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20  structures 77  species 1  interaction 552  sequences 71  architectures

Family: ANATO (PF01821)

Summary: Anaphylotoxin-like domain

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Anaphylatoxin". More...

Anaphylatoxin Edit Wikipedia article

Anaphylotoxin-like domain
PDB 1c5a EBI.jpg
Structure of porcine C5adesArg.[1]
Identifiers
Symbol ANATO
Pfam PF01821
InterPro IPR000020
SMART ANATO
PROSITE PDOC00906
SCOP 1c5a
SUPERFAMILY 1c5a

Anaphylatoxins, or complement peptides, are fragments (C3a, C4a and C5a) that are produced as part of the activation of the complement system.[2] Complement components C3, C4 and C5 are large glycoproteins that have important functions in the immune response and host defense.[3] They have a wide variety of biological activities and are proteolytically activated by cleavage at a specific site, forming a- and b-fragments.[4] A-fragments form distinct structural domains of approximately 76 amino acids, coded for by a single exon within the complement protein gene. The C3a, C4a and C5a components are referred to as anaphylatoxins:[4][5] they cause smooth muscle contraction, histamine release from mast cells, and enhanced vascular permeability.[5] They also mediate chemotaxis, inflammation, and generation of cytotoxic oxygen radicals.[5] The proteins are highly hydrophilic, with a mainly alpha-helical structure held together by 3 disulfide bridges.[5]

Function[edit]

Anaphylatoxins are able to trigger degranulation (release of substances) of endothelial cells, mast cells or phagocytes, which produce a local inflammatory response. If the degranulation is widespread, it can cause a shock-like syndrome similar to that of an allergic reaction.

Anaphylatoxins indirectly mediate:

Examples[edit]

Important anaphylatoxins:

  • C5a has the highest specific biological activity and is able to act directly on neutrophils and monocytes to speed up the phagocytosis of pathogens.
  • C3a works with C5a to activate mast cells, recruit antibody, complement and phagocytic cells and increase fluid in the tissue, all of which contribute to the initiation of the adaptive immune response.
  • C4a is the least active anaphylatoxin.

Terminology[edit]

Although some drugs (morphine, codeine, synthetic ACTH) and some neurotransmitters (norepinephrine, substance P) are important mediators of degranulation of mast cells or basophils, they are generally not called anaphylatoxins. This term is reserved only for fragments of the complement system.

Human proteins containing this domain[edit]

C3, C4A, C4B, C4B-1, C5, FBLN1, FBLN2

See also[edit]

References[edit]

  1. ^ Williamson MP, Madison VS (March 1990). "Three-dimensional structure of porcine C5adesArg from 1H nuclear magnetic resonance data". Biochemistry 29 (12): 2895–905. doi:10.1021/bi00464a002. PMID 2337573. 
  2. ^ Hugli TE (1986). "Biochemistry and biology of anaphylatoxins". Complement 3 (3): 111–27. PMID 3542363. 
  3. ^ Fritzinger DC, Petrella EC, Connelly MB, Bredehorst R, Vogel CW (1992). "Primary structure of cobra complement component C3". J. Immunol. 149 (11): 3554–3562. PMID 1431125. 
  4. ^ a b Rosa PA, Ogata RT, Zepf NE (1989). "Sequence of the gene for murine complement component C4". J. Biol. Chem. 264 (28): 16565–16572. PMID 2777798. 
  5. ^ a b c d Gennaro R, Simonic T, Negri A, Mottola C, Secchi C, Ronchi S, Romeo D (1986). "C5a fragment of bovine complement. Purification, bioassays, amino-acid sequence and other structural studies". Eur. J. Biochem. 155 (1): 77–86. doi:10.1111/j.1432-1033.1986.tb09460.x. PMID 3081348. 

Janeway et al. Immunobiology Garland Science Publishing 2005

External links[edit]

This article incorporates text from the public domain Pfam and InterPro IPR000020

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This is the Wikipedia entry entitled "Fibulin". More...

Fibulin Edit Wikipedia article

Anaphylotoxin-like domain
PDB 1c5a EBI.jpg
Structure of porcine C5adesArg.[1]
Identifiers
Symbol ANATO
Pfam PF01821
InterPro IPR000020
SMART ANATO
PROSITE PDOC00906
SCOP 1c5a
SUPERFAMILY 1c5a

Fibulin (FY-beau-lin) (now known as Fibulin-1 FBLN1) is the prototypic member of a multigene family, currently with seven members. Fibulin-1 is a calcium-binding glycoprotein. In vertebrates, fibulin-1 is found in blood and extracellular matrices. In the extracellular matrix, fibulin-1 associates with basement membranes and elastic fibers. The association with these matrix structures is mediated by its ability to interact with numerous extracellular matrix constituents including fibronectin, proteoglycans, laminins and tropoelastin. In blood, fibulin-1 binds to fibrinogen and incorporates into clots.

