Annexin A5

Protein-coding gene in the species Homo sapiens
ANXA5
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

2XO3, 1ANW, 1ANX, 1AVH, 1AVR, 1HAK, 1HVD, 1HVE, 1HVF, 1HVG, 1SAV, 2XO2

Identifiers
AliasesANXA5, ANX5, ENX2, HEL-S-7, PP4, RPRGL3, annexin A5, CPB-I, VAC-alph
External IDsOMIM: 131230; MGI: 106008; HomoloGene: 20312; GeneCards: ANXA5; OMA:ANXA5 - orthologs
Gene location (Human)
Chromosome 4 (human)
Chr.Chromosome 4 (human)[1]
Chromosome 4 (human)
Genomic location for ANXA5
Genomic location for ANXA5
Band4q27Start121,667,946 bp[1]
End121,696,995 bp[1]
Gene location (Mouse)
Chromosome 3 (mouse)
Chr.Chromosome 3 (mouse)[2]
Chromosome 3 (mouse)
Genomic location for ANXA5
Genomic location for ANXA5
Band3 B|3 17.46 cMStart36,503,072 bp[2]
End36,530,043 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • stromal cell of endometrium

  • smooth muscle tissue

  • Achilles tendon

  • right lung

  • canal of the cervix

  • gallbladder

  • monocyte

  • Descending thoracic aorta

  • ascending aorta

  • islet of Langerhans
Top expressed in
  • utricle

  • vestibular membrane of cochlear duct

  • stroma of bone marrow

  • right lung lobe

  • vestibular sensory epithelium

  • calvaria

  • molar

  • dermis

  • belly cord

  • white adipose tissue
More reference expression data
BioGPS
More reference expression data
Gene ontology
Molecular function
  • phospholipase inhibitor activity
  • calcium ion binding
  • protein binding
  • calcium-dependent phospholipid binding
  • phospholipid binding
  • P-type calcium transporter activity
  • heparin binding
  • peptide hormone binding
  • receptor tyrosine kinase binding
  • molecular adaptor activity
Cellular component
  • membrane
  • focal adhesion
  • intracellular anatomical structure
  • endothelial microparticle
  • extracellular exosome
  • external side of plasma membrane
  • extracellular region
  • cytoplasm
  • cytosol
  • collagen-containing extracellular matrix
Biological process
  • hemostasis
  • negative regulation of coagulation
  • blood coagulation
  • negative regulation of apoptotic process
  • response to organic substance
  • signal transduction
  • negative regulation of catalytic activity
  • platelet degranulation
  • negative regulation of blood coagulation
  • positive regulation of apoptotic process
  • protein homooligomerization
  • negative regulation of sequestering of calcium ion
  • response to calcium ion
  • calcium ion transmembrane transport
  • cellular response to lead ion
  • response to thyroid hormone
  • cellular response to gonadotropin-releasing hormone
  • regulation of flagellated sperm motility
  • negative regulation of prolactin secretion
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

308

11747

Ensembl

ENSG00000164111

ENSMUSG00000027712

UniProt

P08758

P48036

RefSeq (mRNA)

NM_001154

NM_009673

RefSeq (protein)

NP_001145

NP_033803

Location (UCSC)Chr 4: 121.67 – 121.7 MbChr 3: 36.5 – 36.53 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Annexin A5 (or annexin V) is a cellular protein in the annexin group. In flow cytometry, annexin V is commonly used to detect apoptotic cells by its ability to bind to phosphatidylserine, a marker of apoptosis when it is on the outer leaflet of the plasma membrane. The function of the protein is unknown; however, annexin A5 has been proposed to play a role in the inhibition of blood coagulation by competing for phosphatidylserine binding sites with prothrombin and also to inhibit the activity of phospholipase A1. These properties have been found by in vitro experiments.

Pathology

Antibodies directed against annexin A5 are found in patients with a disease called the antiphospholipid syndrome (APS), a thrombophilic disease associated with autoantibodies against phospholipid compounds.

