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274  structures 1986  species 10  interactions 58087  sequences 3078  architectures

Family: fn3 (PF00041)

Summary: Fibronectin type III domain

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This is the Wikipedia entry entitled "Fibronectin type III domain". More...

Fibronectin type III domain Edit Wikipedia article

Fibronectin type III domain
PDB 1ttg EBI.jpg
The tenth type III domain of fibronectin
Identifiers
Symbol fn3
Pfam PF00041
Pfam clan CL0159
InterPro IPR003961
SMART FN3
PROSITE PDOC00214
SCOP 1ttf
SUPERFAMILY 1ttf

The Fibronectin type III domain is an evolutionary conserved protein domain that is widely found in animal proteins. The fibronectin protein in which this domain was first identified contains 16 copies of this domain. The domain is about 100 amino acids long and possesses a beta sandwich structure. Fibronectin domains are found in a wide variety of extracellular proteins. They are widely distributed in animal species, but also found more sporadically in yeast, plant and bacterial proteins.

Human proteins containing this domain[edit]

ABI3BP; ANKFN1; ASTN2; AXL; BOC; BZRAP1; C20orf75; CDON; CHL1; CMYA5; CNTFR; CNTN1; CNTN2; CNTN3; CNTN4; CNTN5; CNTN6; COL12A1; COL14A1; COL20A1; COL7A1; CRLF1; CRLF3; CSF2RB; CSF3R; DCC; DSCAM; DSCAML1; EBI3; EGFLAM; EPHA1; EPHA10; EPHA2; EPHA3; EPHA4; EPHA5; EPHA6; EPHA7; EPHA8; EPHB1; EPHB2; EPHB3; EPHB4; EPHB6; EPOR; FANK1; FLRT1; FLRT2; FLRT3; FN1; FNDC1; FNDC3A; FNDC3B; FNDC4; FNDC5; FNDC7; FNDC8; FSD1; FSD1L; FSD2; GHR; HCFC1; HCFC2; HUGO; IFNGR2; IGF1R; IGSF22; IGSF9; IGSF9B; IL11RA; IL12B; IL12RB1; IL12RB2; IL20RB; IL23R; IL27RA; IL31RA; IL6R; IL6ST; IL7R; INSR; INSRR; ITGB4; Il6ST; KAL1; KALRN; L1CAM; LEPR; LIFR; LRFN2; LRFN3; LRFN4; LRFN5; LRIT1; LRRN1; LRRN3; MERTK; MID1; MID2; MPL; MYBPC1; MYBPC2; MYBPC3; MYBPH; MYBPHL; MYLK; MYOM1; MYOM2; MYOM3; NCAM1; NCAM2; NEO1; NFASC; NOPE; NPHS1; NRCAM; OBSCN; OBSL1; OSMR; PHYHIP; PHYHIPL; PRLR; PRODH2; PTPRB; PTPRC; PTPRD; PTPRF; PTPRG; PTPRH; PTPRJ; PTPRK; PTPRM; PTPRO; PTPRS; PTPRT; PTPRU; PTPRZ1; PTPsigma; PUNC; RIMBP2; ROBO1; ROBO2; ROBO3; ROBO4; ROS1; SDK1; SDK2; SNED1; SORL1; SPEG; TEK; TIE1; TNC; TNN; TNR; TNXB; TRIM36; TRIM42; TRIM46; TRIM67; TRIM9; TTN; TYRO3; UMODL1; USH2A; VASN; VWA1; dJ34F7.1; fmi;

See also[edit]

  • Monobody, an engineered antibody mimetic based on the structure of the fibronectin type III domain

References[edit]

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.

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No Pfam abstract.

Literature references

  1. Bazan JF; , PNAS USA 1990;87:6934-6938.: Structural design and molecular evolution of a cytokine receptor superfamily. PUBMED:2169613 EPMC:2169613

  2. Little E, Bork P, Doolittle R; , J Mol Evol 1994;39:631-643.: Tracing the spread of fibronectin type III domains in bacterial glycohydrolases. PUBMED:7528812 EPMC:7528812

  3. Kornblihtt AR, Umezawa K, Vibe-Pedersen K, Baralle FE; , EMBO J 1985;4:1755-1759.: Primary structure of human fibronectin: differential splicing may generate at least 10 polypeptides from a single gene. PUBMED:2992939 EPMC:2992939


