Summary: Laminin EGF-like (Domains III and V)

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Laminin Edit Wikipedia article

Lamanins are major proteins in the basal lamina (one of the layers of the basement membrane), a protein network foundation for most cells and organs. The laminins are an important and biologically active part of the basal lamina, influencing cell differentiation, migration, and adhesion, as well as phenotype and survival.^[1]

Laminins are trimeric proteins that contain an α-chain, a β-chain, and a γ-chain, found in five, four, and three genetic variants, respectively. The laminin molecules are named according to their chain composition. Thus, laminin-511 contains α5, β1, and γ1 chains.^[2] Fourteen other chain combinations have been identified in vivo. The trimeric proteins intersect to form a cross-like structure that can bind to other cell membrane and extracellular matrix molecules.^[3] The three shorter arms are particularly good at binding to other laminin molecules, which allows them to form sheets. The long arm is capable of binding to cells, which helps anchor organized tissue cells to the membrane.

The laminin family of glycoproteins are an integral part of the structural scaffolding in almost every tissue of an organism. They are secreted and incorporated into cell-associated extracellular matrices. Laminin is vital for the maintenance and survival of tissues. Defective laminins can cause muscles to form improperly, leading to a form of muscular dystrophy, lethal skin blistering disease (junctional epidermolysis bullosa) and defects of the kidney filter (nephrotic syndrome). ^[4]

Types

Fifteen laminin trimers have been identified. The laminins are combinations of different alpha-, beta-, and gamma-chains.^[5]

The five forms of alpha-chains are: LAMA1, LAMA2, LAMA3, LAMA4, LAMA5
The beta-chains include: LAMB1, LAMB2, LAMB3, LAMB4
The gamma-chains are: LAMC1, LAMC2, LAMC3

Laminins were previously numbered - e.g. laminin-1, laminin-2, laminin-3 - but the nomenclature was recently^[when?] changed to describe which chains are present in each isoform. For example, laminin-511 contains an α5-chain, a β1-chain and a γ1 chain.^[2]

Networks

Laminins form independent networks and are associated with type IV collagen networks via entactin,^[6] fibronectin,^[7] and perlecan. They also bind to cell membranes through integrin receptors and other plasma membrane molecules, such as the dystroglycan glycoprotein complex and Lutheran blood group glycoprotein.^[3] Through these interactions, laminins critically contribute to cell attachment and differentiation, cell shape and movement, maintenance of tissue phenotype, and promotion of tissue survival.^[3]^[5] Some of these biological functions of laminin have been associated with specific amino-acid sequences or fragments of laminin.^[3] For example, the peptide sequence [GTFALRGDNGDNGQ], which is located on the alpha-chain of laminin, promotes adhesion of endothelial cells.^[8]

Pathology

Dysfunctional structure of one particular laminin, laminin-211, is the cause of one form of congenital muscular dystrophy.^[9] Laminin-211 is composed of an α2, a β1 and a γ1 chains. This laminin's distribution includes the brain and muscle fibers. In muscle, it binds to alpha dystroglycan and integrin alpha7—beta1 via the G domain, and via the other end binds to the extracellular matrix. Abnormal laminin-332, which is essential for epithelial cell adhesion to the basement membrane, leads to a condition called junctional epidermolysis bullosa, characterized by generalized blisters, exuberant granulation tissue of skin and mucosa, and pitted teeth. Malfunctional laminin-521 in the kidney filter causes leakage of protein into the urine and nephrotic syndrome.^[4]

Laminins in cell culture

Recently, several publications have reported that laminins can be used to culture cells, such as pluripotent stem cells, that are difficult to culture on other substrates. Mostly, two types of laminins have been used. Laminin-111 extracted from mouse sarcomas is one popular laminin type, as well as a mixture of laminins 511 and 521 from human placenta.^[10] Various laminin isoforms are practically impossible to isolate from tissues in pure form due to extensive cross-linking and the need for harsh extraction conditions, such as proteolytic enzymes or low pH, that cause degradation. However, professor Tryggvason's group at the Karolinska Institute in Sweden showed how to produce recombinant laminins using HEK293 cells in 2000. Kortesmaa et al. 2000. This made it possible to test if laminins could have a significant role in vitro as they have in the human body. In 2008, two groups independently showed that mouse embryonic stem cells can be grown for months on top of recombinant laminin-511.^[11]^[12] Later, Rodin et al. showed that recombinant laminin 511 can be used to create a totally xeno-free and defined cell culture environment to culture human pluripotent ES cells and human iPS cells.^[13]

