ANXA2_RAT
ID ANXA2_RAT Reviewed; 339 AA.
AC Q07936;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 188.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
RX PubMed=8389036;
RA Ozaki T., Sakiyama S.;
RT "Molecular cloning of rat calpactin I heavy-chain cDNA whose expression is
RT induced in v-src-transformed rat culture cell lines.";
RL Oncogene 8:1707-1710(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
RA Ernst J.D.;
RL Submitted (MAR-1993) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
RX PubMed=8092993; DOI=10.1042/bj3020425;
RA Upton A.L., Moss S.E.;
RT "Molecular cloning of a novel N-terminal variant of annexin II from rat
RT basophilic leukaemia cells.";
RL Biochem. J. 302:425-428(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT).
RC TISSUE=Pituitary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PROTEIN SEQUENCE OF 2-10; 38-47; 50-63; 69-77; 89-115; 120-145; 158-168;
RP 180-204; 234-245 AND 314-324, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION
RP AT SER-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Fibroblast;
RA Bienvenut W.V., von Kriegsheim A., Kolch W.;
RL Submitted (JUN-2009) to UniProtKB.
RN [6]
RP PROTEIN SEQUENCE OF 38-47; 50-63; 89-115; 136-145; 158-168; 180-196 AND
RP 314-324 (ISOFORMS SHORT/LONG), AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain, and Spinal cord;
RA Lubec G., Afjehi-Sadat L., Kang S.U.;
RL Submitted (JUL-2007) to UniProtKB.
RN [7]
RP SUBCELLULAR LOCATION.
RX PubMed=1618851; DOI=10.1016/s0021-9258(18)42239-9;
RA Mizutani A., Usuda N., Tokumitsu H., Minami H., Yasui K., Kobayashi R.,
RA Hidaka H.;
RT "CAP-50, a newly identified annexin, localizes in nuclei of cultured
RT fibroblast 3Y1 cells.";
RL J. Biol. Chem. 267:13498-13504(1992).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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).
CC {ECO:0000250|UniProtKB:A2SW69, ECO:0000250|UniProtKB:P07355,
CC ECO:0000250|UniProtKB:P07356, ECO:0000250|UniProtKB:Q6TEQ7}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix, basement membrane {ECO:0000269|PubMed:1618851}. Melanosome
CC {ECO:0000250}. Note=In the lamina beneath the plasma membrane.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Short;
CC IsoId=Q07936-1; Sequence=Displayed;
CC Name=Long;
CC IsoId=Q07936-2; Sequence=VSP_000287;
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";
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DR EMBL; X66871; CAA47343.1; -; mRNA.
DR EMBL; L13039; AAA40741.1; -; mRNA.
DR EMBL; S73559; AAB31934.2; -; mRNA.
DR EMBL; S73557; AAB31933.2; -; mRNA.
DR EMBL; BC059136; AAH59136.1; -; mRNA.
DR PIR; S33700; S33700.
DR PIR; S55277; S55277.
DR RefSeq; NP_063970.1; NM_019905.1. [Q07936-1]
DR AlphaFoldDB; Q07936; -.
DR SMR; Q07936; -.
DR BioGRID; 248566; 5.
DR CORUM; Q07936; -.
DR IntAct; Q07936; 5.
DR STRING; 10116.ENSRNOP00000038428; -.
DR iPTMnet; Q07936; -.
DR PhosphoSitePlus; Q07936; -.
DR jPOST; Q07936; -.
DR PaxDb; Q07936; -.
DR PRIDE; Q07936; -.
DR GeneID; 56611; -.
DR KEGG; rno:56611; -.
DR UCSC; RGD:621170; rat. [Q07936-1]
DR CTD; 302; -.
DR RGD; 621170; Anxa2.
DR VEuPathDB; HostDB:ENSRNOG00000010362; -.
DR eggNOG; KOG0819; Eukaryota.
DR HOGENOM; CLU_025300_0_0_1; -.
DR InParanoid; Q07936; -.
DR OMA; EVDLMRI; -.
DR OrthoDB; 856254at2759; -.
DR PhylomeDB; Q07936; -.
DR TreeFam; TF105452; -.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR Reactome; R-RNO-75205; Dissolution of Fibrin Clot.
DR PRO; PR:Q07936; -.
DR Proteomes; UP000002494; Chromosome 8.
DR Bgee; ENSRNOG00000010362; Expressed in jejunum and 19 other tissues.
DR Genevisible; Q07936; RN.
DR GO; GO:1990665; C:AnxA2-p11 complex; ISO:RGD.
DR GO; GO:0005604; C:basement membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:RGD.
DR GO; GO:0005938; C:cell cortex; IDA:RGD.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0001533; C:cornified envelope; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:CAFA.
DR GO; GO:0005769; C:early endosome; ISO:RGD.
DR GO; GO:0005768; C:endosome; ISO:RGD.
DR GO; GO:0070062; C:extracellular exosome; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0019897; C:extrinsic component of plasma membrane; ISO:RGD.
DR GO; GO:0031902; C:late endosome membrane; ISO:RGD.
DR GO; GO:0005811; C:lipid droplet; ISO:RGD.
DR GO; GO:0005765; C:lysosomal membrane; ISO:RGD.
DR GO; GO:0044354; C:macropinosome; IDA:RGD.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0045121; C:membrane raft; IDA:CAFA.
DR GO; GO:0030496; C:midbody; ISO:RGD.
DR GO; GO:0035749; C:myelin sheath adaxonal region; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:1990667; C:PCSK9-AnxA2 complex; ISO:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0098797; C:plasma membrane protein complex; ISO:RGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISO:RGD.
