ANX13_HUMAN
ID ANX13_HUMAN Reviewed; 316 AA.
AC P27216; Q9BQR5;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-2009, sequence version 3.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Annexin A13;
DE AltName: Full=Annexin XIII;
DE AltName: Full=Annexin-13;
DE AltName: Full=Intestine-specific annexin {ECO:0000303|PubMed:1530946};
DE Short=ISA {ECO:0000303|PubMed:1530946};
GN Name=ANXA13; Synonyms=ANX13;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), SUBCELLULAR LOCATION,
RP MYRISTOYLATION AT GLY-2, AND TISSUE SPECIFICITY.
RX PubMed=1530946; DOI=10.1083/jcb.116.2.405;
RA Wice B.M., Gordon J.I.;
RT "A strategy for isolation of cDNAs encoding proteins affecting human
RT intestinal epithelial cell growth and differentiation: characterization of
RT a novel gut-specific N-myristoylated annexin.";
RL J. Cell Biol. 116:405-422(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
RC TISSUE=Colon adenocarcinoma;
RX PubMed=11961095; DOI=10.1093/oxfordjournals.molbev.a004120;
RA Iglesias J.M., Morgan R.O., Jenkins N.A., Copeland N.G., Gilbert D.J.,
RA Fernandez M.-P.;
RT "Comparative genetics and evolution of annexin A13 as the founder gene of
RT vertebrate annexins.";
RL Mol. Biol. Evol. 19:608-618(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [5]
RP FUNCTION (ISOFORMS A AND B).
RX PubMed=27676605; DOI=10.1515/hsz-2016-0242;
RA Fernandez-Lizarbe S., Lecona E., Santiago-Gomez A., Olmo N., Lizarbe M.A.,
RA Turnay J.;
RT "Structural and lipid-binding characterization of human annexin A13a
RT reveals strong differences with its long A13b isoform.";
RL Biol. Chem. 398:359-371(2017).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS), FUNCTION (ISOFORM A), SUBUNIT
RP (ISOFORM A), SUBCELLULAR LOCATION, AND MUTAGENESIS OF GLY-2; 32-THR--GLU-34
RP AND SER-73.
RX PubMed=30610115; DOI=10.1074/jbc.ra118.004571;
RA McCulloch K.M., Yamakawa I., Shifrin D.A. Jr., McConnell R.E.,
RA Foegeding N.J., Singh P.K., Mao S., Tyska M.J., Iverson T.M.;
RT "An alternative N-terminal fold of the intestine-specific annexin A13a
RT induces dimerization and regulates membrane-binding.";
RL J. Biol. Chem. 294:3454-3463(2019).
CC -!- FUNCTION: [Isoform A]: Binds to membranes enriched in
CC phosphatidylserine or phosphatidylglycerol in a calcium-dependent
CC manner (PubMed:27676605, PubMed:30610115). Half-maximal membrane
CC binding requires about 60 uM calcium. Does not bind to membranes that
CC lack phospholipids with an acidic headgroup (PubMed:27676605).
CC {ECO:0000269|PubMed:27676605, ECO:0000269|PubMed:30610115}.
CC -!- FUNCTION: [Isoform B]: Binds to membranes enriched in
CC phosphatidylserine or phosphatidylglycerol in a calcium-dependent
CC manner, but requires higher calcium levels for membrane binding than
CC isoform A. Half-maximal membrane binding requires about 320 uM calcium.
CC {ECO:0000269|PubMed:27676605}.
CC -!- SUBUNIT: [Isoform A]: Monomer and homodimer.
CC {ECO:0000269|PubMed:30610115}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:1530946}. Cell membrane
CC {ECO:0000269|PubMed:30610115}; Lipid-anchor
CC {ECO:0000269|PubMed:30610115}. Cytoplasmic vesicle
CC {ECO:0000250|UniProtKB:Q99JG3}. Note=Myristoylation anchors the protein
CC to the membrane, but the protein also displays calcium-dependent,
CC reversible binding to lipid membranes (PubMed:30610115). Associated
CC with the plasma membrane of undifferentiated, proliferating crypt
CC epithelial cells as well as differentiated villus enterocytes
CC (PubMed:1530946). {ECO:0000269|PubMed:1530946,
CC ECO:0000269|PubMed:30610115}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=A; Synonyms=Anx13A, A13a {ECO:0000303|PubMed:30610115};
CC IsoId=P27216-1; Sequence=Displayed;
CC Name=B; Synonyms=Anx13B, A13b {ECO:0000303|PubMed:30610115};
CC IsoId=P27216-2; Sequence=VSP_000291;
CC -!- TISSUE SPECIFICITY: Detected in epithelial cells in colon and jejunum
CC (at protein level). Detected in epithelial cells in jejunum.
CC {ECO:0000269|PubMed:1530946}.
CC -!- DOMAIN: A pair of annexin repeats may form one binding site for calcium
CC and phospholipid.