Role in neural development

Laminin-111 is a major substrate along which nerve axons will grow, both in vivo and in vitro. For example, it lays down a path that developing retinal ganglion cells follow on their way from the retina to the tectum. It is also often used as a substrate in cell culture experiments. Interestingly, the presence of laminin-1 can influence how the growth cone responds to other cues. For example, growth cones are repelled by netrin when grown on laminin-111, but are attracted to netrin when grown on fibronectin^{[citation needed]}. This effect of laminin-111 probably occurs through a lowering of intracellular cyclic AMP^{[citation needed]}.

Role in cancer

This section's tone or style may not reflect the encyclopedic tone used on Wikipedia. See Wikipedia's guide to writing better articles for suggestions. (July 2012)

The majority of transcripts that harbor an internal ribosome entry site (IRES) are involved in cancer development via corresponding proteins. A crucial event in tumor progression referred to as epithelial to mesenchymal transition (EMT) allows carcinoma cells to acquire invasive properties. The translational activation of the extracellular matrix component laminin B1 (LamB1) during EMT has been recently reported suggesting an IRES-mediated mechanism. In this study, the IRES activity of LamB1 was determined by independent bicistronic reporter assays. Strong evidences exclude an impact of cryptic promoter or splice sites on IRES-driven translation of LamB1. Furthermore, no other LamB1 mRNA species arising from alternative transcription start sites or polyadenylation signals were detected that account for its translational control. Mapping of the LamB1 5'-untranslated region (UTR) revealed the minimal LamB1 IRES motif between -293 and -1 upstream of the start codon. Notably, RNA affinity purification showed that the La protein interacts with the LamB1 IRES. This interaction and its regulation during EMT were confirmed by ribonucleoprotein immunoprecipitation. In addition, La was able to positively modulate LamB1 IRES translation. In summary, these data indicate that the LamB1 IRES is activated by binding to La which leads to translational upregulation during hepatocellular EMT.^[14]

Laminin domains

Laminin Domain I

Identifiers

Symbol

Laminin_I

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Laminin Domain II

Identifiers

Symbol

Laminin_II

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Laminin B (Domain IV)

Identifiers

Symbol

Laminin_B

Pfam clan

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Laminin EGF-like (Domains III and V)

crystal structure of three consecutive laminin-type epidermal growth factor-like (le) modules of laminin gamma1 chain harboring the nidogen binding site

Identifiers

Symbol

Laminin_EGF

Pfam clan

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Laminin G domain

laminin alpha 2 chain lg4-5 domain pair, ca1 site mutant

Identifiers

Symbol

Laminin_G_1

Pfam clan

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Laminin G domain

the structure of the ligand-binding domain of neurexin 1beta: regulation of lns domain function by alternative splicing

Identifiers

Symbol

Laminin_G_2

Pfam clan

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Laminin N-terminal (Domain VI)

Identifiers

Symbol

Laminin_N

Pfam clan

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Laminins contain several conserved protein domains.

Laminin I and Laminin II

Laminins are trimeric molecules; laminin-1 is an alpha1 beta1 gamma1 trimer. It has been suggested that the domains I and II from laminin A, B1 and B2 may come together to form a triple helical coiled-coil structure.^[15]

Laminin B

The laminin B domain (also known as domain IV) is an extracellular module of unknown function. It is found in a number of different proteins that include, heparan sulphate proteoglycan from basement membrane, a laminin-like protein from Caenorhabditis elegans and laminin. Laminin IV domain is not found in short laminin chains (alpha4 or beta3).