Fibulins are secreted glycoproteins that become incorporated into a fibrillar extracellular matrix when expressed by cultured cells or added exogenously to cell monolayers.[2][3] The five known members of the family share an elongated structure and many calcium-binding sites, owing to the presence of tandem arrays of epidermal growth factor-like domains. They have overlapping binding sites for several basement-membrane proteins, tropoelastin, fibrillin, fibronectin and proteoglycans, and they participate in diverse supramolecular structures. The amino-terminal domain I of fibulin consists of three anaphylatoxin-like (AT) modules, each approximately 40 residues long and containing four or six cysteines. The structure of an AT module was determined for the complement-derived anaphylatoxin C3a, and was found to be a compact alpha-helical fold that is stabilized by three disulphide bridges in the pattern Cys14, Cys25 and Cys36 (where Cys is cysteine). The bulk of the remaining portion of the fibulin molecule is a series of nine EGF-like repeats.[4]

Genes[edit]

References[edit]

  1. ^ Williamson MP, Madison VS (March 1990). "Three-dimensional structure of porcine C5adesArg from 1H nuclear magnetic resonance data". Biochemistry 29 (12): 2895–905. doi:10.1021/bi00464a002. PMID 2337573. 
  2. ^ Burgess WH, Argraves WS, Tran H, Dickerson K (1990). "Fibulin is an extracellular matrix and plasma glycoprotein with repeated domain structure". J. Cell Biol. 111 (6): 3155–3164. doi:10.1083/jcb.111.6.3155. PMC 2116371. PMID 2269669. 
  3. ^ Timpl R, Sasaki T, Kostka G, Chu ML (2003). "Fibulins: a versatile family of extracellular matrix proteins". Nat. Rev. Mol. Cell Biol. 4 (6): 479–489. doi:10.1038/nrm1130. PMID 12778127. 
  4. ^ Timpl R, Sasaki T, Chu ML, Pan TC, Zhang RZ, Fassler R (1993). "Structure and expression of fibulin-2, a novel extracellular matrix protein with multiple EGF-like repeats and consensus motifs for calcium binding". J. Cell Biol. 123 (5): 1269–1277. doi:10.1083/jcb.123.5.1269. PMC 2119879. PMID 8245130. 
  5. ^ Fisher SA, Rivera A, Fritsche LG, et al. (April 2007). "Case-control genetic association study of fibulin-6 (FBLN6 or HMCN1) variants in age-related macular degeneration (AMD)". Hum. Mutat. 28 (4): 406–13. doi:10.1002/humu.20464. PMID 17216616. 

External links[edit]

This article incorporates text from the public domain Pfam and InterPro IPR000020


This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Anaphylotoxin-like domain Provide feedback

C3a, C4a and C5a anaphylatoxins are protein fragments generated enzymatically in serum during activation of complement molecules C3, C4, and C5. They induce smooth muscle contraction. These fragments are homologous to a three-fold repeat in fibulins.

Literature references

  1. Pan TC, Sasaki T, Zhang RZ, Fassler R, Timpl R, Chu ML; , J Cell Biol 1993;123:1269-1277.: Structure and expression of fibulin-2, a novel extracellular matrix protein with multiple EGF-like repeats and consensus motifs for calcium binding. PUBMED:8245130 EPMC:8245130

  2. Zuiderweg ER, Nettesheim DG, Mollison KW, Carter GW; , Biochemistry 1989;28:172-185.: Tertiary structure of human complement component C5a in solution from nuclear magnetic resonance data. PUBMED:2784981 EPMC:2784981


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000020

Complement components C3, C4 and C5 are large glycoproteins that have important functions in the immune response and host defence [PUBMED:1431125]. They have a wide variety of biological activities and are proteolytically activated by cleavage at a specific site, forming a- and b-fragments [PUBMED:2777798]. A-fragments form distinct structural domains of approximately 76 amino acids, coded for by a single exon within the complement protein gene. The C3a, C4a and C5a components are referred to as anaphylatoxins [PUBMED:2777798, PUBMED:3081348]: they cause smooth muscle contraction, histamine release from mast cells, and enhanced vascular permeability [PUBMED:3081348]. They also mediate chemotaxis, inflammation, and generation of cytotoxic oxygen radicals [PUBMED:3081348]. The proteins are highly hydrophilic, with a mainly alpha-helical structure held together by 3 disulphide bridges [PUBMED:3081348].

Fibulins are secreted glycoproteins that become incorporated into a fibrillar extracellular matrix when expressed by cultured cells or added exogenously to cell monolayers [PUBMED:2269669, PUBMED:12778127]. The five known members of the family share an elongated structure and many calcium-binding sites, owing to the presence of tandem arrays of epidermal growth factor-like domains. They have overlapping binding sites for several basement-membrane proteins, tropoelastin, fibrillin, fibronectin and proteoglycans, and they participate in diverse supramolecular structures. The amino-terminal domain I of fibulin consists of three anaphylatoxin-like (AT) modules, each approximately 40 residues long and containing four or six cysteines. The structure of an AT module was determined for the complement-derived anaphylatoxin C3a, and was found to be a compact alpha-helical fold that is stabilised by three disulphide bridges in the pattern Cys1-4, Cys2-5 and Cys3-6 (where Cys is cysteine). The bulk of the remaining portion of the fibulin molecule is a series of nine EGF-like repeats [PUBMED:8245130].

Gene Ontology

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Domain organisation

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(65)
Full
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Representative proteomes NCBI
(520)
Meta
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RP15
(14)
RP35
(34)
RP55
(79)
RP75
(202)
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  Seed
(65)
Full
(552)
Representative proteomes NCBI
(520)
Meta
(0)
RP15
(14)
RP35
(34)
RP55
(79)
RP75
(202)
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Curation and family details

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Seed source: Prosite
Previous IDs: none
Type: Domain
Author: Bateman A, SMART
Number in seed: 65
Number in full: 552
Average length of the domain: 35.50 aa
Average identity of full alignment: 37 %
Average coverage of the sequence by the domain: 3.14 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.4 21.4
Trusted cut-off 21.4 21.5
Noise cut-off 20.9 21.1
Model length: 36
Family (HMM) version: 13
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Species distribution

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Interactions

There is 1 interaction for this family. More...

A2M_recep

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the ANATO domain has been found. There are 20 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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