Annexin A5 forms a shield around negatively charged phospholipid molecules. The formation of an annexin A5 shield blocks the entry of phospholipids into coagulation (clotting) reactions. In the antiphospholipid antibody syndrome, the formation of the shield is disrupted by antibodies. Without the shield, there is an increased quantity of phospholipid molecules on cell membranes, speeding up coagulation reactions and causing the blood-clotting characteristic of the antiphospholipid antibody syndrome.
Annexin A5 showed upregulation in papillary thyroid carcinoma.[5]

Laboratory use

Annexin A5 is used as a non-quantitative probe to detect cells that have expressed phosphatidylserine (PS) on the cell surface, an event found in apoptosis as well as other forms of cell death.[6][7][8] Platelets also expose PS and PE on their surface when activated, which serves as binding site for various coagulation factors.

The annexin A5 affinity assay typically uses a conjugate of annexin V and a fluorescent or enzymatic label, biotin or other tags, or a radioelement, in a suitable buffer (annexin V binding to aminophospholipids is Ca2+ dependent). The assay combines annexin V staining of PS and PE membrane events with the staining of DNA in the cell nucleus with propidium iodide (PI) or 7-Aminoactinomycin D (AAD-7), distinguishing viable cells from apoptotic cells and necrotic cells.[9] Detection occurs by flow cytometry or a fluorescence microscope.

Interactions

Annexin A5 has been shown to interact with Kinase insert domain receptor[10] and Integrin, beta 5.[11]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000164111 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027712 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Sofiadis A, Becker S, Hellman U, Hultin-Rosenberg L, Dinets A, Hulchiy M, Zedenius J, Wallin G, Foukakis T, Höög A, Auer G, Lehtiö J, Larsson C (Apr 2012). "Proteomic profiling of follicular and papillary thyroid tumors". European Journal of Endocrinology. 166 (4): 657–67. doi:10.1530/EJE-11-0856. PMC 3315832. PMID 22275472.
  6. ^ Meers P and Mealy T (1994). "Phospholipid determinants for annexin V binding sites and the role of tryptophan". Biochemistry. 33 (19): 5829–37. doi:10.1021/bi00185a022. PMID 8180211.
  7. ^ Koopman G, Reutelingsperger CP, Kuijten GA, Keehnen RM, Pals ST, van Oers MH (Sep 1994). "Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis". Blood. 84 (5): 1415–20. doi:10.1182/blood.V84.5.1415.1415. PMID 8068938.
  8. ^ Vermes I, Haanen C, Steffens-Nakken H, Reutelingsperger C (Jul 1995). "A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V". Journal of Immunological Methods. 184 (1): 39–51. doi:10.1016/0022-1759(95)00072-I. PMID 7622868.
  9. ^ Annexin-FP488 fluorescent staining protocol at Interchim
  10. ^ Wen Y, Edelman JL, Kang T, Sachs G (May 1999). "Lipocortin V may function as a signaling protein for vascular endothelial growth factor receptor-2/Flk-1". Biochemical and Biophysical Research Communications. 258 (3): 713–21. doi:10.1006/bbrc.1999.0678. PMID 10329451.
  11. ^ Cardó-Vila M, Arap W, Pasqualini R (May 2003). "Alpha v beta 5 integrin-dependent programmed cell death triggered by a peptide mimic of annexin V". Molecular Cell. 11 (5): 1151–62. doi:10.1016/S1097-2765(03)00138-2. PMID 12769841.

