ID ANXA2_BOVIN Reviewed; 339 AA. AC P04272; Q3ZCC7; Q5E9B0; DT 01-NOV-1986, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 24-JAN-2024, entry version 196. DE RecName: Full=Annexin A2; DE AltName: Full=Annexin II; DE AltName: Full=Annexin-2; DE AltName: Full=Calpactin I heavy chain; DE AltName: Full=Calpactin-1 heavy chain; DE AltName: Full=Chromobindin-8; DE AltName: Full=Lipocortin II; DE AltName: Full=Placental anticoagulant protein IV; DE Short=PAP-IV; DE AltName: Full=Protein I; DE AltName: Full=p36; GN Name=ANXA2; Synonyms=ANX2; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Kidney; RX PubMed=2945590; DOI=10.1021/bi00364a007; RA Kristensen T., Saris C.J.M., Hunter T., Hicks L.J., Noonan D.J., RA Glenney J.R. Jr., Tack B.F.; RT "Primary structure of bovine calpactin I heavy chain (p36), a major RT cellular substrate for retroviral protein-tyrosine kinases: homology with RT the human phospholipase A2 inhibitor lipocortin."; RL Biochemistry 25:4497-4503(1986). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=16305752; DOI=10.1186/1471-2164-6-166; RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L., RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.; RT "Characterization of 954 bovine full-CDS cDNA sequences."; RL BMC Genomics 6:166-166(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Crossbred X Angus; TISSUE=Ileum; RG NIH - Mammalian Gene Collection (MGC) project; RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP ACETYLATION AT SER-2. RX PubMed=2942542; DOI=10.1016/s0021-9258(18)67409-5; RA Glenney J.R. Jr., Boudreau M., Galyean R., Hunter T., Tack B.; RT "Association of the S-100-related calpactin I light chain with the NH2- RT terminal tail of the 36-kDa heavy chain."; RL J. Biol. Chem. 261:10485-10488(1986). CC -!- FUNCTION: Calcium-regulated membrane-binding protein whose affinity for CC calcium is greatly enhanced by anionic phospholipids. It binds two CC calcium ions with high affinity. May be involved in heat-stress CC response. Inhibits PCSK9-enhanced LDLR degradation, probably reduces CC PCSK9 protein levels via a translational mechanism but also competes CC with LDLR for binding with PCSK9. {ECO:0000250|UniProtKB:P07355}. CC -!- SUBUNIT: Heterotetramer containing 2 light chains of S100A10/p11 and 2 CC heavy chains of ANXA2/p36 (By similarity). Interacts with ATP1B1 (By CC similarity). Interacts with DYSF (By similarity). Interacts with COCH. CC Interacts (via repeat Annexin 1) with PCSK9 (via the C-terminal CC domain); the interaction inhibits the degradation of LDLR. Interacts CC with CEACAM1 (via the cytoplasmic domain); this interaction is CC regulated by phosphorylation of CEACAM1 (By similarity). Interacts with CC APPL2 and APPL1; targets APPL2 to endosomes and acting in parallel to CC RAB5A (By similarity). Interacts with S100A4 (By similarity). May CC interact with UBAP2 (By similarity). {ECO:0000250|UniProtKB:A2SW69, CC ECO:0000250|UniProtKB:P07355, ECO:0000250|UniProtKB:P07356, CC ECO:0000250|UniProtKB:Q6TEQ7}. CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular CC matrix, basement membrane. Melanosome {ECO:0000250}. Note=In the lamina CC beneath the plasma membrane. CC -!- DOMAIN: A pair of annexin repeats may form one binding site for calcium CC and phospholipid. CC -!- PTM: ISGylated. {ECO:0000250}. CC -!