. Checksum: 2AA081CB4E7AC75C	FASTA	357	40,411
	10 20 30 40 50 60 MGRQLAGCGD AGKKASFKMS TVHEILCKLS LEGDHSTPPS AYGSVKAYTN FDAERDALNI 70 80 90 100 110 120 ETAIKTKGVD EVTIVNILTN RSNAQRQDIA FAYQRRTKKE LASALKSALS GHLETVILGL 130 140 150 160 170 180 LKTPAQYDAS ELKASMKGLG TDEDSLIEII CSRTNQELQE INRVYKEMYK TDLEKDIISD 190 200 210 220 230 240 TSGDFRKLMV ALAKGRRAED GSVIDYELID QDARDLYDAG VKRKGTDVPK WISIMTERSV 250 260 270 280 290 300 PHLQKVFDRY KSYSPYDMLE SIRKEVKGDL ENAFLNLVQC IQNKPLYFAD RLYDSMKGKG 310 320 330 340 350 TRDKVLIRIM VSRSEVDMLK IRSEFKRKYG KSLYYYIQQD TKGDYQKALL YLCGGDD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Two human 35 kd inhibitors of phospholipase A2 are related to substrates of pp60v-src and of the epidermal growth factor receptor/kinase." Huang K.-S., Wallner B.P., Mattaliano R.J., Tizard R., Burne C., Frey A., Hession C., McGray P., Sinclair L.K., Chow E.P., Browning J.L., Ramachandran K.L., Tang J., Smart J.E., Pepinsky R.B. Cell 46:191-199(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Placenta.
[2]	"Characterization of the human lipocortin-2-encoding multigene family: its structure suggests the existence of a short amino acid unit undergoing duplication." Spano F., Raugei G., Palla E., Colella C., Melli M. Gene 95:243-251(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Colon endothelium.
[5]	"Analysis of the DNA sequence and duplication history of human chromosome 15." Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C. Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] (ISOFORM 1), VARIANT LEU-98. Tissue: Brain, Colon, Pancreas, Prostate, Skin, Testis and Urinary bladder.
[7]	Bienvenut W.V., Murray L., Brunton V.G., Frame M.C., Bensaad K., Vousden K.H. Submitted (FEB-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-10; 38-47; 50-63; 69-77; 89-115; 153-169 AND 213-220, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, MASS SPECTROMETRY. Tissue: Colon adenocarcinoma and Osteosarcoma.
[8]	"The protein-tyrosine kinase substrate, calpactin I heavy chain (p36), is part of the primer recognition protein complex that interacts with DNA polymerase alpha." Jindal H.K., Chaney W.G., Anderson C.W., Davis R.G., Vishwanatha J.K. J. Biol. Chem. 266:5169-5176(1991) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 11-27; 49-62; 68-77; 120-135; 314-323 AND 329-339.
[9]	"Identification and characterization of alpha-protein kinase C binding proteins in normal and transformed REF52 cells." Hyatt S.L., Liao L., Chapline C., Jaken S. Biochemistry 33:1223-1228(1994) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 15-40 AND 50-63.
[10]	"An endothelial cell-surface form of annexin II binds human cytomegalovirus." Wright J.F., Kurosky A., Wasi S. Biochem. Biophys. Res. Commun. 198:983-989(1994) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 18-37; 119-126; 172-191 AND 301-307, INTERACTION WITH HCMV. Tissue: Umbilical vein endothelial cell.
[11]	"Annexin II is a major component of fusogenic endosomal vesicles." Emans N., Gorvel J.P., Walter C., Gerke V., Kellner R., Griffiths G., Gruenberg J. J. Cell Biol. 120:1357-1369(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 234-241 AND 252-261.
[12]	"The protein-tyrosine kinase substrate p36 is also a substrate for protein kinase C in vitro and in vivo." Gould K.L., Woodgett J.R., Isacke C.M., Hunter T. Mol. Cell. Biol. 6:2738-2744(1986) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-26.
[13]	"An annexin 2 phosphorylation switch mediates p11-dependent translocation of annexin 2 to the cell surface." Deora A.B., Kreitzer G., Jacovina A.T., Hajjar K.A. J. Biol. Chem. 279:43411-43418(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT TYR-24, MUTAGENESIS OF TYR-24.
[14]	"Proteomic identification of proteins conjugated to ISG15 in mouse and human cells." Giannakopoulos N.V., Luo J.K., Papov V., Zou W., Lenschow D.J., Jacobs B.S., Borden E.C., Li J., Virgin H.W., Zhang D.E. Biochem. Biophys. Res. Commun. 336:496-506(2005) [PubMed] [Europe PMC] [Abstract] Cited for: ISGYLATION.
[15]	"Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes." Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F. J. Proteome Res. 5:3135-3144(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. Tissue: Melanoma.
[16]	"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].
[17]	"Cochlin induced TREK-1 co-expression and annexin A2 secretion: role in trabecular meshwork cell elongation and motility." Goel M., Sienkiewicz A.E., Picciani R., Lee R.K., Bhattacharya S.K. PLoS ONE 6:E23070-E23070(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH COCH.
[18]	"The crystal structure and ion channel activity of human annexin II, a peripheral membrane protein." Burger A., Berendes R., Liemann S., Benz J., Hofmann A., Goettig P., Huber R., Gerke V., Tiel C., Roemisch J., Weber K. J. Mol. Biol. 257:839-847(1996) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
+	Additional computationally mapped references.