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR003961

Fibronectins are multi-domain glycoproteins found in a soluble form in plasma, and in an insoluble form in loose connective tissue and basement membranes [PUBMED:3780752]. They contain multiple copies of 3 repeat regions (types I, II and III), which bind to a variety of substances including heparin, collagen, DNA, actin, fibrin and fibronectin receptors on cell surfaces. The wide variety of these substances means that fibronectins are involved in a number of important functions: e.g., wound healing; cell adhesion; blood coagulation; cell differentiation and migration; maintenance of the cellular cytoskeleton; and tumour metastasis [PUBMED:3031656]. The role of fibronectin in cell differentiation is demonstrated by the marked reduction in the expression of its gene when neoplastic transformation occurs. Cell attachment has been found to be mediated by the binding of the tetrapeptide RGDS to integrins on the cell surface [PUBMED:2466295], although related sequences can also display cell adhesion activity.

Plasma fibronectin occurs as a dimer of 2 different subunits, linked together by 2 disulphide bonds near the C terminus. The difference in the 2 chains occurs in the type III repeat region and is caused by alternative splicing of the mRNA from one gene [PUBMED:3780752]. The observation that, in a given protein, an individual repeat of one of the 3 types (e.g., the first FnIII repeat) shows much less similarity to its subsequent tandem repeats within that protein than to its equivalent repeat between fibronectins from other species, has suggested that the repeating structure of fibronectin arose at an early stage of evolution. It also seems to suggest that the structure is subject to high selective pressure [PUBMED:6317187].

The fibronectin type III repeat region is an approximately 100 amino acid domain, different tandem repeats of which contain binding sites for DNA, heparin and the cell surface [PUBMED:3780752]. The superfamily of sequences believed to contain FnIII repeats represents 45 different families, the majority of which are involved in cell surface binding in some manner, or are receptor protein tyrosine kinases, or cytokine receptors.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan E-set (CL0159), which has the following description:

This clan includes a diverse range of domains that have an Ig-like fold and appear to be distantly related to each other. The clan includes: PKD domains, cadherins and several families of bacterial Ig-like domains as well as viral tail fibre proteins. it also includes several Fibronectin type III domain-containing families.

The clan contains the following 63 members:

A2M_N Alpha_adaptinC2 Big_1 Big_2 Big_3 Big_3_2 Big_3_3 Big_3_4 Big_4 Big_5 BiPBP_C BsuPI Cadherin Cadherin-like Cadherin_2 Cadherin_pro CARDB CHB_HEX_C CHB_HEX_C_1 ChitinaseA_N CHU_C Coatamer_beta_C COP-gamma_platf CopC DUF1034 DUF11 DUF1973 DUF2271 DUF4165 DUF4625 DUF916 EpoR_lig-bind Filamin FixG_C FlgD_ig fn3 Fn3_assoc He_PIG HYR IFNGR1 IL6Ra-bind Integrin_alpha2 Interfer-bind Invasin_D3 MG1 Mo-co_dimer Neurexophilin NPCBM_assoc PapD_N PKD PPC Qn_am_d_aIII REJ Rib SoxZ SprB SWM_repeat T2SS-T3SS_pil_N TIG Tissue_fac Transglut_C TRAP_beta Y_Y_Y

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(106)
Full
(58087)
Representative proteomes NCBI
(50190)
Meta
(2367)
RP15
(7000)
RP35
(9544)
RP55
(17225)
RP75
(27544)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(106)
Full
(58087)
Representative proteomes NCBI
(50190)
Meta
(2367)
RP15
(7000)
RP35
(9544)
RP55
(17225)
RP75
(27544)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(106)
Full
(58087)
Representative proteomes NCBI
(50190)
Meta
(2367)
RP15
(7000)
RP35
(9544)
RP55
(17225)
RP75
(27544)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Swissprot_feature_table
Previous IDs: none
Type: Domain
Author: Sonnhammer ELL
Number in seed: 106
Number in full: 58087
Average length of the domain: 84.30 aa
Average identity of full alignment: 20 %
Average coverage of the sequence by the domain: 23.88 %

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 22.1 22.1
Trusted cut-off 22.1 22.1
Noise cut-off 22.0 22.0
Model length: 85
Family (HMM) version: 16
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 10 interactions for this family. More...

IL6 Hormone_recep IL6Ra-bind EpoR_lig-bind IL12p40_C I-set ig Glyco_hydro_28 fn3 Lectin_C

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 fn3 domain has been found. There are 274 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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