Laminin EGF-like

Beside different types of globular domains each laminin subunit contains, in its first half, consecutive repeats of about 60 amino acids in length that include eight conserved cysteines.^[16] The tertiary structure of this domain is remotely similar in its N-terminus to that of the EGF-like module.^[17]^[18] It is also known as a 'LE' or 'laminin-type EGF-like' domain. The number of copies of the laminin EGF-like domain in the different forms of laminins is highly variable; from 3 up to 22 copies have been found. In mouse laminin gamma-1 chain, the seventh LE domain has been shown to be the only one that binds with a high affinity to nidogen.^[19] The binding-sites are located on the surface within the loops C1-C3 and C5-C6.^[17]^[18] Long consecutive arrays of laminin EGF-like domains in laminins form rod-like elements of limited flexibility, which determine the spacing in the formation of laminin networks of basement membranes.^[20]^[21]

Laminin G

The laminin globular (G) domain, also known as the LNS (Laminin-alpha, Neurexin and Sex hormone-binding globulin) domain, is on average between 165 and 220 amino acids in length and can be found in one to six copies in various laminin family members as well as in a large number of extracellular proteins. For example, all laminin alpha-chains have five laminin G domains, all collagen family proteins have one laminin G domain, the CNTNAP proteins have four laminin G domains, while neurexin 1 and 2 each hold six laminin G domains.^[22] On average, approximately one quarter of the proteins that hold laminin G domains is taken up by these laminin G domains themselves.^[22] The C terminus of laminin alpha chain contains a tandem repeat of five laminin G domains, which are critical for heparin-binding and cell attachment activity.^[23] Laminin alpha4 is distributed in a variety of tissues including peripheral nerves, dorsal root ganglion, skeletal muscle and capillaries; in the neuromuscular junction, it is required for synaptic specialisation.^[24] The structure of the laminin-G domain has been predicted to resemble that of pentraxin.^[25]

Laminin G domains can vary in their function, and a variety of binding functions has been ascribed to different LamG modules. For example, the laminin alpha1 and alpha2 chains each has five C-terminal laminin G domains, where only domains LG4 and LG5 contain binding sites for heparin, sulphatides and the cell surface receptor dystroglycan.^[23] Laminin G-containing proteins appear to have a wide variety of roles in cell adhesion, signalling, migration, assembly and differentiation.

Laminin N-terminal

Basement membrane assembly is a cooperative process in which laminins polymerise through their N-terminal domain (LN or domain VI) and anchor to the cell surface through their G domains. Netrins may also associate with this network through heterotypic LN domain interactions.^[21] This leads to cell signalling through integrins and dystroglycan (and possibly other receptors) recruited to the adherent laminin. This LN domain dependent self-assembly is considered to be crucial for the integrity of basement membranes, as highlighted by genetic forms of muscular dystrophy containing the deletion of the LN module from the alpha 2 laminin chain.^[26] The laminin N-terminal domain is found in all laminin and netrin subunits except laminin alpha 3A, alpha 4 and gamma 2.

Human proteins containing laminin domains

Role in culture

Many Christian apologists, most notably Louie Giglio, have written about the fact that laminin is shaped like a Christian cross, comparing the role of the cross in theology and laminin's role in the human body. For example, David D. Swanson states: "Our knowledge of truth is most clearly revealed on the cross of Christ. And what holds the human body together? Laminin. And what does it look like? A cross. Coincidence? Some would say yes, but I think it is yet another way God reveals his glory to us. I think God is the one who holds all things together-our bodies-our world-our lives."^[27] Fazale Rana, a biochemist and apologist, disagrees with Giglio and instead argues that "Instead of pointing to superficial features of biomolecules such as the “cross-shaped” architecture of laminin, there are many more substantive ways to use biochemistry to argue for the necessity of a Creator."^[28]