CC -!- SIMILARITY: Belongs to the annexin family. {ECO:0000255|PROSITE-
CC ProRule:PRU01245, ECO:0000305}.
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DR EMBL; Z11502; CAA77578.1; -; mRNA.
DR EMBL; AJ306450; CAC34622.1; -; mRNA.
DR EMBL; AC135166; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS34939.1; -. [P27216-2]
DR CCDS; CCDS47917.1; -. [P27216-1]
DR PIR; A41733; LUHUIS.
DR RefSeq; NP_001003954.1; NM_001003954.2. [P27216-2]
DR RefSeq; NP_004297.2; NM_004306.3. [P27216-1]
DR PDB; 6B3I; X-ray; 2.60 A; A/B/C=1-316.
DR PDBsum; 6B3I; -.
DR AlphaFoldDB; P27216; -.
DR SMR; P27216; -.
DR BioGRID; 106809; 19.
DR IntAct; P27216; 6.
DR STRING; 9606.ENSP00000262219; -.
DR GlyGen; P27216; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P27216; -.
DR PhosphoSitePlus; P27216; -.
DR BioMuta; ANXA13; -.
DR DMDM; 281185504; -.
DR EPD; P27216; -.
DR jPOST; P27216; -.
DR MassIVE; P27216; -.
DR MaxQB; P27216; -.
DR PaxDb; P27216; -.
DR PeptideAtlas; P27216; -.
DR PRIDE; P27216; -.
DR ProteomicsDB; 54377; -. [P27216-1]
DR ProteomicsDB; 54378; -. [P27216-2]
DR Antibodypedia; 13866; 224 antibodies from 29 providers.
DR DNASU; 312; -.
DR Ensembl; ENST00000262219.10; ENSP00000262219.6; ENSG00000104537.17. [P27216-2]
DR Ensembl; ENST00000419625.6; ENSP00000390809.1; ENSG00000104537.17. [P27216-1]
DR GeneID; 312; -.
DR KEGG; hsa:312; -.
DR MANE-Select; ENST00000419625.6; ENSP00000390809.1; NM_004306.4; NP_004297.2.
DR UCSC; uc003yqt.4; human. [P27216-1]
DR CTD; 312; -.
DR DisGeNET; 312; -.
DR GeneCards; ANXA13; -.
DR HGNC; HGNC:536; ANXA13.
DR HPA; ENSG00000104537; Tissue enhanced (gallbladder, intestine).
DR MIM; 602573; gene.
DR neXtProt; NX_P27216; -.
DR OpenTargets; ENSG00000104537; -.
DR PharmGKB; PA24826; -.
DR VEuPathDB; HostDB:ENSG00000104537; -.
DR eggNOG; KOG0819; Eukaryota.
DR GeneTree; ENSGT00940000159797; -.
DR HOGENOM; CLU_025300_0_2_1; -.
DR InParanoid; P27216; -.
DR OMA; MGNHHAK; -.
DR PhylomeDB; P27216; -.
DR TreeFam; TF105452; -.
DR PathwayCommons; P27216; -.
DR SignaLink; P27216; -.
DR BioGRID-ORCS; 312; 14 hits in 1062 CRISPR screens.
DR GeneWiki; ANXA13; -.
DR GenomeRNAi; 312; -.
DR Pharos; P27216; Tbio.
DR PRO; PR:P27216; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; P27216; protein.
DR Bgee; ENSG00000104537; Expressed in gall bladder and 100 other tissues.
DR ExpressionAtlas; P27216; baseline and differential.
DR Genevisible; P27216; HS.
DR GO; GO:0016324; C:apical plasma membrane; ISS:CAFA.
DR GO; GO:0016323; C:basolateral plasma membrane; ISS:CAFA.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0070382; C:exocytic vesicle; ISS:CAFA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0019898; C:extrinsic component of membrane; IDA:UniProtKB.
DR GO; GO:0045121; C:membrane raft; ISS:CAFA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0005544; F:calcium-dependent phospholipid binding; IDA:UniProtKB.
DR GO; GO:1901611; F:phosphatidylglycerol binding; IDA:UniProtKB.
DR GO; GO:0001786; F:phosphatidylserine binding; IDA:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; NAS:UniProtKB.
DR GO; GO:0042997; P:negative regulation of Golgi to plasma membrane protein transport; ISS:CAFA.
DR GO; GO:0042998; P:positive regulation of Golgi to plasma membrane protein transport; ISS:CAFA.
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; IPR009166; ANX13.
DR Pfam; PF00191; Annexin; 4.
DR PRINTS; PR00196; ANNEXIN.
DR PRINTS; PR01811; ANNEXINXIII.
DR SMART; SM00335; ANX; 4.
DR SUPFAM; SSF47874; SSF47874; 1.
DR PROSITE; PS00223; ANNEXIN_1; 3.