Further reading

  • Cederholm A, Frostegård J (Jun 2007). "Annexin A5 as a novel player in prevention of atherothrombosis in SLE and in the general population". Annals of the New York Academy of Sciences. 1108 (1): 96–103. Bibcode:2007NYASA1108...96C. doi:10.1196/annals.1422.011. PMID 17893975. S2CID 29296971.
  • Schlaepfer DD, Jones J, Haigler HT (Feb 1992). "Inhibition of protein kinase C by annexin V". Biochemistry. 31 (6): 1886–91. doi:10.1021/bi00121a043. PMID 1310621.
  • Huber R, Berendes R, Burger A, Schneider M, Karshikov A, Luecke H, Römisch J, Paques E (Feb 1992). "Crystal and molecular structure of human annexin V after refinement. Implications for structure, membrane binding and ion channel formation of the annexin family of proteins". Journal of Molecular Biology. 223 (3): 683–704. doi:10.1016/0022-2836(92)90984-R. PMID 1311770.
  • Kirsch T, Pfäffle M (Sep 1992). "Selective binding of anchorin CII (annexin V) to type II and X collagen and to chondrocalcin (C-propeptide of type II collagen). Implications for anchoring function between matrix vesicles and matrix proteins". FEBS Letters. 310 (2): 143–7. doi:10.1016/0014-5793(92)81316-E. PMID 1397263. S2CID 9498732.
  • Dawson SJ, White LA (May 1992). "Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin". The Journal of Infection. 24 (3): 317–20. doi:10.1016/S0163-4453(05)80037-4. PMID 1602151.
  • Tait JF, Frankenberry DA, Shiang R, Murray JC, Adler DA, Disteche CM (1992). "Chromosomal localization of the human gene for annexin V (placental anticoagulant protein I) to 4q26----q28". Cytogenetics and Cell Genetics. 57 (4): 187–92. doi:10.1159/000133143. PMID 1683830.
  • Huber R, Römisch J, Paques EP (Dec 1990). "The crystal and molecular structure of human annexin V, an anticoagulant protein that binds to calcium and membranes". The EMBO Journal. 9 (12): 3867–74. doi:10.1002/j.1460-2075.1990.tb07605.x. PMC 552154. PMID 2147412.
  • Huber R, Schneider M, Mayr I, Römisch J, Paques EP (Nov 1990). "The calcium binding sites in human annexin V by crystal structure analysis at 2.0 A resolution. Implications for membrane binding and calcium channel activity". FEBS Letters. 275 (1–2): 15–21. doi:10.1016/0014-5793(90)81428-Q. PMID 2148156. S2CID 8975064.
  • Maurer-Fogy I, Reutelingsperger CP, Pieters J, Bodo G, Stratowa C, Hauptmann R (Jul 1988). "Cloning and expression of cDNA for human vascular anticoagulant, a Ca2+-dependent phospholipid-binding protein". European Journal of Biochemistry. 174 (4): 585–92. doi:10.1111/j.1432-1033.1988.tb14139.x. PMID 2455636.
  • Rothhut B, Coméra C, Cortial S, Haumont PY, Diep Le KH, Cavadore JC, Conard J, Russo-Marie F, Lederer F (Nov 1989). "A 32 kDa lipocortin from human mononuclear cells appears to be identical with the placental inhibitor of blood coagulation". The Biochemical Journal. 263 (3): 929–35. doi:10.1042/bj2630929. PMC 1133519. PMID 2532007.