References

^ Timpl R et al. (1979). "Laminin – a glycoprotein from basement membranes". J Biol Chem 254 (19): 9933–7. PMID 114518.
^ ^a ^b Aumailley M et al. (2005). "A simplified laminin nomenclature". Matrix Biol. 24 (5): 326–32. doi:10.1016/j.matbio.2005.05.006. PMID 15979864.
^ ^a ^b ^c ^d M. A. Haralson and John R. Hassell (1995). Extracellular matrix: a practical approach. Ithaca, N.Y: IRL Press. ISBN 0-19-963220-0.
^ ^a ^b Yurchenko P and Batton BL (2009). "Developmental and Pathogenic Mechanisms of Basement Membrane Assembly". Curr Pharm Des. 15 (12): 1277–94. doi:10.2174/138161209787846766. PMC 2978668. PMID 19355968.
^ ^a ^b Colognato H, Yurchenco P (2000). "Form and function: the laminin family of heterotrimers". Dev. Dyn. 218 (2): 213–34. doi:10.1002/(SICI)1097-0177(200006)218:2<213::AID-DVDY1>3.0.CO;2-R. PMID 10842354.
^ Smith J, Ockleford CD (January 1994). "Laser scanning confocal examination and comparison of nidogen (entactin) with laminin in term human amniochorion". Placenta 15 (1): 95–106. doi:10.1016/S0143-4004(05)80240-1. PMID 8208674.
^ Ockleford CD, Bright N, Hubbard A, D'Lacey C , Smith J, Gardiner L, Sheikh T, Albentosa, M, Turtle K (October 1993). "Micro-Trabeculae, Macro-Plaques or Mini-Basement Membranes in Human Term Fetal Membranes?". Phil. Trans. R. Soc. Lond. B 342 (1300): 121–136. doi:10.1098/rstb.1993.0142.
^ Beck et al., 1999.^[specify]
^ Hall, T. E.; Bryson-Richardson, RJ et al. (2007). "The zebrafish candyfloss mutant implicates extracellular matrix adhesion failure in laminin α2-deficient congenital muscular dystrophy". PNAS 104 (17): 7092–7097. doi:10.1073/pnas.0700942104. PMC 1855385. PMID 17438294.
^ Wewer et al. (1983). "Human laminin isolated in a nearly intact, biologically active form from placenta by limited proteolysis". J Biol Chem. 258 (20): 12654–60. PMID 6415055.
^ Domogatskaya et al. (2008). "Laminin-511 but not -332, -111, or -411 enables mouse embryonic stem cell self-renewal in vitro". Stem Cells 26 (11): 2800–9. doi:10.1634/stemcells.2007-0389. PMID 18757303.
^ Miyakzaki et al. (2008). "Recombinant human laminin isoforms can support the undifferentiated growth of human embryonic stem cells". Biochem. Biophys. Res. Commun. 375 (1): 27–32. doi:10.1016/j.bbrc.2008.07.111. PMID 18675790.
^ http://www.nature.com/nbt/journal/v28/n6/full/nbt.1620.html
^ Petz M, Them N, Huber H, Beug H, Mikulits W. (October 2011). "La enhances IRES-mediated translation of laminin B1 during malignant epithelial to mesenchymal transition.". Nucleic Acids Research 39 (18): 01–13. doi:10.1093/nar/gkr717. PMC 3245933. PMID 21896617.
^ Sasaki M, Kleinman HK, Huber H, Deutzmann R, Yamada Y (November 1988). "Laminin, a multidomain protein. The A chain has a unique globular domain and homology with the basement membrane proteoglycan and the laminin B chains". J. Biol. Chem. 263 (32): 16536–44. PMID 3182802.
^ Engel J (July 1989). "EGF-like domains in extracellular matrix proteins: localized signals for growth and differentiation?". FEBS Lett. 251 (1-2): 1–7. doi:10.1016/0014-5793(89)81417-6. PMID 2666164.
^ ^a ^b Stetefeld J, Mayer U, Timpl R, Huber R (April 1996). "Crystal structure of three consecutive laminin-type epidermal growth factor-like (LE) modules of laminin gamma1 chain harboring the nidogen binding site". J. Mol. Biol. 257 (3): 644–57. doi:10.1006/jmbi.1996.0191. PMID 8648630.
^ ^a ^b Baumgartner R, Czisch M, Mayer U, Poschl E, Huber R, Timpl R, Holak TA (April 1996). "Structure of the nidogen binding LE module of the laminin gamma1 chain in solution". J. Mol. Biol. 257 (3): 658–68. doi:10.1006/jmbi.1996.0192. PMID 8648631.
^ Mayer U, Poschl E, Gerecke DR, Wagman DW, Burgeson RE, Timpl R (May 1995). "Low nidogen affinity of laminin-5 can be attributed to two serine residues in EGF-like motif gamma 2III4". FEBS Lett. 365 (2-3): 129–32. doi:10.1016/0014-5793(95)00438-F. PMID 7781764.
^ Beck K, Hunter I, Engel J (February 1990). "Structure and function of laminin: anatomy of a multidomain glycoprotein". FASEB J. 4 (2): 148–60. PMID 2404817.
^ ^a ^b Yurchenco PD, Cheng YS (August 1993). "Self-assembly and calcium-binding sites in laminin. A three-arm interaction model". J. Biol. Chem. 268 (23): 17286–99. PMID 8349613.
^ ^a ^b Template:Www.uniprot.org
^ ^a ^b Tisi D, Talts JF, Timpl R, Hohenester E (April 2000). "Structure of the C-terminal laminin G-like domain pair of the laminin alpha2 chain harbouring binding sites for alpha-dystroglycan and heparin". EMBO J. 19 (7): 1432–40. doi:10.1093/emboj/19.7.1432. PMC 310212. PMID 10747011.
^ Ichikawa N, Kasai S, Suzuki N, Nishi N, Oishi S, Fujii N, Kadoya Y, Hatori K, Mizuno Y, Nomizu M, Arikawa-Hirasawa E (April 2005). "Identification of neurite outgrowth active sites on the laminin alpha4 chain G domain". Biochemistry 44 (15): 5755–62. doi:10.1021/bi0476228. PMID 15823034.
^ Beckmann G, Hanke J, Bork P, Reich JG (February 1998). "Merging extracellular domains: fold prediction for laminin G-like and amino-terminal thrombospondin-like modules based on homology to pentraxins". J. Mol. Biol. 275 (5): 725–30. doi:10.1006/jmbi.1997.1510. PMID 9480764.
^ Xu H, Wu XR, Wewer UM, Engvall E (November 1994). "Murine muscular dystrophy caused by a mutation in the laminin alpha 2 (Lama2) gene". Nat. Genet. 8 (3): 297–302. doi:10.1038/ng1194-297. PMID 7874173.
^ Swanson, David D. (2012). Learning to Be You. Baker Books. ISBN 1441238492.
^ Rana, Fazale. "Crossed off the List: Is the Cross Shape of Laminin Evidence for the Creator?". RTB. Retrieved 26 July 2013.