DR PROSITE; PS51897; ANNEXIN_2; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Annexin; Calcium;
KW Calcium/phospholipid-binding; Cell membrane; Cytoplasmic vesicle;
KW Lipoprotein; Membrane; Myristate; Reference proteome; Repeat.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:1530946"
FT CHAIN 2..316
FT /note="Annexin A13"
FT /id="PRO_0000067514"
FT REPEAT 14..85
FT /note="Annexin 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01245"
FT REPEAT 86..157
FT /note="Annexin 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01245"
FT REPEAT 169..241
FT /note="Annexin 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01245"
FT REPEAT 245..316
FT /note="Annexin 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01245"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:1530946,
FT ECO:0000269|PubMed:30610115"
FT VAR_SEQ 5
FT /note="H -> HSQSYTLSEGSQQLPKGDSQPSTVVQPLSHPSRNGEPEAPQP (in
FT isoform B)"
FT /evidence="ECO:0000303|PubMed:11961095"
FT /id="VSP_000291"
FT VARIANT 86
FT /note="R -> H (in dbSNP:rs2294013)"
FT /id="VAR_055501"
FT VARIANT 108
FT /note="V -> I (in dbSNP:rs6995099)"
FT /id="VAR_055502"
FT VARIANT 272
FT /note="V -> I (in dbSNP:rs2294015)"
FT /id="VAR_055503"
FT MUTAGEN 2
FT /note="G->A: Loss of myristoylation. Loss of location at
FT the cell membrane."
FT /evidence="ECO:0000269|PubMed:30610115"
FT MUTAGEN 32..34
FT /note="TNE->PGP: Loss of dimerization. No effect on
FT calcium-dependent membrane binding and location at the cell
FT membrane."
FT /evidence="ECO:0000269|PubMed:30610115"
FT MUTAGEN 73
FT /note="S->C: Slightly increased dimerization. Decreases
FT calcium-dependent membrane binding and location at the cell
FT membrane."
FT /evidence="ECO:0000269|PubMed:30610115"
FT CONFLICT 112
FT /note="V -> F (in Ref. 1; CAA77578)"
FT /evidence="ECO:0000305"
FT HELIX 16..41
FT /evidence="ECO:0007829|PDB:6B3I"
FT HELIX 46..60
FT /evidence="ECO:0007829|PDB:6B3I"
FT HELIX 64..69
FT /evidence="ECO:0007829|PDB:6B3I"
FT HELIX 74..83
FT /evidence="ECO:0007829|PDB:6B3I"
FT HELIX 87..98
FT /evidence="ECO:0007829|PDB:6B3I"
FT STRAND 102..104
FT /evidence="ECO:0007829|PDB:6B3I"
FT HELIX 107..113
FT /evidence="ECO:0007829|PDB:6B3I"
FT HELIX 118..132
FT /evidence="ECO:0007829|PDB:6B3I"
FT HELIX 136..143
FT /evidence="ECO:0007829|PDB:6B3I"
FT HELIX 146..156
FT /evidence="ECO:0007829|PDB:6B3I"
FT HELIX 168..183
FT /evidence="ECO:0007829|PDB:6B3I"
FT HELIX 190..199
FT /evidence="ECO:0007829|PDB:6B3I"
FT HELIX 202..216
FT /evidence="ECO:0007829|PDB:6B3I"
FT HELIX 220..225
FT /evidence="ECO:0007829|PDB:6B3I"
FT HELIX 230..256
FT /evidence="ECO:0007829|PDB:6B3I"
FT STRAND 259..262
FT /evidence="ECO:0007829|PDB:6B3I"
FT HELIX 265..274
FT /evidence="ECO:0007829|PDB:6B3I"
FT TURN 275..279
FT /evidence="ECO:0007829|PDB:6B3I"
FT HELIX 280..291
FT /evidence="ECO:0007829|PDB:6B3I"
FT HELIX 295..302
FT /evidence="ECO:0007829|PDB:6B3I"
FT HELIX 306..315
FT /evidence="ECO:0007829|PDB:6B3I"
SQ SEQUENCE 316 AA; 35415 MW; 3F61A1AECE5A067D CRC64;
MGNRHAKASS PQGFDVDRDA KKLNKACKGM GTNEAAIIEI LSGRTSDERQ QIKQKYKATY
GKELEEVLKS ELSGNFEKTA LALLDRPSEY AARQLQKAMK GLGTDESVLI EVLCTRTNKE
IIAIKEAYQR LFDRSLESDV KGDTSGNLKK ILVSLLQANR NEGDDVDKDL AGQDAKDLYD
AGEGRWGTDE LAFNEVLAKR SYKQLRATFQ AYQILIGKDI EEAIEEETSG DLQKAYLTLV
RCAQDCEDYF AERLYKSMKG AGTDEETLIR IVVTRAEVDL QGIKAKFQEK YQKSLSDMVR
SDTSGDFRKL LVALLH
