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Protein

Annexin A2

Gene

ANXA2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. Inhibits PCSK9-enhanced LDLR degradation, probably reduces PCSK9 protein levels via a translational mechanism but also competes with LDLR for binding with PCSK9 (PubMed:18799458, PubMed:24808179, PubMed:22848640).3 Publications

Miscellaneous

It may cross-link plasma membrane phospholipids with actin and the cytoskeleton and be involved with exocytosis.

GO - Molecular functioni

  • cadherin binding involved in cell-cell adhesion Source: BHF-UCL
  • calcium-dependent phospholipid binding Source: UniProtKB
  • calcium-dependent protein binding Source: AgBase
  • calcium ion binding Source: InterPro
  • cytoskeletal protein binding Source: InterPro
  • identical protein binding Source: IntAct
  • phosphatidylinositol-4,5-bisphosphate binding Source: UniProtKB
  • phospholipase A2 inhibitor activity Source: UniProtKB
  • protease binding Source: BHF-UCL
  • Rab GTPase binding Source: Ensembl
  • RNA binding Source: UniProtKB
  • S100 protein binding Source: UniProtKB

GO - Biological processi

  • angiogenesis Source: UniProtKB
  • body fluid secretion Source: Ensembl
  • catabolism by host of symbiont protein Source: AgBase
  • collagen fibril organization Source: Ensembl
  • fibrinolysis Source: Ensembl
  • interleukin-12-mediated signaling pathway Source: Reactome
  • membrane budding Source: UniProtKB
  • membrane raft assembly Source: UniProtKB
  • negative regulation by host of symbiont molecular function Source: AgBase
  • negative regulation of development of symbiont involved in interaction with host Source: AgBase
  • negative regulation of low-density lipoprotein particle receptor catabolic process Source: BHF-UCL
  • neutrophil degranulation Source: Reactome
  • osteoclast development Source: UniProtKB
  • positive regulation of fibroblast proliferation Source: Ensembl
  • positive regulation of low-density lipoprotein particle clearance Source: BHF-UCL
  • positive regulation of low-density lipoprotein particle receptor binding Source: BHF-UCL
  • positive regulation of low-density lipoprotein receptor activity Source: BHF-UCL
  • positive regulation of protein phosphorylation Source: Ensembl
  • positive regulation of receptor-mediated endocytosis involved in cholesterol transport Source: BHF-UCL
  • positive regulation of receptor recycling Source: BHF-UCL
  • positive regulation of vacuole organization Source: AgBase
  • positive regulation of vesicle fusion Source: UniProtKB
  • protein heterotetramerization Source: UniProtKB
  • protein targeting to plasma membrane Source: Ensembl
  • response to thyroid hormone Source: Ensembl

Keywordsi

Molecular functionRNA-binding
LigandCalcium, Calcium/phospholipid-binding

Enzyme and pathway databases

ReactomeiR-HSA-445355. Smooth Muscle Contraction.
R-HSA-6798695. Neutrophil degranulation.
R-HSA-75205. Dissolution of Fibrin Clot.
R-HSA-8950505. Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation.
SIGNORiP07355.

Protein family/group databases

TCDBi1.A.31.1.4. the annexin (annexin) family.

Names & Taxonomyi

Protein namesi
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 namesi
Name:ANXA2
Synonyms:ANX2, ANX2L4, CAL1H, LPC2D
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

EuPathDBiHostDB:ENSG00000182718.16.
HGNCiHGNC:537. ANXA2.

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

Basement membrane, Extracellular matrix, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi24Y → A: Abolishes heat stress-induced cell surface localization. 1 Publication1
Mutagenesisi28 – 36KAYTNFDAE → SAYTNFNAS: No effect on interaction with PCSK9. 1 Publication9
Mutagenesisi37 – 47RDALNIETAIK → SDALNIHTAIM: Slightly decreases interaction with PCSK9. 1 PublicationAdd BLAST11
Mutagenesisi77 – 81RRTKK → AATAA: Strongly decreases interaction with PCSK9. 2 Publications5
Mutagenesisi77 – 80RRTK → AATA: Decreases interaction with PCSK9. Strongly decreases interaction with PCSK9; when associated with K-88. 1 Publication4
Mutagenesisi80 – 84KKELA → GKPLD: No effect on interaction with PCSK9. 1 Publication5
Mutagenesisi88K → A: Strongly decreases interaction with PCSK9; when associated with 77-A--A-80. 1 Publication1

Organism-specific databases

DisGeNETi302.
OpenTargetsiENSG00000182718.
PharmGKBiPA24827.