External links

The Laminin Protein
Laminin at the US National Library of Medicine Medical Subject Headings (MeSH)

Protein: scleroproteins

Extracellular matrix

Collagen

Fibril forming	type I COL1A1 COL1A2 type II (COL2A1) type III type V COL5A1 COL5A2 COL5A3 COL24A1 COL26A1

Other	FACIT: type IX COL9A1 COL9A2 COL9A3 type XII (COL12A1) COL14A1 COL16A1 COL19A1 COL20A1 COL21A1 COL22A1 basement membrane: type IV COL4A1 COL4A2 COL4A3 COL4A4 COL4A5 COL4A6 multiplexin: COL15A1 type XVIII COL18A1 Endostatin transmembrane: COL13A1 COL17A1 COL23A1 COL25A1 other: type VI COL6A1 COL6A2 COL6A3 COL6A5 type VII (COL7A1) type VIII COL8A1 COL8A2 type X (COL10A1) type XI COL11A1 COL11A2 COL27A1 COL28A1

Enzymes	Prolyl hydroxylase/Lysyl hydroxylase Cartilage associated protein/Leprecan ADAMTS2 Procollagen peptidase Lysyl oxidase

Laminin

alpha
- LAMA1
- LAMA2
- LAMA3
- LAMA4
- LAMA5
beta
- LAMB1
- LAMB2
- LAMB3
- LAMB4
gamma
- LAMC1
- LAMC2
- LAMC3

Other

See also: diseases B proteins: BY STRUCTURE: membrane, globular (en, ca, an), fibrous

This article incorporates text from the public domain Pfam and InterPro IPR002049

This article incorporates text from the public domain Pfam and InterPro IPR012679

This article incorporates text from the public domain Pfam and InterPro IPR012680

This article incorporates text from the public domain Pfam and InterPro IPR009254

This article incorporates text from the public domain Pfam and InterPro IPR010307

This article incorporates text from the public domain Pfam and InterPro IPR008211

This article incorporates text from the public domain Pfam and InterPro IPR000034

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.