  • Schlaepfer DD, Mehlman T, Burgess WH, Haigler HT (Sep 1987). "Structural and functional characterization of endonexin II, a calcium- and phospholipid-binding protein". Proceedings of the National Academy of Sciences of the United States of America. 84 (17): 6078–82. Bibcode:1987PNAS...84.6078S. doi:10.1073/pnas.84.17.6078. PMC 299011. PMID 2957692.
  • Funakoshi T, Heimark RL, Hendrickson LE, McMullen BA, Fujikawa K (Aug 1987). "Human placental anticoagulant protein: isolation and characterization". Biochemistry. 26 (17): 5572–8. doi:10.1021/bi00391a053. PMID 2960376.
  • Iwasaki A, Suda M, Nakao H, Nagoya T, Saino Y, Arai K, Mizoguchi T, Sato F, Yoshizaki H, Hirata M (Nov 1987). "Structure and expression of cDNA for an inhibitor of blood coagulation isolated from human placenta: a new lipocortin-like protein". Journal of Biochemistry. 102 (5): 1261–73. doi:10.1093/oxfordjournals.jbchem.a122165. PMID 2963810.
  • Funakoshi T, Hendrickson LE, McMullen BA, Fujikawa K (Dec 1987). "Primary structure of human placental anticoagulant protein". Biochemistry. 26 (25): 8087–92. doi:10.1021/bi00399a011. PMID 2964863.
  • Kaplan R, Jaye M, Burgess WH, Schlaepfer DD, Haigler HT (Jun 1988). "Cloning and expression of cDNA for human endonexin II, a Ca2+ and phospholipid binding protein". The Journal of Biological Chemistry. 263 (17): 8037–43. doi:10.1016/S0021-9258(18)68438-8. PMID 2967291.
  • Grundmann U, Abel KJ, Bohn H, Löbermann H, Lottspeich F, Küpper H (Jun 1988). "Characterization of cDNA encoding human placental anticoagulant protein (PP4): homology with the lipocortin family". Proceedings of the National Academy of Sciences of the United States of America. 85 (11): 3708–12. Bibcode:1988PNAS...85.3708G. doi:10.1073/pnas.85.11.3708. PMC 280287. PMID 2967495.
  • Pepinsky RB, Tizard R, Mattaliano RJ, Sinclair LK, Miller GT, Browning JL, Chow EP, Burne C, Huang KS, Pratt D (Aug 1988). "Five distinct calcium and phospholipid binding proteins share homology with lipocortin I". The Journal of Biological Chemistry. 263 (22): 10799–811. doi:10.1016/S0021-9258(18)38041-4. PMID 2968983.
  • Ahn NG, Teller DC, Bienkowski MJ, McMullen BA, Lipkin EW, de Haën C (Dec 1988). "Sedimentation equilibrium analysis of five lipocortin-related phospholipase A2 inhibitors from human placenta. Evidence against a mechanistically relevant association between enzyme and inhibitor". The Journal of Biological Chemistry. 263 (35): 18657–63. doi:10.1016/S0021-9258(18)37335-6. PMID 2974032.
  • Demange P, Voges D, Benz J, Liemann S, Göttig P, Berendes R, Burger A, Huber R (Jul 1994). "Annexin V: the key to understanding ion selectivity and voltage regulation?". Trends in Biochemical Sciences. 19 (7): 272–6. doi:10.1016/0968-0004(94)90002-7. PMID 7519374.
  • Fernández MP, Morgan RO, Fernández MR, Carcedo MT (Nov 1994). "The gene encoding human annexin V has a TATA-less promoter with a high G+C content". Gene. 149 (2): 253–60. doi:10.1016/0378-1119(94)90157-0. PMID 7958998.