DR GO; GO:0001726; C:ruffle; IDA:RGD.
DR GO; GO:0042383; C:sarcolemma; ISO:RGD.
DR GO; GO:0043220; C:Schmidt-Lanterman incisure; ISO:RGD.
DR GO; GO:0031982; C:vesicle; IDA:RGD.
DR GO; GO:0051015; F:actin filament binding; TAS:RGD.
DR GO; GO:0044730; F:bone sialoprotein binding; IPI:RGD.
DR GO; GO:0005262; F:calcium channel activity; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central.
DR GO; GO:0005544; F:calcium-dependent phospholipid binding; ISO:RGD.
DR GO; GO:0048306; F:calcium-dependent protein binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:RGD.
DR GO; GO:0001786; F:phosphatidylserine binding; IBA:GO_Central.
DR GO; GO:0019834; F:phospholipase A2 inhibitor activity; ISO:RGD.
DR GO; GO:0002020; F:protease binding; ISO:RGD.
DR GO; GO:0044548; F:S100 protein binding; ISO:RGD.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; ISO:RGD.
DR GO; GO:0031267; F:small GTPase binding; IPI:RGD.
DR GO; GO:0046790; F:virion binding; IBA:GO_Central.
DR GO; GO:0001525; P:angiogenesis; ISO:RGD.
DR GO; GO:0007589; P:body fluid secretion; IMP:RGD.
DR GO; GO:0030199; P:collagen fibril organization; ISO:RGD.
DR GO; GO:0042730; P:fibrinolysis; ISO:RGD.
DR GO; GO:0001765; P:membrane raft assembly; ISO:RGD.
DR GO; GO:0042789; P:mRNA transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0032804; P:negative regulation of low-density lipoprotein particle receptor catabolic process; ISO:RGD.
DR GO; GO:0002091; P:negative regulation of receptor internalization; ISO:RGD.
DR GO; GO:0036035; P:osteoclast development; ISO:RGD.
DR GO; GO:0051099; P:positive regulation of binding; ISO:RGD.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IMP:RGD.
DR GO; GO:1905581; P:positive regulation of low-density lipoprotein particle clearance; ISO:RGD.
DR GO; GO:1905597; P:positive regulation of low-density lipoprotein particle receptor binding; ISO:RGD.
DR GO; GO:1905599; P:positive regulation of low-density lipoprotein receptor activity; ISO:RGD.
DR GO; GO:0010756; P:positive regulation of plasminogen activation; ISO:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:RGD.
DR GO; GO:0001921; P:positive regulation of receptor recycling; ISO:RGD.
DR GO; GO:1905602; P:positive regulation of receptor-mediated endocytosis involved in cholesterol transport; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0044090; P:positive regulation of vacuole organization; ISO:RGD.
DR GO; GO:0031340; P:positive regulation of vesicle fusion; ISO:RGD.
DR GO; GO:0072659; P:protein localization to plasma membrane; IMP:RGD.
DR GO; GO:0051917; P:regulation of fibrinolysis; TAS:RGD.
DR GO; GO:0050767; P:regulation of neurogenesis; ISO:RGD.
DR GO; GO:0097066; P:response to thyroid hormone; IEP:RGD.
DR GO; GO:0006900; P:vesicle budding from membrane; ISO:RGD.
DR Gene3D; 1.10.220.10; -; 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:SF18; PTHR10502:SF18; 1.
DR Pfam; PF00191; Annexin; 4.
DR PRINTS; PR00196; ANNEXIN.
DR PRINTS; PR00198; ANNEXINII.
DR SMART; SM00335; ANX; 4.
DR SUPFAM; SSF47874; SSF47874; 1.
DR PROSITE; PS00223; ANNEXIN_1; 4.
DR PROSITE; PS51897; ANNEXIN_2; 4.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Annexin; Basement membrane; Calcium;
KW Calcium/phospholipid-binding; Direct protein sequencing;
KW Extracellular matrix; Isopeptide bond; Phosphoprotein; Reference proteome;
KW Repeat; Secreted; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.5"
FT CHAIN 2..339
FT /note="Annexin A2"
FT /id="PRO_0000067473"
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|Ref.5"
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 VAR_SEQ 16
FT /note="D -> DSQ (in isoform Long)"
FT /evidence="ECO:0000303|PubMed:8092993"
FT /id="VSP_000287"
FT CONFLICT 103
FT /note="L -> F (in Ref. 3; AAB31934/AAB31933)"
FT /evidence="ECO:0000305"
FT CONFLICT 322
FT /note="D -> Y (in Ref. 3; AAB31934/AAB31933)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 339 AA; 38678 MW; 101E67F50C01CF8B CRC64;
MSTVHEILCK LSLEGDHSTP PSAYGSVKPY TNFDAERDAL NIETAIKTKG VDEVTIVNIL
TNRSNAQRQD IAFAYQRRTK KELPSAMKSA LSGHLETVML GLLKTPAQYD ASELKASMKG
LGTDEDSLIE IICSRTNQEL QEINRVYKEM YKTDLEKDII SDTSGEFRKL LVALAKGKRA
EDGSVIDYEL IDQDARELYD AGVKRKGTDV PKWISIMTER SVCHLQKVFE RYKSYSPYDM
LESIRKEVKG DLENAFLNLV QCIQNKPLYF ADRLYDSMKG KGTRDKVLIR IMVSRSEVDM
LKIRSEFKRK YGKSLYYFIQ QDTKGDYQKA LLYLCGGDD
