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Protein

Annexin A2

Gene

ANXA2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

GO - Biological processi

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
MIMi151740 gene
neXtProtiNX_P07355

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
ProteomicsDBi51995
51996 [P07355-2]
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 Expressed in 227 organ(s), highest expression level in epithelium of bronchus
CleanExiHS_ANXA2
ExpressionAtlasiP07355 baseline and differential
GenevisibleiP07355 HS

Organism-specific databases

HPAiCAB004311
HPA046964
HPA061798

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi106799, 123 interactors
ComplexPortaliCPX-130 ANXA2-PCSK9 complex
CPX-850 AHNAK - Annexin A2 - S100-A10 complex
CPX-853 Annexin A2 - S100-A10 complex
CPX-856 SMARCA3 - Annexin A2 - S100-A10 complex
CORUMiP07355
IntActiP07355, 61 interactors
MINTiP07355
STRINGi9606.ENSP00000346032

Structurei

Secondary structure

1339
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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
OMAiLVECFEN
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
IPR037104 Annexin_sf
IPR002389 ANX2
PANTHERiPTHR10502:SF18 PTHR10502:SF18, 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

This entry has 2 described isoforms and 22 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 22 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YL33H0YL33_HUMAN
Annexin
ANXA2
142Annotation score:
H0YKX9H0YKX9_HUMAN
Annexin
ANXA2
134Annotation score:
H0YLV6H0YLV6_HUMAN
Annexin
ANXA2
132Annotation score:
H0YN42H0YN42_HUMAN
Annexin
ANXA2
256Annotation score:
H0YMU9H0YMU9_HUMAN
Annexin
ANXA2
230Annotation score:
H0YMT9H0YMT9_HUMAN
Annexin
ANXA2
133Annotation score:
H0YMD0H0YMD0_HUMAN
Annexin
ANXA2
227Annotation score:
H0YMW4H0YMW4_HUMAN
Annexin
ANXA2
146Annotation score:
H0YN28H0YN28_HUMAN
Annexin
ANXA2
139Annotation score:
H0YKZ7H0YKZ7_HUMAN
Annexin
ANXA2
119Annotation score:
There are more potential isoformsShow all

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
Hs.675947

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

Cross-referencesi

Web resourcesi

Protein Spotlight

Red velvet - Issue 86 of September 2007

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
Hs.675947

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[»]
5LPUX-ray2.10A/B2-339[»]
5LPXX-ray1.90A2-339[»]
5LQ0X-ray2.90A/B2-339[»]
5LQ2X-ray3.40A/B2-339[»]
5N7DX-ray2.30A/B22-339[»]
5N7FX-ray2.30A/B22-339[»]
5N7GX-ray2.95A/B22-339[»]
ProteinModelPortaliP07355
SMRiP07355
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106799, 123 interactors
ComplexPortaliCPX-130 ANXA2-PCSK9 complex
CPX-850 AHNAK - Annexin A2 - S100-A10 complex
CPX-853 Annexin A2 - S100-A10 complex
CPX-856 SMARCA3 - Annexin A2 - S100-A10 complex
CORUMiP07355
IntActiP07355, 61 interactors
MINTiP07355
STRINGi9606.ENSP00000346032

Chemistry databases

ChEMBLiCHEMBL1764938
DrugBankiDB00031 Tenecteplase

Protein family/group databases

TCDBi1.A.31.1.4 the annexin (annexin) family

PTM databases

iPTMnetiP07355
PhosphoSitePlusiP07355
SwissPalmiP07355

Polymorphism and mutation databases

BioMutaiANXA2
DMDMi113950

2D gel databases

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

Proteomic databases

EPDiP07355
MaxQBiP07355
PaxDbiP07355
PeptideAtlasiP07355
PRIDEiP07355
ProteomicsDBi51995
51996 [P07355-2]
TopDownProteomicsiP07355-1 [P07355-1]

Protocols and materials databases

DNASUi302
Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi302
DisGeNETi302
EuPathDBiHostDB:ENSG00000182718.16
GeneCardsiANXA2
HGNCiHGNC:537 ANXA2
HPAiCAB004311
HPA046964
HPA061798
MIMi151740 gene
neXtProtiNX_P07355
OpenTargetsiENSG00000182718
PharmGKBiPA24827
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0819 Eukaryota
ENOG410XPUN LUCA
GeneTreeiENSGT00760000118972
HOGENOMiHOG000158803
HOVERGENiHBG061815
InParanoidiP07355
KOiK17092
OMAiLVECFEN
OrthoDBiEOG091G0H6H
TreeFamiTF105452

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

Miscellaneous databases

ChiTaRSiANXA2 human
EvolutionaryTraceiP07355
GeneWikiiAnnexin_A2
GenomeRNAii302
PROiPR:P07355
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000182718 Expressed in 227 organ(s), highest expression level in epithelium of bronchus
CleanExiHS_ANXA2
ExpressionAtlasiP07355 baseline and differential
GenevisibleiP07355 HS

Family and domain databases

Gene3Di1.10.220.10, 4 hits
InterProiView protein in InterPro
IPR001464 Annexin
IPR018502 Annexin_repeat
IPR018252 Annexin_repeat_CS
IPR037104 Annexin_sf
IPR002389 ANX2
PANTHERiPTHR10502:SF18 PTHR10502:SF18, 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
ProtoNetiSearch...

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: November 7, 2018
This is version 227 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  7. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
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