Laminin EGF-like (Domains III and V) Provide feedback

This family is like PF00008 but has 8 conserved cysteines instead of six.

Literature references

Engel J; , Biochemistry 1992;31:10643-10651.: Laminins and other strange proteins. PUBMED:1420180 EPMC:1420180

Internal database links

Similarity to PfamA using HHSearch:

hEGF

External database links

HOMSTRAD:	EGF_Lam
PANDIT:	PF00053
PRINTS:	PR00011
PROSITE:	PDOC00021
PROSITE profile:	PS50027
Pseudofam:	PF00053
SCOP:	1tle
SYSTERS:	Laminin_EGF

This tab holds annotation information from the InterPro database.

InterPro entry IPR002049

Laminins [PUBMED:2404817] are the major noncollagenous components of basement membranes that mediate cell adhesion, growth migration, and differentiation. They are composed of distinct but related alpha, beta and gamma chains. The three chains form a cross-shaped molecule that consist of a long arm and three short globular arms. The long arm consist of a coiled coil structure contributed by all three chains and cross-linked by interchain disulphide bonds. Beside different types of globular domains each subunit contains, in its first half, consecutive repeats of about 60 amino acids in length that include eight conserved cysteines [PUBMED:2666164]. The tertiary structure [PUBMED:8648630, PUBMED:8648631] of this domain is remotely similar in its N-terminal to that of the EGF-like module (see PROSITEDOC). It is known as a 'LE' or 'laminin-type EGF-like' domain. The number of copies of the LE domain in the different forms of laminins is highly variable; from 3 up to 22 copies have been found. A schematic representation of the topology of the four disulphide bonds in the LE domain is shown below.

         +-------------------+
       +-|-----------+       |  +--------+  +-----------------+
       | |           |       |  |        |  |                 |
     xxCxCxxxxxxxxxxxCxxxxxxxCxxCxxxxxGxxCxxCxxgaagxxxxxxxxxxxCxx
       sssssssssssssssssssssssssssssssssss
'C': conserved cysteine involved in a disulphide bond
'a': conserved aromatic residue
'G': conserved glycine (lower case = less conserved)
's': region similar to the EGF-like domain

In mouse laminin gamma-1 chain, the seventh LE domain has been shown to be the only one that binds with a high affinity to nidogen [PUBMED:7781764]. The binding-sites are located on the surface within the loops C1-C3 and C5-C6 [PUBMED:8648630, PUBMED:8648631]. Long consecutive arrays of LE domains in laminins form rod-like elements of limited flexibility [PUBMED:2404817], which determine the spacing in the formation of laminin networks of basement membranes [PUBMED:8349613].

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 EGF (CL0001), which has the following description:

Members of this clan all belong to the EGF superfamily. This particular superfamily is characterised as having least 6 cysteines residues. These cysteine form disulphide bonds, in the order 1-3, 2-4, 5-6, which are essential for the stability of the EGF fold. These disulphide bonds are stacked in a ladder-like arrangement. The Laminin EGF family is distinguished by having an an additional disulphide bond. The function of the domains within this family remains unclear, but they are though to largely perform a structural role. More often than not, there domains are arranged a tandem repeats in extracellular proteins.

The clan contains the following 13 members:

cEGF DSL EGF EGF_2 EGF_3 EGF_alliinase EGF_CA EGF_MSP1_1 FOLN FXa_inhibition hEGF Laminin_EGF Tme5_EGF_like

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...

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Alignment types

We make a range of alignments for each Pfam-A family:

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full: the alignment generated by searching the sequence database using the HMM
RP15/RP35/RP55/RP75: Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
NCBI: alignment generated by searching the NCBI sequence database using the family HMM
meta: alignment generated by searching the metagenomics sequence database using the family HMM

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You can also change the order in which sequences are listed in the alignment, change how insertions are represented, alter the characters that are used to represent gaps in sequences and, finally, choose whether to download the alignment or to view it in your browser directly.