External links

  • v
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  • 1a8a: RAT ANNEXIN V COMPLEXED WITH GLYCEROPHOSPHOSERINE
    1a8a: RAT ANNEXIN V COMPLEXED WITH GLYCEROPHOSPHOSERINE
  • 1a8b: RAT ANNEXIN V COMPLEXED WITH GLYCEROPHOSPHOETHANOLAMINE
    1a8b: RAT ANNEXIN V COMPLEXED WITH GLYCEROPHOSPHOETHANOLAMINE
  • 1anw: THE EFFECT OF METAL BINDING ON THE STRUCTURE OF ANNEXIN V AND IMPLICATIONS FOR MEMBRANE BINDING
    1anw: THE EFFECT OF METAL BINDING ON THE STRUCTURE OF ANNEXIN V AND IMPLICATIONS FOR MEMBRANE BINDING
  • 1anx: THE CRYSTAL STRUCTURE OF A NEW HIGH-CALCIUM FORM OF ANNEXIN V
    1anx: THE CRYSTAL STRUCTURE OF A NEW HIGH-CALCIUM FORM OF ANNEXIN V
  • 1avh: CRYSTAL AND MOLECULAR STRUCTURE OF HUMAN ANNEXIN V AFTER REFINEMENT. IMPLICATIONS FOR STRUCTURE, MEMBRANE BINDING AND ION CHANNEL FORMATION OF THE ANNEXIN FAMILY OF PROTEINS
    1avh: CRYSTAL AND MOLECULAR STRUCTURE OF HUMAN ANNEXIN V AFTER REFINEMENT. IMPLICATIONS FOR STRUCTURE, MEMBRANE BINDING AND ION CHANNEL FORMATION OF THE ANNEXIN FAMILY OF PROTEINS
  • 1avr: CRYSTAL AND MOLECULAR STRUCTURE OF HUMAN ANNEXIN V AFTER REFINEMENT. IMPLICATIONS FOR STRUCTURE, MEMBRANE BINDING AND ION CHANNEL FORMATION OF THE ANNEXIN FAMILY OF PROTEINS
    1avr: CRYSTAL AND MOLECULAR STRUCTURE OF HUMAN ANNEXIN V AFTER REFINEMENT. IMPLICATIONS FOR STRUCTURE, MEMBRANE BINDING AND ION CHANNEL FORMATION OF THE ANNEXIN FAMILY OF PROTEINS
  • 1bc0: RECOMBINANT RAT ANNEXIN V, W185A MUTANT
    1bc0: RECOMBINANT RAT ANNEXIN V, W185A MUTANT
  • 1bc1: RECOMBINANT RAT ANNEXIN V, QUADRUPLE MUTANT (T72K, S144K, S228K, S303K)
    1bc1: RECOMBINANT RAT ANNEXIN V, QUADRUPLE MUTANT (T72K, S144K, S228K, S303K)
  • 1bc3: RECOMBINANT RAT ANNEXIN V, TRIPLE MUTANT (T72K, S144K, S228K)
    1bc3: RECOMBINANT RAT ANNEXIN V, TRIPLE MUTANT (T72K, S144K, S228K)
  • 1bcw: RECOMBINANT RAT ANNEXIN V, T72A MUTANT
    1bcw: RECOMBINANT RAT ANNEXIN V, T72A MUTANT
  • 1bcy: RECOMBINANT RAT ANNEXIN V, T72K MUTANT
    1bcy: RECOMBINANT RAT ANNEXIN V, T72K MUTANT
  • 1bcz: RECOMBINANT RAT ANNEXIN V, T72S MUTANT
    1bcz: RECOMBINANT RAT ANNEXIN V, T72S MUTANT
  • 1g5n: ANNEXIN V COMPLEX WITH HEPARIN OLIGOSACCHARIDES
    1g5n: ANNEXIN V COMPLEX WITH HEPARIN OLIGOSACCHARIDES
  • 1hak: CRYSTAL STRUCTURE OF RECOMBINANT HUMAN PLACENTAL ANNEXIN V COMPLEXED WITH K-201 AS A CALCIUM CHANNEL ACTIVITY INHIBITOR
    1hak: CRYSTAL STRUCTURE OF RECOMBINANT HUMAN PLACENTAL ANNEXIN V COMPLEXED WITH K-201 AS A CALCIUM CHANNEL ACTIVITY INHIBITOR
  • 1hvd: STRUCTURAL AND ELECTROPHYSIOLOGICAL ANALYSIS OF ANNEXIN V MUTANTS. MUTAGENESIS OF HUMAN ANNEXIN V, AN IN VITRO VOLTAGE-GATED CALCIUM CHANNEL, PROVIDES INFORMATION ABOUT THE STRUCTURAL FEATURES OF THE ION PATHWAY, THE VOLTAGE SENSOR AND THE ION SELECTIVITY FILTER
    1hvd: STRUCTURAL AND ELECTROPHYSIOLOGICAL ANALYSIS OF ANNEXIN V MUTANTS. MUTAGENESIS OF HUMAN ANNEXIN V, AN IN VITRO VOLTAGE-GATED CALCIUM CHANNEL, PROVIDES INFORMATION ABOUT THE STRUCTURAL FEATURES OF THE ION PATHWAY, THE VOLTAGE SENSOR AND THE ION SELECTIVITY FILTER