- MISCELLANEOUS: It may cross-link plasma membrane phospholipids with CC actin and the cytoskeleton and be involved with exocytosis. CC -!- SIMILARITY: Belongs to the annexin family. {ECO:0000255|PROSITE- CC ProRule:PRU01245, ECO:0000305}. CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Red velvet - Issue 86 of CC September 2007; CC URL="https://web.expasy.org/spotlight/back_issues/086"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M14056; AAA30421.1; -; mRNA. DR EMBL; BT021010; AAX09027.1; -; mRNA. DR EMBL; BC102516; AAI02517.1; -; mRNA. DR PIR; A03081; LUBO36. DR RefSeq; NP_777141.1; NM_174716.1. DR PDB; 4X9P; X-ray; 2.01 A; A=1-339. DR PDBsum; 4X9P; -. DR AlphaFoldDB; P04272; -. DR SMR; P04272; -. DR IntAct; P04272; 1. DR STRING; 9913.ENSBTAP00000012655; -. DR ChEMBL; CHEMBL3308972; -. DR iPTMnet; P04272; -. DR PaxDb; 9913-ENSBTAP00000012655; -. DR PeptideAtlas; P04272; -. DR Ensembl; ENSBTAT00000012655.4; ENSBTAP00000012655.3; ENSBTAG00000009615.4. DR GeneID; 282689; -. DR KEGG; bta:282689; -. DR CTD; 302; -. DR VEuPathDB; HostDB:ENSBTAG00000009615; -. DR eggNOG; KOG0819; Eukaryota. DR GeneTree; ENSGT00940000154257; -. DR HOGENOM; CLU_025300_0_0_1; -. DR InParanoid; P04272; -. DR OMA; DLMRIRT; -. DR OrthoDB; 1500773at2759; -. DR TreeFam; TF105452; -. DR Reactome; R-BTA-6798695; Neutrophil degranulation. DR Reactome; R-BTA-75205; Dissolution of Fibrin Clot. DR Proteomes; UP000009136; Chromosome 10. DR Bgee; ENSBTAG00000009615; Expressed in placenta and 106 other cell types or tissues. DR GO; GO:0005604; C:basement membrane; IEA:UniProtKB-SubCell. DR GO; GO:0062023; C:collagen-containing extracellular matrix; IBA:GO_Central. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IDA:AgBase. DR GO; GO:0005768; C:endosome; ISS:UniProtKB. DR GO; GO:0065010; C:extracellular membrane-bounded organelle; IDA:AgBase. DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:AgBase. DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; IDA:AgBase. DR GO; GO:0005634; C:nucleus; IDA:AgBase. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0031982; C:vesicle; IDA:AgBase. DR GO; GO:0005262; F:calcium channel activity; IMP:AgBase. DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central. DR GO; GO:0005544; F:calcium-dependent phospholipid binding; IBA:GO_Central. DR GO; GO:0008092; F:cytoskeletal protein binding; IEA:InterPro. DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IBA:GO_Central. DR GO; GO:0001786; F:phosphatidylserine binding; IPI:AgBase. DR GO; GO:0019834; F:phospholipase A2 inhibitor activity; IBA:GO_Central. DR GO; GO:0002020; F:protease binding; IBA:GO_Central. DR GO; GO:0046790; F:virion binding; IBA:GO_Central. DR GO; GO:0031214; P:biomineral tissue development; IDA:AgBase. DR GO; GO:0070509; P:calcium ion import; IMP:AgBase. DR GO; GO:0070588; P:calcium ion transmembrane transport; IDA:AgBase. DR Gene3D; 1.10.220.10; Annexin; 4. DR InterPro; IPR001464; Annexin. DR InterPro; IPR018502; Annexin_repeat. DR InterPro; IPR018252; Annexin_repeat_CS. DR InterPro; IPR037104; Annexin_sf. DR InterPro; IPR002389; ANX2. DR PANTHER; PTHR10502; ANNEXIN; 1. DR PANTHER; PTHR10502:SF18; ANNEXIN A2-RELATED; 1. DR Pfam; PF00191; Annexin; 4. DR PRINTS; PR00196; ANNEXIN. DR PRINTS; PR00198; ANNEXINII. DR SMART; SM00335; ANX; 4. DR SUPFAM; SSF47874; Annexin; 1. DR PROSITE; PS00223; ANNEXIN_1; 4. DR PROSITE; PS51897; ANNEXIN_2; 4. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Annexin; Basement membrane; Calcium; KW Calcium/phospholipid-binding; Extracellular matrix; Isopeptide bond; KW Phosphoprotein; Reference proteome; Repeat; Secreted; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:2942542" FT CHAIN 2..339 FT /note="Annexin A2" FT /id="PRO_0000067469" FT REPEAT 33..104 FT /note="Annexin 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01245" FT REPEAT 105..176 FT /note="Annexin 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01245" FT REPEAT 189..261 FT /note="Annexin 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01245" FT REPEAT 265..336 FT /note="Annexin 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01245" FT REGION 2..24 FT /note="S100A10-binding site" FT /evidence="ECO:0000255" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0000269|PubMed:2942542" FT MOD_RES 24 FT /note="Phosphotyrosine; by SRC" FT /evidence="ECO:0000250|UniProtKB:P07355" FT MOD_RES 26 FT /note="Phosphoserine; by PKC" FT /evidence="ECO:0000250|UniProtKB:P07355" FT MOD_RES 49 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P07356" FT MOD_RES 152 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P07356" FT MOD_RES 184 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P07355" FT MOD_RES 199 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P07356" FT MOD_RES 227 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P07356" FT CROSSLNK 49 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1); alternate" FT /evidence="ECO:0000250|UniProtKB:P07355" FT CROSSLNK 49 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0000250|UniProtKB:P07355" FT CONFLICT 149 FT /note="E -> G (in Ref. 3; AAI02517)" FT /evidence="ECO:0000305" FT HELIX 35..47 FT /evidence="ECO:0007829|PDB:4X9P" FT HELIX 53..60 FT /evidence="ECO:0007829|PDB:4X9P" FT HELIX 65..79 FT /evidence="ECO:0007829|PDB:4X9P" FT HELIX 83..90 FT /evidence="ECO:0007829|PDB:4X9P" FT HELIX 93..103 FT /evidence="ECO:0007829|PDB:4X9P" FT HELIX 106..117 FT /evidence="ECO:0007829|PDB:4X9P" FT HELIX 125..133 FT /evidence="ECO:0007829|PDB:4X9P" FT HELIX 137..151 FT /evidence="ECO:0007829|PDB:4X9P" FT HELIX 155..162 FT /evidence="ECO:0007829|PDB:4X9P" FT HELIX 165..175 FT /evidence="ECO:0007829|PDB:4X9P" FT HELIX 188..200 FT /evidence="ECO:0007829|PDB:4X9P" FT TURN 201..204 FT /evidence="ECO:0007829|PDB:4X9P" FT STRAND 205..207 FT /evidence="ECO:0007829|PDB:4X9P" FT HELIX 210..219 FT /evidence="ECO:0007829|PDB:4X9P" FT HELIX 222..235 FT /evidence="ECO:0007829|PDB:4X9P" FT HELIX 240..247 FT /evidence="ECO:0007829|PDB:4X9P" FT HELIX 250..264 FT /evidence="ECO:0007829|PDB:4X9P" FT HELIX 266..278 FT /evidence="ECO:0007829|PDB:4X9P" FT STRAND 279..282 FT /evidence="ECO:0007829|PDB:4X9P" FT HELIX 285..295 FT /evidence="ECO:0007829|PDB:4X9P" FT TURN 296..299 FT /evidence="ECO:0007829|PDB:4X9P" FT HELIX 300..311 FT /evidence="ECO:0007829|PDB:4X9P" FT HELIX 315..322 FT /evidence="ECO:0007829|PDB:4X9P" FT HELIX 325..335 FT /evidence="ECO:0007829|PDB:4X9P" SQ SEQUENCE 339 AA; 38612 MW; AA8E2500F4138B3D CRC64; MSTVHEILCK LSLEGDHSTP PSAYGSVKAY TNFDAERDAL NIETAIKTKG VDEVTIVNIL TNRSNEQRQD IAFAYQRRTK KELASALKSA LSGHLETVIL GLLKTPAQYD ASELKASMKG LGTDEDSLIE IICSRTNQEL QEINRVYKEM YKTDLEKDIV SDTSGDFRKL MVALAKGRRA EDGSVIDYEL IDQDARDLYD AGVKRKGTDV PKWISIMTER SVCHLQKVFE RYKSYSPYDM LESIKKEVKG DLENAFLNLV QCIQNKPLYF ADRLYDSMKG KGTRDKVLIR IMVSRSEVDM LKIRSEFKKK YGKSLYYYIQ QDTKGDYQKA LLYLCGGDD //