Downloading

You may find that large alignments cause problems for the viewers and the reformatting tool, so we also provide all alignments in Stockholm format. You can download either the plain text alignment, or a gzipped version of it.

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 (72)	Full (16492)	Representative proteomes				NCBI (15120)	Meta (36)
	Seed (72)	Full (16492)	RP15 (2235)	RP35 (2973)	RP55 (5910)	RP75 (9516)	NCBI (15120)	Meta (36)
Jalview	View	View	View	View	View	View	View	View
HTML	View		View	View
PP/heatmap	₁		View	View
Pfam viewer	View	View

¹Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: available, not generated, — not available.

Format an alignment

	Seed (72)	Full (16492)	Representative proteomes				NCBI (15120)	Meta (36)
	Seed (72)	Full (16492)	RP15 (2235)	RP35 (2973)	RP55 (5910)	RP75 (9516)	NCBI (15120)	Meta (36)
Alignment:
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	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 (72)	Full (16492)	Representative proteomes				NCBI (15120)	Meta (36)
	Seed (72)	Full (16492)	RP15 (2235)	RP35 (2973)	RP55 (5910)	RP75 (9516)	NCBI (15120)	Meta (36)
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

Seed source:

Swissprot_feature_table

Previous IDs:

none

Type:

Family

Author:

Sonnhammer ELL

Number in seed:

72

Number in full:

16492

Average length of the domain:

49.50 aa

Average identity of full alignment:

30 %

Average coverage of the sequence by the domain:

19.94 %

HMM information

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	21.0	13.4
Trusted cut-off	21.0	13.4
Noise cut-off	20.9	13.3

Model length:

49

Family (HMM) version:

19

Download:

download the raw HMM for this family

Species distribution

Sunburst
Tree

Sunburst controls

Show

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.

How the sunburst is generated

The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.

In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:

superkingdom
kingdom
phylum
class
order
family
genus
species

Colouring and labels

Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.

As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.

Anomalies in the taxonomy tree

There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.

Missing taxonomic levels

Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.

Unmapped species names

The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.

So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".

Sub-species

Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.

Too many species/sequences

For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.

Loading sunburst data...

Tree controls

Hide

The tree shows the occurrence of this domain across different species. More...

Species trees

We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.

Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.

If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.

Interactive tree

For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.

We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.

Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.

We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.

You can use the tree controls to manipulate how the interactive tree is displayed:

show/hide the summary boxes
highlight species that are represented in the seed alignment
expand/collapse the tree or expand it to a given depth
select a sub-tree or a set of species within the tree and view them graphically or as an alignment
save a plain text representation of the tree

Loading...

Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

Interactions

There are 2 interactions for this family. More...

Laminin_EGF Ldl_recept_b

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 Laminin_EGF domain has been found. There are 15 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.

Loading structure mapping...

Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

Family: Laminin_EGF (PF00053)

Jump to...

Summary: Laminin EGF-like (Domains III and V)

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Laminin Edit Wikipedia article

Contents

Types

Networks

Pathology

Laminins in cell culture

Role in neural development

Role in cancer

Laminin domains

Laminin I and Laminin II

Laminin B

Laminin EGF-like

Laminin G

Laminin N-terminal

Human proteins containing laminin domains

Laminin Domain I

Laminin Domain II

Laminin B (Domain IV)

Laminin EGF-like (Domains III and V)

Laminin G domain

Laminin N-terminal (Domain VI)

Role in culture

See also

References

External links

Laminin EGF-like (Domains III and V) Provide feedback

Literature references

Internal database links

External database links

InterPro entry IPR002049

Domain organisation

Pfam Clan

Alignments

Alignment types

Viewing

Reformatting

Downloading

View options

Format an alignment

Download options

External links

HMM logo

Trees

Curation and family details

Curation

HMM information

Species distribution

Sunburst controls

Weight segments by...

Change the size of the sunburst

Colour assignments

Selections

Currently selected:

How the sunburst is generated

Colouring and labels

Anomalies in the taxonomy tree

Missing taxonomic levels

Unmapped species names

Sub-species

Too many species/sequences

Tree controls

Annotation

Download tree

Selected sequences

Species trees

Interactive tree

Interactions

Structures