Chemistry databases

ChEMBLiCHEMBL1764938.
DrugBankiDB00031. Tenecteplase.

Polymorphism and mutation databases

BioMutaiANXA2.
DMDMi113950.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00000674702 – 339Annexin A2Add BLAST338

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserine1 Publication1
Modified residuei24Phosphotyrosine; by SRC1 Publication1
Modified residuei26Phosphoserine; by PKC1 Publication1
Modified residuei49N6-acetyllysine; alternateBy similarity1
Cross-linki49Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternateCombined sources
Cross-linki49Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei152N6-acetyllysineBy similarity1
Modified residuei184PhosphoserineCombined sources1
Modified residuei199PhosphotyrosineBy similarity1
Modified residuei227N6-acetyllysineBy similarity1

Post-translational modificationi

Phosphorylation of Tyr-24 enhances heat stress-induced translocation to the cell surface.2 Publications
ISGylated.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP07355.
MaxQBiP07355.
PaxDbiP07355.
PeptideAtlasiP07355.
PRIDEiP07355.
TopDownProteomicsiP07355-1. [P07355-1]

2D gel databases

DOSAC-COBS-2DPAGEiP07355.
REPRODUCTION-2DPAGEiIPI00455315.
P07355.
UCD-2DPAGEiP07355.

PTM databases

iPTMnetiP07355.
PhosphoSitePlusiP07355.
SwissPalmiP07355.

Expressioni

Gene expression databases

BgeeiENSG00000182718.
CleanExiHS_ANXA2.
ExpressionAtlasiP07355. baseline and differential.
GenevisibleiP07355. HS.

Organism-specific databases

HPAiCAB004311.

Interactioni

Subunit structurei

Heterotetramer containing 2 light chains of S100A10/p11 and 2 heavy chains of ANXA2/p36 (By similarity). Interacts with ATP1B1 (By similarity). Interacts with DYSF (By similarity). Interacts with COCH (PubMed:21886777). Interacts (via repeat Annexin 1) with PCSK9 (via the C-terminal domain); the interaction inhibits the degradation of LDLR (PubMed:18799458). Interacts with CEACAM1 (via the cytoplasmic domain); this interaction is regulated by phosphorylation of CEACAM1 (PubMed:14522961).By similarity3 Publications
(Microbial infection) Interacts with human cytomegalovirus (HCMV).1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • cadherin binding involved in cell-cell adhesion Source: BHF-UCL
  • calcium-dependent protein binding Source: AgBase
  • cytoskeletal protein binding Source: InterPro
  • identical protein binding Source: IntAct
  • protease binding Source: BHF-UCL
  • Rab GTPase binding Source: Ensembl
  • S100 protein binding Source: UniProtKB

Protein-protein interaction databases

BioGridi106799. 112 interactors.
CORUMiP07355.
IntActiP07355. 71 interactors.
MINTiMINT-1213203.
STRINGi9606.ENSP00000346032.

Structurei

Secondary structure

1339
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi3 – 8Combined sources6
Helixi35 – 47Combined sources13
Helixi53 – 60Combined sources8
Helixi65 – 79Combined sources15
Helixi83 – 90Combined sources8
Helixi93 – 103Combined sources11
Helixi106 – 117Combined sources12
Beta strandi120 – 122Combined sources3
Helixi125 – 134Combined sources10
Helixi137 – 151Combined sources15
Helixi155 – 161Combined sources7
Helixi165 – 175Combined sources11
Helixi188 – 200Combined sources13
Turni201 – 204Combined sources4
Beta strandi205 – 207Combined sources3
Helixi210 – 219Combined sources10
Helixi222 – 232Combined sources11
Turni233 – 235Combined sources3
Helixi240 – 247Combined sources8
Helixi250 – 264Combined sources15
Helixi266 – 278Combined sources13
Beta strandi279 – 282Combined sources4
Helixi285 – 295Combined sources11
Turni296 – 298Combined sources3
Helixi300 – 311Combined sources12
Helixi315 – 322Combined sources8
Helixi325 – 335Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1W7BX-ray1.52A1-339[»]
1XJLX-ray2.59A/B21-339[»]
2HYUX-ray1.86A32-339[»]
2HYVX-ray1.42A32-339[»]
2HYWX-ray2.10A/B32-339[»]
4DRWX-ray3.50A/B/C/D2-16[»]
4FTGX-ray2.51C/D2-16[»]
4HRHX-ray3.00A/B2-16[»]
ProteinModelPortaliP07355.
SMRiP07355.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP07355.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati42 – 102Annexin 1Add BLAST61
Repeati114 – 174Annexin 2Add BLAST61
Repeati199 – 259Annexin 3Add BLAST61
Repeati274 – 334Annexin 4Add BLAST61

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 24S100A10-binding siteSequence analysisAdd BLAST23

Domaini

A pair of annexin repeats may form one binding site for calcium and phospholipid.