  • 1hve: STRUCTURAL AND ELECTROPHYSIOLOGICAL ANALYSIS OF ANNEXIN V MUTANTS. MUTAGENESIS OF HUMAN ANNEXIN V, AN IN VITRO VOLTAGE-GATED CALCIUM CHANNEL, PROVIDES INFORMATION ABOUT THE STRUCTURAL FEATURES OF THE ION PATHWAY, THE VOLTAGE SENSOR AND THE ION SELECTIVITY FILTER
    1hve: STRUCTURAL AND ELECTROPHYSIOLOGICAL ANALYSIS OF ANNEXIN V MUTANTS. MUTAGENESIS OF HUMAN ANNEXIN V, AN IN VITRO VOLTAGE-GATED CALCIUM CHANNEL, PROVIDES INFORMATION ABOUT THE STRUCTURAL FEATURES OF THE ION PATHWAY, THE VOLTAGE SENSOR AND THE ION SELECTIVITY FILTER
  • 1hvf: STRUCTURAL AND ELECTROPHYSIOLOGICAL ANALYSIS OF ANNEXIN V MUTANTS. MUTAGENESIS OF HUMAN ANNEXIN V, AN IN VITRO VOLTAGE-GATED CALCIUM CHANNEL, PROVIDES INFORMATION ABOUT THE STRUCTURAL FEATURES OF THE ION PATHWAY, THE VOLTAGE SENSOR AND THE ION SELECTIVITY FILTER
    1hvf: STRUCTURAL AND ELECTROPHYSIOLOGICAL ANALYSIS OF ANNEXIN V MUTANTS. MUTAGENESIS OF HUMAN ANNEXIN V, AN IN VITRO VOLTAGE-GATED CALCIUM CHANNEL, PROVIDES INFORMATION ABOUT THE STRUCTURAL FEATURES OF THE ION PATHWAY, THE VOLTAGE SENSOR AND THE ION SELECTIVITY FILTER
  • 1hvg: STRUCTURAL AND ELECTROPHYSIOLOGICAL ANALYSIS OF ANNEXIN V MUTANTS. MUTAGENESIS OF HUMAN ANNEXIN V, AN IN VITRO VOLTAGE-GATED CALCIUM CHANNEL, PROVIDES INFORMATION ABOUT THE STRUCTURAL FEATURES OF THE ION PATHWAY, THE VOLTAGE SENSOR AND THE ION SELECTIVITY FILTER
    1hvg: STRUCTURAL AND ELECTROPHYSIOLOGICAL ANALYSIS OF ANNEXIN V MUTANTS. MUTAGENESIS OF HUMAN ANNEXIN V, AN IN VITRO VOLTAGE-GATED CALCIUM CHANNEL, PROVIDES INFORMATION ABOUT THE STRUCTURAL FEATURES OF THE ION PATHWAY, THE VOLTAGE SENSOR AND THE ION SELECTIVITY FILTER
  • 1n41: Crystal Structure of Annexin V K27E Mutant
    1n41: Crystal Structure of Annexin V K27E Mutant
  • 1n42: Crystal Structure of Annexin V R149E Mutant
    1n42: Crystal Structure of Annexin V R149E Mutant
  • 1n44: Crystal Structure of Annexin V R23E Mutant
    1n44: Crystal Structure of Annexin V R23E Mutant
  • 1sav: HUMAN ANNEXIN V WITH PROLINE SUBSTITUTION BY THIOPROLINE
    1sav: HUMAN ANNEXIN V WITH PROLINE SUBSTITUTION BY THIOPROLINE
  • 2ie6: Annexin V under 2.0 MPa pressure of xenon
    2ie6: Annexin V under 2.0 MPa pressure of xenon
  • 2ie7: Annexin V under 2.0 MPa pressure of nitrous oxide
    2ie7: Annexin V under 2.0 MPa pressure of nitrous oxide
  • 2ran: RAT ANNEXIN V CRYSTAL STRUCTURE: CA2+-INDUCED CONFORMATIONAL CHANGES
    2ran: RAT ANNEXIN V CRYSTAL STRUCTURE: CA2+-INDUCED CONFORMATIONAL CHANGES
  • v
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Cell membrane
Adhesion molecules
Calcium channels
Calcium pumps
GPCRs
Annexins
Intracellular signaling
Second messengers
Intracellular channels
Intracellular pumps
Sensors and chelators
Calcium-dependent chaperones
Calcium-dependent kinases
Calcium-dependent proteases
Indirect regulators
Extracellular chelators
Extracellular matrix proteins
Secreted hormones
Calcium-binding domains