Web resources

Protein Spotlight

Red velvet - Issue 86 of September 2007

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D00017 mRNA. Translation: BAA00013.1.
BT007432 mRNA. Translation: AAP36100.1.
BX640598 mRNA. Translation: CAE45704.1.
AC087385 Genomic DNA. No translation available.
BC001388 mRNA. Translation: AAH01388.1.
BC009564 mRNA. Translation: AAH09564.1.
BC015834 mRNA. Translation: AAH15834.1.
BC016774 mRNA. Translation: AAH16774.1.
BC021114 mRNA. Translation: AAH21114.1.
BC023990 mRNA. Translation: AAH23990.1.
BC052558 mRNA. Translation: AAH52558.1.
BC052567 mRNA. Translation: AAH52567.1.
BC066955 mRNA. Translation: AAH66955.2. Different initiation.
BC068065 mRNA. Translation: AAH68065.1.
BC093056 mRNA. Translation: AAH93056.1.

IPI

IPI00418169.
IPI00455315.

PIR

LUHU36. A23942.

RefSeq

NP_001002857.1. NM_001002857.1.
NP_001002858.1. NM_001002858.2.
NP_001129487.1. NM_001136015.2.
NP_004030.1. NM_004039.2.

UniGene

Hs.511605.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1W7B	X-ray	1.52	A	1-339	[»]
1XJL	X-ray	2.59	A/B	21-338	[»]
2HYU	X-ray	1.86	A	32-338	[»]
2HYV	X-ray	1.42	A	32-338	[»]
2HYW	X-ray	2.10	A/B	32-338	[»]
4DRW	X-ray	3.50	A/B/C/D	2-16	[»]
4HRH	X-ray	3.00	A/B	2-16	[»]

ProteinModelPortal

P07355.

ModBase

Search...

Protein-protein interaction databases

IntAct

P07355. 19 interactions.

MINT

MINT-1213203.

STRING

9606.ENSP00000346032.

PTM databases

PhosphoSite

P07355.

Polymorphism databases

DMDM

113950.

2D gel databases

DOSAC-COBS-2DPAGE

P07355.

REPRODUCTION-2DPAGE

IPI00455315.
P07355.

UCD-2DPAGE

P07355.

Proteomic databases

PaxDb

P07355.

PRIDE

P07355.

Protocols and materials databases

DNASU

302.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000332680; ENSP00000346032; ENSG00000182718.
ENST00000396024; ENSP00000379342; ENSG00000182718.
ENST00000421017; ENSP00000411352; ENSG00000182718.
ENST00000451270; ENSP00000387545; ENSG00000182718.

GeneID

302.

KEGG

hsa:302.

UCSC

uc002agk.3. human.
uc002agm.3. human.

Organism-specific databases

CTD

302.

GeneCards

GC15M060639.

HGNC

HGNC:537. ANXA2.

HPA

CAB004311.

MIM

151740. gene.

neXtProt

NX_P07355.

PharmGKB

PA24827.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG259189.

HOGENOM

HOG000158803.

HOVERGEN

HBG061815.

InParanoid

P07355.

OMA

FIQQDTK.

OrthoDB

EOG4KD6MM.

Gene expression databases

ArrayExpress

P07355.

Bgee

P07355.

CleanEx

HS_ANXA2.

Genevestigator

P07355.

GermOnline

ENSG00000182718. Homo sapiens.

Family and domain databases

Gene3D

1.10.220.10. 4 hits.

InterPro

IPR001464. Annexin.
IPR018502. Annexin_repeat.
IPR018252. Annexin_repeat_CS.
IPR002389. AnnexinII.
[Graphical view]

PANTHER

PTHR10502. PTHR10502. 1 hit.
PTHR10502:SF18. PTHR10502:SF18. 1 hit.

Pfam

PF00191. Annexin. 4 hits.
[Graphical view]

PRINTS

PR00196. ANNEXIN.
PR00198. ANNEXINII.

SMART

SM00335. ANX. 4 hits.
[Graphical view]

SUPFAM

SSF47874. Annexin. 1 hit.

PROSITE

PS00223. ANNEXIN. 4 hits.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P07355.

ChEMBL

CHEMBL1764938.

ChiTaRS

ANXA2. human.

DrugBank

DB00009. Alteplase.
DB00029. Anistreplase.
DB00031. Tenecteplase.

EvolutionaryTrace

P07355.

GenomeRNAi

302.

NextBio

1217.

SOURCE

Search...

Entry information

Entry name

ANXA2_HUMAN

Accession

Primary (citable) accession number: P07355
Secondary accession number(s): Q567R4 , Q6N0B3, Q8TBV2, Q96DD5, Q9UDH8

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1988
Last sequence update:	January 23, 2007
Last modified:	May 29, 2013
This is version 168 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.