Sequence similaritiesi

Belongs to the annexin family.Curated

Keywords - Domaini

Annexin, Repeat

Phylogenomic databases

eggNOGiKOG0819. Eukaryota.
ENOG410XPUN. LUCA.
GeneTreeiENSGT00760000118972.
HOGENOMiHOG000158803.
HOVERGENiHBG061815.
InParanoidiP07355.
KOiK17092.
OMAiFIQQDTK.
OrthoDBiEOG091G0H6H.
TreeFamiTF105452.

Family and domain databases

Gene3Di1.10.220.10. 4 hits.
InterProiView protein in InterPro
IPR001464. Annexin.
IPR018502. Annexin_repeat.
IPR018252. Annexin_repeat_CS.
IPR002389. ANX2.
PANTHERiPTHR10502:SF151. PTHR10502:SF151. 1 hit.
PfamiView protein in Pfam
PF00191. Annexin. 4 hits.
PRINTSiPR00196. ANNEXIN.
PR00198. ANNEXINII.
SMARTiView protein in SMART
SM00335. ANX. 4 hits.
PROSITEiView protein in PROSITE
PS00223. ANNEXIN. 4 hits.

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P07355-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MSTVHEILCK LSLEGDHSTP PSAYGSVKAY TNFDAERDAL NIETAIKTKG
60 70 80 90 100
VDEVTIVNIL TNRSNAQRQD IAFAYQRRTK KELASALKSA LSGHLETVIL
110 120 130 140 150
GLLKTPAQYD ASELKASMKG LGTDEDSLIE IICSRTNQEL QEINRVYKEM
160 170 180 190 200
YKTDLEKDII SDTSGDFRKL MVALAKGRRA EDGSVIDYEL IDQDARDLYD
210 220 230 240 250
AGVKRKGTDV PKWISIMTER SVPHLQKVFD RYKSYSPYDM LESIRKEVKG
260 270 280 290 300
DLENAFLNLV QCIQNKPLYF ADRLYDSMKG KGTRDKVLIR IMVSRSEVDM
310 320 330
LKIRSEFKRK YGKSLYYYIQ QDTKGDYQKA LLYLCGGDD
Length:339
Mass (Da):38,604
Last modified:January 23, 2007 - v2
Checksum:i5126E1337A0CBEA1
GO
Isoform 2 (identifier: P07355-2) [UniParc]FASTAAdd to basket

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

Show »
Length:357
Mass (Da):40,411
Checksum:i2AA081CB4E7AC75C
GO

Sequence cautioni

The sequence AAH66955 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti29A → P AA sequence (PubMed:8110754).Curated1
Sequence conflicti166D → G in CAE45704 (PubMed:17974005).Curated1
Sequence conflicti293V → A in AAH23990 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01298298V → L Polymorphism; does not affect interaction with PCSK9. 2 PublicationsCorresponds to variant dbSNP:rs17845226Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0380911M → MGRQLAGCGDAGKKASFKM in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS10175.1. [P07355-1]
CCDS32256.1. [P07355-2]
PIRiA23942. LUHU36.
RefSeqiNP_001002857.1. NM_001002857.1. [P07355-1]
NP_001002858.1. NM_001002858.2. [P07355-2]
NP_001129487.1. NM_001136015.2. [P07355-1]
NP_004030.1. NM_004039.2. [P07355-1]
XP_016877579.1. XM_017022090.1. [P07355-1]
XP_016877580.1. XM_017022091.1. [P07355-1]
UniGeneiHs.511605.

Genome annotation databases

EnsembliENST00000332680; ENSP00000346032; ENSG00000182718. [P07355-2]
ENST00000396024; ENSP00000379342; ENSG00000182718. [P07355-1]
ENST00000421017; ENSP00000411352; ENSG00000182718. [P07355-1]
ENST00000451270; ENSP00000387545; ENSG00000182718. [P07355-1]
GeneIDi302.
KEGGihsa:302.
UCSCiuc002agk.4. human. [P07355-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiANXA2_HUMAN
AccessioniPrimary (citable) accession number: P07355
Secondary accession number(s): Q567R4
, Q6N0B3, Q8TBV2, Q96DD5, Q9UDH8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: January 23, 2007
Last modified: September 27, 2017
This is version 215 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, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  7. SIMILARITY comments
    Index of protein domains and families